Actions of tetrahydropapaveroline on the cardiovascular system and skeletal muscles of the anaesthetized cat and on guinea-pig soleus muscle in vitro. 1. Tetrahydropapaveroline (THP) and isoprenaline have been compared for effects on heart rate, diastolic blood pressure and contractions of soleus and tibialis muscles in chloralose-anaesthetized cats and on in vitro guinea-pig soleus muscles. 2. All effects of THP were similar to those of isoprenaline. Maximal responses were the same and responses to both drugs were  antagonized by propranolol. 3. THP produced an increase in heart rate, a fall in diastolic blood pressure and a decrease in the tension and degree of fusion of incomplete tetanic contractions of the soleus, being, respectively, 12.9, 14.7 and 19.6 times less potent than isoprenaline. The similarity in potency ratios suggests that THP is a non-selective beta-adrenoceptor agonist. 4. Effects on the guinea-pig soleus in vitro were similar to those in the cat soleus. 5. In the cat, THP enhanced the tension and duration of tibialis twitches, but the tibialis was about ten times less sensitive than the soleus to the effects of THP. 6. THP deepened neuromuscular blockade in partially curarized cat soleus and tibialis preparations. Doses required were ten times greater than for direct depressant effects on the soleus. 7. Agents which depress the tension and fusion of incomplete tetanic contractions of the cat soleus via beta-adrenoceptor stimulation cause tremor in man by peripheral effects on slow muscle fibres. THP is likely to exert such actions. This may explain why levodopa (a precursor of THP) sometimes precipitates a tremor crisis in Parkinsoniam patients, and why Parkinsonian tremor is relatively refractory to levodopa therapy. In such patients combination therapy with levodopa and a peripheral dopa decarboxylase inhibi;or (to reduce levels of THP) or a beta-adrenoceptor antagonist (to block the effects of THP on slow muscle fibres) could be advantageous.


Effects of adrenaline and isoprenaline on hepatic venous haemodynamics and venous return in the dog. 1. The effects of adrenoceptor agonists on venous haemodynamics were examined, utilizing the lower half perfusion method in dogs. 2. Femoral arterial pressure, central venous pressure, thoracic vena caval flow, abdominal vena caval flow, renal venous flow and femoral venous flow were measured simultaneously usning electronic transducers and electromagnetic flow-meters. Hepatic volume change was monitored by the strain-guage arch. 3. Single injections of both adrenaline (1.0 microgram/kg) and isoprenaline (1.0 microgram/kg) intra-aortically produced an increase in venous return, adrenaline transiently and isoprenaline continuously. 4. Epinephrine increased hepatic venous flow, while isoprenaline increased only abdominal vena caval flow. 5. These findings suggest that effects of alpha-adrenoceptors are more pronounced on the hepatic vein, while on other peripheral veins, effects of beta-adrenoceptors are more pronounced.


Tne density of adrenergic nerves at various levels in the guinea-pig lung. 1. Gunea-pig tracheal and lung segments were systematically examined for adrenergic nerves using the fluorescence histochemical technique. Fluorescence in nerves was enhanced with alpha-methylnoradrenaline or by pretreating animals with nialamide. 2. There was a progressive decrese in density of fluorescent fibres in airway smooth muscle from the laryngeal end of the trachea, which was densely innervated, to the bronchioles, which contained only occasional fibres. This was despite obvious fluorescence in blood vessels in the lung. 3. It is suggested that, if adrenergic nerves are involved in reflex bronchodilatation in this species, they directly control larger airways and other factors, e.g. non-adrenergic inhibitory nerves, may be important in the control of smaller airways.


Brain biogenic amines and intravenous self-administration of cocaine in rats. 1. The possible involvent of noradrenaline, dopamine, serotonin and 5-hydorxyindoleacetic acid in the behavioural reinforcement produced by invravenous cocaine has been investigated. 2. rats, in Skinner boxes, were allowed to self-administer cocaine through a chronically implanted jugular vein cannula. A consistent response rate in the order of one self-administration every 10 min was observed with a dose of 3.0 mg/kg cocaine hydrochloride per response. 3. Another group of rats was cannulated and injected with a range of one to six such doses of cocaine at 10 min intervals on the basis of the responding rate, established by rats in the Skinner box. At times of 2,5 and 8 min after each dose of  cocaine, the rats were decapitated and brain concentrations of noradrenaline, dopamine, serotonin and 5-hydroxyindoleacetic acid were determined. 4. The brain levels of noradernaline exhibited a cyclic pattern of rise and fall after each dose of cocaine, which corresponded in its time base with the time interval between responses established by the rats in the Skinner box.


Thromboxane B2 inhibits prostaglandin E2 inactivation by the rat isolated perfused lung. 1. The effect of thromboxane B2 (TxB2) on inactivation of prostaglandin E2 (PGE2) by the rat isolated perfused lung has been studied. 2. TxB2 when infused in low concentrations (100 ng/ml) into the pulmonary artery reduced PGE2 inactivation approximately two-fold. 3. The rat isolated fundus strip was contracted by higher concentrations of TxB2 (1.0 microgram/ml) in the presence of hyoscine, mepyramine, methysergide, phenoxybenzamine and propranolol. The size of contraction was reduced by indomethacin in concentrations known to inhibit prostaglandin synthetase. 4. Thus, in circumstances in which TxB2 and PGE2 are released concomitantly by the lung, low concentrations of TxB2 may augment PGE2 release by reducing its inactivation.


Agonistic and antagonistic actions of 3,4-dihydroxy-substituted phenoxypropanolamines in guinea-pig atria and trachea. 1. Racemic mixtures of noradrenaline, adrenaline, isoprenaline, N-t-butylnor-adrenaline and their corresponding derivatives containing an oxymethylene (OM) link between the phenyl ring and ethanolamine side-chain have been tested for their effects on beta-adrenoceptors in isolated guinea-pig atrial and tracheal preparations. 2. In atrial and in spontaneously contracted tracheal preparations both the parent catecholamines and their corresponding OM-derivatives had a similar order of potency as beta-receptor agonists. 3. In carbachol-stimulated tracheal preparations the OM-derivatives were shown to have partial agonistic actions. 4. As in other phenylethanolamines and phenoxypropanolamines, both the agonistic and antagonistic potency of the OM-derivatives increased with increasing amine substitution.


A sequential study of adrenocorticosteroid level in human pregnancy. 1. Peripheral plasma levels of aldosterone, corticosterone, cortisol, 11-deoxycorticosterone (DOC) and 11-deoxycortisol were measured sequentially throughout pregnancy in eleven women. 2. Mean plasma concentrations were significantly increased above non-pregnant values at 8 weeks for DOC, at 12 weeks for corticosterone, cortisol and 11-deoxycortisol, but not until 24 weeks for aldosterone. 3. It is suggested that during human pregnancy, the maternal adrenal is responding differently to corticotrophin, pituitary or placental, and that other factors, for example prolactin, may be stimulating the adrenal directly or modifying the action of corticotrophin.


Alterations in levels of vascular histamine in the DOCA-hypertensive rat. 1. Histamine was detected in the abdominal aorta and the femoral arteries of normotensive and also DOCA-hypertensive rats. 2. Levels of total histamine (mast cell and non-mast cell histamine) were significantly reduced in both abdominal aorta and the femoral artery of the DOCA-hypertensive rats, relative to the normotensive controls. 3. It is suggested that the diminished level of vascular histamine may be related to the development and/or maintenance of the hypertensive state and is also related to the  reduced magnitude of active reflex vasodilatation.


Effect of cimetidine on the healing of restraint-induced gastric erosions in the rat. 1. Rats after a 24 h restraint developed acute gastric erosions. Cimetidine in a dose of 100 mg/kg body weight was given subcutaneously every 8 h to a group of 150 rats after restraint. A second group received saline subcutaneously (placebo group). 2. Erosions in the placebo group required up to 45 days to heal (median healing time approximately 24 days). Cimetidine treatment reduced the median healing time to approximately 12 days. 3. Cimetidine in this dose promotes healing of acute gastric erosions in the rat induced by restraint.


Changing histopathology patterns in lupus nephropathy. The initial clinical and histologic renal findings and the subsequent course of 90 patients with SLE were evaluated in a study of the natural history of lupus nephropathy. Initial renal biopsy revealed focal glomerulonephritis in 32 patients, diffuse glomerulonephritis in 47, membranous nephropathy in seven and minimal changes in four. Forty-one patients were rebiopsied three months to five years later; ten of 15 patients with focal glomerulonephritis showed progression to diffuse glomerulonephritis or membranous nephropathy, whereas changes in morphologic pattern were less common in the other types of lupus nephropathy. There was no difference between the patients with the focal lesion who progressed and those who did not in age, sex distribution, duration of SLE prior to biopsy, renal function, and serological studies; however, the patients with progression initially had more proteinuria, higher histologic activity on light microscopy, and more intensive glomerular electron-dense deposition. Focal lupus glomerulonephritis progresses frequently to diffuse glomerular involvement. Certain clinical and morphologic findings at initial evaluation may help to predict future progression in the course of lupus nephropathy.


Loss of amino acids during hemodialysis: quantitative and qualitative investigations. In three patients the total amino acid losses (free plus peptide-bound) in dialyzate have been assayed by means of gas-liquid chromatography. During a period 3--4 months the average losses varied from 115--178 mg per kg of body weight per dialysis treatment. The weekly mean essential amino acid losses amounted to 3--4% of the dietary intake. The concentrations in the dialyzate of non-essential amino acid fell considerably during the dialysis procedure, whereas the concentrations of most of the essential amino acids remained at a fairly constant level. It is concluded that considerable quantitative but no qualitative differences exist between the patients with respect to amino acid losses.


Home treatment of uremia with gastrointestinal dialysis. Twenty patients with end-stage renal disease and a creatinine clearance of less than 5 ml/min were tre  ated with oral gastrointestinal (GI) dialysis. The dialyzate contained an electrolyte solution with 180-220mmoles/l of mannitol. In fasting state in the morning the self-prepared 7 liters of dialyzate was drunk at a rate of one glass every 5 minutes for  about 3 hours. Intermittent diarrhea with passage of watery fluid occurred during the whole period. After each treatment the average drop in BUN in individual patients was 11--22%, but no significant decrease in serum creatinine. With twice to thrice weekly GI dialysis uremic symptoms such as anorexia, nauseal and vomiting were usually improved with slight prolongation of life. However, treatment is usually difficult when the patient becomes oliguric or anuric, so its value in long-term management of chronic uremia is limited. Most of our patients either died or shifted to hemodialysis within a few months of institution of the therapy.


Polytetrafluorethylene (PTFE) grafts for hemodialysis. 18 months' experience. 18 months clinical experience with 6 mm polytetrafluorethylene forearm grafts for hemodialysis access has been described. 35 grafts were implanted, all in patients who had unsuitable vessels for construction of a regular Brescia-Cimino forearm fistula. The overall patency was 71% with mean duration of 10.3 months, and at any one time more than 85% of the grafts at risk were functional. Complications, including undesirable flow rates, edema, thrombosis, aneurysm and cardiac failure have been discussed and rational methods of avoidance described. We believe the polytetrafluorethylene (PTFE) graft represents an important advance in hemodialysis access.


Recurrent renal vein thrombosis consequent to membranous glomerulonephritis. The diagnosis by inferior vena cavography of right renal vein thrombosis with extension into the vena cava was made in a 33 year old man with idiopathic membranous glomerulonephritis and multiple pulmonary emboli. After one year of continuous anticoagulant drug therapy with heparin and coumadin, venography showed absence of clots in the vena cava and therapy was discontinued. Proteinuria in excess of 4 g/24 hr continued. Six months later pulmonary emboli recurred and venography again demonstrated large clots in the vena cava and right renal vein. The potential for recurrence of renal vein thrombosis and pulmopnary embolism in the presence of active renal diseases is thus demonstrated.


The effect of energy and nitrogen intake upon urea production in children with uremia and undernutrition. Children with severe uremia who had anorexia were observed in a clinical study center where dietary energy and nitrogen intake could be compared with urea nitrogen production (UNPr). The children received a supplement of dextrose and amino acids at night, ate a self-selected diet and were encouraged to use carbohydrate supplements. Energy intake varied from 22 to 110 kcal/kg/day and nitrogen intake from 105 to 323 mg/kg/day. UNPr was reciprocally related to energy intake. Nitrogen intake minus UNPr, an index of nitrogen balance, was positively related to energy intake. UNPr was not related to nitrogen intake. Nitrogen intake (NI) and NI-UNPr were correlated and the slope of the regression was 1.15. We inferred from the data that low energy intakes (less than 60 kcal/kg/day) were associated with catabolic losses of body protein. Intakes above that level were associated with a low and stable rate of UNPr. The level of energy and nitrogen intake within the range observed limited the rate of nitrogen retention. Once maintenance requirements for energy and nitrogen were satisfied, the efficiency with which nitrogen was used for net protein synthesis was very high.


Rapidly progressive glomerulonephritis in adults: clinical and histologic correlations. The clinical and histological features of 43 patients with rapidly progressive glomerulonephritis were reviewed. All had extensive crescent formation in more than 50 per cent of glomeruli. Three distinct patterns of immunofluorescent staining were identified: linear, granular, and sparse staining. Electron microscopy was valuable in corroborating the results of immunofluorescence. The prognosis was poor, with no patient regaining normal renal function regardless of treatment. Significant differences were observed among patients categorized by immunofluorescent staining. Those with a linear pattern were younger and more commonly had hemoptysis. Patients with sparse immunofluorescent staining had better renal function at the time of presentation and a longer duration of illness.


Focal segmental glomerulosclerosis with rapid decline in renal function ("malignant FSGS"). We describe 11 patients whose renal biopsies showed minimal changes with focal segmental glomerulosclerosis. These patients, in contrast to the majority of patients with similar renal histology, went into renal failure within 2 1/2 years of clinical onset. All were young, severely nephrotic, most hypertensive, with microscopic hematuria, non-selective proteinuria and extreme hypercholesterolemia. Treatment with corticosteroids and cytotoxic drugs was without effect in any patient. Despite rapid decline in renal function, profuse proteinuria and a nephrotic syndrome persisted into terminal uremia and continued even after dialysis had begun. Seven patients were given nine allografts; four grafts failed because of immediate vascular complications, and a persistant nephrotic syndrome was evident in two of the five surviving grafts. This did not, however, lead to graft failure. Two patients died on dialysis because of myocardial problems. These patients with rapid decline in renal function constitute a distinct clinical subgroup amongst those with focal and segmental glomerulosclerosis; it is possible that they have a different primarily vascular pathogenesis in contrast to other patients with similar renal biopsy appearances.


Radiation nephritis and intravascular coagulation. A 23 year old male with embryonal cell carcinoma of the testicle was treated with radiation, receiving 2250 Rads to his abdomen twice, only once with kidney shielding. He developed acute renal failure approximately eleven months later. Associated with the renal failure were hemolytic anemia, thrombocytopenia, hypofibrinogenemia, and other evidence for intravascular coagulation. The kidney biopsy showed fibrinoid necrosis of arteries and arterioles. By electron microscopy, there was extensive endothelial cell damage and subendothelial electron lucent material compatible with radiation nephritis. The renal pathologic abnormalities suggest that the local renal vascular injury induced by radiation could have been responsible for intravascular coagulation in the kidneys and the systemic hematologic abnormalities. Prednisone appeared to accelerate the renal and hematologic dysfunction and heparin is proposed as a more promising therapy.


Failure of plasma exchange and immunosuppression to improve renal function in Goodpasture's syndrome. A young woman with anti-glomerular basement membrane (GBM) antibody mediated rapidly progressive glomerulonephritis and pulmonary hemorrhage was treated with immunosuppression and intensive plasma exchange. She did not have end stage renal failure when therapy was initiated. Despite a dramatic reduction in circulating anti-GBM antibody, renal function progressively decreased. The role of plasma exchange in the therapy of anti-GBM antibody mediated disease remains unclear.


Aspiration biopsy of the kidney with a new fine needle: a way to obtain glomeruli for morphological study. An improved fine needle is described for aspiration of kidney glomeruli. The needle, with a sharp inner edge 0.43 mm in diameter, is less traumatic than ordinary percutaneous kidney biopsy needles. Electron microscopy of specimens aspirated from kidneys of normal rabbits showed well-preserved glomeruli. Twenty-two of twenty-six specimens obtained from human kidneys by fine-needle aspiration contained glomeruli. Electron microscopic study of specimens aspirated from 12 patients showed that the needle provides adequate tissue for the diagnosis of diffuse glomerular diseases. The use of the fine needle widens the scope for studying the relation between glomerular fine structure and renal symptoms in many conditions in which conventional methods would not be justified.


Serum ferritin concentration: a reliable guide to iron overload in uremic and hemodialyzed patients. The inter-relationships between serum ferritin, hemoglobin, serum iron and total body iron stores were studied in 20 patients with chronic renal failure treated conservatively and in 20 patients on regular hemodialysis. There was no relationship between serum iron or transferrin and bone marrow iron deposits, but serum ferritin concentration was a good indicator of increased marrow iron stores. All patients with serum ferritin levels above 300 microgram/l had increased iron stores. Serum ferritin assay is a useful non-invasive technique for detecting iron overload in uremic and hemodialyzed patients.


Prevention of chloramine-induced hemolysis in dialyzed patients. Chloramines, compounds made up of chlorine and ammonia, when present in tap water used for dialysis cause methemoglobinemia and hemolysis. Ascorbic acid addition has been reported to effectively neutralize chloramines in vitro and in patients dialyzed with the single batch dialysis delivery system. We extended these observations to patients dialyzed with the proportioning dialysis delivery system where exposure time of ascorbic acid to chloramines is shorter. This may be important since we found that the half time of the reaction between ascorbic acid and chloramines is 4 minutes. Red cell oxidant sensitivity in 15 patients was assessed by incubating red cells with ascorbate-cyanide and measuring methemoglobin which averaged 2.17 +/- 0.42 g/100 ml (SEM) before dialysis and 2.87 +/- 0.52 g/100 ml after dialysis (NS). Reduced glutathione (GSH) levels were also measured as an index of red cell oxidant damage. GSH decreased from a mean of 7.40 +/- 0.59 micromoles/g Hb before dialysis to 6.98 +/- 0.52 micronmoles/g Hb after dialysis (P less than 0.01). In 2 patients there was no change in 51Cr red cell survival when dialyzed on either the proportioning system or other chloramine free systems. We conclude that addition of ascorbic acid to neutralize chloramines in tap water is also effective when using the proportioning dialysis delivery system.


Uremic cardiomyopathy: studies on cardiac function in the guinea pig. The effects of creatinine (5.6-22.6 mg/100 ml), guanidinosuccinic acid (8.7-35.2 mg/100 ml) and of urea (60-600 mg/100 ml) on the mechanical function and oxygen consumption in isolated guinea pig hearts have been assessed. None of the parameters measured (dp/dt max, dp/dt min and Q O2) was significantly affected by creatinine or guanidinosuccinic acid. However, urea significantly reduced mechanical activity and caused a marked increase of oxygen consumption, indicating impairment of heart function expressed as a diminution of the ratio formula (see text). Pretreatment with creatinine and guanidinosuccinic acid did not alter the effect of norepinephrine on mechanical activity and oxygen consumption when compared with the effects of norepinephrine (1 X 10(-8) g/ml and 1 X 10(-7) g/ml) given alone. In contrast, urea pretreatment lowered the norepinephrine induced increase of left ventricular pressure rise/fall and of oxygen consumption. In addition, reduction of the increase in the ratio formula (see text): after urea perfusion indicates diminution of the "economic" effect of norepinephrine.


Successful treatment of hypernatremic thirst deficiency with chlorpropamide. Two patients with hypodipsia and hypernatremia are described. The first patient, whose hypodipsia was of unknown cause, developed hypernatremia unless large volumes of fluid were urged upon him; upon treatment with chlorpropamide normal serum sodium levels were achieved with spontaneous fluid intake. The second patient had hypodipsia and diabetes insipidus resulting from a craniopharyngioma. Treatment with vasopressin and a prescribed daily water intake resulted in frequent hyper- and hyponatremia, but treatment with chlorpropramide yielded serum sodium values which were more often normal and less variable. In neither patient could the improved water regulation be attributed to an effect of chlorpropamide on renal water excretion. Possible mechanisms for the effect of chlorpropamide on thirst are discussed.


Hemodynamic studies in patients with expanded polytetrafluoroethylene (PTFE) forearm grafts. 21 patients with polytetrafluoroethylene grafts inserted for hemodialysis access were studied to assess the hemodynamic parameters. Mean graft flow was 1.9 l/min with a range of 0.2-3.8 l/min. Intragraft pressure varied from 1 to 83 mmHg and was dependent on systemic pressure, graft flow and the presence of stenotic lesions. Mean cardiac output was 7.1 l/min and index 4.0 l/min and was positively correlated with graft flow. By obtaining this data surgical corrective action was taken in several patients prospectively thus removing the abnormalities and ensuring continued graft patency. The techniques described are reproducible and simple and can be carried out in less than five minutes with minimal patient discomfort or hazard.


Psychogenic aspects of urinary incontinence in women. Gynecologists and other primary care physicians have long recognized the occurrence of psychogenic factors in some patients with urinary incontinence, usually of the urgency or detrusor dyssynergia types. However, to the best of our knowledge this is the first report of psychiatric study of these patients. Eighteen patients were referred following complete gynecologic urology work-up including electronic urethrocystometry and chain cystography. Most of these patients were 40 to 60 years of age, were multiparous, and had had hysterectomies. Major psychiatric findings were a) severe situational problems in all 18 patients, b) chronic depression in 17, and c) hysterical personality traits in 10. Patients whose psychiatric treatment provided some relief of their situational and emotional distress also, concomitantly, had relief of urinary incontinence.


Splenic visualization using 99mTc-methylene diphosphonate in a patient with sickle cell disease. Splenic visualization with a bone-seeking agent 99mTc-methylene diphosphonate (99mTc-MDP) with absence of splenic uptake using sulfur colloid was seen in a 15-year-old boy in sickle cell crisis. Uptake of 99mTc-MDP is probably due to splenic infarction and calcification. This represents a potentially sensitive method for following the functional auto-splenectomy process in sickle cell disease and may also detect the presence of splenic tissue when it is not visualized in a sulfur colloid liver/spleen scan. Splenic visualization by bone-seeking agents should not be confused with skeletal lesions or indicate the presence of an abnormal left upper quadrant mass lesion.


Metastatic abdominal implants of endometrial carcinoma demonstrated on 99mtc-methylene diphosphonate bone scan. Metastatic serosal and omental implants from a primary papillary endometrial carcinoma were well demonstrated by radionuclide uptake on a bone scan utilizing 99mTc-methylene diphosphonate. Imaging of an endometrial malignancy by a 99mTc-labeled phosphate compound has not previously been reported. While the exact mechanism of accumulation in such soft-tissue neoplastic foci is not known, several possibilities have been suggested. In this particular case, the mechanism appears related in some way to the presence of dystrophic calcifications within the metastatic deposits.


Tuberculous meningitis of the Sylvian fissure. A 66-year-old woman had autopsy-proven miliary tuberculosis, with regional involvement of the meninges of the left Sylvian fissure. Radionuclide studies of the brain demonstrated the unusual findings of increased perfusion to the left hemisphere and linear increased activity corresponding to the left Sylvian fissure. Computed tomography of the brain was initially within normal limits at a time when the radionuclide study was clearly abnormal.


Computerized tomography and radionuclide scanning in hepatic disease: a retrospective study. This was a retrospective study of 117 patients, who had both computerized tomography (CT) and nuclear scans of the liver. In the evaluation of hepatic masses, the nuclear and CT scans, demonstrated 83% and 77% of the masses, respectively, in combination they demonstrated 97%. The nuclear scan proved to be a more sensitive procedure for demonstrating the presence of intrahepatic pathology. The CT scans were better able to demonstrate specific disease entities, such as biliary obstruction and fatty infiltration of the liver. CT was also able to evaluate adjacent organs. When used in combination, CT and nuclear scans tended to complement each other and in many cases were helpful in arriving at a more specific diagnosis.


V/Q mismatch without pulmonary emboli in children with histoplasmosis. In two children with histoplasmosis pulmonary perfusion and ventilation studies revealed mismatched abnormalities characterized by almost unilaterally absent perfusion but normal ventilation in the right lung. Chest roentgenograms demonstrated right hilar enlargement and pulmonary contrast angiograms revealed narrowing of the right pulmonary arteries by extrinsic fibrotic granulomata but no pulmonary emboli were present. Fibrosing mediastinitis due to histoplasmosis was found by mediastinoscopic examination in one of the patients. Non-embolic causes of V/Q mismatch lung imaging are discussed briefly, and the correlation with clinical findings is stressed for the diagnosis of pulmonary emboli.


Hepatic scan defects following radiotherapy for lymphoma. Twenty-one patients with lymphoma were evaluated for the presence of hepatic scan defects following radiotherapy to fields which included the left lobe of the liver. Two distinct patterns of hepatic scan defects were noted: (a) a radiation port defect (Type I), and (b) attenuation of the left lobe (Type II). Five of seven patients evaluated within six weeks after radiotherapy demonstrated Type I defects but all seven subsequently developed Type II defects. Seventeen of the 21 patients developed Type II defects which have persisted (follow-up, up to 66 months). These characteristic defects should not be confused with other causes of hepatic scan defects in evaluating patients with lymphoma. The defects occur in a high percentage of patients and may persist for long periods.


Problems in the care of the infant diabetic patient. The unique problems of three infants who developed diabetes mellitus at 13 months of age or younger are discussed. These problems include: the administration of small doses of insulin; the difficulty in attaining control; and the evaluation of urinary sugar content. Suggestions for care are made.


Pharmacokinetics of netilmicin in renal insufficiency and haemodialysis. The pharmacokinetics of intravenously administered netilmicin, an investigational aminoglycoside antibiotic, were studied in 38 patients with creatinine clearance ranging from 150 to Oml/min/1.73m2 in order to determine the influence of kidney function status on the disposition of the antibiotic. The serum disappearance of netilmicin followed first order kinetics and the elimination rate constant decreased proportionally with decreasing renal function. Half-lives averaged 2.2 hours in normal individuals (creatinine clearance greater than 80ml/min/1.73m2) and reached 42 +/- 10 hours (mean +/- SD) in virtually anephric patients. The elimination rate constant lowered proportionally with decreasing renal function. Several linear relationships between pharmacokinetic parameters and renal function indicators were defined. A clinically useful correlation indicates that the half-life may be approximated as 3 times the serum creatinine concentration and may be used for adjustment of dosage of netilmicin in the treatment of patients with impaired renal function. During haemodialysis, netilmicin extraction from the blood reaches 75 +/- 14% (mean +-/ 95% confidence interval) of that of creatinine and 88 +/- 19% of that of blood urea nitrogen.


Pharmacokinetics of lorcainide in man: a new antiarrhythmic agent. A gas liquid chromatographic assay was developed to measure in plasma and urine concentrations of the new antiarrhythmic drug lorcainide, its dealkylated metabolite and an added internal standard of similar structure. The limit of sensitivity was 10ng/ml plasma. In 5 healthy volunteers and in 6 patients with ventricular premature beats (VPB) the pharmacokinetics were determined after a single intravenous dose of 100mg. In 4 of the patients with VPB, the disposition was also evaluated under steady-state conditions following oral administration of 100mg twice daily. In 4 of the healthy volunteers, the bioavailability of a single 100mg(n = 2) and 150mg (n = 2) oral dose was determined. In an additional crossover experiment, bioavailability of a single oral dose of 100 and 200mg was also measured in 2 patients with VPB. Less than 2% of the intravenous dose could be recovered as unchanged lorcainide in the urine, indicating extensive metabolism. The drug was bound to plasma proteins to the extent of 85.0 +/- 5.0% (mean +/- SD) in healthy subjects and 83.3 +/- 2.9% in patients with VPB. Since the plasma levels declined biexponentially after an intravenous dose, data were analysed according to a 2-compartment open model. The elimination half-life (t1/2beta) of 5.1 +/- 0.6h (healthy subjects) was somewhat longer (p = 0.02) in patients with VPB (7.6 +/- 2.2h), but total plasma or blood clearance were very similar; the latter approaching a normal liver blood flow of 1.5L/min. The apparent distribution volumes Vdbeta (8.6 +/- 2.4L/kg vs 10.7 +/- 4.2L/kg) and Vdss (6.4 +/- 2.4L/kg vs 8.8 +/- 3.4L/kg) showed no statistically significant difference between the healthy subjects and patients. After oral doses, high and saturable first--pass hepatic metabolism seems to exist. The crossover experiments in 4 subjects indicated bioavailability of about 1 to 4.5% after a single 100mg dose, between 7 and 20% after a 150mg dose, and between 35 and 65% after a 200mg dose. In contrast, 3 of 4 patients with VPB on oral maintenance therapy exhibited bioavailability of 100%. This indicates that lorcainide belongs to the group of drugs exhibiting non-linear elimination kinetics.


The malleability of infant motor development: cautions based on studies of child-rearing practices in Yucatan. Tests with the Bayley Motor Scale were given to 288 infants, equally divided by sex, in Yucatan, Mexico. These were 2 to 54 weeks in age and came from three sociocultural levels. In comparison to USA infants, early acceleration of motor development was followed by a marked downward trend. This phenomenon, if observed in a single child, may indicate progressive neurologic disease. Child-rearing practices would appear to account for the difference in pattern of test performance.


Linguistic and auditory milestones during the first two years of life: a language inventory for the practitioner. Although language is recognized as one of the best predictors of development, the lack of a simple evaluation tool has contributed to the general pediatrician's unfamiliarity with linguistic milestones. Here described is a 32-item instrument for the recording and assessment by the practicing pediatrician of language milestones during the first two years of life.


The drug lag revisited: comparison by therapeutic area of patterns of drugs marketed in the United States and Great Britain from 1972 through 1976. This study describes rates and patterns of new drug introductions in the U.S. and Britain from January, 1972, through December, 1976, updating an earlier study that described the patterns over the previous decade. This comparative international approach enables overall effects of different regulatory, industrial, and other types of changes in drug research and development in the two countries to be evaluated. Numerical differences persisted. In the 1972 to 1976 period, 82 new drugs appeared for the first time in either country. Only 29% of these became mutually available in both countries, 2.4 times as many becoming available first in Britain as in the U.S. Of the 71% that became exclusively available, 2.6 times as many became available in Britain as in the U.S. More important than numerical data are clinical implications of differences between the countries. The largest differences have narrowed since the previous study, but important categories in which the U.S. still lagged behind Britain in December, 1976, included cardiovascular drugs, peptic ulcer drugs, and central nervous system drugs--including therapies for depression, epilepsy, and migraine. Several factors contributed to the narrowing of U.S.--British therapeutic differences, including more realistic regulatory practices and higher quality clinical studies in the U.S., more conservative practices in Britain, attention drawn by previous studies to anachronisms in the U.S., and industrial changes such as more efficient penetration of the U.S. market by foreign firms. It is difficult to determine the relative contribution of each of these factors to the narrowing of the international difference.


Antihypertensive responses to spironolactone in normal renin hypertension. The antihypertensive effect of spironolactone was studied in 20 patients with essential hypertension and normal stimulated peripheral renin activity (PRA). Single-blind 8-wk treatment periods of placebo, 100, 200, and 400 mg spironolactone were used in consecutive order. Average supine and erect blood pressures were lower than placebo values at the end of each treatment. A prominent orthostatic effect was observed. Changes in blood pressure were not related to changes in body weight, PRA, or blood urea nitrogen. A larger proportion (50%) of patients had a more normal erect diastolic pressure at the end of 400 mg/day than at the end of 100 mg/day (20%), but the response to 400 mg/day could not be predicted from the responses to lower doses. Larger doses of spironolactone were predictably associated with rises in serum potassium, PRA, and aldosterone excretion. Adverse effects were absent during therapy with 100 mg/day but were frequent during 200--400 mg/day. Although there are no apparent advantages in increasing spironolactone from 100 to 200 mg/day in this group of patients with normal renin hypertension, increasing the dose to 400 mg/day resulted in better blood pressure control with more frequent adverse effects.


Dobutamine pharmacokinetics in severe heart failure. Dobutamine pharmacokinetics was investigated in 7 patients with severe cardiac failure. Dobutamine was administered by a constant intravenous infusion at rates of 2.5, 5.0, 7.5, and 10.0 microgram/kg/min. Steady-state plasma levels increased in proportion to the infusion rate, indicating that there was no saturation of the disposition processes. The average total body clearance was found to be 2.35 +/- 1.01 L/min/m2. After termination of the final infusion, plasma levels of dobutamine were monitored to determine the elimination half-life. The disappearance half-life of dobutamine was calculated to be 2.37 +/- 0.7 min and the distribution volume was 0.202 +/- 0.084 L/kg. The limited data suggest that the volume of distribution of dobutamine was related to the extent of edema.


Dose-dependent acebutolol disposition after oral administration. The relationship between dose and area under the blood concentration-time curve has been studied in 6 healthy subjects following both oral and intravenous doses of acebutolol. There is a more than proportional increase in area with increasing oral doses, and the area over a dosing interval following multiple oral doses is greater than the total area after a single dose of the same size. The role of an acetyl metabolite in producing these effects is discussed, as is the relevance of these observations to the clinical use of acebutolol.


Effects of probenecid on furosemide response. Furosemide gains access to its intraluminal site of action by active secretion by the organic acid transport system of the proximal tubule. Inhibition of this transport by probenecid would predictably decrease the effect of furosemide. In this study in 8 normal volunteers, however, the opposite occurred; namely, pretreatment with probenecid increased the overall response to furosemide by prolonging its effect. Sodium excretion in 8 hr due to 40 mg of furosemide rose from 262 +/- 16 to 358 +/- 11 mEq after probenecid. Urine volume increased from 3,265 +/- 275 to 4,165 +/- 183 ml after probenecid. Analysis of the time-course of the increased diuresis and natriuresis showed that probenecid actually decreased the response for the first 60 to 90 min after furosemide but increased the subsequent response sufficiently to result in a greater overall effect. Possible explanations include access of furosemide to its active site from the serum, an effect of probenecid on prostaglandin transport, and a changing pharmacokinetic interaction between probenecid and furosemide.


Placental transfer of furosemide.

Placental transfer of furosemide. After oral administration of furosemide to 18 pregnant women on the day of delivery, substantial concentrations of the drug were detected in umbilical cord vein plasma as well as in amniotic fluid. The ratio between the furosemide concentrations in maternal vein plasma and in umbilical cord plasma increased with time and approximated unity at 8 to 10 hr after administration of the drug. The plasma half-life of furosemide appeared to be longer in the mothers than in nonpregnant healthy volunteers. In one patient the plasma level of furosemide was constant during 5 hr of observation.


Interaction of chloramphenicol with phenytoin and phenobarbital. Case report. The effect of chloramphenicol therapy (48 mg/kg/day) on the serum concentrations of phenytoin and phenobarbital was studied in a patient previously stabilized on anticonvulsant medications. Phenytoin, 12 mg/kg/day, and phenobarbital, 5 mg/kg/day resulted in serum concentrations averaging 10.8 microgram/ml before and 30.5 microgram/ml, after chloramphenicol therapy. A reduction in dose of both phenytoin and phenobarbital was required to minimize adverse effects during the course of chloramphenicol therapy. An average daily dose of phenytoin of 9.1 mg/kg resulted in an average serum concentration of 17.8 microgram/ml. A daily dose of phenobarbital of 4.0 mg/kg resulted in an average serum concentration of 37.1 microgram/ml. These changes indicate 50.5% and 40.4% decreases in clearance of phenytoin and phenobarbital. Multiple-dose nonlinear regression analysis of phenytoin and phenobarbital serum concentration data obtained during chloramphenicol therapy indicated a 62.5% and a 29.5% decrease in clearance. Subsequent serum concentration monitoring demonstrated a similar reduction in phenobarbital clearance when chloramphenicol was added to phenobarbital alone.


Distinctive patterns of amobarbital metabolites. This paper establishes that the relative proportion of amobarbital metabolites in urine is highly variable from person to person and that observations of plasma half-life give no indication of this variability, but it shows that a valid estimate of a given person's metabolite pattern can be obtained by studying a single urine specimen in the postdistributive phase. The two metabolites which were measured in urine accounted on the average of 9 subjects for 80% +/- 3% of the dose with a range from 66% to 94%. The two metabolites were the well known 3'-hydroxyamobarbital (COH) as a product of side chain hydroxylation and N-beta-D-glucopyranosyl amobarbital (N-glu), a glucose conjugate which at some earlier time had been mistaken for an N-hydroxylation product. Among 129 volunteer subjects, the metabolite ratio N-glu/COH showed a median value of about 0.5 with a range from 0 to 2.8. A virtual absence of N-glu was observed in one of the 129 subjects and confirmed by a second administration of amobarbital 3 mo later. Of the 14 subjects with predominant N-glu excretion 4 were of Chinese origin, while there were 6 Chinese among the 115 other subjects (p less than 0.02).


Transplacental passage of diazepam during labor: influence of uterine contractions. The rate of transplacental passage of diazepam (DZ) has been studied in 33 cases of cephalic presentation where operative forceps delivery was indicated by intrauterine hypoxia or by prolonged second stage of labor. The drug (30 mg) was injected intravenously immediately before delivery either during uterine contractions (Group I) or in the relaxation period (Group II) according to a randomized protocol. As judged by the concentration in the newborn and the child/mother concentration ratio at 2 hr after delivery, and the concentration on the second day, the fetal exposure to the drug was probably less when the injection was timed to coincide with uterine contractions. In the group of patients given the drug in the relaxation period, the injection-delivery (I-D) interval was up to 305 sec and the 2-hr child/mother concentration ratio was close to unity in some cases. It therefore appears that the transplacental passage of DZ is rapid when the high initial concentrations in the maternal circulation coincide with favorable conditions for transfer in the relaxation period. Although sleep was induced by the injection of DZ in all of the mothers, the amounts of drug transferred during the short I-D intervals in the present study did not exert delterious effects on the newborn infants.


Effect of ibuprofen on platelet function in normal subjects and hemophiliac patients. New propionic acid derivatives are claimed to induce a lower incidence of gastrointestinal bleeding and hemostatic disturbance than older anti-inflammatory analgesics such as aspirin. One of these (ibuprofen, Motrin) was given (600 mg orally) to normal subjects and hemophiliac subjects on a random, double-blind basis (lactose placebo). Platelet adhesiveness, aggregation, platelet and red cell counts, percent packed cells, percent hemoglobin, serum ibuprofen levels, and modified Ivy bleeding time were measured before and 2 and 24 hr after drug. Predrug and 24-hr postdrug values were normal, but at 2 hr after drug, adenosine diphosphate, epinephrine, and collagen aggregations were inhibited and bleeding times were slightly but significantly prolonged in the ibuprofen-treated normal subjects. The other parameters tested remained unchanged. Similar results were obtained in the ibuprofen-treated hemophiliac patients, although bleeding time was not prolonged. The results suggest that ibuprofen may be given to hemophiliac subjects with greater safety than some of the older anti-inflammatory drugs.


Artistic anatomy, dimensions, and proportions of the external ear. All ears are different, and the degree of difference within the bounds of acceptability is remarkable. To that end, the keys to construction, reconstruction, or modification must be observed in order to mold an ear that "looks right." Simply stated, these keys are as follows: The ear is a flap approximately 50 to 60% as wide as it is high, sitting back one earlength (6.5 to 7.5 cm) from the lateral orbital rim, with the top of the ear level with the brow inclined approximately 20 degrees and protruding 1.5 to 2.0 cm from the head. It is composed of five critical elements: concha, helix, antihelix, tragus, and lobule, and parts of lesser importance including antitragus, intertragic notch, and Darwin's tubercle. The subtleties of form and proportion of its features will be revealed by careful observation and study.


Microvascular surgery in avulsive trauma to the external ear. Ears amputated as part of scalping injuries have a good chance of survival in favorable circumstances. Survival of subtotally amputated ears is probably enhanced materially by arterial repairs. One experience with a completely avulsed ear that was replaced with two arterial repairs and no vein repairs showed initial perfusion, but eventually failed.


Prominent ears.

Prominent ears. The prominent ear deformity can be divided into two basic types, and combinations of the two. Two different operations are proposed to treat the cause of the deformity without foreign bodies or suture tension. The result should be an ideal shape. The ear should also feel normal and should not show any stigma of surgery.


A comparison of methods for measurement of rectal potential difference in man: effects of rectal infusion of amiloride. 1. Two methods for measurement of rectal potential difference in man were compared. A saline-filled catheter technique gave more reproducible results and was better tolerated by patients than the solid probe technique. 2. Infusion of amiloride at a concentration of 4 x 10(-6) mol/l in saline produced a variable fall of potential difference in six normal subjects. Dose-response curves in two subjects showed that complete inhibition of rectal difference occurred at 4 x 10(-5) mol/l and 4 x 10(-6) mol/l respectively. 3. This finding provides additional evidence that rectal potential difference in man results from electrogenic ion transport across the mucosal epithelial cell.


Abnormalities of renal transport of sodium o-[131I]iodohippurate (Hippuran) in essential hypertension. 1. Renal function has been studied in 312 hypertensive patients by quantitative renography with sodium o-[131I]iodohippurate (131I-labelled Hippuran) and estimation of overall effective renal plasma flow. In 59% of the patients the results were normal. 2. Severe hypertension was associated not only with reduced effective renal plasma flow but also a characteristic abnormality of Hippuran transport in 10% of the patients in which there was a wider than normal variation in transit times of Hippuran through the kidney, which may reflect non-uniformity of reabsorption of filtrate by different groups of nephrons. 3. Plasma renin activity was higher in a group of 14 patients with multimodal transit time spectra than in a matched hypertensive control group, with very substantial overlap between the two groups. 4. The renographic abnormality was usually reversed by treatment.


Renal vasoconstriction in glycerol-induced acute renal failure. Studies in the isolated perfused rat kidney. 1. Acute renal failure was produced in rats by the intramuscular injection of glycerol (6.1 mol/l 10 ml/kg). Either 2 or 4--6 h later the right kidney was isolated and perfused for 1 h with an electrolyte solution containing a gelatin preparation (Haemaccel, 35 g/l) at pressures between 90 and 100 mm Hg in a single-pass system. 2. In kidneys taken from rats with acute renal failure renal vascular resistance was markedly increased immediately after the start of the perfusion as compared with control kidneys taken from untreated rats. During the following 30 min of perfusion the resistance progressively decreased and, at 1 h of perfusion, was similar to that in control kidneys or only moderately elevated. 3. Despite the reduction of renal vascular resistance glomerular filtration rate was still markedly increased immediately after the start of the perfusion as compared with control kidneys taken from untreated rats. During the following 30 min of perfusion the resistance progressively decreased and, at 1 h of perfusion, was similar to that in control kidneys or only moderately elevated. 3. Despite the reduction of renal vascular resistance glomerular filtration rate was still markedly impaired after 1 h of perfusion and fractional reabsorption of sodium and water as well as the secretion of p-aminohippurate were diminished. Renal venous renin concentration and renin release were lower in kidneys taken from rats with acute renal failure than in the control experiments. 4. These results suggest that the increase in renal vascular resistance and the stimulation of renin release after injection of glycerol in vivo are the consequence of extra- rather than intra-renal mechanisms.


Bile secretion and bile composition in the freely moving, unanaesthetized rat with a permanent biliary drainage: influence of food intake on bile flow. 1. In freely moving, unanesthetized rats bile flow was measured continuously over the whole day--night cycle. Bile composition was analysed and the influence of food intake on bile flow was investigated. 2. In both sexes a distinct circadian variation of bile production was observed. The mean night-time production was 50% higher than the day-time value for female rats and 38% for male rats. In the morning when the light was switched on, a sharp decrease in secretion rate was prominent and bile flow gradually increased in the afternoon. 3. The pattern of food intake was positively correlated with the pattern of food bile secretion. During fasting only the general level of bile flow decreased, but the circadian variation persisted. Refeeding again increased the mean level of bile flow. 4. The chenodeoxycholate/cholate ratio in these rats with permanent bile fistulae was higher than in rats with "acute" bile fistulae and changed during the day--night cycle. The ratio decreased from 1.01 at 05.00 hours to a minimum of 0.41 at 15.00 hours. 5. During the day--night cycle the sodium, potassium, calcium and cholesterol concentrations were relatively constant. The total bile salt concentration was only slightly changed, so that both the bile salt-dependent fraction and the bile salt-independent fraction were subject to about the same circadian variations.


Partial characterization of aortic renin in the spontaneously hypertensive rat and its interrelationship with plasma renin, blood pressure and sodium balance. 1. A renin-like enzyme in aortic tissue of the spontaneously hypertensive rat was found to be a freely dissociable enzyme (saline homogenization) with an affinity for the renin inhibitor pepstatin. At neutral pH values, the enzyme was active in homologous plasma to produce angiotensin I, and therefore distinct from pseudorenin and cathepsin D. The arterial enzyme and semi-purified renal renin could not be distinguished on the basis of Km values by using homologous renin substrate 2. An inverse relationship between the aortic renin content of the spontaneously hypertensive rat and the progressive increase of systolic blood pressure was observed with age. In contrast to this strain of rat, aortic renin of the normotensive WKY strain did not decline with age. 3. Plasma renin concentration and the aortic renin content of the spontaneously hypertensive rat showed divergent changes in response to a blood pressure fall associated with acute diuretic therapy, chronic administration of hydrallazine and in some animals in response to chronic administration of propranolol. 4. A low sodium diet elevated both plasma and aortic renin and retarded the progressive increase of blood pressure in the spontaneously hypertensive rat. A high sodium diet accelerated the progress of hypertension with no effect on aortic or plasma renin. 5. Antihypertensive therapy (1--6 weeks), resulting in a lowering of conscious systolic blood pressure of the spontaneously hypertensive rat, consistently led to a decrease in aortic renin content.


Validation of "transit renography" for the determination of the intrarenal distribution of plasma flow: comparison with the microsphere method in the anaesthetized rabbit and pig. 1. The spectrum of transit times of sodium o-iodohippurate (Hippuran) through the kidney can be derived from an 131I- (or 123I-) labelled Hippuran renogram by deconvolution. In the rabbit and pig, as has previously been shown in man, the frequency distribution curve for the transit times was bimodal. Since the transit time is likely to be proportional to the nephron length, the area of the first mode is likely to represent plasma flow to the shorter outer cortical nephrons whereas the delayed mode represents flow to the long juxtamedullary nephrons. 2. This interpretation was tested by simultaneously comparing renography with the microsphere method of measuring intrarenal plasma flow distribution in 12 rabbits and two pigs with a variety of anaesthetics. A close agreement was found between both methods for the percentage of plasma flow distributed to the outer cortical nephrons, thus supporting the use of "transit renography" to determine the intrarenal distribution of plasma flow.


Analytical subcellular fractionation of jejunal biopsy specimens: enzyme activities, organelle pathology and response to corticosteroids in patients with non-responsive coeliac disease. 1. Jejunal biopsies from five patients with non-responsive coeliac disease have been subjected to analytical subcellular fractionation and enzymic microassay in order to compare the organelle pathology of this group with untreated but glutensensitive patients. 2. Compared with the gluten-sensitive group these non-responsive patients showed marked reduction of the endoplasmic reticulum enzymes, normal activities of lysosomal enzymes and slightly less severely reduced brush border activities. 3. It is suggested that the present biochemical studies in combination with previous clinical reports and measurements of DNA and protein synthesis by cultured mucosal biopsies delineate non-responsive coeliac disease as a distinct entity. 4. The patients were treated with oral prednisolone (20 mg daily) for between 5 and 9 weeks and the properties of the jejunal biopsies restudied. 5. Although morphologically there was only a partial restoration of the villus architecture the enzymic alterations and organelle abnormalities returned essentially to normal values.


The respiratory response to inhaled carbon dioxide in man after 3 hours exposure to 3% carbon dioxide. 1. The respiratory response to inhaled 3% and 6% CO2 was measured in 10 normal subjects after a 3 h acclimatization period to 3% CO2 in an environmental chamber. Control studies were carried out after a 3 h period of breathing air in the chamber. 2. At the end of the acclimatization period studies were carried out during 20 min periods breathing 3% CO2, 6% CO2 and air. 3. At 2-min intervals during the studies measurements were made of tidal volume (Vt), breathing frequency (fR), minute ventilation (Ve), viscous pulmonary rate of work (Wp) and total viscous rate of work across the lungs and apparatus (Wt). Blood gas tensions were measured at the end of this period. 4. After acclimatization to 3% CO2 there was a significant shift in the response curves Ve/Pa,CO2 and Wt/Pa,CO2 such that subjects showed higher Pa,CO2 values for given values of Ve or Wt. There was no significant change in the slope of the response curves. 5. No correlation was found between the slope of the response curve after the control period breathing air and the degree of shift of the response curve. 6. There was no difference in respiratory pattern or in pulmonary resistance. 7. Similar results were found in two subjects studied after 24 h acclimatization to 3% CO2 but one subject also showed a significant change in the slope of the Ve/Pa,CO2 curve.


The distribution of cardiac output in the anaesthetized spontaneously hypertensive rat. 1. Radioactive 15 micrometer and 50 micrometer diameter microspheres were used to determine cardiac output, its regional distribution and tissue blood flow in adult normotensive Wistar and Okamoto spontaneously hypertensive rats. 2. Cardiac output in the spontaneously hypertensive rats was the same as in Wistar normotensive rats, but its distribution in the hypertensive rats appeared to differ: there was a significant increase in the proportion of microspheres trapped in the liver whereas fewer were found in the gastrointestinal tract. This indicates that a greater fraction of the cardiac output passes along the hepatic artery and less through the splanchnic bed. 3. Blood flow in skin and skeletal muscle in spontaneously hypertensive rats was approximately 50% of that in Wistar normotensive rats.


The effectiveness of planning for community mental health center inpatient units. The number of beds identified among 308 community mental health centers in operation in 1972 bore little relation to inpatient case load or to the proportion of center patients likely to require hospitalization. Analysis of occupancy data indicated that there was a surplus of beds in many centers. These findings suggest a lack of effective planning for community mental health center impact on the nature of psychiatric treatment provided. This is suggested by the close relationship between inpatient capacity and average duration of stay.


Nonprofessionals in the rehabilitation of mentally disordered sex offenders. Eighty-six sex offenders were exposed to a 6-month voluntary program of either group encounters (experimental group) or hobbies and games (control group) led by nonprofessionals. Pre- and posttests included a personality test, an introspective report, and a behavior rating scale. Written ward records were assessed as were the results of a postexperimental prisoner evaluation of the experience. Significant changes were evidenced by encounter subjects in improved feelings of approval of the prison-hospital experience, lessened hostility, and better attendance at the meetings. Encounter subjects were improved in the predicted direction on 55 of the 74 treatment dimensions. Community volunteers were judged moderately successful as lay therapists.


Education as a force for change in mental health settings. The authors focus on the educational process as a force for bringing about changes in the community or within an agency setting. Four change agent roles--specialist, problem solver, consciousness raiser, and advocate--are identified and described. Attention is then focused on criteria for choosing a change agent role. What kind of change is needed? What is the probability of success using a given role? What are the consequences of functioning in a given role? These are three questions an educational change agent should ask before choosing a role as specialist, problem solver, consciousness raiser or advocate.


Curricula of associate degree mental health/human-services training programs. Over 100 community college programs engaged in training people for mental health/human-services employment were studied in order to describe the curriculum most generally offered and variations most frequently found. In general, the programs have developed similarly: major emphasis on experiential learning of group dynamics, on techniques of interpersonal assistance, and on apprenticeship field work experience; and lesser emphasis on the organizational aspects of care and on relevant theoretical literature. Nevertheless, substantial differences exist between programs; for example, the specialization of the curriculum, the credit awarded for field work experience, and the types of settings used for field placements.


Planning community treatment for sex offenders. In California and in Great Britain plans are being made to move the treatment setting for many sex offenders from large state hospitals to community sites. The most useful aspects of the state hospital programs can be adapted to the community setting. In the proposed treatment centers, graded levels of security may include inpatient, half-way house, and outpatient facilities. The therapist will coordinate social and educational programs as well as psychiatric care. Optimally, the community treatment center will have university support so as to facilitate training in forensic psychiatry and research into the etiology and management of sexually aggressive behavior.


Hospital and family cooperating to reduce psychological trauma. In spite of the advantages of increased parent participation in the hospitalization of children, institutions resist change to facilitate family care. The development of one-day surgical units provides increased flexibility and reduces many psychological stresses. A film was made of one child's experience with outpatient herniorraphy after being held by her mother during induction of anesthesia. The film documents one hospital's effort to meet the psychological needs of parents and children; it also helped change inpatient procedures.


Promises, promises or community mental health services and training: ships that pass in the night. In common with other publicly funded human-service programs, community mental health centers are victimized by a political advocacy process that inflates expectations, distorts value judgments and, as a result, helps promote ultimate disillusionment. The problems resulting from this "overpromise" are compounded by the performance of staff who are inadequately trained for their jobs. By and large, the education of mental health professionals does not equip them for work in community mental health centers. What they learn in school is not sufficiently related to what they do. The development of "undisciplined" mental health professionals with degrees in mental health should be considered. Their training would rest on new curricula that reflect the needs of patients in community mental health settings and be free of the constraints inherent in traditional disciplinary models.


Models of staff support for mental health/mental retardation community boards. With the advent of the 1975 Amendments to federal mental health legislation which call for community governing bodies to oversee local mental health services, the question of effective board functioning becomes crucial. This paper describes professional staff roles and staff support models that can be used to enable better functioning of community boards. Questions of placement in the hierarchy and selection of the worker are also addressed.


Clinical interest of coronal and sagittal CT sections. Normal and pathological anatomy of the brain can be studied in different cross-sectional planes. Of specific interest here are sagittal and coronal views obtained by computer reconstruction procedures. The three different planes for the reconstruction of the images are complementary, of real clinical interest, and are particularly useful for an accurate localization of lesions, either for surgical intervention or for radiotherapy planning purposes.


Clinical application of a CT based treatment planning system. An AECL (TP-11) treatment planning system has been modified to allow multiple CT scans to be used directly for dosage calculation and display. This CT/TP-11 system has incorporated the "equivalent tissue-air ratio method" to make corrections for the effects of tissue heterogeneity and the three-dimensional nature of patient shape. In test situations, using an anatomical phantom, an accuracy of ca. 2% has been attained. An investigation has also been made to assess the importance of the reproducibility of patient position and its effect on the validity of such dosage calcualtions. When representing an advance in sophistication of existing facilities, this system has also been designed with practically in mind.


Early diagnosis of tuberculous thoracic aortic aneurysm by computerized axial tomography. A thoracic aortic aneurysm secondary to miliary tuberculosis was successfully diagnosed early in its course in an asymptomatic patient by computerized axial tomography with contrast enhancement. This non-invasive technique, performed on an outpatient basis, led to the rapid and successful treatment of the patient.


The use of computerized tomography in the diagnosis of pulmonary nodules. Pulmonary nodules, in particular the solitary pulmonary nodule or coin lesion, have presented diagnostic difficulties to the specialist in chest diseases. The controversy over managing such lesions ultimately involves the question of whether a given nodule is benign or malignant, and the reports of diagnostic experiences vary considerably. The criteria for diagnosing and managing pulmonary nodules prior to the advent of computerized tomography (CT) were based on anatomic descriptions from conventional and specialized X-ray techniques and on pathological consideration of tissues obtained by invasive techniques. The mathematical manipulation of the absorption coefficients of nodular lesions in the lungs, obtained in a non-invasive manner using CT, can provide additional criteria for diagnosing such lesions. In our study 20 nodules (6 malignant, 14 benign) were retrospectively studied with CT, and from the results it appears that there are distinctive patterns for malignant and benign lesions. We have explained our procedure in this paper and presented an illustrative case study.


Variations in the measurement of regional cerebral blood volume by CAT. The cerebral blood volume (CBV) has been measured by transverse axial tomography. The attenuation coefficient of 100 "pixels" located in a well determined region was measured before and after injection of a contrast material (Telebrix 38). The attenuation coefficient of blood samples was measured by CT in a phantom. Blood samples were drawn before and after injection at the same time as the tomographic section (time: half rotation of the scanner). The volume was calculated by the (formula: see text). The values obtained with very early measurements (1--5 min after injection), were very close to those measured by other methods (3--5 ml/100 ml). For 5 patients, the CBV was measured by the same method at different times: 20 measures between 2 and 50 min after the injection. The CBV seemed to vary in function with time according to the equation: CBV in ML%: ate-bt + Vo (t = time in minutes: a = integration constant, a = 1.94; b = time constant, b = 0.089; Vo = real CBV). The apparent variation of CBV was the result of two factors related to the blood-brain barrier, (1) water movement from the extravascular space towards the intravascular space, related to the hyperosmolarity of the contrast medium. The variations of osmolarity and haematocrit values measured after contrast injection did confirm this hypothesis; and (2) iodine movement from the intravascular space towards the extravascular space, due to the toxicity of the material (hyperosmolarity, Na ions, etc). The measurement of CBV by CT is only possible if the contrast materials do not modify the blood-brain barrier. The use of actual materials allows the study of the blood-brain barrier behaviour and enables to make an estimate of the cerebral extra-cellular space. But CT is not a right method of CBV measurement with the contrast medium in use nowadays.


Clinical symptomatology and computerized tomography in brain metastasis. In 50 patients with a diagnosis of brain metastasis, a study was made commencing with the appearance of the first neurological symptom. Severe headaches were observed in 48% of the patients, followed by a change in character in 11% and motor disorders in 11%. The search for initial neurological signs will help dictate the precise moment of using the scanner to confirm the diagnosis, thus hopefully allowing for a quicker treatment and improving the survival rates of these patients.


The role of computed tomography in the evaluation of upper cervical spine pathology. A series of nine patients with symptoms referable to the upper cervical spine were recently studied by both conventional radiographic techniques and computed axial tomography (CT), in an attempt to ascertain the effectiveness of CT in evaluating upper cervical spine pathology. We found CT a useful tool in diagnosing a variety of pathological conditions in this region, particularly when they involve subtle neural arch fractures, rotational deformities, or compromise of the neural canal.


Ultrasonography and CT scanning: a comparative study of abdominal aortic aneurysms. CT scanning has been successfully used in the evaluation of the abdominal aorta in over 70 patients. Half of this group, with abdominal aneurysms, was also studied by ultrasonography and the results compared. Both techniques proved equally reliable in the diagnosis of this entity. Closer correlation to the aneurysmal diameter measured at surgery was obtained by CT scanning; underestimation of size by ultrasonography was a frequent finding. Aortic lumen and intra-aneurysmal thrombus were also more clearly demonstrated by CT when contrast enhancement was added. Evaluation of aneurysmal length is done more effectively by ultrasonography although sagittal reconstruction by CT has been now attempted.


Radiation dose and labeling of hippuran. Renal morphology and renal function were studied with iodine-123-hippurate in 98 patients with various renal diseases. Sequential scintigraphy with iodine-123-hippurate demonstrates much better renal blood flow, morphology and function than iodine-131-hippurate. A method of labeling hippurate in a short time (2 h) with high efficiency (95--100%) is described. Radiation exposure to various organs was calculated and significant differences in radiation exposure to the thyroid are demonstrated.


Sensitivity and specificity of radioisotope renography in renovascular hypertension. Effective drug therapy for hypertension modifies the urgency of establishing a diagnosis of renal arterial stenosis. The cost of establishing a diagnosis must be considered with other factors in determining the usefulness of renography in renovascular hypertension. Recently published studies estimate the cost effectiveness of this procedure based on some data from a cooperative study of renal vascular hypertension. The small but costly incidence of false positives contributes significantly to the total cost of patient screening. Careful attention to technical details that are presented here could reduce false positives without sacrificing the true positives. However, even with increased specificity economic considerations would indicate limiting a screening program to younger patients or those in whom a drug regimen is unsuccessful.


Gray scale echography of unilateral renal disease. Gray scale ultrasound is a reliable noninvasive method of demonstrating renal pathology. It is simple nontraumatic, nonionizing and can be readily utilized in the differentiation of cystic and solid lesions.


Echotomography in unilateral renal disease. A review of about 300 patients with unilateral renal disease shows that echography is valuable for a correct diagnosis in numerous cases. The authors emphasize the role of A-B mode ultrasonographic scanning in the exploration of IVP nonvisualized kidneys, renal trauma, and other disorders.


Determination of renal circulation by means of angiocinedensitometry. This new X-ray method is based on the densitometric measurement of the speeds and the flow of injected contrast media during an angiographic examination of the vessels and the parenchyma of the kidney. Pairs of highly sensitive photoconductive cells and a Wheatstone bridge circuit are used. Minimal doses of contrast media can be detected before vascular reaction influences the renal circulation. The measurement of various parameters allows the simultaneous hemodynamic analysis of kidney function and of factors related to the morphological substrate.


Indications for rapid sequence urography after washout (reinjection) in the diagnosis of renovascular hypertension. 38 hypertensive patients suspected of renovascular hypertension were examined with rapid sequence urography, washout, aortography or selective renal arteriography. When discordant results were found between rapid sequence urography and washout, we used a particularly helpful procedure which we define reinjection or rapid sequence urography after washout: washout is followed by the injection of a second 50-cm3 dose of contrast agent and five more roentgenograms at 1-min intervals. In our series, reinjection allowed correct diagnosis in 66% of the cases with discordant results and confirmed diagnosis in 83% of the cases of renovascular hypertension.


Observations on the use and limitations of renal vein renins in hypertensive patients. From our consecutive series of renal vein renin studies in 170 patients with kidney disorders and hypertension, we present those cured by surgical correction of a unilateral renal artery stenosis during the period 1973--75. The renin secretion patterns of these patients range between no demonstrable abnormality, even with a stimulating procedure using dihydralazine 7.5 i.v., and massive renin secretion already during basal conditions. Thus, the renin secretion may not be increased even after stimulation in some patients with durable unilateral renovascular hypertension. This fact may be explained by the rise of the systemic blood pressure, eventually maintained by sodium and water retention and accompanied by adaptive changes in the contralateral kidney. The perfusion pressure is thereby kept normal in the affected kidney, eliminating a stimulus for renin secretion. It is likely that many cases of renovascular hypertension pass through an early stage where no involvement of the renin-angiotensin system may be discovered. Of course, these patients will also benefit from surgery. The conclusion is that renin studies for diagnostic purposes should be performed when patients are on treatment and kept normotensive for some time, and that an additional challenge of the perfusion pressure, i.e., by use of dihydralazine, intravenously should be performed.


Plasma renin activity in renal veins of renovascular patients. PRA was simultaneously measured in both renal veins and in a peripheral vein of patients with essential (6) and renovascular (37) hypertension. In renovascular patients suppression or renin secretion from the contralateral kidney was always observed: otherwise in patients with essential hypertension both kidneys contribute to peripheral PRA. The suppression of renin secretion from the ischemic kidney either by nephrectomy or by revascularization, joins with normalization either of peripheral PRA or of blood pressure. This finding points to the role of the renin-angiotensin system in the genesis of human renovascular hypertension.


Correlation between evolution and treatment of hypertension in unilateral renal disease and values of renin activity in renal venous blood. 93 patients with renal hypertension and renal vein PRA determination were studied during 1--5 years follow-up. They were separated in two groups of medical and surgical treatment. Medical treatment is able to normalize blood pressure even in cases with high asymmetric PRA. 9 of 16 patients could be cured or improved in the surgical group and 14 of 22 in the medical group. The best results were obtained if beta-blockers were included in the drug regimen: cured or improved were 7 of 33 patients in medical treatment without beta-blockers, 17 of 28 in surgical treatment, and 31 of 32 in medical treatment including beta-blockers with or without hydralazine and/or diuretics.


Renal secretion of inactive renin.

Renal secretion of inactive renin. Human plasma contains a non-dialyzable factor which is not enzymatically active in its native form but shows renin-like activity after exposure to low pH (inactive renin). In 3 out of 13 patients with renovascular hypertension the renal to peripheral vein ratio for inactive renin on the affected side was above 1.40, indicating renal release of this form of renin. In 4 cases a high renal to peripheral vein ratio for active renin was associated with a ratio for inactive renin below 0.80, indicating renal activation of circulating inactive renin. The results suggest a renal mechanism for modulating the degree of activation of renin. They have some practical implications for the pre-operative evaluation of patients with renovascular hypertension.


Peripheral handling of angiotensin II and blood pressure control in hypertensive patients with unilateral and bilateral renal disease. PRA, AII CR, AII E and cardiac output have been measured in 9 normals and in 22 hypertensives: 8 with URD, 12 with BRD and 2 with MHY. PRA, as well as AII E, shows the highest values in BRD and MHY patients. AII CR is directly correlated with blood pressure levels in URD and BRD patients (p less than 0.05 and p less than 0.001, respectively). A significant positive correlation is found between AII E and TPR (within each group of patients and among all subjects) and between PRA and TPR within the hypertensive patients. These data suggest that peripheral handling of AII is involved in the control of blood pressure in the patients studied.


Effects of saralasin on blood pressure, renin and renal blood flow in unilateral renovascular hypertension. The effect of saralasin, a competitive inhibitor of angiotensin II, was assessed in hypertensive patients with unilateral renal artery stenosis after furosemide application. A significant fall of systemic arterial blood pressure, an increase of renal venous renin activity, significantly on the stenosed side in patients without arteriosclerosis of the contralateral kidney, and an almost equal decrement of renal blood flow in both kidneys were observed. Conceivably saralasin exerts different sodium-dependent effects on peripheral angiotensin II and specific intrarenal vascular receptors.


Effects of 1-sar-8-ala-angiotensin II on arterial pressure, renin and aldosterone in hypertension. 1-Sar-8-ala-angiotensin II did not change intra-arterial pressure in 25 sodium replete hypertensive patients, whilst the pressure changes were closely related to the plasma renin level during sodium depletion (r = -0.87; n = 32). The study indicates that arterial pressure is not dependent on angiotensin II in sodium replete patients and in sodium deplete subjects with low PRC, while it is angiotensin dependent during sodium depletion in the others. Plasma renin is unaffected in sodium replete subjects, but increases during saralasin in sodium deplete conditions. Saralasin stimulates aldosterone secretion only in sodium replete patients.


Role of renal prostaglandins in circulatory homeostasis. The evidence is reviewed that prostaglandins of renal origin through (i) their local actions on renal blood vessels, and (ii) complex interactions with the nervous adrenergic and the endocrine vasoactive renin-angiotensin-aldosterone and kallikrein-kinin systems, may participate in the regulation of excretory functions of the kidney and thereby contribute to circulatory homeostatic mechanisms.


Prostaglandins in renovascular and renal hypertension. PG A1, B1, E2, F1,2alpha and PRA have been measured in 8 hypertensive patients with unilateral renal arterial stenosis, 7 hypertensive patients with unilateral renal atrophy and 20 control normotensive subjects. PRA and PGA1 were significantly increased in patients with renovascular hypertension but not in patients with atrophy. PGE2 and PGF1,2alpha were increased in both groups of patients, especially on the stenotic or atrophic side. The increase of PGA1 and PGE2, represents a secondary antihypertensive, diuretic and natriuretic mechanism, the increase of PGF1,2alpha a direct hypertensive mechanism.


Determination of total, divided and regional tubular clearance and excretion by compartmental analysis of camera renograms. A method to analyze the camera renogram is described in a mathematical manner. It is based on a 6-compartment model, which simulates the hippurate in vivo kinetics. Results are transfer rate constants from which the tubular clearance (by multiplying with the plasma volume) and additionally excretory parameters can be derived. The method is quick and simple and needs a gamma-camera and a small data processing system only, but no special equipment and no blood sampling.


Comparison of different methods of clearance determination. Clearance determination by compartmental analysis of hippurate renograms was compared in 30 cases to the conventional PAH and to the partly shielded whole body counting technique. Good correlations between compartmental analysis and PAH method (r = 0.96) as well as the whole body technique (r = 0.94) were found. Correlation between PAH and whole body method was not always satisfactory (r = 0.85). In an additional study influence of greater count rates become obvious: correlation coefficients increase from 0.89 (131I-hippurate, n = 97) to 0.95 (123I-hippurate, n = 38). Determination of the divided clearance correlates well (r = 0.95). Using 123I-hippurate all the information available by radioisotopic kidney investigations can be obtained in a one-step procedure.


Unilateral estimation of glomerular filtration rate with 99mTc-DTPA. There is one renal disease in which unilateral estimation of GFR is desirable for clinical purposes: chronic pyelonephritis. Considering the possibilities for complications to determine unilateral renal function by ureter catheter just in this group of patients, we tried to estimate unilateral GFR with 66mTc-DTPA after a single injection of 5 mCi i.v. on the basis of blood samples at 90, 110 and 130 min after injection and evaluation of gamma-camera data from 25 to 35 min after administration of the dose. 31 patients were studied. In arenal patients clearance values were 7.5 ml/min (+/- 10.47 ml/min), unilaterally nephrectomized patients showed zero values for the removed kidney. Normal patients had a mean GFR of 107 +/- 17.7 ml/min with a partition between right and left kidney of 54.2 +/- 10 to 52.75 +/- 8.5 ml/min. Patients without urinary tract obstruction and unilateral renal disease had values of 27.1 +/- 11 ml/min for the diseased kidney while the normal kidneys gave a mean value of 59.6 ml/min (+/- 13 ml/min). In the presence of urinary tract obstruction, data could not be correlated to the state of renal function. This shows that unilateral estimation of GFR using 99mTc-DTPA is basically possible, but that it is useless in obstructive kidney disease.


Unilateral kidney blood flow measurement using the 81Rb/81mKr ratio. A new method has been developed for the continuous quantification of kidney blood flow, utilizing the unique physical and biological properties of the radioactive tracer couple: rubidium-81/krypton-81m. After intravenous injection, 81Rb concentrates primarily in the kidneys, where it continuously generates the radioactive inert gas 81mKr. This ultrashort-lived isotope is continuously washed out from the tissue at a rate proportional to the blood flow. The radiation emitted from within the kidney is externally detected and analyzed to yield the 81Rb/81mKr ratio. 21 animal experiments have confirmed that this ratio is at any time an accurate measure of the kidney perfusion. The 81Rb/81mKr ratio method has proved to provide a non-invasive way to selectively quantify the blood flow in each kidney, to monitor perfusion changes and to image the distribution of blood flow in a functional scintigram.


Limits of sensitivity of radiopertechnetate flow studies in the detection of asymmetrical renal perfusion. A canine model has been devised using electromagnetic flowmeter probes to study the sensitivity of radiopertechnetate renal angiography. Highly significant correlations were obtained when the measured flow rates were compared with normalized values of the peak activity and uptake slopes for each kidney. Analysis of the data suggests the unilateral renal disease associated with less then 20% difference in flow between the kidneys may not be diagnosed reliably from the pertechnetate perfusion test.


New developments in renal physiopathology acquired using a quantitative renal functional test: the 197Hg uptake test. The renal function of 331 obstructive uropathies, of which 112 were unilateral, were studied using the radioactive Hg renal uptake technique. The results obtained lead to the following observations: (1) Kidneys silent because of a chronic pelviureteric obstruction maintain a minimum function representing approximately one quarter of the normal value, which does not seem to be improved following the removal of the obstruction. (2) Operative relief of obstruction in unilateral obstructive uropathy, except for cases of silent kidneys, is followed by a significative improvement in the function of the kidney on the operated side in more than a third of the cases studied. (3) In 43% of obstructive uropathies considered as unilateral, the functional value of the two kidneys is decreased.


Effects of aldosterone and deoxycorticosterone on the urniary excretion of kallikrein and of prostaglandin E-like substance in the rat. Deoxycorticosterone (5 mg) and aldosterone (0.25 mg), given to rats for 14 days, increased the urinary excretion of kallikrein and of prostaglandin E-like substance and produced polyuria, but affected neither sodium excretion nor blood pressure. These results suggest that interactions of mineralocorticoid hormones, kinins and of prostaglandins may be important in the maintenance of salt-water homeostasis.


What makes the renin-angiotensin system a pathogenic factor? Three types of renal hypertension in the rat have been compared with respect to blood pressure increase, activity of the RAS, and secretion of aldosterone and corticosterone: type I - unilateral stenosis of the renal artery in the presence of an intact contralateral kidney; type II - unilateral stenosis of the renal artery after contralateral nephrectomy; type III - bilateral stenosis of the renal arteries. Blood pressure rose more rapidly and reached higher values in type II and type III hypertension than in type I hypertension. In the latter group, the activity of the RAS was more stimulated than in types II and III. The marked stimulation of the RAS in type I hypertension is ascribed to the negative fluid and sodium balance, which is the consequence of a pressure-induced diuresis of the unclamped contralateral kidney. Suppression of the activity of the RAS by a 4-week pretreatment with DOC-TMA and saline or by the administration of DOCA and saline as from the induction of renal artery stenosis did not prevent the development of hypertension caused by the clamping of one renal artery (type I). In spontaneously hypertensive rats of the stroke-prone substrain, high dietary salt intake caused higher blood pressure values and a higher incidence of cerebral lesions than normal dietary salt intake. Low salt intake was followed by a marked stimulation of the RAS, but blood pressure rose only slightly and no symptoms of cerebrovascular lesions were observed. It is concluded that neither in hypertension induced by renal artery stenosis nor in spontaneously hypertensive rats, the RAS contributes significantly to the increase in blood pressure nor does it play a major part in the pathogenesis of vascular lesions. These seem to be related to the retention of sodium, which may be obtained by renal artery stenosis, by excessive salt intake, or by the administration of a mineralocorticoid and salt.


Prostaglandins and renal function.

Prostaglandins and renal function. Prostaglandins modulate the effects of vasoactive hormones by attenuating the renal actions of the renin-angiotensin system and contributing to and, perhaps, mediating some of those of the kallikrein-kinin system. A prostaglandin mechanism participates in the regulation of renin and erythropoietin release. When renal function is compromised, the circulation to the kidney is sustained by a major prostaglandin component withdrawal of which results in significant hemodynamic effects, particularly reduction of blood flow to the inner cortex and medulla.


Antihypertensive effect of volume depletion: interrelation with renal prostaglandins. Since the original studies of Patak et al. in 1975 revealed that the antihypertensive and natriuretic effects of furosemide were markedly blunted or abrogated by indomethacin in both normotensive and hypertensive man, it has been postulated that the ameliorative effects of furosemide in human essential hypertension might be mediated by release of intrarenal prostaglandins. To study the direct effects of furosemide on prostaglandin biosynthesis and release, slices of rabbit renal medulla were incubated in Krebs-Ringer bicarbonate buffer, glucose 10 mM, 1-14C-arachidonic acid (AA) 10 microM, HSA /g/100 ml, 30 min 37 degrees C. Measurements were made of radioactive AA leads to PGE2, and total endogenous immunoreactive PGE2 production (iPGE2) with and without the addition of furosemide (10 microgram/ml) to the media. In the absence of furosemide AA leads to PGE2 was 73 +/- 22 nmol/30 min/g and in the presence of furosemide it fell to 30 +/- 4 nmol/30min/g. iPGE2 was 33 +/- / ng/30 min/mg and decreased to 25 +/- 3 mg with furosemide. These results indicate that the natriuresis and antihypertensive effect of furosemide in vivo, which is associated with a significant increase in urinary PGE2, is not the result of a direct stimulation of furosemide on prostaglandin synthesis but may result from a decrease in PGE metabolism, conversion to another biologically active prostaglandin or possibly be a reflection of events secondary to a direct effect of furosemide on renal hemodynamics and electrolyte excretion.


Renal prostaglandins in the control of renin. The biochemical processes which transform baroreceptor, beta-adrenergic and macula densa signals into an increase or a decrease of renin secretion are unknown. Evidence is presented that the renal PG system is intimately involved in the mechanisms regulating the release of renin. In vivo stimulation of renal PG synthesis by arachidonic acid (C20:4) or furosemide increases renin release. PG synthesis inhibitors decrease basal renin release and reduce the renin release following stimulation with C20:4, furosemide and renal ischemia. In vitro, C20:4 and the PG-endoperoxides stimulate renin release from the rabbit kidney cortex whereas PGF2alpha inhibits it. This suggests an intrinsic role in the renin release mechanism of PGs, synthesized at or near the juxtaglomerular apparatus. The operation of this PG effect on renin release may depend upon a salt intake related control of PG synthesis and of conversion of PGE2 to PGF2alpha. Increased or decreased renal PG synthesis may also be the primary event leading to elevated or reduced renin levels in some clinical disorders. In Bartter's syndrome, the elevated renin levels may result from an increase in PG synthesis or a decrease of PGF2alpha formation. In benign, uncomplicated essential hypertension, decreased renal PG synthesis or increased PGS2alpha formation may be the primary mechanism which reduces renin release and renal blood flow.


The Old Hag phenomenon as sleep paralysis: a biocultural interpretation. This paper describes a syndrome of psychological and physical symptoms involving body paralysis and hallucinations traditionally interpreted in Newfoundland as an attack of 'Old Hag'. Folk theories of cause and treatment are outlined based on 13 months of field research in a community on the northeast coast of Newfoundland. Data derived from the responses of 69 adults to the Cornell Medical Index (CMI) indicate that there are no significant differences in psychological or physical illness complaints between adults who have experienced the Old Hag and adults who have not had this experience. The striking similarity between the Old Hag experience and a clinical condition called sleep paralysis is analyzed, and the implications of viewing the Old Hag as sleep paralysis are discussed within the context of current theoretical issues in transcultural psychiatry.


Ethnicity and patterns of help-seeking.

Ethnicity and patterns of help-seeking. This study reconstructs and analyzes pathways of help-seeking traveled by severely disabled mental patients in the community. Ethnicity is a prime factor in differentiating patterns of help-seeking in that Chinese patients are kept for prolonged periods of time within their families in the beginning of pathways, while Anglo-Saxons and Middle Europeans are referred by their families or themselves to multiple social and mental health agencies. Native Indians are referred by persons other than family members or themselves between social and legal agencies in the community. Eventually all of these pathways lead to psychiatric inpatient intervention. There are major impediments to treatment in these patterns, most notably isolation and deterioration of patients within confines of families or lack of coordination of agencies in the community. Recommendations aimed at the improvement of treatment in the community are presented in light of these findings.


The Shetland Islands: the effects of social and ecological change on mental health. The authors review the literature concerning the mental health and social effects of industrialization, urbanization and the transition from a rural to an industrial society. They point out the need for prospective and longitudinal studies. To illustrate a working model of the type of research needed, the authors describe a long-term study now underway in the Shetland Islands. This research investigates the effects that rapid social and ecological change (from the North Sea oil developments) will have on the islanders. To test the hypothesis that the changes, associated with the construction of Europe's largest oil port in these previously isolated rural islands, will have a deleterious effect on the Shetlanders' health and way of life, a prospective study has been initiated that contains two sub-studies. The General Survey involves monitoring reported data on ecological, epidemiological and sociological change and is intended to provide an overview of the general impact of the oil developments. The Individual Survey involves interviewing two populations (total N = 533) and is designed to examine individuals' reactions to change and variables associated with those reactions. The target population live in a conservation region where they are not likely to be directly affected by the oil developments. Baseline findings are presented from the General Survey concerning psychiatric morbidity, crime, divorce and suicide and from the Individual Survey that focus on the prevalence of medical and psychiatric symptoms and illnesses.


Sorcerers, saints and charlatans: black folk healers in urban America. Case histories of black Americans who believe their illness has been caused by sorcery have been reported with increasing frequency in the clinical literature. Such individuals often believe that their problems are not amenable to orthodox medical regimens and they may leave treatment to seek out a folk healer. Healers believed to be able to cure sorcery are viewed ambivalently as they are though able to magically cause illness as well as cure it. There is little information available on such individuals or their modes of treatment, making it difficult to assess their abilities. This article reviews what is known about such individuals, including an attempt to learn more about those who have advertised in a large city newspaper. It is concluded that some of these individuals provide a useful service to their clients but that many others use their reputations as manipulators of occult powers to extract money from the poor and gullible.


Pain and analgesics.

Pain and analgesics. The problem of pain and its treatment is reviewed, particularly in relation to advanced cancer and other chronic conditions in which persistent pain demands relief. The nature of pain, its assessment and treatment options are discussed briefly, as is the use of different types of analgesics to raise the patient's pain threshold. The importance of regular reassessment of the patient and his needs, and the settling of realistic analgesic treatment objectives, such as an initial target of a pain-free full night's sleep, is stressed.