The mechanical etiology of spondylolysis and spondylolisthesis. There are 3 mechanisms that may result in failure of the neural arch with or without displacement of the vertebral body of the pathological vertebral: flexion overload, unbalanced shear forces and forced rotation. It is understood that all types of overload may be applied simultaneously and in various combinations. Of all the forces acting on the lumbar spine torsional violence is the most disruptive of the neural arch. Besides causing olisthesis, it is also capable of producing lysis of the pars especially  if the dorsal spine has the added restraint of high tensile stresses in the posterior ligamentous system. Under normal conditions, the L5-S1 intervertebral joint is subject to the highest forces and it therefore receives the first damage. However, in the presence of antiverse process, damaging stress occurs in the next higher joint. While the antitorsional large transverse process may protect the L5-S1 joint from torsion, it may not protect the L5 vertebra from excessive flexional strains that may fracture the pars. Though lysis may occur in both instances, paradoxically spondylolysis and spondylolisthesis are mutually exclusive conditions. It has long been thought that shear force imbalance was the causative agent in olisthesis. This mechanism remains unconvincing except possibly in instances where there is a pathological condition affecting the skeletal tissue.


Effect of lordosis on the stress in the lumbar spine. A simple mathematical model is used to explore the influence of lordosis on the stress in the human spine. It is shown that flatter spines would tend to fail by flexion while spines with more lordosis would tend to fail by torsion.


Mechanical factors in spondylolisthesis and spondylolysis. Anterior displacement in spondylolisthesis is a slow process. The forces contributing to anterior shear arise from the vertical load on the spine above the lesion, from activity in the muscles of the spine and trunk, and from the effects of movements. The shear is normally resisted by the annulus fibrosus, compression of the facets at the apophyseal joints, and by tension in the anterolateral layers of cortical bone in the pars interarticularis. The anterior shear-strength of the disk is not known though Cyron and Hutton have shown that it is a major contributor to the total stiffness; in the early stages of spondylolysis it provides the only resistance. The capacity of the pars for resisting tensile forces anteriorly has been studied in tests of single vertebrae in which posterior forces were applied to the inferior articular processes. Forces at failure at L4 and L5 have been reported at up to 2500 N by Cyron et al. and up to 5800 N by Lamy et al. with means of 1800 N and 3200 N respectively. The mean posterior displacement of the inferior facets reported by Cyron et al. was 6.5 mm at failure. Too little is known of the mechanical factors in the etiology of spondylolysis for a definition of the postures and movements of the body which put the lumbar neural arch at greatest risk. While a combination of fatigue-failure and high strain-rate of forces induced in extended postures seems likely, further investigations are needed to elucidate the pathogenesis in many cases.


Standing roentgenograms in spondylolisthesis. Lateral roentgenograms of 50 patients with spondylolisthesis were made in the recumbent and standing positions and compared. Thirteen (26%) showed an increase in the percentage of displacement on standing. Those patients with demonstrable change appeared to have a higher incidence of severe symptomatology. Apparent spondylolysis on recumbent roentgenograms may change to spondylolisthesis on standing lateral roentgenograms. Degenerative spondylolisthesis may be more apparent on standing lateral roentgenograms.


Operative treatment of spondylolisthesis in young patients. In a series of 91 patients under 20 years of age with lytic spondylolisthesis treated by different operations, 66 (73%) showed a displacement of more than 30 per cent at admission. If the displacement exceeds 30 per cent, it often progresses to a subtotal olisthesis. Spinal fusion should be performed before the displacement exceeds a third of the length of the vertebra. A posterior fusion with two massive tibial grafts was carried out in 78 patients (87.5%). Concurrent with fusion laminectomy was performed in 18 patients. Anterior vertebral body fusion was performed in 3 patients and posterolateral fusion in 10, in 4 of these as a secondary operation. Laminectomy alone was carried out in 4 patients, 3 of these having a total olisthesis. Laminectomy without fusion should be performed only in exceptional cases in young patients. Non-union or uncertain union after the primary operations occurred in 17 cases (19.5%); 15 reoperations were performed in 13 patients. The degree of displacement at operation did not influence the results. A progression of displacement despite dorsal fusion was observed in 14 patients. The final results of operative treatment were: good in 55 patients (60.4%); satisfactory in 23 (24.1%); unsatisfactory in 13 (15.5%). Posterolateral fusion seems to be preferable to posterior fusion.


Treatment of spondylolisthesis and spondylolysis in children. There are 2 fairly common types of spondylolisthesis in children - dysplastic and isthmic. The dysplastic type is secondary to congenital defects at the lumbosacral joint. The isthmic is usually due to a fatigue fracture of the pars interarticularis but there is also an hereditary element in this type. Most children with spondylolisthesis never develop significant symptoms and even of those who do, the vast majority can be treated without surgery. If symptoms persist or if further olisthesis is occurring, a one-level spinal fusion done through a paraspinal approach is recommended. It is most important not to allow olisthesis to develop to the point that the child shows the cosmetically undesirable stigmata characteristic of the condition. Solid fusion can be obtained in every case and will stop further slip.


Hemolytic anemia and edema as the initial signs in infants with cystic fibrosis. Consider this diagnosis even in absence of pulmonary symptoms. This is a report of five infants eventually proven to have cystic fibrosis of the pancreas, who presented with hemolytic anemia and edema. Since the sweat test is often unreliable in edematous states, the possibility of cystic fibrosis should be considered. Use of either a protein hydrolysate or addition of pancreatic enzymes will improve nutritional status, and when edema disappears, a definite sweat test can be performed. Evidence of vitamin E deficiency in some of the cases is presented, and the possibility of this as a cause of anemia is raised.


The susceptibility of adolescent girls to rubella. Observations on 297 girls in Toronto. Since serum rubella H-I antibody titers of 297 adolescent girls showed 25.3 per cent to be susceptible, we support the recommendation that all susceptible girls be immunized, provided of course that after individual evaluation there is no risk of pregnancy at the time of immunization or in the ensuing two months.


Lead on painted handles of kitchen utensils. The lead content of paint on wooden handles of kitchen utensils ranged from 0 to 9.7 per cent (97,000 ppm). Yellow paint showed the highest concentration of lead followed by green and red colors. The values of lead often exceeded the legal limit on toys and paint for use indoors.


Adverse drug reactions-a matter of opinion. The accurate identification of adverse drug reactions (ADRs) is difficult because ADRs usually present no unique clinical or laboratory findings that demarcate them from the manifestations of concurrent illnesses. The identification of ADRs depends on the clinical assessments of physicians-sometimes the clinician treating the patient and at other times a clinical pharmacologist. Considering the complex and subjective nature of clinically identifying ADRs, how accurately are ADRs identified? To answer this question, three clinical pharmacologists each independently evaluated 60 selected cases to determine if medication, alcohol, or "recreational" drugs had caused the hospitalization. The three clinical pharmacologists agreed on only 30 cases (50%), and 27 of these were thought to be unrelated to medications. In 19 of the 30 cases about which the clinical pharmacologists disagreed, they disagreed on whether or not a medication-or alcohol-related event had occurred at all. The clinical pharmacologists disagreed with the physicians treating the patient in 22% to 37% of the cases, but because of the differences among the pharmacologists, the treating physicians agreed with at least one of them in 95% of the cases. Complete agreement between the clinical pharmacologists and the treating physicians occurred in 47% of the cases. This degree of disparity in the clinical identification of ADRs shows that the evaluation of ADRs is subjective and imprecise. The accurate identification of ADRs awaits the development of an objective technique for recognizing ADRs.


Effect of lidocaine on right ventricular muscle refractoriness. The effect of clinical doses of lidocaine on ventricular refractoriness was investigated in man. Effective refractory period (ERP) and functional refractory period (FRP) were determined in 11 normokalemic patients via a catheter at the right ventricular apex using programmed extra-stimuli and a ventricular electrogram recorded from the pacing catheter. No subject had recent ischemia or infarction. Measurements were repeated after clinical doses of lidocaine that produced therapeutic blood levels. Lidocaine caused no significant change in ERP or FRP during ventricular or atrial drive, or sinus rhythm with unchanged cycle length (CL). During sinus rhythm ERP/CL was unchanged. In 4 of 5 patients, lidocaine did not abolish echo phenomena observed during ventricular drive. This study demonstrates that ventricular refractoriness can be safely measured in man. Clinical doses of lidocaine did not alter right ventricular refractory periods. Lidocaine action is not explained by alteration of ventricular refractoriness, at least in muscle remote from the site of acute infarction.


Serum triiodothyronine levels in patients receiving L-thyroxine. Serum triiodothyronine (T3) and thyroxine (T4) levels were measured in 103 adult patients receiving sodium L-thyroxine (Synthroid), 0.2 or 0.3 mg daily for at least 3 mo, as suppression or replacement therapy. All were judged to be clinically euthyroid at the time of the measurements. The mean +/-SD T3 level during treatment was 130.3 +/-47.5 ng% and the mean T4 level was 11.0 +/-2.0 mug%. In normal untreated euthyroid subjects, the mean T3 level was 115.4 +/-26.0 ng% and the mean T4 level was 8.0 +/-1.7mug%. When sodium L-thyroxine was added in vitro to the stored sera of 10 hypothyroid patients to produce serum T4 levels equivalent to those that the patients later showed in vivo while on therapy, the cross-reaction was 0.85%. Thus at a mean T4 level of 11.0 mug%, there was a mean T3 level of 93.5 ng% that could be attributed to the added thyroxine itself. This cross-reaction was found to be due to contamination of the added sodium L-thyroxine with T3 and not due to cross-reactivity of the T3 antibody in the immunoassay system with T4. For 3 other brands of sodium L-thyroxine, the T3 contamination of the added T4 was 0.75%, 0.55%, and 0.40%. When 6 hypothyroid patients were given 5 mug of L-triiodothyronine (Cytomel) daily for 4 wk, there was no rise in serum T3 levels. When the same patients were switched to sodium L-thyroxine, 0.2 mg daily, serum T3 levels rose from a mean +/-SD of 60.0 +/-16.3 ng% to a mean of 130.0 +/-38.0 ng%. It would thus appear that in patients receiving sodium L-throxine therapy, the resulting serum T3 levels are due to extrathyroidal conversion of the administered T4 to T3, and not to the T3 present in the L-thyroxine administered.


Absorption, metabolism, and excretion of hydrochlorothiazide. 14C-hydrochlorothiazide (hct) was administered orally (n=4) and iv (n = 2 to healthy subjects. The gastrointestinal absorption ranged between 60% and 80%, most of it took place in the duodenum and the upper jejunum. The radioactivity was eliminated mainly in the urine, while no sigificant biliary excretion was observed. Chromatographic analysis of the urinary radioactivity demonstrated that greater than 95% of the absorbed or injected 14C-hct was excreted unchanged. The radioactivity in plasma during the first 10 hr after oral administration declined with a fast phase but the levels of label thereafter suggested a slow phase. The existence of such a phase was verified in 1 subject given 75 mg hct orally. His plasma levels of hct (determined with gas-liquid chromatography) declined according to a 2-compartment model, the half-lives of the alpha-and beta-phases being 1.7 and 13.1 hr, respectively. Hct accumulated in the blood cells and the ratio between the radioactivity in cells and that in plasma averaged 3.5. The fate of a single dose of 14C-hct in 2 hypertensive patients treated with the drug chronically was similar to that in the healthy subjects. A third patient, who had slightly elevated serum creatinine, eliminated hct more slowly than the others. Like the healthy subjects, the patients eliminated hct to greater than 95% in unchanged form.


Furosemide and bumetanide: a study of responses in normal English and German subjects. Diuretic responses to oral administration of 1 mg bumetanide and 40 mg furosemide were determined in double-blind, crossover balanced trials in 10 normal English subjects and 6 normal German subjects. In each experiment the 0- to 8-hr urine volume and sodium excretion were significantly higher after bumetanide, potassium excretion did not differ, and the Na/K ratio, although higher after bumetanide, was not significantly different by analysis of variance. In German subjects the diuretic and natriuretic responses to both drugs were greater and the potassium excretion less than in English subjects. In the English, the pretreatment 24-hr urinary Na/K ratio correlated with the urinary Na/K ratio response to both drugs and with the potassium excretion after furosemide. The mean plasma uric acid before treatment correlated with the Na/K ratio and potassium excretion after furosemide. Aldosterone excretion did not correlate with response to either diuretic. The mean pretreatment 24-hr log10 Na/K ratio in the two treatment periods of the English and German subjects correlated with the mean sodium excretion, potassium excretion, and log10 Na/K after the two diuretics, thus providing a partial explanation for intersubject and interstudy variation. Pretreatment log10 Na/K could also explain intrasubject variation, justifying its use as a covariate in covariance analysis. This demonstrated that at this dose ratio the urinary log10 Na/K ratio response to bumetanide was significantly higher than that to furosemide.


Effect of smoking on theophylline disposition. The pharmacokinetics of theophylline were examined in a group of nonsmokers and in heavy smokers (1 to 2 packs/day) before and 3 to 4 mo after cessation of cigarette smoking. The half-life of theophylline in smokers averaged 4.3 (SD = 1.4) hr, significantly shorter than the mean value in nonsmokers (7.0, SD =1.7 hr). The apparent volume of distribution of theophylline was somewhat larger in smokers (0.50 +/-0.12 L/kg) than in nonsmokers (0.38 +/-0.04 L/kg). The body clearance of theophylline was appreciably larger and relatively more variable in smokers (100 +/-44 ml/min/1.73 m2) than in nonsmokers (45 +/-13 ml/min/1.73 m2). Serum concentrations of thiocyanate, a biotransformation product of cyanide which is inhaled with smoke, were used to monitor the smoking status of the subjects. The body clearances of theophylline showed a good correlation (r = 0.785, p less than 0.001) with the serum thiocyanate concentrations. Of the 8 smokers, only 4 managed to refrain from smoking for at least 3 mo, and these subjects showed no significant change in theophylline elimination. The increase in theophylline clearance caused by smoking is probably the result of induction of drug-metabolizing enzymes that do not readily normalize after cessation of smoking.


Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect. The serum protein binding and elimination kinetics of warfarin were determined in 31 patients with cardiovascular disease who were taking warfarin regularly. The free fraction of warfarin in the serum ranged from 0.00436 to 0.0189, indicating 98.11% to 99.56% protein binding. There was no apparent relationship between the extent of protein binding of warfarin and the concentration of albumin or total protein in the serum. The estimated total body clearance of warfarin in the patients ranged from 1.16 to 4.35ml/hr/kg of body weight and correlated significantly with the free fraction of warfarin in serum. This correlation has been predicted on theoretical grounds and shows that serum protein binding is a major determinant of the elimination kinetics of warfarin in man and an important cause of interindividual variations in its body clearance. The interindividual variation of free warfarin concentrations in the serum of patients with similar prothrombin times was somewhat smaller than the variations in total serum-warfarin concentrations and in the daily dose of warfarin. There was no correlation between prothrombin time and the concentration of free warfarin in serum, indicating that variables other than protein binding also affect the anticoagulant response of patients.


Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels. The influence of various test meals and ingested fluid volumes on the bioavailability and pharmacokinetics of propoxyphene and its major metabolite norporpoxyphene has been studied in healthy human subjects. The absorption of drug was delayed by all test meals, but the overall efficiency of absorption was either not affected or was slightly increased. Increased fluid volume intake decreased propoxyphene bioavailability. Plasma levels of metabolite correlated well with levels of unchanged drug, particularly in the first 2 hr after dosing, but were not markedly influenced by treatments.


Disposition kinetics of two oral forms of quinidine. There are relatively few studies on the disposition properties of quinidine. We have studied in 10 normal subjects conventional quinidine sulfate and a slow-release quinidine bisulfate. Single and repetitive doses were given; blood and urine concentrations were measured by the method of Cramer and Isaakson. After a single dose of two tablets of quinidine sulfate (400 mg), the average peak concentration was 2.13 +/-0.22 mug/ml (+/-SEM); following two tablets of the slow-release form, the average peak concentration was 1.17 +/-0.12 mug/ml. T-max was approximately 2 hr with quinidine sulfate and 4 hr with quinidine bisulfate. One fourth of both forms of the drug was recovered in the urine. Total body clearance was 0.36 L/kg-hr and renal clearance was 117 +/-22ml/min for both. With multiple dosing the serum quinidine concentration was higher than these predicted from the results of the single-dose study. Based on the mean estimates of quinidine half-life of 6 hr, a rapid method for achieving steady-state levels of quinidine would be to give an initial dose twice that of the maintenance dose. With the slow-release product if an equivalent dose was given every 12 hr, the mean steady-state quinidine serum concentration would be approximately the same.


Intestinal absorption, demethylation, and enterohepatic circulation of imipramine. The intestinal absorption and metabolism of single oral doses of imipramine (ip) have been studied in man by portal catheterization. The concentration of ip and the formed desipramine (dmi) was followed in blood-plasma obtained from the portal and cubital veins. The absorption of ip seemed to be completed 80 min after the administration of the drug. There was no sign of demethylation of ip during the passage across the intestinal wall. Evidence was found of an enterohepatic circulation of both ip and dmi.


Pivampicillin and ampicillin in bile, portal and peripheral blood. In 7 patients with a catheter in the portal vein and a T tube in the common bile duct, the concentration of unhydrolyzed pivampicillin and of ampicillin was measured simultaneously in portal and peripheral blood and in bile after oral administration of 700 mg pivampicillin. In both portal and peripheral circulation of concentration of unhydrolyzed pivampicillin was always less than 1% of the levels of ampicillin, indicating the effectiveness of the intestinal mucosa in the hydrolysis of pivampicillin. Evidence for the ability of the liver to excrete ampicillin against a concentration gradient into the bile was established by direct measurements. Only about 1% of the dose given could be recovered in the bile. There was an unexplained reduction of about 70% in the absorption of the drug induced by the catheter itself.


Anorectal pruritus after intravenous hydrocortisone sodium succinate and sodium phosphate. A double-blind study demonstrated that single intravenous doses of 100, 200, or 400 mg of hydrocortisone sodium succinate and hydrocortisone sodium phosphate were similar in eosinophil suppression, elevation of glucose, white blood count differential shifts (polymorphonuclear cells, lymphocytes, and monocytes), and urinary excretion of sodium and potassium but not in incidence of side effects. More subjects receiving hydrocortisone sodium phosphate experienced systemic or localized adverse effects than those receiving hydrocortisone sodium succinate. The most common side effect was burning or itching in the anorectal area, which occurred in 16 of 18 subjects medicated with hydrocortisone sodium phosphate, in 1 subject of 6 treated with placebo (saline), and in none who received the sodium succinate. The effect is attributed to the phosphate steroid and appears to last as long as it takes to convert to cortisol.


Studies on digitalis. VI. The effect of heparin on serum protein binding of digitoxin and digoxin. The aim of the present study was to investigate the nature of the previously reported changes in the serum protein binding of digitoxin and digoxin in uremic patients under treatment with hemodialysis. Kinetic studies on protein binding during hemodialysis showed that the free fraction of digitoxin rose from 2.6% to 6.9% after 5 min of hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from 78.3% to 87.1% during the same period. In vitro hemodialysis experiments showed that such changes occurred only in vivo. Injection of heparin (5,000 IU) to control subjects produced similar kinetic changes in the protein binding of digitoxin and digoxin. Free fatty acids changed in the same way. These results indicate that the heparin-induced release of free fatty acids causes displacement of digitoxin and digoxin from their albumin-binding sites. Patients on hemodialysis have lower serum levels of digitoxin and cardioactive metabolites (mean, 8.9 ng/ml) than control patients (mean, 16.7 ng/ml) (p less than 0.005) on similar doses (mean, 0.085 mg/day). They should be maintained on the same digotoxin doses as uremic and control patients, but serum digitoxin levels should be adjusted to 10 to 15 ng/ml in hemodialysis patients compared to 15 to 25 ng/ml in uremic patients and in patients with normal renal function.


Cardiovascular effects of a new inotropic drug in dog and normal man. Cardiovascular effects of 1-butyl-3(1-(6,7-dimethoxyquinazolin-4-yl) piperidin 4 yl urea) (BDPU) were studied in 16 anesthetized dogs and in 7 healthy male volunteers. In animal experiments intravenous doses of 100, 250, and 500 mug/kg/min produced dose-related, significant increases in cardiac output and peak left ventricular dp/dt. No changes in heart rate and blood pressure occurred at 100 mug/kg/min, whereas higher doses caused falls in both systolic and diastolic blood pressures, accompanied by significant rises in heart rate. Inotropic effects could also be demonstrated in man. Changes of the systolic time intervals were dose-related and began at 64 mug/kg/min. At 250 mug/kg/min, the highest dose administered, the pre-ejection period decreased by 14.8 +/- 4.42 msec and its ratio with left ventricular ejection time by 0.049 +/- 0.017 against their respective control values (p less than 0.01). In contrast to animal experiments, no hypotension or tachycardia was observed in any subject. Pharmacokinetic studies showed a plasma elimination half-life of 76 +/- 3 min (mean +/- SE). There were no subjective side effects and standard laboratory tests were not altered, but there was a slight but significant rise in the urinary enzymes, lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT), which persisted up to 7 days.


Impaired plasma protein binding of phenytoin in uremia and displacement effect of salicylic acid. The plasma protein binding of phenytoin (DPH) was studied by equilibrium dialysis at 37 degrees C in plasma from uremic patients and healthy subjects. Scatchard plot analyses demonstrated a decreased association constant Ka for the DPH-albumin interaction in the uremic plasma (mean 1.76 - 10(3) M-1 +/-SD 0.12 and a mean 4.10 - 10(3) M-1 +/- SD 0.24 in normal plasma). Studies on separated fractions of serum did not indicate any significant binding of DPH to proteins other than albumin. The nonlinear mathematical relationship between bound DPH and serum albumin could be linearized at low drug concentrations by plotting the ratio of bound/unbound DPH against albumin concentration. The displacement effect of salicylic acid at a concentration of 276 mug/ml (2mM) and DPH was considerable in plasma from normal subjects. In uremic plasma the effect was of much smaller magnitude.


Kinetics and dose calculations of amikacin in the newborn. The pharmacokinetics of a new aminoglycoside, amikacin, was evaluated in 37 infants between 1 and 34 days old. Fifteen were below 2,500 gm in weight. Initial studies, including intravenous infusion in some of the infants, indicated that the disposition of amikacin was best described by a 2 compartment model. The absorption was evaluated in 8 of the infants after intramuscular injection of 7.5 mg amikacin per kilogram of body weight. The absorption rate, estimated by the tmax, was significantly faster than reported in adults. The total body clearance and apparent volume of distribution were studied in 22 infants after the same dose of amikacin intramuscularly. The body clearance expressed in relation to body surface or body weight was significantly less than in adults and correlated with the postnatal age. No correlation could be demonstrated between clearance and gestational age or birth weight. The volume of distribution per kilogram was significantly greater than in adults. On the basis of the derived kinetic parameters, a dose schedule is presented. In 5 children there was a reasonable agreement between the measured and predicted serum levels.


Pentobarbital elimination in patients with poor renal function. Drug oxidation is slowed in experimental uremia in animals but has been reported to be normal or accelerated in uremic patients. Eleven normal subjects and 9 uremic patients were each given 100 mg pantobarbital orally. Several blood samples were drawn over a 36-hr period starting on the morning after the dose. Plasma pentobarbital concentration was measured by GLC. The log concentration values were graphed against time elapsed after dose for each patient, and the plasma T/2 and extrapolated value of concentration at the time of drug administration (Co) were determined. The T/2 values in normals ranged from 18 to 48 hr; mean, 26.5 +/- 9.2 (SD). In uremic patients, T/2 values are 10 to 38 hr, mean, 21.3 +/- 8.7. Four of the uremic patients had T/2 values below 18 hr (which was the lowest in the normals). The apparent volumes of distribution of pentobarbital (aVD = dose divided by Co) were 62 +/- 25 L in the normal subjects and 58 +/- 24 L in the uremic patients. The four uremic patients with the short T/2 values tended to have small apparent volumes of distribution so that the metabolic clearnce rates (aVd X 0.693 divided by half-life) were normal in 3 of them. We conclude that pentobarbital elimination is normal in renal failure. Some uremic patients have short plasma T/2 values for pentobarbital, and these more likely result from low apparent volumes of distribution with normal metabolic clearance rates than from accelerated metabolism of pentobarbital.


Elimination of antipyrine and benzo[a]pyrene metabolism in cultured human lymphocytes. A strong correlation was found in a carefully selected homogenous population (n = 57) between antipyrine plasma half-life and the percent induction of aryl hydrocarbon hydroxylase by 3-methylcholanthrene in mitogen-stimulated lymphocytes from the same individual. The correlation coefficient of r = 0.923 indicates that antipyrine and benzo[a]pyrene share one or several common determinants that are responsible for the observed interindividual variation in the oxidation rates of the two compounds. When a heterogenous population (n = 80) was studied, the above correlation was not found (r = 0.425).


The clearance of antipyrine and indocyanine green in normal subjects and in patients with chronic lever disease. The pharmacokinetics after oral administration of 1,200 mg antipyrine and intravenous administration of 0.5 mg/kg indocyanine green have been investigated in 6 normal subjects and in 20 patients with chronic liver disease of varying etiology. Severe impairment of liver function associated with a decrease in serum albumin, elevation in serum bilirubin, or prolongation in prothrombin time correlated with a fall in the clearance of both drugs. The clearance of the two drugs correlated well in normal subjects and in patients with chronic liver disease. The presence of a surgical portacaval anastomosis was associated with a lower indocyanine green clearance for comparable clearance of antipyrine. The concept of functioning hepatic parenchymal mass is proposed as a common rate-limiting parameter for the elimination of the two drugs.


Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin. Five patients received a small oral dose of warfarin during and after recovery from acute viral hepatitis. Mean (+/- SD) clearance, volume of distribution, and half-life of the drug were 6.1 +/- 0.9 ml/hr/kg, 0.09 +/- 0.04 L/kg, and 23 +/- 5 hr, respectively, during the acute period. After apparent recovery, observed values were 6.1 +/- 0.7 ml/hr/kg, 0.21 +/- 0.02 L/kg, and 25 +/- 3 hr. These differences were not significant. Pattern of renal elimination of warfarin metabolites and drug protein binding did not change between the two phases. During the acute period of illness, prothrombin time increased in 2 of the 5 subjects, but remained within normal limits in all participants during the recovery period. This study shows that warfarin disposition may not change as a consequence of mild or moderate hepatic impairment.


Dicloxacillin and cloxacillin: pharmacokinetics in healthy and hemodialysis subjects. Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose).


Skin reaction. A quantitative system for measurement of radiosensitisation in man. Areas of skin have been irradiated using a radio-strontium plaque giving 800 to 1100 rad. Visual ranking of the reactions produced proved to be the best method of measuring the response. Erythema was poorly related to dose but in most cases the amount of pigmentation produced was directly related to it. This system, for use in the testing of radiosensitisers, allows a quantitative estimate of enhancement of response to be made.


Clinical testing of the radiosensitiser Ro-07-0582. II. Radiosensitisation of normal and hypoxic skin. The effectiveness of the radiosensitiser Ro-07-0582 has been tested in man by observing the skin reaction after irradiation using a radio-strontium source with and without administration of the drug. The skin reaction technique has been extended so that skin was irradiated when at low oxygen tension (hypoxic) as well as when fully oxygenated (oxic). Limbs have been made hypoxic by occlusion of the circulation using a sphygmomanometer cuff. To this has been added the prior use of an Esmarch's bandage to reduce the volume of blood in the skin and the enclosing of the limb in a bag of nitrogen. The Oxygen Enhancement Ratios obtained without the sensitiser in nine studies using this system ranged from 1-64 to 2-46. Using Ro-07-0582 skin reactions after oxic exposures were not enhanced but those after hypoxic exposures were markedly increased. The Relative Sensitising Efficiency expresses, as a percentage, the restoration of the sensitivity of cells protected by hypoxia. In six cases where Ro-07-0582 was given in doses ranging from 81 to 165 mg/kg, efficiencies ranged from 27 to 71%. These results can be compared with three studies using metronidazole where efficiencies ranged from 11 to 15%. Using comparable dosage Ro-07-0582 seems approximately three times more effective than metronidazole. In this first study in man, Ro-07-0582 appears to be a highly effective radiosensitiser of hypoxic cells.


The effect of immobilisation on localisation error in the radiotherapy of head and neck cancer. With the use of treatment verification films for the detection of localisation error (LE), a study was undertaken to determine the effect of change in position and immobilisation on LE in the radiotherapy of patients with head and neck cancer. For those patients not immobilised and treated in the lateral position, 28 errors were recorded in a review of 172 films, giving an error incidence of 16%. For patients immobilised by bite block and treated in the supine position, a total of four errors were recorded on review of 382 films, giving an error incidence of 1%. The reduction of LE from 16% to 1% by supine positioning and bite block immobilisation was significant with a P value of less than 0.001. The potential significance of LE in relation to CNS injury and tumour recurrence is discussed.


Keloid scars: a new method of treatment combining surgery with interstitial radiotherapy. A method is described for the treatment of the linear keloid scar, by surgical excision and post-operative irradiation delivered locally to the base of the sutured edges of the scar, by an iridium-192 wire. The wire is after-loaded into a plastic tube using the technique described by Paine (1972). A dose of 2000 rad is delivered at a point 2-5 mm from the axis of the wire, opposite its mid-point. Thirty cases have been treated by this method with a follow-up period of two years or longer; five recurrences were found at six months, and a further one by two years. No complications were observed. It is suggested that this represents a rather lower recurrence rate than has been achieved by other methods, and that the dose to the tissue surrounding the scar is less than that which would be the case with conventional superficial radiotherapy - an important consideration in the treatment of young patients, with benign conditions, by irradiation.


On long-term survivals in non-Hodgkin's lymphoma with 'gentle' treatment. Eighty-seven cases of non-Hodgkin's lymphomas from the Southern California Permanente Medical Group have been reviewed. The patients were treated between 1953 and 1960, all in an era of 'minimal' radiotherapeutic and chemotherapeutic treatment. The favourable prognostic factors for long-term survival using gentle treatment are, firstly, nodular pattern, presenting in clinically localised Stages I and II and, secondly, diffuse well-differentiated lymphocytic lymphoma (DLWD) presenting either in a localised or generalised fashion. In this series moderate dose irradiation (2500 rad) to involved areas with or without modest chemotherapy has resulted in the survival of 26 out of 32 DLWD patients for more than five years and in most cases for over ten years.


Scleroderma and carcinoma of the lung.

Scleroderma and carcinoma of the lung. Two cases of scleroderma and carcinoma of the lung are reported. The 16 previously reported cases in the English literature are reviewed and tabulated in an attempt to determine the pathological and clinical presentation of carcinoma of the lung superimposed on the sclerodermal lung. When patients with scleroderma develop a change in pulmonary symptoms, a superimposed cancer of the lung should be suspected. The relationship between interstitial pulmonary inflammatory disease and cancer of the lung is discussed.


Destroyed lung. A report of cases in West Indians and Australian Aborigines. A series of patients with total destruction of one lung by bronchiectasis and a normal contralateral lung is reported. Eight cases were West Indians of Negro race and four were Australian Aborigines. The bronchiectasis appears to be of post-infective type and is related to the poor social conditions under which the affected people live. It has also been noted in other developing countries or in under-privileged races in developed countries.


131I Rose Bengal scanning and clearance ratios in the investigation of jaundiced patients. It may be difficult to distinguish between obstructive and non-obstructive jaundice despite the use of clinical, biochemical and radiographic tests. Endoscopic cannulation tests promise to be the most accurate means of separating the two groups, but they are not yet widely available, and are not entirely safe. In contrast, the 131I-Rose Bengal test is simple, safe and comparatively widely available. Its accuracy in 70 jaundiced patients is reviewed to determine whether it still has a place in the investigation of jaundiced patients. Blood clearance traces, intestinal radioactivity traces and serial abdominal scans were done during a period of 3 h. The blood clearance ratios were not helpful discriminators, and the most helpful information was the timing of intestinal radioactivity. Its rapid appearance excluded mechanical obstruction. A delay of up to 3 h in its appearance was characteristic of cholestasis. A delay of more than 3 h was found in all cases of mechanical obstruction, but also in ten cases of severe cholestasis which could not be distinguished from those with mechanical obstruction. A follow-up examination within another ten days was of diagnostic value in two of these cases and the overall accuracy of the test was 86%. The potential value of prolonging the test to 24 h is discussed. It is concluded that the 131I-Rose Bengal test is a helpful diagnostic discriminator in the great majority of patients with jaundice. It is offered as a screening procedure for specialised techniques.


Thermography and radiology complimentary methods for the study of inflammatory diseases. The authors have correlated the findings of thermography and radiology in some inflammatory lesions. The two investigations are complementary. Thermography demonstrates changes of vascularity in the acute phase of a lesion whereas radiology is of value in showing structural changes.


Single bolus versus drip infusion for intravenous cholangiography. Biliary tract visualisation in 50 patients examined by infusion of methylglucamine iodipamide was compared, by double-blind technique, to cholangiograms obtained in 50 other patients by a single bolus injection. The infusion technique did not give better results than the single bolus method. In another group of 20 patients, each individual was examined by both methods. The radiographs, read in a double-blind manner, showed both methods to be comparable in demonstrating the biliary system. It seems that other means have to be designed and employed in order to improve the radiographic delineation of the biliary tract.


Gas contrast studies of the biliary tract following reconstructive surgery. Forty-seven patients who had previously undergone reconstructive surgery were examined on 70 occasions by gas contrast cholangiography after drinking carbonified water in order to outline the biliary tract. In the light of subsequent clinical and operative findings the radiological appearances are analysed and the value of the technique assessed. There was a close correlation between failure to visualise the biliary tract and obstruction of the anastomosis (85% accurate).


The microvasculature of the spleen.

The microvasculature of the spleen. A method for examining the microvasculature of the dog spleen by angiography is described and the findings are related to morphological studies. The marginal sinus of the lymphoid follicle has been shown to be an important part of the vascular pathway in the spleen. It allows intimate mixing of blood elements and spleen cells and it is suggested that this plays an important immunological role. The control of blood flow to the lymphoid follicle is discussed but requires further elucidation.


Angiographic anatomy of the right heart. Casts of human hearts were prepared and photographed to illustrate the anatomy of the right heart chambers and ventricular septum. The casts were used to illustrate the anatomy of certain common pathological abnormalities of the ventricular septum and the appearances compared to angiocardiograms.


The effect of repeated phlebotomy on bilirubin turnover, bilirubin clearance and unconjugated hyperbilirubinaemia in the Crigler-Najjar syndrome and the jaundiced Gunn rat: application of computers to experimental design. 1. A multicompartmental model of erythrokinetics and bilirubin production has been developed to predict the consequences of chronic phlebotomy on daily bilirubin turnover. 2. Control values for four physiological variables including bilirubin turnover were determined in a 20-year-old woman with type I congenital nonhaemolytic jaundice (Crigler-Najjar syndrome). With these base-line data, the model predicted the following changes during phlebotomy: a 34% fall in bilirubin turnover; a 240% increase in the haemoglobin content of bone-marrow erythroid precursors; a 25% fall in the half-life of 51Cr-labelled erythrocytes; a characteristic alteration of the erythrocyte survival curve after labelling with [2-14C]glycine. 3. On the assumption, previously validated in normal volunteer subjects and patients with Gilbert's syndrome, that hepatic bilirubin clearance was independent of turnover and would therefore remain unchanged, a fall in plasma unconjugated bilirubin concentration during phlebotomy from 436 to 282 mumol/1 was expected. 4. Accordingly, the patient underwent phlebotomy 350 ml/week for 2 months, and 500 ml/week during an additional 3 months. Appropriate studies during phlebotomy confirmed each of the predictions in paragraph 2 above. In particular, turnover fell by 31%. Unexpectedly, plasma unconjugated bilirubin remained essentially unchanged. Analogous results were observed in phlebotomized jaundiced Gunn rats. 5. Kinetic studies in both the patient and the rats demonstrated that the failure of plasma unconjugated bilirubin to fall in parallel with bilirubin turnover resulted from a prolongation of the terminal half-life of radioactively labelled bilirubin and a fall in bilirubin clearance in every instance. 6. These studies indicate that (a) in congenital non-haemolytic jaundice, bilirubin clearance is uniquely influenced by bilirubin turnover and (b) compartmental modelling and kinetic studies are useful for predicting and interpreting the results of both physiological experiments and experimental therapeutic regimens.


The relation between functioning parietal cell and gastrin cell masses in two groups of duodenal ulcer patients. 1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects. 2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess. 3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid "normosecretors" and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low. 4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hyper-secretors but the values for the latter were not different from normal subjects. 5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups. 6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients. 7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass.


Disappearance of 125I-labelled and unlabelled insulins from blood in normal and injured rats. 1. The disappearance from blood of either 125I-labelled bovine insulin or unlabelled rat insulin after a single intravenous injection has been studied in rats. 2. The disappearance of the labelled insulin was slower than that of native insulin. 3. Ether anaesthesia produced a significant impairment, and bilateral nephrectomy a very marked impairment, of disappearance of the labelled insulin, suggesting that changes in the removal of this tracer may nevertheless parallel changes in the metabolism of native insulin. 4. Simultaneous intravenous injection of unlabelled bovine insulin (1 unit/kg) did not affect disappearance of the labelled insulin. 5. A 20% full-thickness scald injury, produced 2 h previously, had no significant effect on disappearance of the labelled insulin, either with or without the simultaneous administration of unlabelled bovine insulin. 6. The disappearance of unlabelled rat insulin from plasma was also similar in control and scalded rats. 7. It was concluded that the half-life of plasma insulin in the rat, as estimated by either of the techniques used, is not significantly affected by this severe non-haemorrhagic injury.


Turnover of plasma glucose and free fatty acids in patients on the first day after myocardial infarction. 1. The turnover of plasma glucose and free fatty acids was measured in ten patients within 24 h of the onset of symptoms of acute myocardial infarction and in two with symptoms of acute myocardial ischaemia. The measurements were repeated in seven of the patients 12-40 weeks after the acute episode. 2. Both for the patients with acute myocardial infarction alone and for all the individuals studied the turnover of glucose increased with plasma glucose concentration but was not related to the turnover of free fatty acids or the plasma concentrations of free fatty acids, insulin or total catecholamines. There was no obvious difference in the nature of the glucose turnover-concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination. 3. For all the individuals studied the turnover of free fatty acids increased with the concentration of these but was not related to the turnover of glucose or the plasma concentrations of glucose, insulin or total catecholamines. There was no obvious difference in the nature of the free fatty acids turnover-concentration relaionship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination.


Renal haemodynamics and plasma renin in patients with essential hypertension. 1. Blood pressure, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in twenty-three patients with essential hypertension and in twenty-one control subjects. Plasma renin concentration was measured in all the hypertensive patients and in fifteen control subjects. 2. GFR and RPF were similar in the hypertensive group and in the control group, whereas the renal vascular resistance was significantly higher in the hypertensive patients. GFR and RPF decreased with increasing blood pressure in both groups. Increasing age induced a further reduction in GFR and RPF in the control subjects but not in the hypertensive patients. 3. Plasma renin concentration in the hypertensive group did not differ from that in the control subjects. The concentration was not correlated to age in either the hypertensive or normal group. 4. Plasma renin index was positively correlated to GFR and RPF and inversely correlated to filtration fraction and renal vascular resistance. 5. It is concluded that GFR and RPF depend on blood pressure in both hypertensive patients and normotensive control subjects. In contrast to the control group, the age effect was negligible in the hypertensive group. It is suggested that renin release depends on changes in renal vascular resistance in the arterioles at the glomerulus and the results support the baroreceptor theory of renin release.


Effect of vasopressin on plasma volume and renin release in man. 1. Arginine vasopressin was infused into seven healthy young male volunteers at 12-5 and 25 units/min for 1 h at each dose. Plasma renin activity fell sharply and progressively in each subject. The mean fall was 47% and 66% of the initial value at the end of the lower and higher rates of arginine vasopressin infusion respectively; over 70% of the observed fall in plasma renin activity occurred at the end of the first infusion period. 2. The majority of the plasma arginine vasopressin concentrations achieved were within the physiological range observed after fluid deprivation and orthostatic stress in man, particularly at the lower rate of infusion. 3. There was no change of arterial pressure, despite a slight bradycardia at the lower rate of infusion; at the higher rate of infusion, there was only a very slight pressor response. 4. There was a concomitant and significant fall of plasma protein concentration and peripheral venous packed cell volume without any significant change of plasma sodium concentration or plasma osmolality, implying an expansion of plasma volume. 5. The results indicate that, in man, physiologically relevant amounts of arginine vasopressin suppress the rate of renin secretion indirectly by increasing the plasma volume at the expense of the extravascular fluid volume.


Biochemical and morphological studies on human jejunal mucosa maintained in culture. 1. The combination of a wire-mesh support with the roller-tube technique is described as a procedure for the culture of human jejunal mucosa in vitro. 2. The technique has been applied to fragments (approximately 10 mg) of jejunal biopsies from both normal subjects and patients with coeliac disease. 3. The cultured tissue has been shown by radio-autography to incorporate [3H]leucine into proteins of the villus epithelial cells and [3H]thymidine into nucleic acid, predominantly by the enteroblasts. 4. Although the tissue protein DNA contents fall during culture, it was found that the combined tissue and medium DNA content remained constant during culture and may be used as a reference for enzyme and biochemical studies on cultured intestinal biopsies.


The porphyrinogenic effects of kryptopyrrole in the rat and the occurrence of urinary kryptopyrrole in human hereditary hepatic porphyria. 1. Kryptopyrrole (2,4-dimethyl-3-ethyl pyrrole) was shown to elevate the urinary porphyrin excretion and the hepatic content of porphyrins in the rat. The simultaneous administration of sigma-aminolaevulinic acid increased these effects. 2. Kryptopyrrole was present in the urine of patients with hereditary hepatic porphyria, in attack and in remission, but not in those with latent porphyria.


The renal handling of insulin and thyroid hormones in normal man. 1. The renal extraction of insulin and thyroid hormones T3 and T4 was studied in man by right renal vein catheterization. 2. The mean renal extraction of insulin was 0-46, suggesting that the right renal vein should be utilized in comparable studies. 3. No renal extraction of thyroid hormones was detected.


The effect of anaesthesia of the airway in dog and man: a study of respiratory reflexes, sensations and lung mechanics. 1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man. 2. In the dog, the cough reflex was abolished and the Hering-Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs. 3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering-Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The Ve/CO2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation. 4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic. 5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10-20 min.


The relation between potassium in body fluids and total body potassium in healthy and diabetic subjects. 1. The concentration of potassium in the erythrocytes and the plasma of forty-one normal subjects and twenty-five diabetic patients was measured and the results were used to calculate the total amount of potassium in the erythrocyte mass and the total amount of potassium in the plasma. The total body potassium was measured in a whole-body monitor. 2. In normal subjects a close correlation was found between total erythrocyte potassium and total body potassium and also between total plasma potassium and total body potassium. 3. The regression relation between total body potassium and total erythrocyte potassium in normal subjects was used to predict the total body potassium in diabetic patients. There was reasonable agreement between the measured and predicted total body potassium but there was poor agreement between the measured total body potassium and that predicted from the patient's height and age or height and age or height, weight and age.


The encephalopathic action of five-carbon-atom fatty acids in the rabbit. 1. Five-carbon-atom organic acids (C-5 acids) have been administered intravenously to rabbits with ventriculocisternal perfusion and continuous electroencephalographic recording (EEG). The concentration of the acids in the cerebrospinal fluid (CSF) perfusate have been compared with changes in integrated low-frequency activity in the EEG. 2. The C-5 acids investigated were those accumulating in inborn errors of metabolism, i.e. isovaleric acid, beta-methylcrotonic acid, tiglic acid and alpha-keto- and alpha-hydroxy-isovaleric acid. There activity was compared with that of valeric acid. 3. Valeric acid and isovaleric acid produced coma and pronounced increase in slow-wave electrical activity and these changes paralleled the increase in concentration of the acids in the CSF perfusate. 4. The concentration of beta-methylcrotonic acid and tiglic acid in the CSF perfusate reached values comparable with valeric acid and isovaleric acid but showed less encephalopathic activity. An interaction between beta-methylcrotonic acid and isovaleric acid was observed. 5. Although the concentrations of alpha-ketoisovaleric acid and alpha-hydroxyisovaleric acid rose to the lesser extent in the CSF perfusate, changes in rousability of the animal and in the EEG recording were demonstrated. 6. It is concluded that all the C-5 acids tested have encephalopathic activity although this is lessened by the presence of either a double bond or an oxygenated functional group.


Effect of inhibition of gluconeogenesis on ammonia production in the perfused rat kidney. 1. Gluconeogenesis from lactate or from glutamine is inhibited by 90-100% by sodium quinolinate (1 mmol/l) or 3-mercaptopicolinate (150 nmol/l) in the perfused rat kidney. L-Tryptophan is not metabolized and is without effect. 2. Lactate uptake and glucose production are inhibited to the same degree by 3-mercaptopicolinate in the kidneys of well-fed or starved rats. 3. Inhibition of gluconeogenesis from glutamine (1 mmol/l) by 3-mercaptopicolinate is accompanied by 50% inhibition of ammonia production, and 34% inhibition of glutamine uptake, in the kidneys of acidotic rats. Ammonia production from glutamine was not inhibited in kidneys from non-acidotic rats. 4. It is concluded that the increased rate of gluconeogenesis from glutamine which occurs in acidotic rats is an essential and primary event regulating all of the increase in ammonia formation.


Absorption of galactose by the rat small intestine in vivo: proximal-distal kinetic gradients and a new method to express absorption per enterocyte. 1. The absorption in vivo of D-galactose by the rat small intestine has been examined in proximal jejunum and distal ileum by use of a recirculation-perfusion technique. 2. Multiple sequential perfusions over 4 h produced no subsequent functional or morphological damage in the perfused segments. 3. Absorption of galactose from 8 and 64 mmol/l solutions was found to be independent of flow rate over the range 1-0-6-5 ml/min. 4. Galactose absorption in both the jejunum and the ileum exhibited saturation kinetics of the Michaelis-Menten type, and phlorrhizin sensitivity. Sorbose was only absorbed minimally. These observations demonstrate that galactose is absorbed by carrier-mediated transport and that there is no significant passive diffusive component in vivo. 5. Under the stated experimental conditions, the maximum absorptive capacity was 4-5 times greater in the jejunum than in the ileum. The Michaelis constant for galactose was higher in the jejunum than in the ileum. 6. Enterocytes were isolated from perfused segments and quantified by DNA assay with a correction for yield. In this manner, the absorptive capacity per enterocyte was calculated. 7. The maximum absorptive capacity per enterocyte was 3-5 times greater in the jejunum than in the ileum.


Studies of amino acid and protein metabolism in normal man with L-[U-14C]tyrosine. 1. Six men were infused intravenously for 10 h with a tracer amount of L-[U-14C]tyrosine while on a standardized food intake. 2. Measurements of plasma L-[14C]-tyrosine specific radioactivity and the excretion rate of 14CO2 were made at frequent intervals and showed plateau labelling of plasma and expired carbon dioxide within 6-8 h. The tyrosine flux was calculated from the specific radioactivity in plasma at plateau value. 3. The excretion rate of 14CO2, corrected for retention of label within the bicarbonate pool, showed that oxidation accounted for 20% of the tyrosine flux. Urinary excretion of label was negligible. 4. Rates of protein synthesis were calculated from the flux of tyrosine after subtracting the proportion oxidized. Although the mean rate of synthesis was consistent with other measurements of protein turnover, the individual values ranged from 284 to 387 g/day. The variation was not reduced by relating turnover to body weight, lean body mass or energy expenditure. 5. Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism. The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover.


Haemodynamic studies in dogs with chronic bile-duct ligation. 1. Dogs with bile-duct ligation retain salt and water and form ascites. The present study was under-taken to examine the role of haemodynamic factors in the aetiology of this sodium retention. 2. Haemodynamic studies were performed in five dogs before and 5 weeks after bile-duct ligation. 3. After the operation there was an insignificant fall in mean arterial pressure, a significant rise in mean cardiac index and significant fall in mean total peripheral resistance. 4. It is concluded that heart failure is not a factor in renal sodium retention of the dog with bile-duct ligation, since the central venous pressure was not elevated. 5. The haemodynamic pattern and the tendency to salt retention in the dog with chronic bile-duct ligation closely resemble findings reported in patients with cirrhosis of the liver, and it is suggested that oedema formation in patients with cirrhosis of the liver and dogs with chronic bile-duct ligation shares a common aetiology.


The effect of active immunization against aldosterone on the colonic potential response and sodium excretion in rabbits. 1. A group of rabbits was actively immunized against aldosterone and their subsequent response to infused aldosterone and to dietary sodium restriction was compared with that of a control group. 2. Colonic electrical potential difference (CP) was used as an index of relative mineralocorticoid activity in both groups of animals. 3. Infusion of aldosterone produced a rise in CP to a maximum of -50 to -70 mV at rates of infusion of 55-270 pmol min-1 kg-1. In contrast, the immune group showed no change until infusion dose rates of 2700 pmol min-1 kg-1 were used. 4. During dietary sodium restriction, CP increased in normal rabbits to a significantly greater degree than in immune animals although cumulative urinary sodium losses were the same in both groups. 5. The ability of the immune animals to remain in sodium balance despite physiological aldosterone blockade suggests that aldosterone is not an essential component of their sodium-conservation mechanisms.


"Bicarbonate resistant" metabolic acidosis in association with ethylene glycol intoxication. A case of massive ingestion of ethylene glycol is described. The clinical characteristics of this disorder such as persistent metabolic acidosis and oxaluria as well as changes in serum osmolality that may accompany ingestion of certain toxins are emphasized. The rapid clearance of ethylene glycol from the blood during hemodialysis is noted and the use of ethyl alcohol to block metabolic conversion of ethylene glycol to oxalic acid, which is also a toxin, is described. The importance of early diagnosis and therapy is stressed.


Salicylate poisoning complicated by fluid retention. We have presented two cases of salicylate poisoning that demonstrate fluid retention in the face of adequate hydration, resembling the syndrome of inappropriate secretion of ADH. These cases necessitated marked alterations from normal fluid therapy. Mannitol was found to be an effective, albeit transient, diuretic for treating the acute symptoms associated with fluid retention, but only strict fluid restriction resulted in a prompt and satisfactory diuresis.


1,1,1-trichloroethane: report of a fatal intoxication. TCE was indicated in the accidental death of a woman cleaning up a paint spill in an enclosed, poorly ventilated room. Blood and tissue concentrations of TCE were measured by head-space gas chromatography. The concentrations found were compared with previously reported concentrations concluding that the demonstrable presence of TCE in blood at a concentration above 1.0 to 1.5 mg/100 ml would be consistent with death. However, the rapid dissipation of TCE from blood dictates that its presence in post mortem samples at any concentration must be considered as a factor in determining the cause of death.


Cadmium, lead, and copper blood levels in normal children. Cadmium, lead, and copper levels were measured in duplicate whole blood samples from 60 apparently normal children, ranging in age from 2 months to 13 years, who were hospitalized for elective surgery. Metals were measured by atomic absorption  spectroscopy after the samples were chemically oxidized and digested. Cadmium was concentrated by dithizone extraction before analysis. Blood cadmium averaged 0.66 mug/100 gm, with a standard deviation of 0.25. No samples had cadmium concentrations less than could be detectable. The average concentration of lead was 15.7 mug/100 gm with a standard deviation of 6.33. Copper averaged 123 mug/100 gm with a standard deviation of 35.5. Tolerance intervals were calculated for each metal in order to estimate the bounds of whole blood metal values in normal children. The intervals containing 95% of normal values with a probability of .95 were 0.22-1.70 mug Cd/100 gm, 0.87-30.5 mug Pb/100 gm, and 40.0-206 mug Cu/100 gm.


Influence of "thickening" agents on the antidotal efficacy of activated charcoal. The addition of "thickening" agents such as bentonite and carboxymethylcellulose to activated charcoal slurries considerably improves the palatability of this antidote yet does not reduce the efficacy of the activated charcoal in reducing the gastrointestinal absorption of aspirin. Flavoring of such preparations may further enhance this palatability.


Community absorption of the mentally ill: the new challenge. In 1975, twelve years after enactment of the Community Mental Health Centers Act, we find one of the greatest obstacles to fulfillment of our hopes to be pervasive hostility to acceptance of the mentally ill in many communities. The River Region Program has hurdled this obstacle by breaking the artificially large mental health catchment areas into manageable segments of 16 smaller service areas close to the people it serves in seven counties of Kentucky. In each of these service areas it has involved a broad spectrum of citizens in the planning of every service. All of this is of particular relevance today in light of the supreme Court's Donaldson decision, that mentally ill persons cannot be confined involuntarily if they are not dangerous and can live safely in the outside world. The "outside world" must be prepared to receive these people, and we in the mental health field must do our job in this vital preparation.


Crisis intervention: effects of crisis intervention on family survivors of sudden death situations. A controlled study that examined the effects of a short-term crisis service given to a group of families recently bereaved through a sudden death within the family is reported. The results reveal that sudden death does have a major impact on recently bereaved families in terms of increased risk of ill health, poor coping behavior, and disturbed social functioning when compared to nonbereaved families. However, the short-term crisis service appeared to have no major impact upon postbereavement adjustment. Discussion centered around possible reasons for failure of the short-term crisis services.


A mental health interaction program in a community college. This paper presents an interaction program between a community college and two community mental health resources in the college's geographical area as viewed from the vantage point of the college. As described in a complementary paper written by the same authors viewing the interaction from the vantage point of one of the mental health agencies, the primary aim in these interactions is to provide improved mental health services through cooperative training of college counselors and psychiatric residents. In addition, from the college's view a secondary aim has been the freeing of counselors for more functions of an educational and outreach nature.


A study of paraprofessionals in mental health. This article summarizes data gathered on 15 paraprofessional training programs sponsored by the National Institute of Mental Health (NIMH). Data on the backgrounds of trainees working as paraprofessionals are presented along with a breakdown of the kinds of tasks in which they are employed, as well as characteristics linked with ratings of success and retention in the programs. Trainees tended to be employed in a wide variety of tasks, often at rather sophisticated levels. Analysis of the tasks indicates that projects are fulfilling the NIMH New Careers goal of contributing to greater community impact in mental health. Results corroborate earlier findings that para professionals have been accepted both by professionals and clients.


The Alabama "right to treatment" case: an opportunity not to be missed. Recent pessimistic criticism of right to treatment decisions is unwarranted. The developing law contains a great deal of flexibility, and this can be creatively utilized to secure resources for community-based services. Courts' emphasis on the physical framework of care is an intentional effort to avoid interfering with program decisions and thus represents a reaffirmation of confidence that professionals can, if provided adequate resources, be relied on to make program decisions. Time should not be spent decrying the effect of an undesirable development of right to treatment law, but rather in formulating and stimulating development of the law in a manner consistent with current trends in the delivery of services.


Two studies of comparative stigma: employer attitudes and practices toward rehabilitated convicts, mental and tuberculosis patients. Two studies compared the effects of stigmatization on two questionnaire measures of social distance and on offers of employment in retail sales. Employers' questionnaire responses revealed less social distance only with tuberculosis patients, compared to exconvicts, exmental patients or marginally adjusted individuals, all of whom did not differ among themselves. There were no differences in the number or conditions of retail sales job offers obtained by six competent experimenters role playing each of three stigmatizing conditions. The results of the studies are seen as reducing concern over the recent changes in California mental health laws which make involuntary commitment in mental hospitals more difficult and may increase the number of convicts who would otherwise become mental patients. Satisfactory employment, often related to low prisoner and mental patient recidivism rates, may be equally accessible to competent exmental patients and felons.


A profile of the rural community mental health center. This paper-part of a national study of community mental health worker role activism-compares community mental health center with their counterparts in other geographic areas. Rural workers were most likely to view their centers as being most like social agencies. Their endorsement of community mental health ideology was also significantly higher. Role was measured from two perspectives: organizational and personal. Again, staff at rural community mental health centers were significantly different: They endorsed the highest levels of both organizational and personal activism and showed the least discrepancy between the two. It is concluded that rural community mental health centers and their staff represent an important and unique response to the problem of community mental health services delivery.


Teaching nuns' perceptions of white and black pupils as a function of authoritarianism and other factors. A sample of 283 teching nuns described the White Pupil, the Black Pupil, and the Ideal Pupil on an adjective description form. A Prejudice score was computed by subtracting the Ideal minus Black differences summed across 52 items from the Ideal minus White differences. Analyses based on 269 subjects revealed that neither age nor amount of prior contact with minorities predicted level of prejiduce. However, high and low-F-scale scorers differed significantly on the Prejudice score and on selected pupil perception factors. Implications in regard to training programs on racial attitudes were discussed.


Effectiveness of college students in an incentive community program for chronic hospitalized patients. The study describes and assesses an incentive community program implemented by college students for all of the chronic hospitalized patients living in a locked ward. Behavioral ratings of ward behavior and discharge rates were significantly higher for the experimental than for matched control patients. Bed-wetting was eliminated in 70% of the bed-wetting patients. Students rated the incentive community program more effective in changing the behavior of patients than students' ratings of a case-aide program. No differences in patient behaviors were found between the incentive community and case-aide program.


Evaluation of televised anticipatory guidance to primiparae. In a controlled study, programs offering televised anticipatory guidance to primiparae during the immediate postpartum period were shown to have a beneficial effect on a mother's perceptions of her infant as measured by the Neonatal Perception Inventory (NPI). Among mothers viewing the programs, a significant increase occurred (P less than .01) in the number having a positive perception of their infants at age 1 month. Since the Neonatal Perception Inventory has proved a reliable indicator of a child's emotional well-being at age 4 1/2, televised guidance is recommended as an effective, economical measure with a potential for reducing the incidence of emotional disorder in children.


Community mental health ideology scale: social work norms. The present study reports mean scores obtained by two groups of professionals deeply involved in the community mental health movement on the Community Mental Health Ideology Scale. Professional social workers and social work graduate students were not included in the scale makers original criterion group. The high mean scores obtained by these groups led the authors to the conclusion that social workers show the potential for a strong role in the "third phase" of mental health care and delivery.


An evaluative paradigm for community mental health centers using an automated data system. A methodology is presented for the evaluation of community mental health centers using data routinely collected by an automated patient management system (Multistate Information System). Four community mental health centers whose catchment areas were widely diverse in composition participated in the study. A generalized evaluation paradigm was developed with measures and objectives formulated to analyze various stages of care as patients progressed through the community mental health center system. The stages covered were admission, initial modality of service, service delivery in terms of types and amounts of services rendered and termination. Each other was analyzed independently of the others and it was ascertained that the methodology produced useful and informative evaluative data across all four centers.


[Use of sulfonylurea preparations in the treatment of children with diabetes mellitus]. Compensation with normoglycemia and aglycoseurea for periods of from 6 months to 6 years was reached in 53 patients suffering from manifest diabetes mellitus, as a result of application of sulphanilurea preparations. Of this number 34 children were under insulin therapy before the beginning of sulphanilamide treatment. In 8 cases sulphanilurea preparations were cancelled with persistence of stable compensation; in 5 of them there occured normalization of GTT and in 2 GTT became doubtful. A necessity of using insulin occurred later in 21 of 53 patients (in 3 temporarily and in 18 -- constantly) as a result of intercurrent diseases, stress situations or frequent coarse breaks in the diet.


On bleeding and clotting problems in post-traumatic states. The most common bleeding and clotting problems in post-traumatic states are reviewed. The normal response of the coagulation system and the fibrinolytic system to trauma is described; this response must be considered when studying the abnormal situations. The laboratory tests need not be numerous or sophisticated but they must be repeated often enough to understand and interpret the data. A proper understanding of these abnormalities forms the rational basis for the correct choice of therapy, and is of utmost importance in the management of post-traumatic patients.


Thromboembolic disease: prophylaxis and treatment. Thromboembolic disease ranks among the most dangerous and common complication in the postoperative or post-traumatic patient. As previously mentioned, the incidence is increasing and fatalities from this complication have also risen substantially. The pathogenesis of thromboembolic disease and the predictability of its occurrence remain elusive. Based upon evidence suggesting that the thrombotic process may begin during surgery, greater attention should be given to the use of prophylactic agents before as well as during the operative procedure. The search continues for a safe, oral agent uniformly effective in preventing thromboembolism.


Blood viscosity changes after trauma. Use of dextran-40 in correction of microcirculatory insufficiency. Trauma causes a definite increase in packed cell viscosity and intravascular cellular aggregation. As a result, total body oxygen consumption decreases markedly. When packed cell viscosity is lowered by infusion of dextran-40, total body oxygen consumption progressively increases to normal values. It does not appear unreasonable to conclude that in traumatized patients, restoration of microcirculatory blood flow is of great importance in reestablishing an effective circulating blood volume and that normalization of blood viscosity after trauma may be of considerable benefit.


Acute respiratory failure.

Acute respiratory failure. There appears to be a great similarity between all of the various types of Adult Respiratory Distress Syndromes (ARDS) in that they are all characterized by progressively increasing interstitial edema in the lungs and a reduced functional residual capacity. Early diagnosis is mandatory and therapy should be started as soon as there is a reasonable suspicion, based on the patient's injury or illness and the previous condition of his lungs, that acute respiratory failure is developing. Sepsis, shock, CNS or thoracic disease and trauma are important associated factors. Blood gas changes usually cannot be appreciated clinically until the respiratory problem is quite severe. Accordingly, serial blood gas analyses should be performed on any patient who has a reasonable chance of developing ARDS. We have found that changes in the estimated AaDO2 on room air are especially helpful. Any deterioration in the patient's clinical condition, blood gases or ventilatory effort should be considered as an indication for early ventilatory assistance. Control of the primary process, careful dehydration, high tidal volumes, and PEEP are the mainstays of therapy. Serial blood gases and careful observation of the patient's effective compliance are essential to determine the optimal ventilator setting and the optimal amount of PEEP. Recently intermittent mandatory ventilation (IMV) with very large amounts of PEEP have been reported to be of value. Early administration of massive steroids should be considered if the patient fails to respond promptly to correction of the underlying etiologic problem, particularly sepsis, careful progressive dehydration and optimal expansion of the alveoli, with high tidal volumes and PEEP.


The acutely dypsneic patient.

The acutely dypsneic patient. The limited variation of pulmonary responses to disease--dyspnea, cough, production of adventitious sounds, sputum production, and hemoptysis--complicates the differential diagnosis of the acutely ill patient with obvious severe pulmonary disease. This paper attempts to reinforce and redefine this problem: acute cardiac and pulmonary dyspnea can generally be separated by quick but careful clinical analysis; mis-diagnosis may lead to disaster since effective treatment of one is frequently harmful to the other.


Hypocalcaemia of acute pancreatitis: the effect of hypoalbuminaemia. Hypoalbuminaemia has been consistently observed in a prospective study of 130 patients with acute pancreatitis. A study was initiated, therefore, to find out if the hypocalcaemia of acute pancreatitis could be explained by the associated hypoalbuminaemia. 64.4% of all serum calcium results were in the apparently hypocalcaemic range. A comparable incidence of hypoalbuminaemia was observed. The 'uncorrected' total serum calcium and serum albumin showed a similar pattern in their daily changes and also a significant correlation overall. When correction of serum calcium was made for albumin levels, only 10.9% of all results represented varying degrees of 'true' hypocalcaemia. Mortality and severity of acute pancreatitis related as closely to hypoalbuminaemia as to uncorrected hypocalcaemia. It is concluded that a low serum albumin should be regarded as the most common cause of a low serum calcium in acute pancreatitis. Routine albumin administration is proposed, a procedure which has been shown to be associated with improved mortality rate and morbidity in this disease.


Patient tolerance of long-term diuretic/potassium supplement therapy. Forty patients with congestive heart failure or hypertensive heart disease were given long-term maintenance treatment with a combined bumetanide/slow-release potassium supplement preparation ('Burinex K'). Stabilised doses ranged from 0.5 mg to 2 mg bumetanide with from 7.7 mmol to 30.8 mmol potassium. Patients took doses either at 9 a.m. or at 5 p.m. daily during a series of alternate 2 to 4-weekly treatment periods. Analysis of patient preference for morning or evening diuresis showed that the majority (72.5%), including all 18 patients who went out to work, preferred the evening regimen. Bumetanide proved to be a highly effective diuretic, irrespective of time of administration. Evening diuresis was associated with a statistically significant increase in the 24-hour excretion of sodium. Serial laboratory analyses showed no clinically significant changes in serum potassium or other parameters examined an in contrast to other diuretics bumetanide produced no significant hyperuricaemic effects.


Treatment of hay fever in general practice by hyposensitization, using 'Pollinex'. Twenty-six patients from a general practice suffering with clear-cut seasonal rhinitis due to grass pollen were treated with 3 injections, at 10 to 14 day intervals, of a modified grass pollen allergens tyrosine adsorbate ('Pollinex'), prior to the 1975 pollen season. Of the 26 patients, only 6 had previously had variable forms of hyposensitization. Despite the very high pollen counts in the 1975 pollen season the overall success rate of the hyposensitization was 73% and results were better in the patients who had not been previously hyposensitized. There was only one adverse local reaction to the injection which was not severe enough to discontinue the treatment.


An ophthalmic study of ibuprofen in rheumatoid conditions. A total of 247 patients suffering from rheumatoid arthritis and allied conditions were referred for routine ophthalmological examination with particular reference to ocular rheumatoid involvement. Of these, 197 were already receiving ibuprofen before their first assessment while 50 had a baseline assessment before commencement of ibrupofen therapy. All patients were examined on at least two occasions. No macular lesions were discovered which could be directly attributed to ibuprofen therapy.


Intravenous fusidic acid ('Fucidin') in the management of severe staphylococcal infections: a review of 46 cases. Case reports are reviewed of 46 patients with severe, life-threatening infections, mainly staphylococcal, who were treated with intravenous fusidic acid. Overall, 22 (48%) patients survived and 24 died, 10 of these within 24 hours of commencing treatment with fusidic acid. Thirty-nine patients received unsuccessful antibiotic therapy prior to the administration of fusidic acid. It was not possible to relate prior antibiotic treatment to outcome, and, in such severe infections, complicating diseases had an adverse effect upon survival. It is concluded that intravenous fusidic acid ('Fucidin') has an important place in the treatment of severe staphylococcal infections.


Cephradine in the treatment of chronic recurrent infections of the urinary tract. Twenty-two patients with chronic recurrent bacterial urinary tract infection, most of whom had underlying physical abnormalities of the tract, were treated with 500 mg cephradine 4-times daily for 10 to 15 days. Eight patients remained completely clear of infection after 2 to 3 months of treatment. This was regarded as a satisfactory result in view of the difficulty in treating this type of case and considering previous unsuccessful courses of antibacterial therapy.


Isosorbide dinitrate and intra-aortic balloon pumping in preinfarctional angina. Effects on central circulatory dynamics. The dynamics of the central circulation were measured by a radionuclidic technique in 18 men with high-risk preinfarctional angina who received therapy with isosorbide dinitrate (n equals 18), intra-aortic balloon pumping (n equals 8), or both (n equals 8). Administration of 5 mg of isosorbide dinitrate sublinqually was associated with a reduction in stroke volume index (SVI), cardiac index (CI), systemic arterial blood pressure, and left ventricular end-diastolic volume (LVEDV) and with increased left ventricular ejection fraction (LVEF). Intra-aortic balloon pumping did not alter SVI or CI, but decreased systolic blood pressure and LVEDV and increased LVEF and diastolic blood pressure. The combination of therapy with isosorbide dinitrate and intraaortic balloon pumping resulted in decreased SVI, systolic blood pressure, and LVEDV and increased LVEF. Thus, therapy with isosorbide dinitrate reduced left ventricular preload, and intra-aortic balloon pumping reduced blood pressure, which resulted in a decreased LVEDV and an increase in LVEF. Therapy with isosorbide dinitrate and intra-aortic balloon pumping act to alter central circulatory dynamics in favor of reducing myocardial oxygen demand.


A trial of aerosolized theophylline in relieving bronchospasm. Theophylline was administered as an aerosol to nine patients with known bronchospastic disease. No significant improvement in the forced expiratory volume in one second was observed after administration of aerosolized theophylline, although improvement did occur following administration of aerosolized isoproterenol. The theoretic mechanisms of bronchodilator aerosols are discussed, as well as the possible reasons for not obtaining a response with administration of theophylline.


Marked depth of ST-segment depression during treadmill exercise testing; indicator of severe coronary artery disease. This study was designed to evaluate whether treadmill stress testing would facilitate selection of patients with advanced coronary artery disease and, specifically, whether markedly abnormal ischemic responses could be used as indicators of severity of disease. Among 59 consecutive patients with documented coronary artery disease having both maximal treadmill testing and coronary angiographic studies, 15 (group 1) had normal responses to exercise, 18 (group 2) showed 1 to 2.9 mm "ischemic" (flat or downward-sloping) ST-segment depression, and 26 (group 3) demonstrated marked (or equal to 3 mm) ischemic responses. Group 3 had statistically significant higher incidences of triple-vessel disease (18/26; 69 percent) and proximal lesions of the left anterior descending coronary artery (24/26; 92 percent), compared with group 1 (2/15 and 10/15, respectively) and group 2 (6/18 and 12/18, respectively). Group 3 also manifested more extensive disease than groups 1 and 2 (judged by scoring system of Friesinger et al), with a score of 11 or more in 18 of 26 patients. We conclude that marked depth of "ischemic" ST-segment depression aids in identifying that subgroup of the coronary population with severe coronary artery disease and, therefore, serves as a useful means of culling out patients with a potentially serious prognosis who might benefit from intensive diagnostic or therapeutic interventions.


Postinfarctional ventricular septal rupture. Clinical approach and surgical results. This study represents an analysis of 13 cases of ruptured interventricular septum occurring as a complication of myocardial infarction. The cases considered appeared to divide themselves into two groups. One group survived the septal rupture for weeks or months and underwent surgery in the chronic stage. The patients in the other group were diagnosed and underwent surgery in the acute stage because of clinical indications of a rapidly deteriorating situation. There were four serious complications resulting from extensive cardiac catheterization and angiographic procedures. Those patients who were diagnosed using bedside balloon-directed catheterization techniques had no serious complications. The data indicate that: (1) the diagnostic approach should be executed quickly and by simple methods; (2) it is possible to operate successfully upon these patients in the acute phase of their disease; and (3) because of the unpredictable course and rapid deterioration, these alternatives should be strongly considered.


Retroperitoneal air dissection associated with mechanical ventilation. The radiologic patterns, etiology, and possible consequences of gas dissection into the retroperitoneal space from pulmonary sources are reviewed in three patients requiring mechanical ventilation. Airway disruption appears to be related to peak airway pressures, underlying pulmonary disease, and the patient's hemodynamic condition and may cause different forms of interstitial emphysema and air embolization, which may lead to severe respiratory or circulatory dysfunction. Gas migration to the retroperitoneum and, secondarily, into the peritoneal cavity should be considered in the differential diagnosis of free intra-abdominal gas.


Treatment of anaerobic pulmonary infections; carbenicillin compared to clindamycin and gentamicin. Twenty-three patients with anaerobic infections of the lung were treated with either two antibiotics, clindamycin and gentamicin (11 patients) or with a single antibiotic, carbenicillin (12 patients). Cultures were obtained prior to therapy, either by transtracheal needle aspiration (17 patients) or thoracocentesis (six patients). Anaerobic bacteria were found in all. Fifteen patients had aerobic and facultative bacteria in addition. The anerobic isolates were peptostreptococci (12), peptococci (12), Bacteroides organisms (eight), clostridia (three), actinomycetes (two), eubacteria (one), and fusobacteria (one). Aerobes included streptococci (nine), enterococci (seven), Neisseria organisms (two), Klebsiella organisms (one), Citrobacter organisms (one), Pseudomonas organisms (one), Mycobacterium tuberculosis (two), and Nocardia (one). The two patients with pulmonary tuberculosis with anaerobic and superinfection received antituberculosis chemotherapy in addition. Therapeutic response was considered excellent in both groups. This suggests that carbenicillin may be used as a single antibiotic in the treatment of anaerobic and mixed infections of the lung.


Deaths and complications associated with fiberoptic bronchoscopy. A questionnaire was sent to 1,041 owners of fiberoptic bronchoscopes requesting data about complications of bronchoscopic examination; 323 (31 percent) of the questionnaires were returned. From approximately 48,000 procedures, ten deaths were reported and are described. Information about two additional deaths not obtained from data on the questionnaires is also included. All patients who died had either myocardial disease, severe chronic pulmonary disease, serious pneumonia, or cancer. Two deaths were associated with evidence on necropsy of fresh myocardial infarctions that had been unsuspected prior to the procedure. Two deaths occurred after administration of local anesthesia prior to bronchoscopic examination. Two were patients who previously had slowly hemorrhaging tumors that hemorrhaged massively following, respectively, forceps biopsy and saline lavage. Four brushes broke off in bronchi. Ten cardiac arrests and 41 life-threatening reactions to anesthesia also occurred.


Diagnostic accuracy in lung cancer; comparison of techniques used in association with flexible fiberoptic bronchoscopy. Flexible fiberoptic bronchoscopic examination was performed 254 times in 228 patients in a prospective study to determine what specimens would give the greatest yield in the diagnosis of lung cancer. In addition, we questioned whether postbronchoscopic sputum specimens were still the most accurate method of diagnosing lung cancer, as they had been when only the rigid bronchoscope was available. Material for cytopathologic examination was obtained from bronchial brushings, bronchial biopsy, bronchial brushings in saline solution, bronchial washings, and three postbronchoscopie sputum specimens. In the latter part of the study, patients with peripheral tumors were studied with the aid of biplane fluoroscopic techniques. Bronchial brushings and bronchial biopsy each yielded the highest percentage of positive specimens (65 percent); postbronchoscopic sputum specimens were less frequently positive (40 percent). The combination of bronchial brushings and bronchial biopsies gave the optimum overall accuracy (79 percent). Bronchial washings and postbronchoscopic sputum specimens did not add significantly to diagnostic yield, and we conclude that they should no longer be part of the diagnostic procedures routinely ordered. In peripheral lesions, diagnostic accuracy was greatly enhanced in the cases where biplane fluoroscopic techniques were employed.


Superimposition of transmural infarction following acute subendocardial infarction; how frequent? Thirty-five consecutive patients with acute subendocardial infarction admitted to the coronary care unit during a 15-month period were identified and analyzed for location of infarction, and for the in-hospital course in terms of recurrent chest pain, the occurrence of a second infarction, and the clinical status at the end of hospitalization. Thirteen patients developed a transmural infarction sometime between 3 and 21 days (average, ten days) after the initial subendocardial infarction. The transmural infarction was defined by a separate episode of severe and prolonged chest pain, late development of QRS alteration, and an appropriate elevation of the creatine phosphokinase concentration. Our experience with acute subendocardial infarction, hertofore regarded as a relatively benign event, indicates that the immediate prognosis of the patient who sustains his first episode of subendocardial infarction is not at all benign, and, indeed, subendocardial infarction frequently heralds transmural infarction within the acute phase of the disease.


Influence of alterations in the hematocrit upon the P wave and the QRS complex. The net effect of intracavitary blood mass on cardiac dipole is believed to augment its radial components and reduce the tangential components. Commonly known as the Brody effect, it results from the lower resistivity of intracavitary blood mass as compared to the surrounding tissues (the short-circuiting effect). Thus, an increase in hematocrit should reduce and a decrease in hematocrit augment the Brody effect. It has generally been assumed that the initial portion of the process of ventricular depolarization and the left maximal spatial vector (LMSV) represent the radial components, while the terminal portion of the process of ventricular depolarization and the right maximal spatial vector (RMSV) represents the tangential components of cardiac dipole. Furthermore, the atrial accession is believed to be tangential. Based on this Brody effect, it is anticipated that an improvement of anemia, as indicated by an increase in hematocrit, would tend to reduce the initial portion of the QRS, and LMSV, but enhance the terminal portion of the QRS, and the P-wave amplitude; however, the results of this study were not in agreement with such predictions. With an improvement of anemia, a significant number of cases showed no essential changes in these electrocardiographic factors or even showed reactions oppisite to the Brody effect. This probably indicates that there are many other factors which might modify the Brody effect.


Recurrent reciprocating tachycardias in the Wolff-Parkinson-White syndrome; control by the use of a scanning pacemaker. Frequent episodes of arrhythmias in patients with the Wolff-Parkinson-White syndrome are sometimes unresponsive to medical management. Recent emphasis has been placed on the role of surgery as a means of effectively controlling these patients' tachyarrhythmias; however, in some patients the use of permanent pacing has been espoused as an effective means of controlling arrhythmias. This report documents the efficacy of a new pacemaker with rate-scanning features, which offers significant technical advantages. Subsequent follow-up has documented the efficacy of this unit in the management of a young woman with type-A Wolff-Parkinson-White syndrome and previously intractable arrhythmias.