A computer program for simulating a distributed metabolic system. Distribution volumes in a simulated organism. A metabolite or hormone is distributed with non-uniform concentration throughout some volume within an intact organism. Various methods involving radioactive tracers are used to estimate the total mass of the metabolite and its volume of distribution. The calculations of mass and volume are based on very simple models, and cannot usually be validated by measurements on the real animal. Hence we have developed a computer program for simulating a metabolic system with convective and diffusive transport. The tracer experiments can be simulated by solving the differential equations for convective diffusion by finite element methods. Thus the total metabolic mass and distribution volume can be both 'measured' and calculated by all the standard techniques. In this way some mathematical methods currently in general use can be seen to be patently incorrect, and others quite acceptable. The concept of a metabolic doublet was introduced, by analogy with an electrical dipole.


A program for generation and selection of possible conformations of cyclic molecules. An algorithm has been developped for the computer generation of the possible conformations of non-planar cyclic molecules. This algorithm has been used successfully to select the known conformations of the ribose ring, of substituted cyclohexane and of disulfide bridged peptides. Its use may be extended to open molecules when the end-to-end distance is known or imposed.


The detection of doubtful data: the program DOUBT. The problem of the detection of erroneous data has led us to define the 'doubtful patients' as patients who have a small density. Our program DOUBT computes the densities associated with each patient by using the method of n nearest neighbors. Then the program allows us to define a density limit, and chooses the patients who have a smaller density then the doubtful patients. The remaining patients may be classified by the program.


A computer feedback system for clinical research. This paper presents a computerized data base management and information retrieval system for a heroin addiction research clinic, which has potential application for any type of clinical research. It describes data input checking programs, file structures, and output programs. The system contains several interesting features: built-in feedback error detection and correction; patient month matrix formatting and data compression; and a virtual blocking system to reduce the size of the files.


The management of melanoma.

The management of melanoma. Total surgical excision of melanoma is necessary to prevent potentially fatal distant metastases in vital organs. Systemic management includes the use of hormones, chemotherapy, and immunotherapy.


Sézary syndrome.

Sézary syndrome. A case of Sézary syndrome is presented and the clinical, histologic, and laboratory findings are reviewed.


Successful treatment of psoriasis of the nails. Psoriasis of fingernails and toenails presents a challenge that has not been met by the available therapeutic modalities. Three cases of treatment with x-ray therapy of varying intensities are presented herein. Cure was acheived in all three cases with no x-ray sequelae.


Lupus erythematosus and vitamin E: an effective and nontoxic therapy. Despite conflicting opinions, our personal experience and a number of reviewed clinical reports indicate that vitamin E, properly administered in adequate doses, is a safe and effective treatment for chronic discoid lupus erythematosus, and may be of value in treating other types of the disease. A possible mechanism leading to the development of autoimmune diseases, including lupus erythematosus, is discussed, together with a rational approach aimed at the cellular level, rather than at attacking the body's immune defenses, which could lead to increased susceptibility to malignant and infectious diseases.


Pseudofolliculitis barbae. Medical consequences of interracial friction in the US Army. Pseudofolliculitis barbae (PFB) is a minor disease affecting only, and almost all, blacks who shave. Because of a continued requirement by the US Army of clean shaven faces, significant interracial turmoil and animosity has been aroused. Unclear standards of care of the disease and haphazard policing of shaving habits led to a chaotic process with effective dermatologic care almost paralyzed by the hostile parties. Randomly approached lower-ranking enlistees and draftees are much more likely to complain about their disease, even if minor, and are more likely to refuse to shave and be unkempt even without permission to grow a beard (in contravention of Army regulations). Career black enlistees are likely to under-report the severity of their disease and not seek medical help, possibly because of fear of continuous harassment and inability to be promoted by their superiors. Lotion depilatories, or hair clippers, combined with routine lifting of ingrown hairs, are the most effective treatments, although complete cessation of shaving is first required.


Reactions to manganese and cadmium in tattoos. Concomitant allergic reactions to manganese and cadmium sulfide developed in a patient in tattooed areas. Although the reaction to cadmium was elicited by sunlight, attempts to reproduce it with artificial long-wave ultraviolet light were unsuccessful.


Factitious pseudoainhum of the nipple.

Factitious pseudoainhum of the nipple. A patient with a cosmetically disfiguring swelling of his nipple for many years was found to have factitious mechanical pseudoainhum. The possibility of occult mechanical constriction as the cause of acute or chronic deformities of appendages is emphasized.


The comparative efficacy of betamethasone dipropionate cream and ointment formulations in the treatment of psoriasis. A double-blind, multicentered, cooperative study performed by twelve investigators with 195 patients with chronic psoriasis was undertaken to compare the relative efficacy of betamethasone dipropionate in ointment and cream formulations. After one week of the two week study, those patients treated with the ointment preparation experienced a significantly greater decrease in the severity of psoriatic signs and symptoms and a greater frequency of complete remission. This study verifies vasoconstriction assay data and more rigorously supports the medical opinion that betamethasone dipropionate and possibly other corticoids in ointment formulation are superior to cream formulations in the early treatment of moderate to severe psoriasis.


[A new method of pericardiocentesis and quantification of pericardial effusions by echocardiography (author's transl)]. With a new method for safe and complete evacuation of pericardial effusions it was possible to check the quantification of pericardial fluid is was possible to check the quantification of pericardial fluid by echocardiography. Using a formula based on the assumption that in systole the pericardial fluid is distributed equally around the contracting heart (like a coat enveloping a sphere), it was demonstrated that pericardial effusions ranging from 250 to 600 ml could be fairly accurately measured. Smaller effusions were not so readily determined. Effusions over 600 ml could be only roughly measured, usually being underestimated.


[Recurrence of Crohn's disease after surgical treatment]. The probability of recurrence was determined in 58 patients after intestinal resection for Crohn's disease using the statistical method of death tables. Within the first 10 years after resection a recurrence must be expected in 84.1% of patients. In 41.6% of cases a second resection becomes necessary. Age, sex, and disease duration preoperatively had no influence on the recurrence. Curative treatment of Crohn's disease is not possible by surgery and the indication for operation should thus be limited primarily to life-threatening complications.


[Immunisation against influenza with a new subunit vaccine tested on children at risk (author's transl)]. The efficacy and tolerance of Sandovac, a new subunit vaccine, was tested in 104 children and juveniles aged 2 1/4 to 17 years, at five children's clinics. Sandovac 1000 was given to 39 children, Sandovac 2000 to 65. The vaccine was well tolerated, no appreciable side effects--local or systemic--having been recorded. The efficacy of Sandovac was checked by determining the antibody titre against haemagglutinin and neuraminidase in 36 children before and 28 days after vaccination with SAndovac 1000. The conversion rate with haemagglutination-inhibiting antibody titres type A strain Victoria was 100% and type B strain Hong Kong 86%. The geometric mean values rose by a factor of 29 for type A and 7.4 for type B. For the neuraminidase-inhibiting antibodies the factors were 3.15 with type A and 5.83 with type B. Titre increases by a factor of at least 1.5 occurred in 75 and 84%, respectively of vaccinated children.


[Catheter recanalization of a post-traumatic occlusion of the popliteal artery (author's transl)]. An acute occlusion of the popliteal artery occurred in an 19-year-old football player as a result of a kick into the back of the knee. Twenty months later recanalization was successfully accomplished by percutaneous transluminal catheter dilatation. It is concluded that not only atheromatous but also post-traumatic arterial occlusions can be successfully treated by this method.


[The composition of alcoholics anonymous in the Federal Republic of Germany (author's transl)]. In this, the first, enquiry of Alcoholics Anonymous in the Federal Republic of Germany, undertaken with the support of the AA organisation, nearly 1200 members of various group meetings (most of them weekly attenders) answered an extensive questionnaire, randomly distributed. The results indicate a steady growth of this self-help organisation over the years, at about 30% yearly, to a projected total of 23 000 in 1980. Comparison with similar enquiries in the USA indicates that the German AA consist of younger age-groups. No regional differences emerged from these largely group-demographic data.


[Ventricular arrhythmias in mitral valve prolapse syndrome (author's transl)]. Long-term ECG monitoring over 22 hours and exercise ECGs were performed in 72 patients with mitral valve prolapse syndrome. 70% of the patients had ventricular arrhythmias. In 28% severe arrhythmias in the form of multifocal atopic beats and ventricular runs were demonstrated. Long-term ECG monitoring was a suitable method for detection of these arrhythmias and superior to exercise ECG. Clinical, electrocardiographic and echocardiographic findings could not be correlated to the severity of ventricular arrhythmias.


[Pseudocysts and retention cysts in acute and chronic pancreatitis (author's transl)]. 42 cases of pancreatic cyst in acute (22 cases) pr chronic (20 cases) pancreatitis were seen between 1962 and 1976. Analysis of the case data revealed the following: (1) exact assignment of the cyst to acute or chronic pancreatitis is often possible only by long-term observation; (2) the cysts of chronic pancreatitis are not a uniform group: some (8 cases) apparently occurred in acute pancreatitis through necrotic episodes (pseudocysts), others (12 cases) by a retention mechanism; these "retention cysts" develop later in the course of chronic pancreatitis than the pseudocysts and produce a different clinical picture with better prognosis; (3) barium meal and retrograde cholangiopancreatography proved of diagnostic value' (4) if the cysts persist for more than six weeks operation is indicated because of the high incidence of complications.


[Intravenous re-infusion of ascitic fluid in patients with treatment-resistant cirrhotic ascites (author's transl)]. Unmodified ascitic fluid was re-infused into 14 patients with treatment-resistant cirrhotic ascites. Re-infusion lasted for 41 hours, divided over five days, with an average duration of 8 3/4 hours per day. Weight reduction averaged 10.5 kg, decrease in abdominal circumference 13 cm. Urine production rose by an average of + 23.7%. Azotaemia and abnormal serum electrolytes levels tended towards normal.


[Influence of digitalis on pindolol activity in exercise-induced cardiac failure in patients with coronary disease (author's transl)]. The activity of the beta-receptor blocker pindolol (0.4 mg i.v.) was investigated alone and in combination with digitalis (moderately fast loading) in 12 patients with coronary heart disease and without manifest signs of cardiac insufficiency. These patients showed pathological increase of left ventricular filling pressure during exercise testing. The exercise-induced rise of the mean pulmonary arterial and capillary pressures were increased by pindolol. Concurrently the increase of cardiac frequency was clearly diminished during ergometry (from 107/min without pindolol to 96/min, P less than 0.005). Digoxin given orally for an average of 5 days prevented the pressure increase in the pulmonary circulation induced by pindolol during exercise testing and at rest. The frequency reducing effect of pindolol was potentiated by digitalis. Use of digitalis alone did not influence mean exercise-induced pressure increase of the pulmonary circulation. In fact in some cases deterioration of these parameters was observed.


[Results of selective proximal vagotomy for gastroduodenal ulcer (author's transl)]. Between 1971 and 1976 selective proximal vagotomy (SPV) was performed in 526 patients with uncomplicated duodenal ulcer and in 37 with gastric ulcer. The operative mortality was 0.18%. The post-operative course was without complication in 90%. One to five years post-operatively 75% of patients with duodenal ulcer were largely without symptoms (Visick I and II), a dumping syndrome was present in 6.5%, diarrhoea in 4.2%, gastric outlet stenosis in 1% and recurrent ulcer in 10.9% of patients who could be re-examined. Recurrent ulcer occurred in eight of 36 patients re-examined after SPV for gastric ulcer. Results of SPV so far have shown it to be a useful alternative to gastric resection in the treatment of duodenal ulcer. But its place in the treatment of gastric ulcer remains undecided.


[Alteration of TSH secretion in children with goitre after short-term treatment with potassium iodide (author's transl)]. 300 microgram of potassium iodide daily were administered over a period of two weeks to 12 children with goitre. Basal TSH concentrations, maximal TSH increase after TRH and integrated TSH secretion after TRH were significantly decreased in this group whereas the increase of total thyroxine (T4-RIA) did not reach significance. It appears that in the development of iodine deficiency goitre in children a sensitive feed-back system is predominant. Early administration of iodine or even better general iodinated salt prophylaxis seem to be the pathogenetically correct approach in solving the common goitre problem.


[Diagnosis of bacterial endocarditis involving three valves by echocardiography (author's transl)]. Endocarditis was suspected in a 66-year-old man who had enterococcal septicaemia. Thrombotic involvement of the mitral, aortic and tricuspid valves by the endocarditis was demonstrated by echocardiography, the diagnosis and localisation of the endocarditic deposits being confirmed at necropsy, the patient's condition making operative treatment impossible. The characteristic echocardiographic finding was of abnormal echos from the valves with largely normal valve movements. Atrial myxoma and artefacts had to be considered in the differential diagnosis.


[Upper-abdominal ultrasonography and ERCP? (author's transl)]. Endoscopic retrograde cholangiopancreatography (ERCP) as well as upper-abdominal ultrasonography were performed on 134 patients. Organ structure was optimally demonstrated by ultrasonography in 94 patients (70.2%) and partially in 29 (21.6%) Comparing the diagnostic assessment in 62 patients who had undergone 73 tests and had subsequently been operated on (57) or examined post-mortem (5) there was a statistically significant advantage of ERCP in diseases in which the choledochal duct had been involved. The method was successful in 95% of cases of choledocholithiasis (20 cases) compared with 45% by ultrasound and in 85% of cases of gall-bladder carcinoma which also involved the choledochal duct (38% by ultrasound). In clinically manifest carcinoma of the head of the pancreas (9 cases) and cholecystolithiasis (19 cases) ultrasonography provided the correct diagnosis in 89%, while the results for ERCP were 56% and 74%, respectively.


[Do aerosol propellants produce a bronchoconstrictor effect? (author's transl)]. 25 asthma patients regularly showed an increase in respiratory resistance, as measured by the oscillation method, after propellant from a dosage aerosol had been sprayed into their buccal or nasal cavity. This effect, which was also seen in three laryngectomised patients, could be blocked by ipratropium bromide, an anticholinergic agent. Evidently it is due to a bronchoconstrictor reflex elicited by the local low-temperature stimulus produced by the propellant.


[Treatment of haemorrhages in a haemophiliac with factor-VIII inhibitor (author's transl)]. In a 33-year-old man with haemophilia A, due to the presence of a factor VIII inhibitor, severe bleeding followed a tooth extraction. It could not be stopped by ordinary factor-VIII substitution or administration of activated prothrombin complex. Before starting substitution treatment it was necessary to decrease the inhibitor concentration in plasma. This was possible by plasma exchange with a blood-cell separator: an exchange volume of 4 litres proved to be sufficient. The inhibitor-containing plasma was replaced by fresh plasma and cryoprecipitate. It was possible to increase the haemostatic activity of the transfused factor VIII by combination with activated prothrombin complex. The inhibitor kinetics remained uninfluenced. A delayed plasmapheresis was without effect as a result of an antibody booster by previous factor-VIII substitution.


Propionyl-CoA carboxylase deficiency with overflow of metabolites of isoleucine catabolism at all levels. An 11-year old girl with spastic paraplegia and mental retardation has suffered from attacks of metabolic acidosis since the age of 18 months. "Ketotic hyperglycinemia" was diagnosed when she was 3 years old. Reinvestigation at 9 1/2 years included a two-day load with L-isoleucine, and propionyl-CoA carboxylase assay in cultured fibroblasts. The following compounds increased following the load: 3-hydroxypropionic acid, 2-methyl-3-hydroxybutyric acid, 2-ethylhydracrylic acid, 3-hydroxy-n-valeric acid, 3-oxo-n-valeric acid, 2-methyl-3-oxobutyric acid, 2-oxo-3-methylvaleric acid, 2-methyl-3-oxovaleric acid, N-tiglylglycine, methylcitric acid and butanone. Small amounts of alloisoleucine appeared in plasma. Propionyl-CoA carboxylase deficiency was suggested by this metabolite pattern and demonstrated in cultured fibroblasts.


Rheumatoid arthritis and growth retardation in children: treatment with human growth hormone. Twenty patients with rheumatoid arthritis or Still's disease associated with growth failure were treated with human growth hormone, 7.5 to 17 U/m2 body surface per week. Five patients did not respond with better growth. In the remainder the mean growth rate increased from 1.9 cm/year (range: 0 to 3.3) to 6.2 cm/year (range: 3.6 to 12) over 5 to 7 months. Twelve patients treated for longer periods increased their mean growth rate from 2.6 cm/year (range: 0.7 to 5.7) to 6.3 cm/year (range: 2.4 to 9.7) and continued to grow during a second year of treatment. Growth velocity decreased in 6 patients when the hGH therapy was discontinued. The causes for this improvement in growth are possibly multifactorial: the growth rate is depressed by the severity of the disease and high-dose glucocorticoid therapy. Increases of growth rate occurred during improvements in the disease, reduction of steroid medication, as a result of therapy with human growth hormone, and because of puberty in some patients. Human growth hormone seemed to improve the underlying condition of four of the patients but had no influence on the disease in the remaining children.


Lactose intolerance associated with cataracts. A 50-day-old boy with severe lactose intolerance is described. In addition to vomiting, failure to thrive, dehydration, metabolic acidosis and amino aciduria, bilateral cataracts were also found. At three months of age, a computerized axial tomography scan and an electroencephalogram were abnormal, and myoclonic spasms began at the age of seven months.


Acute bone marrow necrosis caused by streptococcal infection. An 8 year old boy with a furuncle on the dorsum of the right foot, high fever, severe pain in the right knee joint, slight hepatosplenomegaly, leukopenia and thrombocytopenia was admitted with the working diagnosis of acute leukemia. However, an abundance of necrotic cells, together with clusters of streptococci, could be demonstrated in the bone marrow aspirate. After antibiotic therapy the boy recovered completely.


Parachute mitral valve, coarctation of aorta, radius aplasia, and omphalocele in an infant with the trisomy 18 syndrome. A premature infant with trisomy 18 had cardiac defects including parachute mitral valve, coarctation of the aorta, and a subcristal ventricular septal defect. The parachute mitral valve was funnel-shaped with a moderately-thick cone of fibrous tissue around the annulus and an eccentric orifice. Many forms of congenital cardiac defects have been described in the 18 trisomy syndrome. However, parachute mitral valve has not, to our knowledge, been part of the spectrum of cardiac defects in trisomy 18. Other anomalies were absent radii, omphalocele, and cleft palate and cleft lip; these have been observed previously in the 18 trisomy syndrome.


Effect of digoxin on left ventricular contractility in newborns and infants estimated by echocardiography. In view of the known susceptibility of newborns to digoxin intoxication this study was undertaken in order to evaluate the effect of a relatively low digoxin dose on left ventricular contractility of newborn infants. Left ventricular ejection time, enddiastolic diameter and endsystolic diameter were measured by echocardiography before digitalization as well as between 2 and 4 h after the first digoxin dose (group 1 : 16 patients) or after full digitalization (group 2 : 12 patients). From these data, shortening fraction (SF) and mean velocity of fiber shortening (mean Vcf) were calculated. We found that SF and mean Vcf increased significantly in both groups after the first digoxin dose and after full digitalization. The increase was equal in newborns and infants. The mean plasma digoxin concentration after full digitalization was 2.2 ng/ml (range 0.7--4.4 ng/ml). These results demonstrate clearly the positive inotropic effect of a relatively low digoxin dose in newborns.


His bundle block and concealed His bundle premature depolarization. His bundle electrocardiograms were recorded from a patient with previously unexplained PR prolongations or shortenings suggestive of both type I and II second degree AV block. The conduction disturbances were due to the association of concealed His bundle depolarizations (H') not propagated to atria or ventricles with first degree AV block in the His bundle. These data strongly suggest that frequent spontaneous His bundle depolarizations are another manifestation of a disease process involving the His bundle, a kind of "Sick--His bundle syndrome".


Clinical assessment of infarct size by serial determinations of serum creatine phosphokinase activity. Infarct size (IS) was estimated from serial total creatine phosphokinase (CK) changes in 82 patients with acute myocardial infarction (MI). Anteroseptal and inferior MI involved a relatively small mass of myocardium (16.0 +/- 6.4 and 24.7 +/- 10.0 CK-g-eq respectively); anteroapical and inferoposterior MI had an average IS of 35.9 +/- 15.9 and 32.8 +/- 13.8 CK-g-eq respectively (NS); extensive anterior and inferoposterolateral MI had an average IS of 57.8 +/- 20.1 and 51.1 +/- 11.5 CK-g-eq respectively (NS). Left ventricular failure (LVF) correlated with estimated IS and not with location of the infarct. In patients with an IS ranging from 30 to 50 CK-g-eq, the incidence of LVF was 33%. In patients with an IS greater than 50 CK-g-eq, the incidence of LVF was 65%. Out of the 6 patients who died, 3 had an IS greater than 60 CK-g-eq. 3 groups of patients could be identified from the duration of the CK release time: in group I (mean = 20 +/l h; n = 61), infarct size was highly correlated with peak CK activity (r = 0.93); in group II (mean = 39 +/- 7 h; n = 17) the correlation between IS and peak CK activity was poor (r = 0.59) and might indicate a gradual necrosis; in group III (n = 4) patients with reinfarction showed a second peak on the descending limb of the CK activity curve. Follow-up information was available in 96% of the 76 survivors. At the end of the follow-up (18.1 +/- 10.8 mth) IS was not significantly different in patients with LVF (42.7 +/- 17.5 CK-g-eq) and in those without LVF (34.7 +/- 19.7 CK-g-eq).


Ebstein's anomaly: late results of surgical correction. Between 1969 and 1976, 10 severely disabled patients with Ebstein's anomaly were operated on at the National Heart Hospital using replacement of the tricuspid valve with mounted aortic homografts [9] or dura mater valve [1], plication of the atrialized right ventricle [10], and closure of an associated interatrail communication. 7 survivors have been followed up from 2 to 9 yr. 5 are asymptomatic. Symptomatic tricuspid regurgitation developed in 2 patients; from a paravalvar leak of the tricuspid homograft in one, and in the other calcification with stenosis in an irradiated homograft, 2.5 and 7.5 yr later. Permanent pacemakers were needed in 2 patients, 3 wk and 18 mth after surgery for symptomatic heart block. Despite corrective surgery for the structural abnormalities in Ebstein, late results remain influenced by disorders of rhythm and conduction disturbances, degenerative changes in the valves used for replacement and the intrinsic primary myocardial disease. Such "corrective" procedures in patients with Ebstein's anomaly can result in maintained symptomatic improvement but must be regarded as palliative surgery.


The reduction by training of CO2 output during exercise. 5 men underwent a 10-wk endurance training programme which resulted in an 18% increase in max VO2 from a mean of 3.1 l/min. Measurements were made at 2 submaximal O2 intakes of 1.2 and 2.0 l/min to examine the physiological interdependence of mechanisms changed by training. At both levels of VO2, reductions were observed following training in cardiac frequency (fc), CO2 output (VCO2), respiratory exchange ratio (R), ventilation (VE), alveolar-arterial PO2 difference (A-aPO2) and blood lactate (La); the changes were statistically significant at the higher VO2. No change was observed in cardiac output, blood free fatty acids (FFA) and blood glycerol (gly). A small increase was found in arterial PCO2 (PaCO2) and HCO3-. Changes in fc were not significantly related to changes in other variables. The reductions in La were related to falls in VCO2 and VE, and inversely related to increases in PaCO2. Only a portion of the fall in R could be ascribed to increased usage of fat as a fuel, the main factor being a fall in lactate production. Reductions in A-aPO2 were due to decreases in PAO2 and falls in R, with no change in venous admixture. Changes in FFA and gly were small and not related to changes in other variables. Training led to an increased usage of aerobic metabolic pathways. The resultant fall in lactic acid production led to a fall in VCO2 and maintained HCO3-. These changes accounted for a marked reduction in VE following training.


Prevalence and significance of the fourth heart sound (S4) in presumably healthy middle-aged men, with particular relation to latent coronary heart disease. As part of a cardiovascular survey phonocardiography and auscultation concentrating on the presence/absence of S4 were studied prospectively in 1714 presumably healthy men aged 40--59 yr. The following conclusions were reached: (1) routine phonocardiograms revealed an S4 in greater than 50%; (2) auscultation suggested the presence of S4 in greater than 30%; (3) interobserver variation was approximately 1/6 in the blind interprelation of the phonocardiograms by 2 observers; (4) approximately 3/4 of reported audible S4s were correctly identified; (5) a direct association between S4 and the length of the PQ (PR) interval was found, and (6) a positive association between higher blood pressure and S4, but (7) no association to age, latent coronary heart disease (CHD) nor various CHD risk factors. Thus an S4 is of little diagnostic value in screening of apparently healthy middle-aged subjects, but probably is not a completely innocent finding as suggested recently by some investigators.


The effect of a new calcium antagonist (Ro 11-1781) on the cardiac conduction system in man. Using His bundle electrograms and atrial pacing the effects of Ro 11-1781, a new calcium antagonist, was studied in 13 patients with normal A--V conduction. Following an intravenous bolus of 2 mg/kg Ro 11-1781 the A--V nodal conduction time (A--H interval) was prolonged in all patients during sinus rhythm, atrial incremental and premature pacing. Wenckebach periods above the bundle of His occurred at lower atrial driving rates following the drug. The functional and effective refractory period of the A--V node were prolonged after the administration of Ro 11-1781. No significant effect of Ro 11-1781 on the remainder of the conduction system was observed. Heart rate and the corrected sinus node recovery time changed variably. The increase of the A--H time in response to Ro 11-1781 was completely reversed by Atropine.


Ventricular preexcitation due to anomalous nodo-ventricular pathways: report of 3 patients. 3 patients with paroxysmal palpitations had surface electrocardiographic evidence of type B preexcitation with a small positive delta wave in lead V1. At study all patients had an abnormally short H-V interval. Programmed atrial premature stimuli at progressively shorter coupling intervals resulted in prolongation of AV conduction time and increasing preexcitation. In 2 patients early atrial premature stimuli elicited atrial echo beats or sustained tachycardia with preexcited QRS complexes. In these patients the accessory pathway did not appear to be involved in the tachycardia circuit. It is postulated that the site of reentry is within the AV node with preexcitation occurring as the result of conduction in an anomalous node-ventricular pathway. In the 3rd patient, preexcitation occurred within a restricted range of coupling intervals of an atrial premature stimulus. The electrophysiological responses of nodo-ventricular and His-ventricular pathways to atrial stimulation are compared and contrasted.


Congenitally complete heart block with an interrupted Mönckeberg sling. The conducting tissues are described in a case of congenitally corrected transposition. The patient was known to have suffered from congenital complete atrioventricular block. In the heart, both anterior and posterior nodes and bundles were found to coexist. The two bundles shared a common bifurcation. Neither of the two nodes connected with their respective bundles. The different morphology of the two sites of fibrous interruption may be explained by differences in embryonic development.


The influence of dopamine on active sodium transport across frog skin measured as short circuit current. The influence of dopamine (DA) on short circuit current (SCC) across isolated Rana esculenta skin was studied to determine whethera a DA receptor system exists in that cell membrane model and what is the influence of DA on SCC. Experiments were carried out with both alpha- and beta-adrenergic blockers and cocaine present in the Ringer solution. DA in cumulative doses added to the inner Ringer solution stimulated SCC in a dose-dependent manner. Apomorphine (10(-5) M) shifted the DA dose--response curve to the left and increased the maximum DA response. Haloperidol (10(-9) M) antagonized the effects of the DA depressing maximum response as well. Imidazole (10(-8) M and 10(-9) M) antagonized the influence of DA in a manner similar to haloperidol. It appeared that there were DA receptors in frog skin and that haloperidol as well as imidazole were DA antagonists which acted non-competitively.


Cardiovascular and respiratory effects of some anesthetics in the decerebrate rat. The cardiovascular and respiratory effects of pentobarbital, ketamine, chloralose and urethane were studied in decerebrate rats. All the anesthetics reduced blood pressure and heart rate. Pentobarbital, chloralose and ketamine, but not urethane, reduced respiratory rate. None of these agents had a significant effect on tidal volume. All these anesthetics significantly attenuated the carotid occlusion, tilt and sodium cyanide chemo-receptor response. These results suggest that the decerebrate rat may be a more suitable preparation, compared to the anesthetized one, for studying cardiovascular and respiratory responses in this species.


Use of the rabbit transverse stomach-strip to identify and assay prostacyclin, PGA2, PGD2 and other prostaglandins. The preparation and use of the rabbit transverse stomachstrip as an isolated assay tissue for prostaglandins is described. The tissue is relaxed by low concentrations of PGE2, PGA2 and PGD2 and contracted by prostacyclin (PGI2) and PGF2alpha. The decomposition product of prostacyclin, 6-oxo-PGF1alpha, has little effect, whereas the endoperoxide PGH2 and thromboxane A2 cause a small contraction. Arachidonic acid also contracts the tissue and this response is abolished by indomethacin. This tissue also responds to low concentrations of histamine, acetylcholine, noradrenaline and bradykinin. In conjunction with other bioassay tissues such as the rat stomach strip and rabbit coeliac artery, the rabbit transverse stomach strip provides a convenient method of detection of identification of known arachidonic acid metabolites.


Effects of chemical sympathectomy on hypertension and stroke in stroke-prone spontaneously hypertensive rats. Neonates of male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with 6-hydroxydopamine (6-OHDA) on two different schedules. Peripheral sympathectomy, which was evaluated by the pressor response to exogenous noradrenaline (NA) or by the decrease in NA content of the spleen, was more evident in the NB-8 group (treated on 8th and 15th day after birth) than in the NB-1 group (treated at 6, 24 and 72 h after birth). The reduction of the NA content in the cerebral cortex was more prominent in the NB-1 group than in the NB-8 group. The blood pressure from 7 to 23 weeks of age was lower in the treated groups: NB-8 less than NB-1 less than control. Therefore, the reduction of blood pressure in the treated groups could be related to the severity of peripheral sympathectomy. The incidence of sroke was also lower in the treated groups: 38, 11 and 0% in the control NB-1 and NB-8 groups, respectively. Loading with 1% NaCl solution from 11 weeks of age enhanced the rise in blood pressure and increased the incidence of stroke in each group of rats: 100, 20 and 40% in the control. NB-1 and NB-8 groups, respectively. However, the onset of stroke after exhibiting a severe hypertension (greater than 200 mmHg) was delayed in the treated groups. It seems that the activated tone in the peripheral sympathetic nerve is likely to participate in the development of spontaneous hypertension. In addition to the high blood pressure level, the activated tone of sympathetic nerve innervating the cerebral vasculature may be partly involved in the development of stroke in the new strain of the SHR rats, SHRSP.


Renal effects of propranolol, practolol and butoxamine in pentobarbital-anesthetized rats. The renal effects of the beta-adrenergic blockers, propranolol, practolol and butoxamine, were examined in pentobarbital-anesthetized rats. All the beta-blockers, infused i.v., increased urine volume (V), urinary sodium excretion (UNaV) and p-aminohippuric acid clearance without change in inulin clearance. Indomethacin, an inhibitor of prostaglandin biosynthesis, did not affect the renal effects of these beta-blockers. Phentolamine abolished the renal effects of practolol, but not those of propranolol and butoxamine. Haloperidol abolished the renal effects of propranolol and butoxamine, but not those of practolol. A high correlation was found between the increased UNaV and the increased urinary phosphate excretion by butoxamine but not by propranolol and practolol. Therefore, it is suggested that alpha-adrenergic stimulation is involved in the mechanism of diuresis by practolol, a beta1-blocker, and that dopaminergic stimulation is involved in the diuresis caused by butoxamine, a beta2-blocker. Propranolol is similar to butoxamine, and partially similar to practolol.


GABA-mediated potentiation of amine release from nigrostriatal dopamine neurones in vitro. The uptake and release of 3H-dopamine was studied in slices of corpus striatum and substantia nigra in the presence of nialamide. High potassium triggered the outflow of tritium in both brain structures and this release was potentiated by GABA in a dose related fashion, whereas the spontaneous overflow of radioactivity was unchanged. This action of GABA was mimicked by the GABA-T antagonists aminooxyacetic acid and ethanolamine-O-sulphate, but not by the GABA analogues muscimol, 3-aminopropanesulphonic acid, gamma-hydroxybutyrate or beta-(p-chlorophenyl)-GABA. The response to GABA was not blocked by picotoxin, which itself facilitated the evoked release of 3H-dopamine, nor by bicuculline or the omission of calcium ions from the bathing medium. GABA facilitation of K+-evoked 3H-dopamine release was increased significantly on reducing tissue thickness and following prolonged incubation with GABA. GABA also potentiated the depolarization induced outflow of 3H-noradrenaline, 3H-5-hydroxytryptamine and 3H-histamine without affecting their initial accumulation. Veratridine, amphetamine and cold dopamine also raised the output of 3H-dopamine, but none of these releases was altered by GABA. The uptake of 3H-dopamine, but not that of 14C-GABA, was considerably attenuated in 6-hydroxydopamine lesioned corpora striata. The possible mechanism(s) of this stimulatory action of GABA is discussed.


Effect of prostaglandin endoperoxide analogue on canine renal function, hemodynamics and renin release. We studied the effect of a stable, cyclic ether analogue of prostaglandin endoperoxide (EPA) on canine renal function, hemodynamics, and renin release. Infusion of EPA into one renal artery decreased renal blood flow in a dose dependent manner. At a dose of 10(-7) g/kg/min the renal blood flow decreased from a baseline of 384 to 267 ml/min/100 g. This flow decrease was unaltered by phentolamine and saralasin, but was potentiated by prior treatment with indomethacin. Urine flow, glomerular filtration rate, sodium, and potassium excretion all decreased in a dose dependent manner; however, neigher fractional excretion of sodium nor free water clearance showed any significant change, making direct tubular effects of EPA unlikely. EPA caused a significant increase in renin release that was completely blocked by prior treatment with indomethacin. We conclude that EPA is a potent renal vasoconstrictor and that this vasoconstriction is responsible for the renal functional changes observed. Renin release is not a direct effect of EPA but probably is secondary to an endogenously generated prostaglandin. Since EPA mimics the effects of natural prostaglandin endoperoxides on smooth muscle in vitro, it is possible that prostaglandin endoperoxide-induced vasoconstriction in vivo modulates the effects of their vasodilatory products, prostaglandin E2 and I2.


Enhanced naloxone potency and the development of narcotic tolerance. When various biogenic amine modifying drugs were administered to mice which were pretreated with morphine, none of the drugs except atropine and haloperidol altered the usual doubling of the naloxone efficacy which is observed in morphine-pretreated mice. Atropine appeared to decrease the potency of naloxone. Haloperidol, which did not alter naloxone potency in normal mice, further increased the naloxone potency in morphine-pretreated mice. When the biogenic amine modifiers were injected chronically to mice during the development of morphine tolerance, again none of the drugs, except haloperidol and atropine altered the development of tolerance. Haloperidol appeared to enhance and atropine to inhibit the degree of tolerance. These results indicate that it is the alteration in the narcotic-induced enhancement of naloxone potency and not the mere alteration of noloxone potency by various drugs, which can be used as an indicator of the alterations in the development of tolerance.


Kinetics of somatostatin inhibition of pentagastrin-stimualted gastric acid secretion. Dogs with gastric fistulae and denervated gastric pouches received graded doses of pentagastrin with and without a background infusion of somatostatin (1 microgram kg-1 h-1). Similarly, graded doses of somatostatin (0.25, 0.5, 1, 2 and 4 microgram kg-1 h-1) were infused after a steady state gastric secretion had been achieved with pentagastrin (1.5 microgram kg-1 h-1), about twice the dose required to produce half maximal (D50) response. Somatostatin inhibited pentagastrin-stimulated gastric acid secretion with competitive inhibition kinetics, but its precise site of action remains uncertain. The minimum effective dose of somatostatin on a twice D50 dose of pentagastrin was 0.25 microgram kg-1 h-1.


Alternative mechanisms for the potentiation of the relaxation evoked by isoprenaline in aortae from young and aged rats. The action of cinnarizine and flunarizine on the relaxant effect of isoprenaline was studied in the isolated rat aorta and was compared with the action of papaverine. The results show that isoprenaline-induced relaxation and K+ contraction were reduced. On the contrary, in the presence of papaverine, isoprenaline relaxation and K+ contraction were reduced. On the contrary, in the presence of papaverine, isoprenaline relaxation was enhanced by cinnarizine and flunarizine at concentrations which were lower that those required for inducing an inhibition of the contraction evoked by K+ in the presence of 1.25 mM CaCl2; with concentrations higher than 10(-8) M both isoprenaline relaxation was enhanced and K+ contraction was depressed in a dose-dependent manner. In aged rats, isoprenaline-induced relaxation was tachyphylactic. The tachyphylaxis was prevented by cinnarizine and flunarizine. The present observations indicate that several processes might be responsible for potentiating isoprenaline action.


A comparison of the inhibitory effect of cinnarizine and papaverine on the noradrenaline- and calcium-evoked contraction of isolated rabbit aorta and mesenteric arteries. The inhibitory effects of cinnarizine and papaverine on the noradrenaline- and Ca-induced contraction of the rabbit thoracic aorta and mesenteric arteries have been compared. Papaverine was equally effective in reducing the contractile response evoked from both thoracic aorta and mesenteric arteries by the two modes of stimulation. Cinnarizine blocked the Ca-evoked contraction of the depolarized vessels but was less effective against the noradrenaline-induced contraction of the mesenteric arteries and even failed to antagonize the response of the thoracic aorta to noradrenaline. In Ca-free medium noradrenaline (10-5 M) evoked a fast non-sustained contraction. After readmission of CaCl2 a slow sustained contraction developed. In mesenteric arteries exposed to noradrenaline, cinnarizine selectively blocked the Ca0 dependent response while papaverine inhibited the initial fast response more than the Ca0 dependent one. These results suggest that cinnarizine and papaverine antagonize vascular contraction by different mechanisms. Cinnarizine seems to act by reducing membrane permeability to extracellular calcium. Papaverine inhibits the contraction by a main action on intracellular sequestration of activator calcium and to a lesser degree by an action similar to that of cinnarizine.


The effect of clonidine on centrally and peripherally evoked submaxillary salivation. In anaesthetised cats, clonidine (10 microgram/kg, i.v.) produced a 60% reduction in submaxillary salivation induced by brain stem stimulation at 10 and 15 Hz and reductions of 35 and 15% in salivation evoked by chorda tympani nerve stimulation at 5 and 15 Hz respectively. Pretreatment with clonidine (20 microgram/kg/day, orally) for 28 days reduced peripherally evoked salivation by 45%. These results suggest that both central and peripheral mechanisms are involved in the diminished salivation produced by clonidine, and the reduction on peripheral stimulation may reflect the presence of presynaptic alpha-adrenoceptors inhibiting cholinergic transmission.


In vivo rate of serotonin synthesis in brain and spinal cord of young, spontaneously hypertensive rats. The accumulation of 5-hydroxytryptophan (5-HTP) following decarboxylase inhibition was measured in hypothalamus (HYP), pons-medulla (PM) and spinal cord (SC) of 4- and 8-week-old spontaneously hypertensive (SH) and normotensive (WKY) rats. Using this method, a significant increase in the in vivo activity of tryptophan hydroxylase was observed in the PM and SC of 4-week-old, but not 8-week-old SH rats. These findings show a transient elevation in rate of 5-HT synthesis prior to the onset of hypertension, which does not appear to continue during the maintenance phase.


Vestibular, auditory, and somatic input to the posterior thalamus of the cat. The responses of 157 neural units in the magnocellular (mc) and parvocellular (pc) components of the medial geniculate nucleus (MG) and other nuclei of the posterior (PO) thalamic group were recorded and analyzed. Units were tested for a response to electrical stimulation of the vestibular nerve, natural auditory and electrical cochlear nerve stimulation, and natural stimulation of joint, muscle, and cutaneous receptors of the limbs, trunk, and neck (somatic stimulation). Only 45% of the units responded to these stimuli. Twenty-four percent of the responsive units were multimodal, responding to more than one stimulus. All multimodal units were activated by auditory stimuli. More units responding to vestibular stimulation were found in mcMG than in pcMG or other components of the PO group. Potentials evoked by vestibular nerve stimulation were recorded in all 3 regions with latencies of 5--25 msec. No evidence was found for a thalamic relay from vestibular nerve to cortex in the area investigated, since the recorded latency for activity from vestibular nerve stimulation was longer than the latency of responses recorded in the cortex. This region of the thalamus appears to be important for reception of auditory information and integration with vestibular and somatic modalities.


Morphological features of physiologically identified hypothalamic neurons as revealed by intracellular marking. In the in vitro slice preparation intracellular recordings and injections of procion yellow (PY) were made in neurons of the hypothalamus. Of these neurons, one medial preoptic-anterior hypothalamus (MPO-AH) and four arcuate-ventromedial hypothalamus (ARC-VM) neurons were driven by electrical stimulation of the median eminence area (ME). Two other MPO-AH and five other ARC-VM neurons were driven by stimulation of the stria terminalis (ST). On the basis of the PY injections two morphologically distinct cell types were delineated: a larger multipolar cell type with a polygonal perikaryon was found with equal frequency in the MPO-AH and the ARC-VM. A smaller fusiform cell type was encountered mainly in the ARC-VM. On the secondary dendrites of both cell types spine-like appendages were seldom seen, but dendritic swellings were common. Some of the dendrites projected to capillaries in both areas and presumably contacted them. The axons were usually tortuous and could only be traced a short distance.


Behavioural studies of spatial vision in cats reared with convergent squint: is amblyopia due to arrest of development? Visual acuity and contrast sensitivity were measured behaviourally in normal adult cats and cats reared with monocular convergent squint from 3, 6, 8, 12, and 24 weeks of age. The visual acuity of the squinting eye was significantly lower than that of the non-squinting eye in cats with squint from 3, 6, and 8 weeks of age. No significant difference in acuity between eyes was found in the 12- and 24-week squinting cats and in the controls. Contrast thresholds at all spatial frequencies tested (range 0.13--2.0 c/degrees) were higher in the squinting eye than in the non-squinting eye of cats with squint from 3 and 6 weeks of age, but differences were greater at the higher spatial frequencies. In the 8-week squinting cat, contrast thresholds were increased only at higher spatial frequencies. No significant differences in contrast sensitivity were found in the cat with squint from 24 weeks of age and in the controls. The degree of disturbance of spatial vision in squinting cats was most related to the age at onset of the squint, i.e., the earlier the onset, the more profound the amblyopia. The period of susceptibility extended from about 3 to 12 weeks of age. When compared with data on the development of visual acuity in kittens, the pattern of results from the present study suggests that convergent squint can arrest the development of spatial vision.


Coding of small sinusoidal frequency and amplitude modulations in the inferior colliculus of 'CF-FM' bat, Rhinolophus ferrumequinum. Single neurons in the inferior colliculus of the Greater Horseshoe bat, Rhinolophus ferrumequinum, showed two broad categories of response patterns to sinusoidally frequency (SFM) or amplitude (SAM) modulated stimuli. Tonic responding cells (best excitatory frequency (BEF) between 10 and 90 kHz) showed a rough sinusoidal modulation of the discharge pattern to SFM. Transient responding neurons generally showing on- or off-responses to pure tones, (BEF between 65 and 88 kHz), displayed highly synchronized discharge patterns to SFM-cycles (Fig. 1). Modulation rates between 20 and 100 Hz were most effective and some neurons encoded modulation rates up to 350 Hz (Figs. 2 and 3). The SFM responses were best synchronized to the modulation envelope for center frequencies in the upper portion of the tuning curve (Figs. 4 and 5). Sharply tuned neurons with BEF around 80 kHz had the lowest threshold for modulation depth (+/- 10 Hz or 0.025%) (Fig. 6). In general, SAMs evoked the same type of response patterns and were encoded down to modulation index of 3% (Fig. 7). The fine frequency and amplitude discriminations for periodical modulations by collicular neurons is discussed as related to the detection and discrimination performance of bats, when preying on flying insects in clustered surroundings.


The role of binocular neurons in the cat striate cortex in combining information from the two eyes. Cats were raised under conditions of daily alternating monocular exposure, so that each eye received normal input, but the animals were never allowed to use both eyes simultaneously. With single cell recording techniques it could be shown that this led to a severe disturbance of the normal binocularity of cortical neurons. The cats were trained by operant techniques in a two-choice box to discriminate with each eye non-retinotopic stimulus pairs. To test the ability to combine binocular signals it was tested whether the learned discrimination would transfer to red/green colored stimuli which were viewed dichoptically through appropriately colored contract lenses. The arrangement was such that the positive stimulus could be distinguished from the negative stimuli only when the signals from both eyes were combined and used simultaneously. All cats showed immediate transfer, from the monocularly learned discrimination task to the dichoptic paradigm. This indicates that the presence of a normal population of binocular cortical cells in area 17 is not a prerequisite for the ability to use binocular cues for the solution of a pattern discrimination task.


Distribution of thalamo-caudate neurons in the cat as demonstrated by horseradish peroxidase. Distribution of thalamocaudate neurons in the cat was examined by means of the horseradish peroxidase (HRP) method. After injection of HRP into the head of the caudate nucleus (Cd), thalamic neurons labeled with HRP were observed mainly in the rhomboid nucleus (Rh), central medial nucleus (Ce), centre médian-parafascicular complex (CM-Pf) as well as in the midline and intralaminar regions surrounding the mediodorsal nucleus (MD). Distribution of HRP-labeled neurons in the centrolateral nucleus (CL) were localized in the medial parts of the nucleus. Many HRP-labeled neurons were also seen in the substantia nigra (SN) and retrorubral nucleus (Rr). Additionally, HRP-labeled neurons were found in the ventrolateral portions of the anteromedial nucleus (AM), lateral portions of the MD, ventral tegmental area of Tsai (vT) and the midline raphe nuclei, such as the rostral lineal (rL), central lineal (cL) and dorsal raphe (dR) nuclei.


Fluorescence histochemical observations on the distribution of exogenous dihydroisoquinoline in the rat brain. The distribution of fluorescence in the rat brain after i.p. or intracerebral (i.c.) injections of a fluorescent dihydroisoquinoline derivate of dopamine was studied. After low i.p. doses (50 mg/kg of body weight) the fluorescence was totally confined to the capillary endothelial cells in the cerebral cortex, neostriatum, and substantia nigra (Sn). After large i.p. doses (500 mg/kg) fluorescent material was also present in the neuropil of all the regions studied and some cells of the cerebral cortex and SN. Ater injections to the neostriatum or SN fluorescence was observed in the endothelial cells and some small to medium-sized rounded cells in both regions. A conspicious dark area contrasting with the background fluorescence was constantly present around capillaries, and this area was in contact with nonfluorescent multibranched cells of astrocytic type. In fluorescent cells the fluorescence was present both in the cytoplasm and the nucleus.


Characteristics of wrist joint receptors in the cat. A branch of the dorsal interosseous nerve is described, which innervates the dorsal aspect of the wrist joint capsule of the cat. Recordings of the whole wrist joint nerve showed no tonic activity until the wrist was flexed to within 45 degrees of full flexion (about one third of the normal range). There was no tonic activity at full extension or at intermediate postions. 110 single afferents from the wrist joint capsule were isolated from dorsal root filaments. Their responses to movement of the wrist and other mechanical stimuli were examined, and their conduction velocities measured. 31 were slowly adapting, 41 were phasic, 9 were Pacinian corpuscle-like, 7 were weakly activated, and 22 were not activated by the mechanical stimuli which were used. Slowly adapting receptors responded only when the joint was in a flexed position as would be expected from the whole nerve data. Conduction velocities for the 4 classes of responding mechanoreceptors were not significantly different, and fell in the group II range. Fibre diameter histograms of myelinated axons in the wrist joint nerve showed peaks in the group II and group III range. Intravenous injection of succinylcholine showed no increase in whole nerve activity attributable to muscle spindles, and had a negligible effect on identified receptors in the wrist joint capsule.


Potential noradrenergic regulation of serotonergic neurons in the median raphe nucleus. Pharmacological and morphological evidence suggests that the functional activity of serotonergic neurons may be regulated by catecholamines. We have attempted to reveal a potential pathway by which this interaction might occur. Rats received bilateral knife cut lesions of the ventral noradrenergic bundle which severed the A-1 and A-2 cell body contributions to this projection. Controls received a sham lesion into the cerebellum. Two weeks later all animals were sacrificed, and norepinephrine and serotonin levels were measured in discrete nuclei of the brain. Lesion placement was confirmed histofluorometrically. Serotonin levels in the median raphe nucleus were significantly reduced by 40%, but levels of serotonin were unaffected in the dorsal raphe nucleus and 8 serotonergic terminal regions. The lesions did not affect levels of norepinephrine in the locus coeruleus, cingulate cortex, or habenula. This study suggests that a noradrenergic projection to the median raphe nucleus from the A-1 and A-2 cell body groups may modulate serotonergic neuronal function.


Compartments in the striatum of the cat observed by retrograde cell labeling. The distribution of neurons giving rise to striatal efferent projections has been studied in the cat by the aid of Mesulam's histochemical methods following large injections of horseradish peroxidase into the pallidum and substantia nigra. The findings suggest that neurons of medium size form a major fraction of the efferent neurons of the striatum and that these neurons are grouped into geometrically complex, three-dimensional networks.


Coding of visual information by units in the cat cerebellar vermis. Extracellular records were made of the responses to precisely controlled stationary or moving visual stimuli of 174 units in the cerebellar vermis of cats anaesthetised with chloralose. Identified Purkinje cells and unidentified units responsed similarly. Responses to ON and to OFF steps of a stationary light bar had different characteristics. Some units showed changes in the form of their ON responses related to different positions of the stimulus in their large receptive fields. In some cases changes in response latency from different field positions were also noted. Some units responded only to binocular stimulation and others gave much larger responses to binocular than to monocular stimulation. In addition, some were sensitive to the relative retinal disparity of images and, of these, several were sensitive to vertical as well as to horizontal retinal disparity. Sinusoidally-moving light bars gave responses consisting of one or two bursts of impulses per cycle; the most effective frequency was about 3 Hz. These responses may represent detection of the instant of maximum velocity. The relatively precise coding of retinal disparity in spite of the large size of receptive fields and the coding of position within these large fields is discussed. A possible function for the disparity-sensitive units in the control of vergence is suggested and the relation of this control to visual depth detection and to the estimation of the absolute distance of objects from the animal is discussed.


Series ventilation, diffusion in airways, and stratified inhomogeneity. Functional inhomogeneity in lungs, meaning local variance of PCO2 and PO2 in alveolar space, may be of parallel and/or series nature. The effects of both kinds of inhomogeneity are qualitatively similar (decrease of the efficiency of alveolar gas exchange) and difficult to differentiate by experimental analysis. As far as diffusive mixing is concerned, methods specifically suited for detection and quantification of stratified inhomogeneities are based on separation of multiple test gases of differing diffusivity. The results of studies by such methods indicate that for alveolar O2 exchange the resistance attributable to stratification is in most cases less than the reciprocal pulmonary diffusing capacity for O2. In the conventional analysis of alveolar gas exchange, effects of stratification would contribute to alveolar dead space ventilation or would be incorporated in the pulmonary diffusing capacity.


Collateral ventilation.

Collateral ventilation. Ventilation may bypass obstructed airways through collateral channels, including interalveolar pores of Kohn, bronchiole-alveolar communications of Lambert, and interbronchiolar pathways of Martin. Resistance through these channels, like resistance through small airways, increases with decreasing lung volume and with hypocapnia. But whereas the distention of collateral channels and small airways by a variety of factors is similar, the efficiency of ventilation through collateral channels is less than the efficiency through airways. Gas inspired through collateral channels is contaminated with alveolar gas from surrounding lung so that the dead space for collateral ventilation is increased. When one part of the lung ventilates out of phase with the surrounding lung, pulmonary interdependence promotes more homogeneous ventilation. In the presence of airways obstruction, interdependence may be a primary factor governing the rate of collateral ventilation. In man, collateral ventilation is unimportant in normal lungs. However, with disease, it may be critical in producing or compensating for abnormalities. For example, the long time constant for collateral ventilation in the middle lobe may be responsible for atelectasis, which results in the middle lobe syndrome. On the other hand, the short time constant for collateral ventilation in emphysema may be essential for the distribution of ventilation beyond obstructed airways.


Phylogeny of fever.

Phylogeny of fever. Vertebrates from fishes through mammals develop fevers in response to infection with various species of bacteria. In all vertebrates studied, these fevers were reduced by administering drugs known for their antipyretic properties in mammals. Based on the many similarities in the febrile response among the various vertebrate classes, it appears likely that fever is a primitive immunological response that has had a long phylogenetic history. The widespread occurrence of fever, an energetically expensive phenomenon, is further support for the hypothesis that fever is adaptive (beneficial to the infected host).


Ontogeny of fever.

Ontogeny of fever. The newborn of the sheep and the guinea pig are refractory to bacterial pyrogen. The newborn lamb does not get fever and the newborn guinea pig only gets fever to large doses of intravenous bacterial endotoxin. It would appear that the lack of febrile response to endotoxin occurs beyond the stage of production of endogenous pyrogen and may represent either an immaturity of the brain mechanisms for heat production and heat conservation, which are driven by endogenous pyrogen, or, as evidence is presented, there may be a circulating endogenous antipyretic substance present in the circulation of the newborn lamb and there is evidence that such a substance is present in the circulation of the ewe close to term. Possible relevance of these findings to lack of fever in the infected human neonate is discussed.


Fever versus hyperthermia.

Fever versus hyperthermia. A variety of conditions that result in the elevation of body temperature are described and discussed. These hyperthermias are divided into four categories; fever, exercise hyperthermia, hyperthermias due to inadequate means of heat dissipation, and hyperthermias resulting from pathological or pharmacological impairments of thermoregulatory mechanisms. A comparison of the physical and physiological characteristics of these hyperthermias is presented and distinctions are drawn on the basis of these characteristics. Fever is shown to differ markedly from all other forms of hyperthermias. Specifically, the elevation in body temperature encountered during fever is a regulated rise that is defended by fully functional thermoregulatory mechanisms; the thermopreferendum is also elevated in fever, particularly at the onset or "chill phase"; and aspirin-like drugs can intervene in febrile hyperthermia and will return body temperature to its normal level. No other forms of hyperthermia possess these characteristics and thus only fever can be attributed to an upward displacement of the "set point" for body temperature regulation. Furthermore, in attempting to control rises in body temperature, it is apparent that aspirin is effective only in fever, while whole-body cooling is all but ineffective. In all other forms of hyperthermia, whole-body cooling is the only effective treatment.


Production of endogenous pyrogen.

Production of endogenous pyrogen. The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.


Prostaglandin metabolism in the fetal and maternal vasculature. The capacity of fetal and maternal blood vessels to synthesize the antithrombotic vasodilator agent prostacyclin (PGI2) suggests that this substance participates in the circulatory adjustments to pregnancy. We studied the capacity of fetal and maternal blood vessels to metabolize [1(-14)C]arachidonic acid; thin-layer chromatography was used to separate PGE2, PGF2alpha, and 6-keto-PGF1alpha (the stable hydrolysis product of PGI2), and these were then quantitated by scintillation counting. Fetal vascular tissues (aorta, ductus arteriosus, and pulmonary arteries) generated tenfold more PGI2 than PGE2. Prostacyclin accounted for more than 50% of the prostaglandins synthesized by fetal blood vessel measured by recovery of its hydrolysis product, 6-keto-PGF1alpha. In contrast, in the mature animals, the aorta and pulmonary artery generated less PGI2 than did fetal tissue, whereas the mesenteric arteries exhibited high biosynthetic capacity comparable to that of the fetal vasculature. Release of prostaglandins by the umbilical blood vessels and ductus arteriosus was also measured by mass fragmentography. The identity of 6-keto-PGF1alpha was confirmed by mass spectroscopy. The high and almost identical capacity of all fetal blood vessels, except the umbilical arteries and veins, to synthesize PIG2 could reflect an important role for this prostaglandin in the regulation of the fetal circulation.


Juvenile-onset diabetes HLA-A, -B, -C, and -DR alloantigens. We studied the distribution of HLA-A, -B, and -C antigens in 94 juvenile-onset diabetic patients and of HLA-DR antigens in 62 of these patients. The frequencies for HLA-B15, -B40, and -Cw3 were significantly increased in the patient group as compared with the control group. With respect to the B-cell specificities, DRw4 was significantly increased in the patients. Analysis of the data to detect the possible presence of primary and secondary associations between HLA alleles and diabetogenic gene(s) indicated that DRw4 possessed a primary association with the diabetogenic gene(s). As a result, B15, B40, and Cw3 possessed secondary associations.


Regional distribution and concentration of pancreatic polypeptide in the human and canine pancreas. The regional concentrations of pancreatic polypeptide (PP), insulin, and glucagon and the cellular distribution of PP were studied in 13 human and nine canine pancreases by radioimmunoassay, immunoperoxidase localization, and cell quantitation. PP concentration was highest in both the uncinate process and the head of the human pancreas and in the right lobe of the canine pancreas. In contrast, glucagon and insulin levels were higher in the body and tail of both the human and canine pancreases. Human F-cells, which contain PP, were located primarily at the periphery of the islets, although a few F-cells were scattered throughout the ducts and acini. Canine F-cells were located in ducts, acini, and islets; the relative proportion of canine F-cells in the endocrine and exocrine tissues differed according to location. Cellular quantitation of F-cells in both species correlated significantly with the tissue concentration of PP in all regions studied, validating the use of morphometric techniques to quantitate the regional distribution of PP.


Detection of early retinal changes in diabetes by vitreous fluorophotometry. A series of 77 patients with overt diabetes and with apparently normal fundi on ophthalmoscopy and fluorescein angiography was examined by vitreous fluorophotometry. Breakdown of the blood-retinal barrier, which appears to be the earliest clinically detectable change in the retina in diabetes, was a constant finding. Quantitative measurement by vitreous fluorophotometry of the breakdown of the blood-retinal barrier could be correlated with degree of metabolic control and previous duration of diabetic disease. Significantly higher vitreous fluorophotometry values, indicating a more marked breakdown of the blood-retinal barrier, were recorded in patients under poor metabolic control than in patients whose diabetes was under relatively better control. Similarly, patients who has had diabetes for longer periods of time showed higher vitreous fluorophotometry values than those recorded in patients with diabetes of shorter duration.


Effect of verapamil on insulin response to alcohol hypoglycemia in patients with primary hyperparathyroidism. In hypercalcemic patients with primary hyperparathyroidism who were fasted over a prolonged period, alcohol ingestion induced a significant fall in glucose whereas insulin remained unchanged. The hypercalcemic patients thereby differed from normocalcemic subjects, who showed a significant decline in both glucose and insulin when alcohol was ingested after a prolonged period of fasting. An increased uptake of calcium into the beta-cells appears to have been a prerequisite for the occurrence of an unchanged insulin secretion during alcohol hypoglycemia in hypercalcemic patients, since a calcium-blocking agent, verapamil, infused intravenously during and after alcohol ingestion, brought about a normalization of the insulin response to alcohol hypoglycemia in such patients.


Inhibition of glucagon secretion by diazoxide in vitro. The effect of diazoxide on the secretion of glucagon and insulin was studied using the isolated perfused rat pancreas. The perfusate concentration of D-glucose was kept constant at 5.6 mM. Five secretagogues of both glucagon and insulin--10 mM L-arginine, 5 mM L-leucine, 1.4 muM prostaglandin F2alpha, 100 nM bovine growth hormone, and 10 nM theophylline--were administered individually in the presence or absence of 325 muM diazoxide. Basal secretion of glucagon or insulin was not discernibly affected by diazoxide. With diazoxide the secretion of glucagon was (a) abolished completely in response to L-arginine or L-leucine; (b) inhibited partially in response to prostaglandin F2alpha; (c) unaltered in response to growth hormone; and (d) unchanged or, at times, enhanced in response to theophylline. On the other hand, the secretion of insulin induced by each of these agents was inhibited effectively by diazoxide. (a) Diazoxide inhibits the secretion of glucagon as well as insulin in response to certain secretagogues independent of any changes in prevailing levels of glucose. (b) At the concentration tested, diazoxide is a more potent and consistent inhibitor of the release of insulin than of glucagon.


Somatostatin and pancreatic polypeptide secretion: effects of glucagon, insulin, and arginine. The isolated perfused canine pancreas with duodenal exclusion was used to examine islet hormone output in response to arginine and exogenous glucagon and insulin. Exogenous glucagon (100 ng/ml) stimulated insulin and somatostatin secretion, which occurred in a biphasic pattern. The insulin response to glucagon was markedly enhanced by increased perfusate glucose, unlike the somatostatin response, which was little affected. The insulin and somatostatin responses were seen between 15 and 45 s after the glucagon stimulus. Pancreatic polypeptide secretion was uninfluenced by exogenous glucagon. Biphasic release of glucagon, somatostatin, and pancreatic polypeptide was evoked by 10 mM arginine, the responses first being apparent within less than 30 s. Exogenous insulin (50 mU/ml) infused for 10 min had no statistically significant effect on glucagon, somatostatin, or pancreatic polypeptide secretion. This study suggests that these four islet hormones may all be involved in the dynamic mechanisms of nutrient metabolism. In addition, potential intra-islet paracrine effects are identified.


Lipid abnormalities in untreated maturity-onset diabetics and the effect of treatment. Plasma cholesterol and serum triglyceride levels and frequency of lipoprotein abnormalities were investigated in 126 untreated maturity-onset diabetics and 126 age- and sex-matched control subjects. Serum triglyceride levels were higher (mean: 1.67 mmol/l) and type IV hyperlipoproteinaemia occurred more frequently (16.7%) in the diabetic group as compared with the controls (1.29 mmol/l and 4.8% respectively). These findings were not explained by an excessive frequency of renal disease, hypertension or drug treatment amongst the diabetics. Normal men showed higher serum triglyceride (mean: 1.36 mmol/l) and lower plasma cholesterol (mean: 5.6 mmol/l) levels than normal women (1.21 mmol/l and 6.4 mmol/l respectively). No sex difference was seen amongst the diabetics. Triglyceride levels fell after one month of dietary treatment but only remained lowered in diabetics who required sulphonylureas for glycaemic control. After treatment for one year the correlation between serum triglycerides and blood glucose rose from r = 0.15 (NS) before treatment to r = 0.43 (p less than 0.001). Similarly the correlation between serum triglycerides and ponderal index rose from r = 0.19 (NS) to r = 0.28 (p less than 0.02).


Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Kidney size and glomerular volume. Kidney weight and glomerular volume have been studied in groups of insulin-treated streptozotocin diabetic rats maintained at high, or nearly normal plasma glucose levels. Kidney weight and glomerular volume in these groups were compared to a non-diabetic control group. --Rats with nearly normal plasma glucose levels (95 +/- 35 to 182 +/- 20 mg/100 ml) had the same kidney weight as the non-diabetic controls, 1.04 +/- 0.14 and 1.07 +/- 0.09 g, respectively. In the rats with constant high plasma glucose (338 +/- 71 to 555 +/- 86 mg/100 ml) kidney weight was significantly increased, 1.73 +/- 0.20 g, compared to each of the two other groups. Glomerular volume was 0.559 millimicron3 in the diabetic animals with nearly normal plasma glucose, a value very close to that of the non-diabetic controls, 0.587 milimicron3. In animals with high plasma glucose concentrations glomerular volume was 0.775 millimicron3, 2 p less than 0.03 compared with both other groups. --The study indicates that good diabetic control for 6 months prevents the development of large kidneys and large glomeruli in dibatic rats.


Blood glucose regulation using an open-loop insulin delivery system in pancreatectomized dogs given glucose infusions. I. Portal square waves. This study characterizes the glycaemic and insulin responses of a group of 5 anaesthetized dogs to a portal glucose infusion of 10 mg/kg/min before and after pancreatectomy. Insulin was administered intraportally to the pancreatectomized dogs according to a simple preprogrammed waveform composed of a constant basal rate of 0.35 +/- 0.02 mU/kg/min which was increased to 2.00 mU/kg/min at the time of the 60 minute glucose challenge. When this square waveform was applied the glycaemic response was similar to that seen in the normal controls in the baseline and challenge periods. Blood glucose concentration differed significantly (p less than 0.05) only from 20 to 100 minutes after the end of the challenge when it was higher by 20 +/- 1 mg/dl. Insulin levels were not significantly different from controls. It may be concluded that normoglycaemia and normoinsulinaemia can be maintained by a simple constant rate of portal insulin delivery while the blood glucose response to a glucose infusion can be ostensibly normalized without hyperinsulinaemia simply by enhancing insulin delivery during the challenge. The feasibility of this approach implies that with further development of the preprogrammed waveforms and with a greater understanding of their characteristics portable insulin delivery systems may be realized which accomodate more physiological challenges. The portal route for insulin delivery may however be necessary if peripheral hyperinsulinism is inappropriate.


Effect of gestational diabetes on insulin receptors in human placenta. The aim of this work was the characterization of insulin binding to a partially purified preparation of plasma membranes from gestational diabetic placenta in order to establish a comparison with normal pregnancy. A decrease in the number of insulin receptors per mg protein in placenta from gestational diabetic mothers was found. Comparable inhibitory effects of unlabelled insulin suggest that the binding affinities were similar in both groups of patients. The ability of the placental preparation to degrade 125I-insulin was not significantly different in both situations. The existence of a negative feed-back regulation of the insulin receptors in placental membranes was suggested by the fact that plasma insulin levels were significantly higher in the gestational diabetic mothers.


Wedged and free hepatic venous pressure measured with a balloon catheter. The accuracy and reliability of a balloon catheter for measuring wedged hepatic venous pressure (WHVP) were evaluated in 82 simultaneous determinations using the balloon catheter technique and the direct measurement of portal venous pressure. These measurements showed a close positive correlation (r = 0.97) over a wide range of pressures in 12 normal and 4 cirrhotic dogs. Studies were then performed in 13 cirrhotic patients in whom the balloon catheter was introduced using the Seldinger technique. Free hepatic venous pressure (FHVP) was measured with the balloon undistended. By distending the balloon to occlude the hepatic vein, the WHVP was recorded. Comparison of FHVP and WHVP with the conventional and balloon techniques revealed a close positive correlation (r = 0.89 and 0.93, respectively). The correlation was virtually perfect for the hepatic venous pressure gradient (WHVP-FHVP, r = 0.98). The balloon technique offers many advantages over the conventional approach, including the ease of achieving and demonstrating the wedged position from the femoral approach, the ability to measure the free and wedged pressure repeatedly without manipulating the catheter, and the measurement of pressure in a larger, more representative segment of the liver.


Utilization of a radioiodinated bile salt for kinetic studies and hepatic scintigraphy. Studies in nonhuman mammals. An 125I- or 131I-labeled bile salt derivative, cholylglycyliodohistamine, has been synthesized and purified. The bile salt derivative is rapidly cleared from the circulation when injected intravenously into rats and rabbits. Ten minutes after injection, approximately 50% of the recovered bile salt derivative was in the jejunum and ileum, and 36% was found in the liver. Sixty minutes after injection, 99% of the recovered radioactivity was found in the luminal gastrointestinal tract. The isotope was cleared from the circulation of rabbits with a t1/2 of approximately 2 min. Hepatic scintigraphy using rabbits demonstrated rapid uptake by the liver and excretion into the intestine. Quantitative analysis of scintigraphy showed an uptake rate of 14%/min and a subsequent excretory rate of 4.6/min.


Effect of colchicine on guinea pig intrinsic factor-vitamin B12 receptor. Colchicine can induce the malabsorption of vitamin B12 and other nutrients. Previous investigations have suggested but not proved that this malabsorption was due to a lesion in the ileal mucosa. Employing the receptor assay of M. Katz and B. A. Cooper (J Clin Invest 54:733-739, 1974), the authors have observed a dose-related, reversible reduction in the quantity of intrinsic factor-vitamin B12 (IF-B12) receptor (from 5.78 ng to 1.3 ng of B12 binding) in the intestinal mucosa of guinea pigs fed 0.05-0.25 mg/100 g colchicine/day for 3 days. Malabsorption of vitamin B12 was also demonstrated in vivo in similarly treated animals. Increasing intestinal motility with cascara sagrada had no effect on the IF-B12 receptor. The quantity of IF-B12 receptor and the amount of vitamin B12 absorbed increased markedly to greater than normal levels during recovery from a 3-day course of colchicine. The total number of intestinal cells decreased after colchicine administration and increased during recovery; however, the fluctuations observed were not sufficient to explain the changes in the quantity of receptor. Histologic examination of the ileal mucosa showed a decrease in the population of villus cells after colchicine. The correlation between the changes in receptor quantity and in vivo B12-absorption prove that the IF-B12 receptor is a critical limiting factor in B12 absorption.


Effect of dopamine on human gastric and pancreatic secretion. It has previously been shown that dopamine stimulates pancreatic exocine secretion and inhibits acid secretion in the dog. In this study, the authors have investigated the effect of dopamine on human gastric and pancreatic secretions. In 6 subjects, dopamine produced a dose-dependent inhibition of pentagastrin-stimulated acid secretion, an effect that was suppressed when the subjects received haloperidol. In 6 other subjects, dopamine infusion did not modify basal pancreatic secretion, and dopamine inhibited pancreatic enzyme secretion during secretin-cholecystokinin infusion. Dopamine also caused a rise in plasma glucagon and insulin. The effects on pancreatic enzyme secretion and plasma glucagon were not antagonized by haloperidol. The results suggest that dopamine is inhibitory for human gastric secretion. The authors did not observe a stimulatory effect of dopamine on human pancreatic exocrine secretion as has been observed in dogs.


Secretory behavior and ultrastructural changes in mouse gallbladder principal cells after stimulation with cholinergic and adrenergic drugs. A morphometric study. Principal cells of mouse gallbladder epithelium were subjected to a quantitative electron microscope study after in vivo and in vitro exposure to pilocarpine, noradrenaline, atropine, and phenoxybenzamine. Stereologic measurements were performed on randomly selected principal cells, and special interest was paid to changes in the size of the secretory granule population of the cells. Thirty minutes after in vivo and in vitro stimulation with pilocarpine, there was a significant decrease of the volume density of the glycoprotein-containing granules in the principal cells. Thirty minutes after in vivo administration of the cholinergic antagonist atropine, a significant increase of this parameter was observed. In vitro incubation for 30 min with a combination of pilocarpine and atropine extinguished the pilocarpine-induced effect on the secretory granules. Noradrenaline and phenoxybenzamine (an alpha-adrenergic blocking agent) in vivo and in vitro (30 min) had no effect on the volume density of the secretory granules. The authors' findings suggest that principal cells of the mouse gallbladder epithelium exhibit an increased rate of secretion of glycoprotein granules after stimulation in vivo and in vitro with cholinergic agents, whereas adrenergic agents are without effect.


Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin. Toxins produced by Clostridium difficile have been implicated in the etiology of antibiotic-induced colitis. Clostridium difficile antitoxin is not available, but recent studies have shown that toxins present in the feces of patients with this disease are neutralized by Clostridium sordellii antitoxin. We found that C. sordellii antitoxin neutralized toxins produced in broth cultures of either C. sordellii or C. difficile and that passive immunization with C. sordellii antitoxin before challenge with clindamycin prevented colitis in hamsters. Significantly fewer antitoxin-treated animals than unimmunized controls developed diarrhea and died with hemorrhagic colitis. Administration of 300 U of antitoxin parenterally either on the day of challenge with clindamycin or 24 hr later provided significant protection (25% mortality vs. 100% mortality in controls, P less than 0.01). None of eight animals given antitoxin (300 U) both on the day of challenge and 24 hr later died. Filtrates prepared from cecal contents of dead or killed hamsters were tested for toxicity by intraperitoneal injection into hamsters and by addition to monolayers of monkey kidney cells. Fecal filtrates from antitoxin-protected animals were not toxic in these assays, but filtrates from control animals were uniformly toxic. Passive immunization against clostridial toxins was protective against clindamycin-associated colitis in this model. This finding further substantiates the importance of these toxins in the pathogenesis of antibiotic-induced colitis.


Role of clostridial toxin in the pathogenesis of clindamycin colitis in rabbits. The pathophysiology of antibiotic-associated colitis was studied in rabbits with severe ileocolitis induced by oral administration of clindamycin. Cell-free, sterile filtrates of cecal contents of rabbits with clindamycin colitis contained a toxin that was lethal for mice and cytotoxic for HeLa-cell monolayers. The toxin was heat labile, was inactivated by pronase but not trypsin, and had a mol wt by gel filtration on Sephadex G-100 of 45,000. The toxin was neutralized by antiserum to Clostridium perfringens type E, but not by other clostridial antisera. The toxin also caused severe necrosis of rabbit rectal epithelium during 18-hr organ culture, which could be completely reversed by neutralization with C. perfringens type E antiserum. These studies indicate that clindamycin colitis in rabbits is caused by overgrowth of a clostridial species, which releases a heat-labile toxic protein of mol wt of 45,000 capable of necrosing colonic epithelial cells.


Colonic tuberculosis diagnosed by colonoscopic biopsy. A patient with pulmonary tuberculosis and a constricting transverse colon lesion on barium enema was found at colonoscopy to have a 1.5 X 3.0 cm ulcer with irregular, edematous borders. Multiple colonoscopic biopsies of the ulcer revealed acid-fast bacilli with absence of granulomas. Previously, the diagnosis of colonic tuberculosis had been thought to require laparotomy for confirmation. The authors now suggest that colonoscopic biopsy may be a desirable alternative in selected cases.


[Childhood and prepuberal schizophrenia ]. The author gives a short review of modern aspects concerning schizophrenia in childhood. Very early forms of the preschool age are excluded for nosological reasons. Age-specific phenomenology, differential diagnosis, course and prognosis as well as the outcome of the disease are discussed.


[Biological availability of Ossin, a sodium-fluoride dragee for osteoporosis therapy]. The bioavailability of Ossin, a drug for the treatment of osteoporosis, containing 40 mg of NaF, was investigated. Because of the enteric coating of the tablet, intestinal absorption occurs when the tablet leaves the stomach. The sustained release of the F--in the intestine results in a slow F-- -absorption. Maximal F-- -serum concentrations are reached more than 4 hours after absorption has begun. In contrast to non-sustained release NaF tablets the slow absorption of Ossin leads to lower, and less variable F-- -serum concentrations. Following administration of 1 tablet Ossii b.i.d., the steady state concentrations were between 130 and 220 ng/ml. The absorption was at least 86%. As calculated by the renal F-- -elimination, the therapeutically important F-- -retention in bone amounted to more than 50%. The enteric coating of the Ossin tablets, the low and relatively steady F-- -serum concentrations and the high F-- -retention in bone, are expected to contribute to an improvement in tolerance and therapeutic efficacy in the treatment of osteoporosis.


[Legislation on logopedics. Documentation on the draft for a federal law on the profession of speech therapist]. A law for studying logopedics was established by the authorities of the Federal Republic of Germany. On account of a political concept of education the conditions for admittance studying logopedics are based on an extremely low level. Reasons for rejecting these admitting conditions are displayed from a phoniatrical view.


Linking deinstitutionalization of patients with hospital phase-down: the difference between success and failure. Deinstitutionalization of patients is an inevitable forerunner of hospital phase-down or closure, but if the two processes are carried out at the same time, they will be counterproductive. An evaluation of the combined deinstitutionalization and phasing down of a state hospital in Pennsylvania indicated conflicts in the areas of case management, community and political support, and administrative flexibility. A substantial problem was that deinstitutionalization is time-consuming and must be flexible enough to allow for the development of essential community supports and for largely unpredictable reactions from patients, families, communities, and service providers. Conversely, hospital consolidation must be relatively quick and inflexible to permit the orderly redisposition of staff and patients, reduce unnecessary staff resistance and anxiety, and withstand changing political pressures.


National trends in hospitalization.

National trends in hospitalization. The past two decades have witnessed several important trends in mental health care: a decline in the resident census in public mental hospitals, an increase in outpatient treatment and facilities, relative stability in the number of hospitalization episodes per 100,000 population, and briefer duration of hospitalization. The combined result of these trends is increased pluraslism, diversity, and deinstitutionalization in mental health care. The changes are primarily the consequences of the success of psychopharmacologic agents, new forms of psychotherapy, changing attitudes of the public and the profession, and increased financial support by the federal government.


Short-term hospitalization and the medical model. In recent years there has been a significant decrease in the length of hospital stays for psychiatric patients. The author examines whether the shorter stays are justified by results of controlled studies and, if so, what is the most appropriate hospital milieu for short-term units. He summarizes several studies supporting his opinion that short-term hospitalization is usually indicated for the majority of patients, provided that continuity of care is ensured and that supervised living arrangements are available for patients who require them. He believes a medical-model milieu with a clear structure and delineation of roles is most appropriate for short-term in-patient units.


Intensive psychiatric care for adolescents and young adults: a model for treatment and evaluation. The authors' model for the hospital treatment of severely disordered adolescents and young adults calls for a categorization of the patient's major characteristics that are relevant to treatment along six axes: symptoms and signs, previous course of the disorder, social functioning, work or school functioning, family or other living situation, and sense of identity. They present a case study of a 19-year-old male patient to demonstrate how the model works.


Hospitals in the 1980s: service, training, and research. Several factors press for change in the psychiatric hospital of the 1980s, including knowledge obtained from recent controlled studies of outcome of different approaches and length of hospital stay, changes in the social-political-economic climate, and new methods of organizing the delivery of services. In the proposed model of inpatient treatment, the primary use of hospitalization will be for brief treatment (three to 21 days). For a very small subgroup, longer hospitalization may be needed. The hospital will also be used for triage and disposition of persons with a broad range of problems, which will rarely take more than three days. Complementary changes will be required in training and research; a promising training model may be continuous care teams by which trainees can manage chronic, multiproblem patients through different levels of care within and outside the hospital. Research must move to the out-of-hospital settings if the new patterns of care are to be understood and improved.


Providing cost-effective psychotherapy in a Health Maintenance Organization. The authors share responsibility for providing psychotherapy for adults and children who are subscribers to the Health Maintenance Plan, Cincinnati. The limited resources in such a setting led them to combine the general-systems-theory proposition that the least expensive defenses against stress should be used first with the principle of effective parsimony, which calls for a particular sequence of action in providing mental health care. Thus their approaches include involving the patient in planning the frequency of therapy sessions, including entire families in the sessions, and setting reasonable goals and time frames for meeting the goals. They also use nonmedical mental health professionals, under the supervision of a psychiatrist, and other primary providers in the HMO who are interested in psychotherapy and are willing to call on a psychiatrist when necessary.


Children's rights in Michigan: new law and old paternalism. A variety of civil, treatment, and environmental rights of patients in Michigan's state institutions, private facilities, and community mental health services are protected by the state's mental health code. Any complaint of a violation of a right must be investigated; if it is substantiated, remedial action must be taken and must be reported to the complainant. The complaints of children in institutions, or others acting in their behalf, cluster around three major rights: protection from abuse, treatment suited to condition, and a safe, sanitary, and humane living environment. The author discusses a number of problems that the state office of recipient rights has encountered in dealing with alleged violations of children's rights.


Need to shape public policy challenges health professionals. Health care professionals can and should participate in the government's decision-making process process regarding health policy development. They can do so in a variety of ways ranging from writing to legislators, to supporting their professional associations' lobbying activities, to working within government through fellowship and personnel exchange programs between government and the private sector. This article describes some techniques that health care professionals can apply and some attitudes that they can develop in order to interact effectively with government and public officials.


Systems approach is needed for data processing function. Computers have the capability of providing a picture of the whole organization if used properly and with creativity. To ensure that the flow of information within the hospital is optimal, administration should provide leadership and involve the entire management team.


System allocates scarce data processing resources. The data processing function consists of two separate components--operations and development. The first, which is the day-to-day business of the data processing department, requires very little external input. Development, however, requires close collaboration between the data processing department and the user department. The system described in this article ensures that collaboration.


Technology evaluation roundtable discusses role of private sector. Working from the premise that health care technology should be studied from a multiperspective approach rather than a unidirectional approach, a group of health care opinion leaders gathered to discuss how private or public-private sector efforts could lead to this broad-based approach and to more effective and efficient utilization of health technology.


Are mobile CT scanners in your hospital's future? This article discusses some of the major considerations involved in the decision to use mobile computerized tomography scanners. In addition, the article describes the current status of reimbursement, analyzes physician acceptance of mobile CT units, and provides an example of a mobile CT in operation.


Students climb on the CPR bandwagon.

Students climb on the CPR bandwagon. The importance of teaching cardiopulmonary resuscitation to the general public cannot be stressed enough. Extending this attitude, East Liverpool (OH) City Hospital took its community education program into an area school and developed a pilot CPR program for students. In conjunction with the program, teachers from this and other schools were trained as CPR instructors.


Responsibility and authority must match in nursing management. Throughout one hospital's nursing management structure, the authority delegated to the nurse managers is commensurate with the responsibility delegated to them. This approach has helped to ensure that they can fulfill their responsibilities, has changed the roles of nurse managers at all levels throughout the structure, and has provided a system that is highly responsive to operational and personnel problems and concerns.