Physical studies of chromatin. The recombination of histones with DNA. Experiments have been carried out to define clearly which histone combinations can induce a higher order structure when combined with DNA. The criterion for a higher order structure being the series of low-angle X-ray diffraction maxima nominally at 5.5 nm, 3.7 nm, 2.7 nm and 2.2 nm. Such a pattern, with resolution similar to that of H1-depleted chromatin, is readily attainable by recombining histones H2A + H2B + H3 + H4 with DNA using a salt-gradient dialysis method. However, the use of urea in the recombination procedure is shown to be detrimental to the production of a higher order structure. Low-angle ring patterns are not obtained by recomgining DNA with single pure histones or any combination of histone pairs exept H3 + H4. The diffraction maxima from the latter are, however, weaker than those from chromatin and there are pronounced semi-equatorial arcs. The presence of a third histone, either H2A or H2B in the H3 + H4 recombination mixture tends to distort the recognised low-angle pattern. It is concluded that the histone pair H3 + H4 is essential for the formation of a regular higher order structure in chromatin, although for a complete structural development the presence of H2A + H2B is also required.


A proton-relaxation-time study of the conformation of some purine and pyrimidine 5'-nucleotides in aqueous solution. The measurement of proton relaxation time T1 in a series of purine and pyrimidine 5'-nucleotides has been carried out to investigate their conformation in dilute neutral aqueous solutions. The interpretation of relaxation data has been performed with the help of computer calculations taking into account the different conformers of the ribose ring and of the exocyclic group. It has been found that all nucleotides under study show nearly the same preferential orientations of the base defined by gamma0 = 70 degrees +/- 10 degrees in the syn range. A more elaborate treatment, using an angular distribution derived from calculated potentials on 5" -GMP gives theoretical relaxation times in close agreement with experimental ones.


[Hypertension and bilateral stenosis of the renal artery associated with congenital hypoplasia of the intrahepatic bile ducts (author's transl)]. Report of a 10-year-old boy with congenital hypoplasia of the intrahepatic bile ducts, the socalled MacMahon-Thannhauser-Syndrome. The patient had been suffering from a varying degree of jaundice since his 2nd day of life and from pruritus since his 21st month of life. Furthermore, he had hepatomegaly, a systolic cardiac murmur, hypogenitalism, retarded growth, and finally hypertension. Transitory xanthomas existed between 1 3/4 and 2 3/4 years of age. Signs of persistent intrahepatic cholestasis was manifested by increased levels of bilirubin and bile acids in serum as well as raised activities of leucine aminopeptidase, gamma-glutamyl transpeptidase and alkaline phosphatase. Pathological values of serum glutamic dehydrogenase pointed to a persistent destruction of liver cells. Without treatment, the activities of vitamin K dependent clotting factors were decreased. Cholesterol, phosphatides and triglycerides in serum were increased and lipoprotein-X was detectable. Aortography revealed stenosis of both renal arteries. An exploratory laparotomy and 5 liver biopsies led to the diagnosis of hypoplasia of the intrahepatic bile ducts. Therapeutic trials with steroids and the anion exchange resin "cholestyramine" were ineffective. Phenobarbital relieved the pruritus. Parenteral administration of fat soluble vitamins restored the activity of vitamin K dependent clotting factors to normal. The high blood pressure fell significantly due to treatment with adelphan. The etiology of hypoplasia of the intrahepatic bile ducts is unknown. It may be a malformation or an obliteration secondary to inflammation. In our patient, narrowing of the renal arteries, increase of plasma-renin activity and hypertension were probably secondary to hyperlipidemia. It has been suggested that hyperlipemia secondary to cholestasis may be due to a disturbance of lipoprotein metabolism. A review of reports on 118 patients suffering from intrahepatic bile ducts hypoplasia is included.


Corticosteroid treatment of juvenile chronic polyarthritis over 22 years. Between the years 1952 and 1974, 1293 children aged from 1-14 years with the adult type of rheumatoid arthritis and Still's disease were admitted, of whom 793 or 61.2% received oral corticosteroids, mostly in the form of continuous therapy. In all children with Still's syndrome (476 cases, of whom 84.4% received corticosteroid therapy), as well as in 75% of the children with rheumatoid arthritis (817 cases, 47.1% under corticosteroid treatment) the therapy had already been initiated by the referring institutions. The mortality and morbidity of corticosteroid treated children is compared with the results from the precortisosteroid era. The influence upon rheumatic activity as well as on joint pathology was compared in groups of patients with rheumatoid arthritis with and without steroid therapy. Corticosteroid therapy led to a significant reduction in the early mortality from myo- and pericarditis in Still's syndrome. On the other hand, the late mortality of 5% was encumbered with a high incidence of direct sequelae of longterm corticosteroid therapy and secondary diseases, especially amyloidosis. Furthermore, more than half of the children on longterm treatment had severe irreversible, and partially fatal lesions. The results of the present investigation strongly suggest that the indications for and the manner of using corticosteroids in treating rheumatoid arthritis and Still's syndrome ought to be revised.


Comparative HGH response to i.v. glucagon and i.v. arginine stimulation tests in children and adolescents. Thirty-seven children and adolescents of several diagnostic entitites (constitutional growth retardation, diabetes mellitus and pituitary insufficiency) were tested with an i.v. bolus injection of glucagon for plasma human growth hormone (HGH) response. Most of the subjects were also tested for the same purpose by the arginine stimulation test, and the data were compared. It was found that i.v. glucagon is a potent stimulus of human growth hormone release. The HGH is released in two peaks, the first one occuring within 30 min, most probably by a direct effect. The second peak occurs after 120 min, most probably as a secondary effect caused by the drop in blood glucose after its initial rise, which is induced by glucagon. The peak concentrations of HGH induced by glucagon, were very similar to those provoked by i.v. arginine in the same subjects.


Mitral valve prolapse in children with secundum--type atrial septal defect (ASD II). A left ventricular angiocardiogram for evaluation of the mitral valve in patients with uncomplicated secundum type atrial septal defect has been proposed in a recent paper by Victoria et al. (1974). These authors observed 8 children with a ballooning mitral valve and ASD II. They stressed the necessity of performing a left ventricular angiocardiogram in every patient with ASD II. To challange their proposal, the angiocardiograms of 78 children with secundum type ASD were reviewed. Of these 89 angios 34 were performed using the left ventricle (LV) as injection site while 55 times the injection was made in other parts of the heart, e.g. left atrium, pulm. art., right ventricle, right atrium. All 34 LV angios, but only 12 of the others allowed an evaluation of function and morphology of the mitral valve. Of the 46 angiocardiograms 27 (58.7%) revealed an intact, normally closing and opening mitral valve. In the remaining 19 (41.3%) various grades of ballooning or mild prolapsing of one or two leaflets of the mitral valve could be detected. The "scallops" were minimal in 12, moderate in 4 and pronounced in 3 cases. A mild regurgitation was seen in 1 patient only. No patient had the pronounced ballooning observed by Victoria et al. On auscultation only 1 case had the apical murmur of mitral regurgitation. The ECG of our 19 "positive" cases did not show signs of left atrial or left ventricular hypertrophy. A left axis deviation was found in 1 patient. During surgery no structural abnormality of the mitral valve was noted. Postoperative reevaluation of the mitral valve (including left ventricular contrast injection) in 10 cases revealed no change of mitral valve appearance in 8, a decrease of the ballooning in one, and an increase in another patient. It is concluded that prolapses of the mitral valve are seldom of such a degree as to cause dysfunction in children with secundum type ASD. The indications for performing a left ventricular injection of contrast material are the clinical signs of mitral valve regurgitation and/or left axis deviation in the ECG.


Studies of malformation syndromes of man XIB: the cerebro-hepato-renal syndrome of Zellweger: comparative pathology. A study of 11 autopsied cases of the cerebro-hepato-renal syndrome of Zellweger (ZS) is reported. All cases had severe, persistent congenital hypotonia, hepatic lobular disarray, renal cortical cysts and pulmonary hypoplasia. Many had cardiovascular malformations, hepatomegaly, cerebral cortical gyral maldevelopment and pancreatic islet hyperplasia. Additional, less frequent findings are delineated. Results of iron content studies of hepatic and renal tissues are related to age of survival and possible development of fibrosis.


[On the embryo-fetal alcohol syndrome (author's transl)]. The symptomatology in 24 patients with the embryo-fetal alcohol syndrome in this study corresponded essentially to the clinical picture described by Lemoine et al., and Jones et al., although we were not able to confirm the maxillary hypoplasia and microphthalmia mentioned in the latter. In addition, we observed in 2 girls a virilization of the genitalia which corresponded to female pseudohermaphroditism. Auxologically a nearly regular pattern of the parameters measured was found. The intra-uterine hypotrophy continues after birth. In particular, the head circumference, reflecting the brain growth, remains low. The cerebral damage leads to oligophrenia with a typical pattern of psychic and motor behaviour. Moderate cases tend to improve. Concerning the pathogenesis, the clinical observations in connexion with recent animal experiments permit the following conclusions. Neither the malnutrition nor the liver damage of the mothers are necessary presuppositions. Ethanol itself appears to play the main teratogenetical rôle. Acetaldehyde, which is the primary metabolite of ethanol, is cytotoxic too. However, the liver of the embryo and the fetus, in consequence of its deficient alcohol dehydrogenase content, is not able to metabolize ethanol.


[Generalized familial semibenign BCG infection, salmonella osteomyelitis and intestinal pseudotuberculosis--due to a familial defect of the macrophage system? (author's transl)]. Two siblings became very ill after BCG inoculation in the newborn period. A generalized BCG infection was assumed from the clinical symptomatology and the histological findings. Later on the boy suffered from enteric salmonellosis and osteomyelitis caused by the same organism, and as a todler he had intestinal pseudotuberculosis. Prompt recovery took place under selective antibiotic therapy. No known immunodeficiency disease could be correlated with this familial syndrome of increased susceptibility to intracellular vital microbes. A defective function of the patients macrophage system is suspected.


[Constitutional familial leucocytopenia with partial Pelger anomaly and delayed development of bone (author's transl)]. The clinical and hematological findings in 4 boys of a family with a chronic constitutional leukocytopenia are described. Possible X-chromosomal sex-linked genetic transmission, the benign clinical course as well as the association with clinical and cytological hints of the involvement of the lymphatic cellular immunological system suggest a disease of its own. It was classified as a mild form of myelolymphatic insufficiency similar to reticular dysgenesis. The significance of Pelger-Huët anomalies of neutrophils demonstrated in the blood of the mother and of Pelger-like forms in the blood of children are discussed.


[Chronic pseudomalignant immuneproliferation (Canale-Smith syndrome) (author's transl)]. A case of chronic lymphadenopathy and splenomegaly existing over a period of 11 years, with a variety of acquired deficiencies of immunity and autoimmune phenomena, is described. It is almost identical with the 5 children reported in 1967 by Canale and Smith as a new benign syndrome "chronic lymphadenopathy simulating malignant lymphoma". The relationship to similar disorders with lymphadenopathy and immunological abnormalities is discussed.


[Antireticulin antibodies and precipitating antibodies to food proteins in the sera of children with coeliac disease (author's transl)]. Sera from 41 children suffering with histologically proven coeliac disease and from 40 healthy control children were investigated for the presence of antireticulin antibodies and precipitating antibodies to a watery extract of wheat flour and to cow's milk. Antireticulin antibodies were demonstrated by means of indirect immunofluorescence using sections of fresh rat kidney as substrat. For the detection of precipitating antibodies a combination of electrophoresis and immunodiffusion was used. Serum antireticulin antibodies were found in 11/13 children (85%) with active coeliac disease, in 7/17 children (41%) with clinically and biochemically silent coeliac relapse and in 0/16 children with treated coeliac disease. Serum precipitating antibodies to wheat flour and cow's milk were found respectively in 3/13 children (23%) and 2/13 children (15%) with active coeliac disease and in 1/16 children (6%) with treated coeliac disease. Precipitating antibodies could not be detected in the sera of 17 patients with silent relapse of coeliac disease. In the sera of 40 controls neither antireticulin nor precipitating antibodies were detectable. The presence of antireticulin antibodies in serum did not correspond to the presence of serum precipitins to wheat flour and cow's milk. The significance of serum antireticulin antibodies for screening investigations and for follow-up studies is discussed.


Facial myokymia and brain stem tumor.

Facial myokymia and brain stem tumor. An autoptic case of facial myokymia in glioma of the pons is described. The facial myokymia was the only symptom for many years. The authors emphasize the importance of the facial myokymia as a precocious sign of pons tumor and stress the meaning of the EMG in the differential diagnosis between facial myokymia in brain stem tumor and facial hyperkinesa in other diseases.


A case of new dysautonomia-like disorder found in Japan. I. Clinical and metabolic studies. A case of new dysautonomia-like disorder in a Japanese infant is reported. The patient showed almost all of the essential criteria for the diagnosis of familial dysautonomia. Results of pharmacologic tests and urinary excretion patterns of catecholamines and their metabolites were also compatible with the disorder. But he lacked some important clinical findings, such as lifelong hypolacrimia, skin blotching, excessive sweating and labile blood pressure. Precise observations of clinical features and literatures on non-Jewish cases of familial dysautonomia lent evidence that this case suffered from a new dysautonomia-like disorder.


"Locked-in" syndrome. A clinico-pathological study of two cases. Two new examples of "locked-in" syndrome are reported. The patients are mute and quadriplegic; they present a bilateral horizontal gaze palsy. Contact can be established through preserved vertical eye movements demonstrating therefore that the patients are not comatose. Postmortem examination reveals in both cases a thrombosis of the basilar artery with an infarction of the ventral rostral pons extending dorsally into the paramedian tegmental area. The main clinical features of this syndrome and their anatomical correlates are discussed.


Radicular symptoms in tuberculosis. A case report. A case of tuberculous radiculitis in the lumbosacral region resulting in flaccid paresis of the lower limbs is presented. The primary site of tuberculosis was the intestine. Hematogenic dissemination resulted in organ tuberculosis of the third lumbar vertebra and left kidney. The infection spread locally into the lumbosacral dura and nerve roots. A decline in general immunological resistance lead to fatal dissemination of the disease into the meninges, lungs, liver, left adrenal and right kidney. Differential diagnostic problems, especially the Guillain-Barré syndrome, are discussed.


Effects of some drugs on electrical activity of the gut in the postoperative period. Myoelectrical activity of the gut has been studied in the postoperative period on 54 patients who underwent cholecystectomy. They have been divided into one control group and four other groups which were treated with pentagastrin, cholecystokinin, prostigmine or coherin (a posterior pituitary extract). In all patients, bursts of spikes were recorded during the early postoperative period. However, the slow waves were strongly disturbed at this time. Pentagastrin, CCK-PZ and prostigmine had no effect on the slow waves, while they increased the frequency of the spikes. These substances did not reduce the duration of the 'physiological' ileus. On the contrary, coherin was found to improve the regularity of the slow waves and to reduce the duration of the 'physiological' ileus.


Changes in vascular permeability associated with acetic acid-induced gastrin ulcer in rats. Gastric ulcer was induced in rats by application of acetic acid to the anterior wall of the stomach. Leakage of circulating albumin into the gastric wall was estimated by intravenous injection of radioactive albumin and determination of the radioactivity in different samples of the stomach wall. The protein leakage was found to be markedly increased in the anterior wall of the stomach, the increase being most pronounced close to the ulcer. The leakage remained fairly constant during the first 10 h of the experiment. The protein content of the posterior wall was about the same as in animals on which a sham operation had been performed. The protein leakage was associated with considerable oedema formation. The protein leakage indicates that inflammatory mediators are released in a wide area around the ulcer. The present experimental model offers an opportunity to find out which mediators are involved in the lesion.


Proximal selective vagotomy without pyloroplasty. A randomized clinical study. 50 consecutive male patients with a proven duodenal ulcer disease without pyloric stenosis were electively treated with a proximal selective vagotomy. They were randomized in a group with and a group without pyloroplast. Up to now (1-3 years follow-up) no recurrences were found, and only two patients have major complaints (Visich grading 3). There are no differences between the two groups, as judged by the clinical result, the pentagastrin test, the Hollander test (2-DODG stimulation), and the gastrin analysis. Pyloroplasty therefore is not needed. Although the vagotomy which completely preserves antral motility is mostly incomplete in the Hollander test, it is sufficient as judged by the clinical results and the acid response.


Metastasis formation after intravenous tumour cell injection in thrombocytopenic rats. Induced thrombocytopenia has been found to decrease metastasis formation after intravenous tumour cell injection which emphasizes the importance of platelets in metastasis formation. Using a syngeneic 20-methylcholanthrene-induced fibrosarcoma in rats, the effect of platelet reduction was investigated in combination with trauma and infusion of dextran 1000. It was found that platelets were important for the increased formation of metastases after trauma but not for the increased formation of metastases after infusion of dextran 1000. Thus, trauma and dextran 1000 stimulate metastasis formation by different mechanisms. Possible explanations are discussed.


Blood volume partition after acute cholestasis in the rat. A method involving isotope labelling of blood components and then rapid freezing of intact rats, was used for evaluation of the blood content in liver, spleen and gastrointestinal (GI) tract in cholestatic animals. For comparison also another important blood depot, i.e. the lungs were examined. After 4 days of cholestasis the animals were hypovolemic, however, the partition of blood in the liver and GI tract was unchanged or even increased. In contrast the lung blood volume and the erythrocyte content of the spleen were markedly reduced. Three days later the animals had regained their normal blood volume, but still there was a redistribution of blood from the lungs and spleen to the liver and GI tract. We suggest that during cholestasis the depot function of the splanchnic vessels is disturbed. This might be one factor of importance for development of the hepatorenal syndrome.


Quantitative correlations between chemical structure and affinity for acetylcholine receptors. The affinity constants (log K, pA2) of 128 quaternary ammonium compounds belonging to several different series have been correlated linearly with the hydrophobicity (piR) constant, the dipole moment (muR), and the number of hydroxyl groups (nOH) of the side chain; the dependence on the hydrophobicity constant of the quaternary ammonium head (pi-N identical to) is shown to be parabolic. A correlation coefficient of 0.96 is obtained for all the compounds using only 4 independent variables (6 terms). Based on the quantitative correlation obtained, intermolecular forces involved in the drug-receptor interaction are discussed. Further molecular modifications to enhance the affinity to cholinergic receptors are suggested.


Effects of reserpine, guanethidine and methyldopa on cardiac output and its distribution. In anaesthetized rats with a renal model of hypertension, effects of reserpine, guanethidine and methyldopa on cardiac output (the dye-dilution method) and its distribution among the heart, the lung, the kidney, the large and small intestine, the stomach, the liver, the spleen, skeletal muscle and skin (the rubidium method) were studied. Several hours administration of all three drugs under study, a definite decrease in cardiac output was observed. Cardiac output then escaped from the influence of the drugs despite a reduction in heart rate. Fall of arterial pressure 24 hr after administration of the drugs was only due to the decrease in total peripheral resistance. Effects of the drugs on distribution of cardiac output were studied at the time when cardiac output was not changed to any significant extent. Under this condition the features common to all the drugs were an increase of the cardiac output fractions to the gastro-intestinal tract and a decrease to the heart and the spleen. This fact indicates that decrease in resistance of gastro-intestinal vascular region plays a basic role in the hypotensive effect of reserpine, guanethidine and methyldopa.


The effect of biogenic amine modifiers on morphine analgesia and its antagonism by naloxone. The stimulation of dopaminergic receptors, inhibition of serotonin synthesis or blockade of muscarinic receptors by various modifiers led to inhibition of morphine analgesia in mice. Blockade of dopaminergic receptors or the increase in serotonergic or cholinergic activity resulted in the enhancement of morphine analgesia. Serotonergic and cholinergic systems are proposed as positive and the dopaminergic system as negative modulators of morphine analgesia. The modulation of naloxone antagonism was much more complicated than that of morphine analgesia and often the effect of biogenic amine modifiers on antagonism differed from that on analgesia. The fact than biogenic amine modifiers do not affect morphine analgesia and naloxone antagonism by a similar pattern suggests that interaction of narcotics and narcotic antagonists with analgesic receptors may not be exactly the same.


Effect of anticholinergic drugs on gastro-intestinal absorption of L-dopa in rats and in man. Plasma L-DOPA levels in rats receiving L-DOPA by the oral route were decreased by the concomitant administration of trihexyphenidyl. Following systemic L-DOPA administration no differences were observed between control and trihexyphenidyl-treated rats. Effects similar to those of trihexyphenidyl were observed with atropine. These results indicate that trihexyphenidyl decreases L-DOPA gastrointestinal absorption probably by delaying gastric emptying. The presence in humans of this interaction between the two antiparkinsonian drugs was suggested by similar findings made either in a group of normal volunteers or in a group of parkinsonian patients. These observations suggest that at the clinical level in selected cases the concomitant administration of trihexyphenidyl to patients receiving L-DOPA may decrease the therapeutic efficacy of L-DOPA by reducing its gastrointestinal absorption.


Antitussive activity of some naturally occurring cannabinoids in anesthetized cats. Experimental cough was elicited in pentobarbital-anesthetized cats by either electrical stimulation of the superior laryngeal nerve or by mechanical stimulation of the tracheal mucosa. Intravenous administration of delta9-tetrahydrocannabinol (THC) effectively reduced the amplitude of the cough response in both these models of experimentally induced cough with ED50 values (AtD50) of 1.84 and 0.78 mg/kg, respectively. This cough suppressant activity of THC was more similar to codeine-PO4 than dextromethorphan-HBr. On the other hand, both cannabinol (CBN) and cannabidiol (CBD) were devoid of antitussive activity at doses as high as 10.0 mg/kg.


On the mechanism of histamine action in cardiac muscle. The effect of histamine on electrical and mechanical properties of guinea-pig ventricular muscle fibers was investigated. It was found that the drug decreased in rate of tension development, the rate of fall of the twitch and decreased the time to peak tension. The height of the plateau of the action potential was increased by histamine and this seems to explain, at least, part of the drug action on heart contractility. The uptake and efflux of 45Ca were both increased by the drug. The positive inotropic action of histamine is largely dependent on the external calcium concentration and temperature and is abolished in low Na solution. It was found that histamine has a marked relaxing action which is probably related to increased Ca sequestration by the sarcotubular system. The drug also produced a decrease in post-extrasystolic potentiation.


The effects of cocaine and diphenhydramine upon the reactivity of rat vas deferens to supramaximal doses of noradrenaline and of other agonists: the mode of action of cocaine. The effects of cocaine on responses to supramaximal concentrations of agonists have been studied in preparations of rat vas deferens. Cocaine 10 muM decreased the mean time to peak and increased the mean magnitude of responses to noradrenaline but not to supramaximal field stimulation of sympathetic fibres, to high potassium or to methoxamine. Diphenydramine 10 muM affected responses to noradrenaline similarly. It is proposed that the prejunctional action of cocaine and of diphenhydramine to reduce the rate of neuronal uptake of noradrenaline may provide a sufficient explanation for the enhanced reactivity of the vas deferens to noradrenaline, as this would allow an increased rate of rise of amine concentration at the receptors. Cocaine also enhanced the reactivity of the vas deferens to acetylcholine. The basis of this enhancement by cocaine of the reactivity of the vas deferens to acetylcholine remains to be established, but clearly is not mediated postjunctionally since responses to carbachol were not similarly affected.


Release of smooth muscle-contracting substances from isolated perfused lungs. Infusion of tryptamine (1-4 mug/ml) through the pulmonary circulation of rat isolated lung perfused with Krebs solution caused release of a mixture of spasmogens contracting isolated smooth muscle preparations. One component of this mixture had biological activity comparable to E-type prostaglandins. Other components included a slow reacting substance comparable to SRS-A and a rabbit aorta-contracting substance comparable to RCS. Infusions of 5-hydroxytryptamine, acetylcholine and histamine (0.5-2 mug/ml) also caused release. Release induced by the tryptamines but not that by acetylcholine and histamine was prevented by methysergide whereas acetylcholine-induced release was prevented by hyoscine which did not affect tryptamine-induced release. The tryptamines and histamine released spasmogens from dog isolated lungs but only histamine was effective in guinea-pig lungs. We conclude that amine-induced release from isolated lungs is a fairly general phenomenon and that it may represent an endocrine function of lung.


The development of a reliable and sensitive bioassay for gastrin in body fluids. The sensitivity and reliability of the Ghosh and Schild rat stomach preparation was improved by implantation of bulky intragastric cannulae, recirculation of the perfusate and measurement of conductivity instead of pH. With these procedures, the threshold values for gastrin I were in the range of 1-2 ng. In attempts to increase the sensitivity further it was shown that neither vagotomy nor antrectomy influenced the sensitivity of the method. The threshold values were not lowered by attempts to reduce gastrin metabolism through nephroligature or small bowel resection. Although rats fitted with portacaval shunts did raise the threshold, the limited increase in sensitivity was also achieved by selecting the rats that gave an initially high response to a test dose of gastrin thus avoiding the complicated shunt operation. The assay procedure enabled statistically valid measurements of gastrin in plasma and from tumour extracts from patients suffering from the Zollinger-Ellison Syndrome to be assayed using a 2 + 2 block design.


The effect of dimethylaminoadamantane on neuronal membranes. The effect of dimethylaminoadamantane (DMAA), an amantadine derivative with an anti-Parkinson property, on rat sensory nerve fibres was studied with the sucrose gap method. DMAA 10(-4) M in normal Locke solution reduced the spike amplitude without changing the resting potential, increased the membrane resistance and depressed repetitive spike activity elicited by depolarizing currents. From experiments performed with changed concentrations of sodium, potassium, calcium and chloride ions in the suspension medium it appears that the permeability of sodium, potassium and chloride ions is reduced by DMAA. The possible implication of the membrane effects of the drug in its action on dopaminergic transmission in the brain is discussed.


Mechanism of the histamine-induced positive inotropic action in cardiac muscle. Histamine, a positive inotropic agent which elevates cyclic AMP, was tested for ability to induce Ca2+ channels in 3 preparations of embryonic (16-day-old) chick ventricular myocardial cells whose fast Na+ channels were blocked by tetrodotoxin or voltage inactivated in 25 mM K+. In such inexcitable cells, histamine (10(-6)M) rapidly (1-3 min) induced slowly rising, overshooting, plateau-like responses accompanied by contractions. Mn2+, D600, or H2-receptor blocking agents abolished the slow responses. These results suggest that the positive inotropic action of histamine, like that of catecholamines, is mediated by an increased availability of slow Ca2+ channels.


The effect of corticosteroids and hemicholinium-3 on choline uptake and incorporation into acetylcholine in rat diaphragm. The glucocorticoids prednisolone and dexamethasone antagonize the inhibition by hemicholinium-3 of both the rate of choline uptake and the incorporation of choline into acetylcholine in the rat diaphragm. Aldosterone has no such effects. It is concluded that the beneficial effect of glucocorticoids in the treatment of myasthenia gravis may be due not only to immunosuppression, but also to some direct effect on presynaptic events perhaps via a choline carrier or an enzyme of choline metabolism.


Classification and discrimination for data analysis in pharmacology. Classification and discrimination are described as methods of inference and decision-making in pharmacological data analysis. Principal components and multiple discriminant analysis are applied to animal and human spectra of the neuroleptics. A preliminary step is required to separate differences in potency from the spectral information.


Histopathological effect of thiourea on the ovarian tissues of Sarcophaga ruficornis (Fabr.). The primary target of thiourea in female Sarcophaga are the follicles in the ovarioles. The follicle cells as a result become syncytial and their nuclei get pycnotic, inhibiting the transport of nutrient material into the nurse cells and of yolk into the oocytes. The subnormal eggs produced are not viable.


Nuclear pores in the spermatozoon of the rat. The paper describes a hexagonal array of nuclear pores in a non-redundant region of the nuclear envelope underlying the basal surface of the rat spermatozoon head. It is concluded that intranuclear material protruding through these pores is the cause of the characteristic rows of circular 'bumps' found in surface replicas of this region.


Mitotic activity of adrenal medullary cells in the mouse at different ages and following unilateral adrenalectomy. The number of mitoses as well as the number of the cells of the adrenal medulla was determined in the mouse at various ages and after unilateral adrenalectomy. It was found that a decrease in the mitoses and an increase in the cell number occurs up to 4 months. In 12-month-old rats, mitoses, although rare, are still present. No changes in the mitosis and cell number was observed after unilateral adrenalectomy.


Experimental allergic encephalomyelitis in T-lymphocyte deficient rats. Thymectomized, lethally irradiated rats reconstituted with syngeneic bone marrow were injected with rat brain in complete Freund adjuvant mixture. Both, they and sham-thymectomized, irradiated and bone marrow protected rats displayed a higher incidence of leg paralysis than normal non-irradiated animals. Thymectomy lowered the incidence of the disease.


Auto-oxidation of hemoglobin in plasma.

Auto-oxidation of hemoglobin in plasma. The rate of auto-oxidation of human hemoglobin to methemoglobin was measured in plasma at 37 degrees C. Half-lives of hemoglobin were found to be 20 h, 12 h and 7 h at the oxygen tensions of 126, 57 and 23 mm Hg, respectively.


Sexual steroids and monamine metabolism during gestation. The experiments show influence of progesterone and estradiol on regulation of enzymes of monamine metabolism, MAO and COMP during pregnancy. Both the hormones inhibit enzymes MAO and COMPT in the adrenals when determined at 0 h parturition. Estradiol has stronger inhibitory effect than progesterone. The results provide evidence for important endocrine implication during pregnancy for processes of monamine regulation.


[Early effects of growth hormone on blood and urinary inorganic phosphorus in the rat (author's transl)]. From the kinetic study of the effects of one single growth hormone (GH) injection on the phosphate metabolism, it appears that the influence of GH on the serum phosphate level is biphasic: a decrease is followed by an increase. Conversely GH leads to an early decrease of the urinary phosphate excretion.


[Simple chromosome banding technique for farm animal investigations]. For routine cytogenetic investigations, a simple banding technique on chromosomes is described. Used on different cell material, a visible banding appearance is produced which makes the typing of chromosomes precise and fast. On 2 examples of cattle and rabbit chromosomes, the identification of a centric fusion and a trisomic is shown.


Distribution of type A and B monamine oxidase activities in the central nervous system of rat and chick. The distribution of type A and B monamine oxidase (MAO) activities in the central nervous system (CNS) of rat and chick was investigated using 5-hydroxytryptamine and beta-phenylethylamine as specific substrates. The distribution of type A MAO was similar to that of type B MAO in rat CNS, but quite different in chick CNS. This may be ascribed to the difference in animal species. The major part of MAO activity in the spinal cord was found to be type A.


Wireless microphone for studies of animal vocalizations. A microphone collar for obtaining good quality recordings of animal vocalizations is described. An inexpensive, commercially available wireless microphone was modified and mounted on a collar with a hearing-aidbattery pack. The complete assembly weighs 25 g, and is readily accepted by domestic cats.


[Cholesterol 7alpha-hydroxylase activity of the rat liver after hypophysectomy and administration of hypophyseal hormones (author's transl)]. In order to elucidate the role of the hypophysis in the regulation of cholesterol 7alpha-hydroxylase activity, male and female rats hypophysectomized on day 50 of life were treated with different hypophyseal hormones and tested on day 85 of life. Only a crude extract from human hypophysis and ovine prolactin was able to enhance the enzyme activity, thereby restoring the level of intact controls.


[Autosomal chromosometranslocation of piebald cattle and brown cattle (author's transl)]. Different autosomal chromosome fusions at piebald cattle and brown cattle are described. In randomly investigated breeds of cattle in Germany, we found 1/25 translocation in piebald cattle and a 1/29 Robertsonian fusion in brown cattle. Fertility differences were investigated.


The effect of plant growth substances and natural products on RNA and DNA synthesis in leukocytes. The effect of auxins, cytokinins, gibberellins and phenolics on the incorporation of uridine and thymidine into the nucleic acids of human leukocytes was examined. Both the stimulation and inhibition of the incorporation of the precursors was noted. The auxins consistently promoted the incorporation of uridine.


Structural changes of deoxyribonucleoprotein fibres following gamma-irradiation under aerobic and hypoxic conditions. The DNP fibres gamma-irradiated under aerobic condition showed a reduction of their diameter, while no remarkable changes were observed in the DNP fibres irradiated under hypoxic condition by scanning electron microscopy.


Gene amplification in oocytes of the rove beetle Creophilus maxillosus (Staphylinidae, Coleoptera-Polyphaga). The extra-DNA body was found, for the first time, in oocytes of an insect with telotrophic ovary. Dispersion of this body is accompanied by an enormous increase of nuclear volume and production of multiple nucleoli. It is suggested that the extra-DNA contains a huge mass of nucleolus organizers.


Influence of progesterone on protein and RNA synthesis in cultured chick embryo liver cells. Chick embryo liver primary cultures, when added with progesterone, exhibit, in comparison with the controls, a normal growth, a decline of both 3H-uridine uptake and incorporation into total RNA, a decline of 3H-leucine and 14C serine incorporation into the proteins. Progesterone is not able to stimulate phosvitin synthesis induction.


Enhanced inhibition of RNA synthesis by amanitins in in vitro cultured cells. The inhibition of RNA synthesis by alpha-amanitin on in vitro cultured cells is very slow. The action of various analogueoreover pretreatment of cell cultures with DEAE-dextran greatly enhanced the effect of beta-amanitin.


Cell types originating from kidney explants of young and old mice. Explants from young and old mouse kidneys give rise to two different cell types when placed in organ culture dishes. The two cell types differ in morphology and ability to grow in vitro. Explants from young mice give rise to one predominant cell type; those from old mice give rise to another. Our data supports the mosaic theory of aging.


[Studies on stable and during early imbibition phases synthesized poly(A)-RNA of Agrostemma githago embryos (author's transl)]. RNA isolated from dry embryos of Agrostemma githago seeds contains poly(A)-sequences, but in very small amounts. In the early phase of imbibition, an intensive synthesis of poly(A)-containing RNA is brought about. The importance of this synthesis of poly(A)-RNA is discussed.


Deep temporal lobe projections to the nucleus of the diagonal band of Broca. Electrophysiological studies with acutely prepared cats found that stimulation of deep temporal lobe structures (e.g., amygdala, prepyriform cortex) evoked responses in the nucleus of the diagonal band of Broca. An analysis of field, extra- and intracellular unitary responses points to the existence of a monosynaptic excitatory connection.


The renal concentrating ability of newly born Brattleboro rats (hereditary diabetes insipidus). In Brattleboro rats, there was no difference in urine osmolality between animals with and without diabetes insipidus after water deprivation up to age 14 days, and it appeared at age 18 days due to increase of osmolality in non-diabetic individuals.


Use of indomethacin to reverse neonatal hypotension. Treatment with indomethacin elevated systemic arterial pressure and pulmonary vascular resistance in hypotensive newborn goats. Indomethacin may be of value in restoration of systemic arterial pressure in stress-induced hypotension.


Effect of different bathing media on the short-circuit current across the intestine of the rat and guinea-pig. The changes in short-circuit current occurring when one or both solutions bathing the intestine of rat or guinea-pig mounted in flux chambers were recorded. The results with the guinea-pig can be explained in terms of diffusion potentials arising from the ionic replacements, and an electrogenic sodium pump, sensitive to ouabain, in the contraluminal membrane of the cell. In the rat, the situation is more complicated, and the enterocyte probably possesses an electrogenic sodium pump in the brush-border membrane.


Capillary lengths and areas, and intercapillary distances in tissue near the human knee. Quantiative stereological electron microscopy has been used to investigate the capillary lengths, surface areas and intercapillary distances in the tissues around the human knee, the synovial membrane, synovial capsule, fat and tendon. The vascularity of these regions was much less than in other areas of the body, especially muscle.


Dog behaviour as related to spinal cord temperature. 3 dogs could behaviourally modify their own spinal cord temperature (Tspin. cord). In a hot environment, 2 dogs did not cool their spinal cord, 1 dog warmed it. The higher the environmental temperature, the higher the chosen Tspin. cord. These results seem to imply that this latter dog tended, in warm environment, to behaviourally reduce: Ts greater than Tspin. cord (Ts mean skin temperature). Data obtained previously support this explanation.


The relation between capillaries and neurons in the caudal neurosecretory system of Pomatomus saltatrix. The caudal neurosecretory system of Pomatomus saltatrix was examined. Particular interest was devoted to the perikarya of the neurosecretory cells. The majority of these cells were characterized by a close association with the capillary network. The cells appeared to ensheath the capillaries thus bringing the nucleus and perinuclear cytoplasm into close association with the capillaries.


Influence of thalamic stimulation on cortical epileptogenic focus. Single stimuli applied to the non-specific thalamic nuclei do not change the activity of a cortical epileptogenic focus whereas rhythmic stimulation of these structures transforms the interictal activity into an ictal one.


Influence of the visual cortex upon collicular evoked responses in the rabbit. In rabbit, the depression of the visual cortex by KCl showed an enhancement of the collicular evoked potentials. This enhancement revealed that the visual cortex had exerted a tonic type influence upon the superior colliculus.


Effect of subdiaphragmatic vagotomy on production of gastric ulcers in pylorus-ligated albino rats. A reduction in volume and free and total acidity of gastric content was noted along with reduction in ulcer index, with a shift of the site of ulceration from fundus to the glandular part of the stomach, following vagotomy in pylorus-ligated rats. Low volume and acidity explains the absence of ulcers in the fundus, but the increased involvement of glandular part in ulceration is possibly due to weakening of the mucosal barrier following vagotomy.


Effect of cholestasis and biliary diversion on the absorption of Na octanoate in the rat. The intestinal absorption and portal vein transport of Na octanoate by isolated jejunal segments perfused in vivo were unchanged in rats studied 48 h after bile duct ligation or fistula.


The influence of lithium on serum ceruloplasmin. Serum ceruloplasmin oxidase activity did not change in mice treated orally for 120 days with Li2CO3 (0.58 mEq/kg/day). After a single i.p. injection of LiCl (20 mEq/kg), a significant activation of ceruloplasmin was observed.


Effect of colchicine on polymerization of tubulin from rats, mice, hamsters and guinea-pigs. Colchicine-inhibition of polymerization of tulbulin from rats, mice, golden hamsters and guinea-pigs was studied to determine if species differences in tubulin sensitivity to colchicine might parallel species variation in colchicine toxicity. It was found that polymerization of tubulin is nearly equally sensitive to colchicine in all four species.


Distribution of the blood flow supplied by the vertebral artery in rats: anatomical, functional and pharmacological aspects. In rats, the vertebral artery make only a minor contribution to the blood perfusion of the ponto-medullary area. This was measured with radioactive microspheres and was confirmed by methylmetacrylate casts and local injection of a centrally acting hypotensive drug.


Histamine receptors in the cat mesenteric circulation. The distribution of histamine receptors was studied in the isolated perfused vascular bed of the cat terminal ileum. The results indicated that the depressor effect of histamine is mediated through the stimulation of metiamide-sensitive H2-receptors, while the pressor effect of the amine is mediated by the stimulation of mepyramine-sensitive H1-receptors.


Protection by cerium chloride on CCl4-induced hepatotoxicity. Pretreatment of rats with cerium chloride, an inhibitor of the DMES, protect against CCl4 intoxication. The protection was obtained against the fatty infiltration in the liver, the decrease of triglyceride secretion from the liver into the plasma compartment, the polysomal disaggregation and the rise of serum transaminases.


Possible role of extracellular matrix vesicles in initial calcification of healing rachitic cartilage. Fluid (20-30 nl) was aspirated by a modified renal micropuncture technique from vitamin D-, phosphate-deficient rats. The fluid revealed a mineral forming agent which could be sedimented at 140,000 X g for 8 hours, was resistant to acid demineralization, but was destroyed by heating, freezing and thawing as well as sonication, and blocked by phospholipase A at 10-5 M but not at 10-7 M. Electron microscopic study of the fluid sediment revealed images consistent with matrix vesicles. These data are consonant with the view that matrix vesicles, their remnants, or closely associated structures comprised the mineral forming agent.


Analysis of matrix vesicles and their role in the calcification of epiphyseal cartilage. Extracellular matrix vesicles, which have been shown to be associated with initial calcification of cartilage, were isolated, characterized, and studied with 45calcium isotope to determine whether they could form mineral in vitro. It was found that the isolated matrix vesicles contain a phosphatase, active at neutral pH, which has a very wide specificity and will hydrolyze a variety of nucleotide triphosphates, diphosphates, monophosphates, and other phosphate-containing substrate and metabolites. Acid phosphatase, beta-glucuronidase, and cathepsin D were found to be in the cell fractions, in lysosomes; these enzymes are not present in matrix vesicles and this is additional evidence for the difference between matrix vesicles and lysosomes. Matrix vesicles were found to take up 45Ca even in the presence of low levels of Ca and P1 and also to facilitate precipitation of hydroxylapatite when incubated under physiological conditions in the presence of ATP and other phosphate-containing substrates. Systematic electron probe analysis of a septum of epiphyseal cartilage indicates that matrix vesicles gradually accumulate calcium and then phosphorus and thus facilitate the advance of the calcification front. Adjoinging nonvesicular matrix in the hypertrophic zone, cell cytoplasm, and cell processes had very low levels of calcium and phosphorus in a region where matrix vesicles showed high levels of these elements. New concepts are put forward that take accounts of these findings which provide a better understanding of the sequence of mineralization in growth cartilage.


Histochemical localization of calcium in growth plate mitochondria and matrix vesicles. K-pyroantimonate is an anion that forms an electron-dense precipitate with cellular cations that is readily visualized at the ultrastructural level. The staining process is made relatively specific for calcium by comparing pyroantimonate treated sections to sections pretreated with ethylene glycol-bis-N,N'-tetraacetic acid, a chelating agent that removes calcium but not other cellular cations. By these means, it is shown that the antimonate-calcium complex is located predominantly in mitochondria and cell membranes throughout most of the growth plate. In the degenerating zone, however, there is a gradual loss of stain complex from the mitochondria and cell membranes and a concomitant accumulation of the stain complex by matrix vesicles. The latter are the initial site of mineralization in the growth plate as detected by these means. Thus, this study suggests that intracellular calcium plays a significant role in matrix calcification.


Calcification of rachitic cartilage to study matrix vesicle function. Growth plate cartilage from rachitic rats was studied to assess the role of extra-cellular matrix vesicles in the reinstitution of calcification during healing. The concentration and distribution of matrix vesicles was found to be normal in rachitic growth plate, and although the rachitic cartilage matrix was largely uncalcified, an occasional vesicle did contain internal mineral. Matrix vesicles served as initial loci for mineralization when healing was brought about either by in vivo injection of phosphate or in vitro incubation of growth plates in a metastable calcifying solution. During in vitro calcification a distinct line of mineralization developed in the upper growth plate which was shown by electron microscopy to reflect mineralization by the vesicles. The appearance of this vesicle-associated calcification line was inhibited by preheating or repeated freezing and thawing, and by 30 minutes preincubation in deoxycholate, ethane-1-hydroxy-1,1-diphosphonate, or beryllium sulfate. Our results suggest that vesicle calcification is dependent on the structural and enzymatic integrity of the vesicle membrane. Enzymes that may well play a role in vesicle calcification are phosphatases (e. g., alkaline phosphatase, pyrophosphatase and ATPase), which are known to be concentrated in vesicle membranes.


Calcification of matrix vesicles in human aortic valve and aortic media. Calcification of human aortic valve and aortic media occurs regularly, increases with age, and is distinctively associated with a zone of lipid accumulation. Ultrastructurally, the accumulated lipids are seen as cellular degradation products derived from senescent and degenerate fibrocytes and smooth muscle cells. The products when deposited in the matrix are morphologically similar to the matrix vesicles described in other calcifying tissues, and serve as the initial site of calcification rather than collagen or elastic fibers. Scattered among the smaller and more typical matrix vesicles, there are seen frequently giant vesicle-like structures measuring several microns in diameter. Many of these large calcified bodies contain needle-shaped, radially arranged apatite crystal deposits. Some of the large calcifying bodies are bounded by folded structures suggesting a membrane component, at times obscured by a more dense floccular osmiophilic deposition. Alcianophilic apparent proteoglycan particles are also adherent to these large calcified bodies. The substance forming the large calcified bodies might be a complex of phospholipids derived from cell membrane and proteoglycan derived from ground substance, this combination possible serving as a nidus for calcification.


Matrix vesicles in aging cartilage.

Matrix vesicles in aging cartilage. The calcification process that occurs in aging has been studied with the electron microscope in costal and tracheal cartilage of rats and in human costal cartilage. In these tissues, the early stage of the calcification process is induced and regulated by matrix vesicles in the same way as it occurs in epiphyseal cartilage, bone, and dentine. However, the spreading of inorganic substance from vesicles into the surrounding matrix is frequently impaired in aged cartilage, either because of a too low concentration of calcium ions, or because the structure of the cartilage matrix is not suitable for inorganic substance deposition. This shows that matrix vesicles have a calcium affinity and calcium-binding potentiality greater than that of other components of the cartilage matrix. Most matrix vesicles are produced by "Verdämmerung der Zellen." This degenerative process of the chondrocytes leads also to the formation of pericellular halos consisting of aggregates of amorphous substance and thin filaments. Part of the material that forms these aggregates seems to be produced by disruption of matrix vesicles. Within this disruptive material, thick collagen fibrils can be formed. Moreover, this material seems capable of inducing calcification. These findings suggest that matrix vesicles, by releasing their content into the matrix, can be involved in some way in collagen formation, and that the released material maintains the calcium affinity and calcium-binding property it has within the vesicles.


Role of matrix vesicles in calcification. The role of matrix vesicles in the calcification process was investigated in vitro. Isolated vesicles were unable to transport calcium actively. The ATPase activity was not stimulated by calcium in the presence of an optimal magnesium concentration. At a physiological substrate concentration of pyrophosphate, the pyrophosphatase had a pH optimum around 7.0. The vesicles nucleated calcium phosphate precipitation independently of the presence of hydrolyzable phosphate compounds. It is suggested that vesicles induce calcification by nucleating calcium phosphate precipitation and through the local destruction of pyrophosphate, a crystallization inhibitor.


Renal kallikrein: its localization and possible role in renal function. The distribution of kallikrein in dog kidneys was studied. It was found that kallikrein decreased from the outer to the inner cortex and that the medulla and papilla had very little kallikrein. The site of kallikrein secretion in the nephron was also studied by performing stop-flow techniques in dogs. The highest kallikrein concentration was found in the fractions with the lowest sodium concentration. It was concluded that kallikrein is secreted into the urine at the level of the distal tubule by either the tubule itself or by a structure related to this part of the nephron. In addition, the possible involvement of the kallikrein-kinin system in the regulation of sodium excretion was investigated. Circulating kinins and urinary kallikrein were increased in saline-loaded dogs. Urinary kallikrein also increased in dogs that have "escaped" the sodium-retaining effect of desoxycorticosterone. Experiments in rats with different sodium intake showed a relationship between water and sodium excretion and urinary kallikrein. These data suggest that the kallikrein-kinin system could participate in the regulation of the renal function at the level of the distal tubule or collecting duct.


Urinary kallikrein in hypertensive animal models. Urinary kallikrein excretion was studied in a number of animal models of hypertension. Kallikrein excretion was subnormal in spontaneously hypertensive rats as compared to Wistar/Kyoto rats and in rats made hypertensive by a clip on one renal artery. Kallikrein excretion was supranormal in rats made hypertensive by desoxycorticosterone and salt and in rats receiving desoxycorticosterone alone. It was subnormal after bilateral adrenalectomy. Kallikrein excretion increased in normotensive rats fed a low-sodium diet but was unchanged by a high-sodium diet. Thus, kallikrein excretion responded to changes in activity of sodium-retaining steroids and was not correlated with excretion of salt or water. In studies in dogs with stenosis of one renal artery kallikrein excretion was decreased on the stenoic side and the decrease correlated highly with the reduction in renal blood flow. While the role of the kallikrein-kinin system is still unclear the data indicate that the kidney may modify the initiation or maintenance of hypertension via this potent vasodilator system.


Relationships among urinary kallikrein, mineralocorticoids and human hypertensive disease. Urinary kallikrein excretion is reduced in patients with hypertension of unknown etiology. In addition, the excretion of this renal, kinin-forming enzyme was found to be elevated in hypertensive patients with primary aldosteronism. Aldosterone regulates kallikrein excretion, as normal subjects show increased kallikrein excretion in response to a low sodium intake, high potassium intake, or the synthetic mineralocorticoid, fludrocortisone, whereas kallikrein excretion falls during treatment with spironolactone. The relationship between kallikrein excretion and aldosterone activity may directly reflect the intrarenal activity of the kallikrein-kinin system, as determined by studies of kallikrein levels from isolated renal cells or of plasma kinin levels in man in response to postural changes or saline loads. Some patients with essential hypertension do not show a normal increase in kallikrein excretion in response to low dietary sodium intake despite an apparently normal aldosterone response, suggesting that there may be a defect in the renal kallikrein-kinin system in these patients. Whether these findings are of pathogenetic significance in human hypertensive disease remains to be determined.


Postcoital test: physiologic basis, technique, and interpretation. The postcoital test determines the adequacy of sperm and the receptivity of cervical mucus. It is the only test which evaluates the interaction between sperm and the female genital tract fluids. The Sims-Huhner test should be an integral part of an infertility investigation, but it must not be used as a substitute for semen analysis. Since cervical mucus accurately reflects the ovarian cycle, the PC test is a useful indicator of the endocrine preparation of the female reproductive system. It is also an important method for the evaluation of a variety of contraceptive steroids which may act directly or indirectly upon cervical secretion. For best results the test should be properly timed, meticulously performed, and knowledgeably interpreted.


Artificial insemination using donor semen: a review of 171 cases. This report represents a summary of our experience with 171 unselected cases of artificial insemination by donor (AID) over a 4-year period. It must be stressed that the study was retrospective and subject to many of the problems of analyzing such data. However, the information gained may aid the clinician in his approach to candidates for AID. The most critical points revealed by the survey are as follows: 1. Age, length of infertility, and proven fertility, within certain limitations, appear not to be of prime importance in determining the outcome of AID. 2. Of those patients conceiving, the majority will do so within three cycles of exposure, and 90% will have done so within six cycles of exposure. 3. An adequate trial of AID therapy should last at least 6 months. 4. Although the frequently reported conception rate of up to 70% may be expected in patients with correctable anovulation or with normal reproductive organs, a marked diminution in the success rate should be expected in candidates with disorders such as endometriosis, tubal disease, pelvic adhesions, and uterine abnormalities.


Homologous artificial insemination and oligospermia. Of approximately 339 patients evaluated at a private infertility service over a 5-year period, 24 couples underwent homologous artificial insemination (AIH). Nineteen of these were performed to circumvent the problem of oligospermia, and only one pregancy was achieved in this group; conceivably this pregnancy could have occurred by chance. The difficulty in controlling the numerous variables in a clinical fertility study and the limitations of the present methodology are also discussed. It would appear that the use of AIH to circumvent oligospermia has not been successful. However, the present series is rather small. AIH should continue to be offered to couples who have a well-defined indication such as impotence, premature ejaculation, or any anatomical defect which prevents successful intromission. The use of AIH for patients with mild oligospermia but excellent sperm motility probably deserves a limited trial, since it is less expensive and may offer some chance for success.


The association of D-group chromosomal translocations and defective spermatogenesis. D-group chromosome translocations have been associated in isolated cases with infertility in males. In this study, we demonstrated the effect of a translocated D-group chromosome on spermatogenesis as it had segregated among three male members of one family. Although the father, who carried the translocation, was obviously fertile, the effects of the translocations on his sperm were noted in the morphologic examination. This study demonstrates the need for more careful evaluation of patients with chromosomal abnormalities for effects on spermatogenesis. Furthermore, it shows the possibility of autosomal chromosomal influences on testicular function.


An investigation of plasma hormone levels before and after vasectomy. A prospective study of effects of vasectomy on the plasma levels of testosterone, estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)  was instituted. Postvasectomy plasma hormone levels were compared with prevasectomy, base line levels. Beginning at 6 months after vasectomy, mean plasma testosterone levels demonstrated a statistically significant elevation, mean plasma estradiol levels were lower, mean plasma LH levels were elevated, and mean plasma FSH levels were unchanged. By 2 years after vasectomy, a slight plasma FSH elevation had occurred, plasma estradiol levels had returned to base line, and plasma testosterone and LH levels remained elevated. These changes, although significant statistically, did not exceed the normal ranges found in normal adult males in our laboratory and were of unclear physiologic significance. Thus, it can be concluded from this study of 56 men studied for 2 years, 148 men studied for 1 year, and 182 men studied for 6 months after vasectomy that no adverse hormonal effects of vasectomy have been demonstrated.


Endocrine effects of vasectomy in man.

Endocrine effects of vasectomy in man. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and free testosterone index (FTI) were measured serially in 11 fertile men, ages 25 to 40, 4 weeks before to 40 weeks after elective vasectomy. During the 1st week postvasectomy there was a significant fall in FSH levels (P less than 0.001) and FTI (P less than 0.05), with recovery by 2 weeks. This acute response may be due to general surgical stress. Thereafter, the over-all mean FSH level was significantly (P less than 0.05) below the prevasectomy level; over-all levels of LH, T, and FTI did not change. We speculate that this decline in mean FSH levels is compatible with the existence of an as yet unidentified T-independent testicular factor influencing FSH production.


Lipid and carbohydrate metabolic studies after one year of megestrol acetate treatment. A prospective study of lipid and carbohydrate metabolic parameters was made in 22 women who had taken a daily oral dose of 0.5 mg of megestrol acetate for contraception for 1 year. Studies of the fasting blood cholesterol and triglyceride levels demonstrated no significant change. A 3-hour oral glucose tolerance test was performed before and after 1 year of treatment. After therapy, the fasting blood glucose levels were normal but the 0.5- and 2-hour levels were elevated. All but one of the plasma insulin levels were elevated at the 1-year test. Since body weights and the fasting levels of plasma growth hormone were unchanged, they were probably not involved in the carbohydrate alteration. These results point out the need for long-term studies and the necessity for investigating the metabolic effects of all progestogen contraceptives.


In vitro studies of ovulation in the perfused rabbit ovary. A system has been developed for the perfusion of the rabbit ovary in vitro. At laparotomy, the ovarian artery is cannulated and perfused with M 199 tissue culture medium containing insulin and heparin, then removed with its vascular pedicle intact. Perfusion at 37 degrees C is maintained by using a capillary oxygenator and Buchler roller pump. The functional integrity of the perfused ovary is confirmed by serial determinations of the perfusate pH, glucose and lactate concentrations, and by ovarian histology. This in vitro model was used to study the mechanism of ovulation. One group of isolated rabbits received human chorionic gonadotropin (50 IU, intravenously) and, 8 hours later, one ovary was removed and perfused; the contralateral ovary remained in situ, serving as an in vivo control. Serial observations for follicle development and rupture were made over the subsequent 7-hour interval. The occurrence of ovulation in vitro was documented by time-lapse photography. In each animal, comparisons made between the in vitro and in vivo ovary indicated that the rate and time of follicle maturation and ovulation were comparable. Ovulation occurred between 10 and 15 hours after administration of human chorionic gonadotropin in both preparations.


Failure to observe testosterone-induced nucleus-lysosome interaction in rat ventral prostate. The possibility that sex steroids act to promote the association of lysosomes with nuclei was studied by 2 methods in the secretory epithelium of ventral prostate of castrated rats treated with androgens: (a) electron microscopic (EM) examination of intact tissue and (b) study of fresh nuclear suspensions isolated from prostate homogenates using the fluorescing dye acridine orange (AO) and EM. AO-stained particles in nuclear suspensions were found to correspond to either (i) section granules, (ii) primary lysosomes or (iii) heterogenous dense bodies (HDB), considered to be lysosomes. Intact prostate tissue and crude nuclear suspensions were studied in adult rats 3-21 days after castration and in normal rats. Changes in nuclear architecture are evident 8 days or more after castration; the number of HDB increase while secretion granules and primary lysosomes decrease. Whether from prostate of castrated, normal or hormone-treated animals, a small number of the lysosomal HDB or primary lysosomes are seen closely apposed to epithelial cell nuclei. In response to short-term testosterone administration (15 or 60 min) in 10- and 21-day castrate rats, chromatin distribution appears to become more condensed; yet the number of associations of nuclei with lysosomal elements does not change. These studies of androgen action in rat ventral prostate (a classical target organ for the study of androgen action) provide no evidence to support the idea that lysosomal association with, or invasion of, nuclei in target cells is a general feature of sex steroid hormone action.


Incorporation of (5-3H) uridine into ribonucleotide pools and RNA during thyroxine-induced metamorphosis of Xenopus laevis tadpoles. Incorporation of [3H] uridine into the ribonucleoside triphosphates UTP and CTP, total RNA, and nuclear and cytoplasmic RNA was followed in Xenopus laevis tadpole liver during thyroxine (T4)-induced metamorphosis. Pool sizes of UTP and CTP were found to remain unchanged, although turnover the ribonucleoside triphosphates was found to be greatly stimulated after 4 days of hormone treatment. The time course of labeling of the 40-S pre-rRNA was very similar to that of UTP in both thyreostatic and T4-treated tadpoles, thus reflecting a direct relationship between turnover of the immediate precursors and labeling of RNA. Although a faster depletion of labeled UTP and pre-rRNA (precursor ribosomal RNA) was noted in T4-treated tadpoles, labeled cytoplasmic rRNA continued to accumulate almost linearly for 25 h. In thyreostatic larvae no further increase in labeled cytoplasmic rRNA occurred beyond 4 h of labeling. From these results we conclude that both enhanced transcription and more effective utilization of pre-rRNA are responsible for the net accumulation of rRNA observed on the 4th day of T4-induced metamorphosis.


Inhibition by six somatostatin analogs of plasma growth hormone levels stimulated by thiamylal and morphine in the rat. Administration of sodium thiamylal (50 mg/kg,i.p.) and morphine (3 mg/animal,s.c.) leads to high plasma levels of growth hormone (GH) with a maximum measured approximately 30 min after injection. When the same dose of morphine is administered 60 and 120 min later and small additional doses of thiamylal are injected to maintain the animals deeply anesthetized, constant high levels of plasma GH are maintained up to the last interval studied (3 h). This in vivo model has been used to evaluate the potency and duration of action of somatostatin and of six of its analogs by serial blood sampling of animals bearing a cannula inserted into the right superior vena cava. A significant inhibitory effect of somatostatin (45% inhibition) is observed 15 min after a s.c. injection of 1 mug of the peptide while a near maximal effect (90-95% inhibition) is found at a dose of 25 mug. Both the degree of inhibition and duration of action of somatostatin are dose-dependent. Inhibitory activities equivalent to 1-250 mug of somatostatin can be measured with the model described. [Tyr1] somatostatin, [D-Ala1]somatostatin, [N-acetyl-Cys3] somatostatin and [N-benzoyl-Cys3] somatostatin have activities indistinguishable from somatostatin itself while [D-Lys4] somatostatin and [des-amino1, des-carboxy14] somatostatin have approximately 10% the activity of the natural hypothalamic peptide. This in vivo model offers advantageous characteristics of precision and reproducibility for the evaluation of potency of inhibitors of GH release.


Neonatal androgenization: effects of responsiveness of ovarian alkaline phosphatase to gonadotropins. Five-day-old female mice were injected subcutaneously with 100 mug of testosterone benzoate in oil, or with oil only. At various ages thereafter, they received either 5 I.U. human chorionic gonadotropin (hCG) per 10 g body weight or saline only, and were killed 24 h later. Alkaline phosphatase activity was measured in whole ovarian homogenates. Neonatal androgenization failed to affect the early phases of ovarian responsiveness, but selectively abolished both the normal rise in alkaline phosphatase which precedes the onset of puberty and the responsiveness of the enzyme to hCG stimulation at this time.


Role of the hypophysis in estrogen-mediated induction of enzymes in the regenerating liver from castrated male rats. Perfusions with corticosterone, of isolated regenerated livers from adult male rats, subjected to castration, partial hepatectomy and hypophysectomy with or without estradiol treatment during parenchymal regeneration, yielded very similar patterns of biliary steroid metabolites. The degree of steroid conjugation was lower than that seen in livers from normal, untreated, adult male rats. In operated animals, with or without estradiol benzoate treatment, ring A-reduced 20-keto metabolites constituted about 20%, whereas metabolites with a 20-hydroxy group made up approximately 80% of the corticosterone metabolites formed. Furthermore, no 15-hydroxylated metabolites derived from corticosterone, quantitatively the most important compounds in bile from female rats, could be detected in bile from these treated male animals.  However, livers from male rats which had been castrated, hepatectomized and treated with estradiol benzoate during liver regeneration, produced 15-hydroxy-tetrahydrocorticosterone to the same extent as female rat livers, when perfused with corticosterone. The results obtained indicate that the effects of estradiol on the induction and differentiation of steroid metabolizing enzymes in the regenerating liver are pronounced and manifested only in the presence of an intact hypophysis.


Action of hydrocortisone at a translational level in the rat liver. Administration of hydrocortisone to adrenalectomised rats elevated levels of both free and membrane-bound polysomes in liver and led to marked shifts in their sedimentation profiles in favour of heavier polysomes. The rate of nascent polypeptide formation was also found to be enhanced in response to the hormone but this effect was mainly confined to the site of free polysomes. These results suggest that besides its well-known potentiating action at the transcription level, the hormone elicits selective stimulatory response at the translation level.


Florid diabetic retinopathy and its response to treatment by photocoagulation or pituitary ablation. A group of 34 patients with florid diabetic retinopathy are reported. Nine of these had at least one eye untreated and of these only two maintained vision at one year-the others were blind. Ten patients had 11 florid eyes treated by photocoagulation. At one year six were blind and five had good vision. At two years only three could still see. Of 20 pituitary-ablated patients with 29 florid eyes, only three were blind at one year. Even at five years, 12 of 17 eyes could see and only two patients were blind. The one- and two-year visual acuities were significantly better in the pituitary ablated eyes than in the untreated and photocoagulated ones (p = 0.01-0.03). It is suggested that for this rare form of retinopathy pituitary ablation remains the treatment of choice if vision is to be maintained.


Interaction of somatostatin, glucagon, and insulin on hepatic glucose output in the normal dog. The interaction of insulin and glucagon during infusion of somatostatin (SRIF), which suppresses secretion of these hormones, was investigated in normal, postabsorptive, concious dogs. Hepatic glucose output (production) and over-all glucose uptake by the tissues was measured with 3-3H-glucose, administered by a priming injection along with a constant infusion. Infusion of SRIF (1.5-5.0 mug/min) for 90 minutes resulted in a moderate hypoglycemia associated with a decrease in glucose production. In some animals glucose production and plasma glucose levels returned to normal before the end of SRIF infusion. Glucose uptake tended to follow plasma glucose levels. Upon termination of SRIF infusion, glucose production and uptake and plasma glucose increased sharply.


Prevalence of diabetes in Michigan school-age children. A mail survey of Michigan school districts elicited information of 2,816 children and adolescents with diabetes, a rate of 1.6 per 1,000. Rates were higher for females than males and for whites than non-whites and increased with advancing age. A total of 15.5 per cent were reported to be not receiving insulin by injection.


Metabolism of forearm tissues in man. Studies with glucagon. The role of glucagon in regulating peripheral tissue metabolism in man was assessed in the present studies. To do this, glucagon was infused for two hours into the brachial artery to produce a high but physiologic increment in the glucagon content of arterial blood supplying ipsilateral tissues. Metabolic effects on muscle and on subcutaneous adipose tissue plus skin were sought in seven overnight-fasting subjects and seven subjects starved briefly (60 hours). In the overnight-fasted group the infusion increased bassl glucagon concentration by 1,216 pg./ml. but was without effect on forearm tissue metabolism of glucose, lactate,glycerol, or amino acids. Starvation significantly reduced basal insulin (11.0 to 7.4 muU./ml.) and increased endogenous glucagon (116 to 134 pg./ml.). Basally, there was substantial ketone utilization and a decrease in glucose consumption by both muscle and subcutaneous adipose tissue plus skin. The glucagon infusion increased basal glucagon by 784 pg./ml. Muscle balances of glucose, lactate, acetoacetate, amino acids, and glycerol were unaffected. The metabolism of glucose, lactate, acetoacetate, glycerol, and free fatty acids by subcutaneous adipose tissue plus skin was also unchanged. It is concluded that physiologic increments of glucagon lasting two hours are without effect on forearm tissues in overnight-fasted and briefly starved man.


Continuous extracorporeal monitoring of animal blood using the glucose electrode. A continuous extracorporeal monitoring system for blood glucose employing an electrochemical sensor is described. The sensor, about the size of a nickel, is rapid, is specific for glucose, generates its own power, and consists of two galvanic oxygen electrodes. Over one oxygen electrode is affixed a plastic matrix to which glucose oxidase is covalently bound; a blank matrix is over the other, which serves as a reference. Oxygen is consumed in the glucose-oxidase-containing matrix, decreasing the current from the underlying oxygen electrode. The current decrease is nonlinearly proportional to the glucose concentration. The sensor is clamped between small blocks of plastic fitted with inlet and outlet nipples so that blood pumped from the animal passes over the two electrodes and thence to an automated chemical analysis for comparison. Blood is collected and anticoagulant added in a double-lumen catheter. Blood is withdrawn at the rate of 1 cc. per hour. Results obtained by use of the system in rabbits are reported. The capacity of the system to continuously monitor changes in blood glucose produced by repeated glucose tolerances is shown in hypo-, normo-, and hyperglycemic animals. Some properties of the system and its calibration are discussed.


Saline lavage: a rapid, effective, and acceptable method for cleansing the gastrointestinal tract. The standard preparation for cleansing the gastrointestinal tract for diagnostic studies such as barium enema usually involves dietary restrictions, purgatives, and cleansing enemas. This preparation is time consuming, often uncomfortable for the patient, and frequently unsuccessful. In this study, we examined the efficacy of saline lavage (without dietary restrictions or cleansing enemas) as a gentle, alternative method for cleansing the bowel, and compared lavage to the standard castor oil method of bowel preparation. Lavage cleansing was preferred by 75% of patients who had previously experienced a castor oil preparation. Although 11% of patients could not consume an adequate (4-liter) lavage volume, there was no significant difference in preparation success rate between the remaining lavage patients and the castor oil patients. Total preparation time for lavage (3 +/- 1 hr) was 60% less than for castor oil. The anticipated dehydration produced by castor oil and the hydration produced by lavage were confirmed. No significant changes were noted, however, in serum electrolytes with either method of preparation. Additional early studies are promising for the lavage method when used in inflammatory bowel disease patients and as a cleansing preparation for colonoscopy.


Psychiatric illness and the irritable bowel syndrome. Practical implications for the primary physician. Twenty-nine consecutive outpatients with irritable bowel syndrome were given structured psychiatric interviews, as were 33 consecutive medical controls who did not have irritable bowel syndrome. All were from an internal medicine group practice. Seventy-two percent of irritable bowel syndrome subjects had psychiatric illness, with hysteria and depression the most prevalent syndromes. Only 18% of controls had psychiatric illness. The primary physician made an accurate psychiatric assessment in only 28% of the subjects. An awareness of his patient's psychiatric illness is necessary for the physician to provide effective treatment, as for depression, and to spare the patient needless medications, hospitalizations, and surgery, as with hysteria.


The radiological demonstraction of colorectal polyps undetected by endoscopy. In a consecutive series of 800 routine double contrast studies of the colon, 119 polyps were diagnosed radiologically in 78 patients. Follow-up studies were available in 46 patients with 72 polyps. Ultimately, 56 of these polyps were confirmed (55 by endoscopy and 1 by repeat radiology). Six of these polyps had been missed on the initial endoscopic examination. The missed polyps are usually located in the rectum behind a valve of Houston or in any area of the colon where there is sharp angulation. Radiologists and endoscopists should be aware of these as potential endoscopic blind spots. These cases illustrate the importance of higg quality radiological study of the colon and the complementary nature of radiology and endoscopy in the detection of colorectal polyps.


The effect of acute hyperglycemia on meal-stimulated gastric, biliary, and pancreatic secretion, and serum gastrin. The effects of hyperglycemia on pancreatic, biliary, and gastric secretory responses to meals have not been hitherto quantified in man. In the present study seven normal volunteers were fed on two occasions a 500-ml liquid test meal containing fat and protein. During one of the meals the subjects were made acutely hyperglycemic with intravenous glucose, whereas in control experiments, each subject received intravenous saline in place of glucose. A jejunal perfusion method was used to measure pancreatic outputs of trypsin and biliary outputs of bile salts for 150 min after the meal; the same method was used to quantify indirectly the amount of acid secreted by the stomach in the 150-min period. Serum gastrins were also measured basally and at intervals after the meal. Hyperglycemia suppressed serum gastrin, gastric acid production, trypsin secretion, and bile salt output in response to the test meal.


Absorption of short chain fatty acids from the human jejunum. Jejunal absorption of acetate, propionate, and butyrate--the three predominant short chain fatty acids (SCFA's) in small and large intestinal contents--was studied in 5 volunteer subjects. A triple-lumen perfusion technique was employed; the test solutions were isotonic and contained 0, 5, 10, 25, 40, or 50 mM of a SCFA as the sodium salt. Intermittent secretion of small amounts of acetate and butyrate occurred during 3 of 15 control perfusion periods, and the concentrations measured in intestinal samples exceeded those reported for circulating plasma. The three SCFA's were absorbed rapidly and at equal rates. Absorption rates rose in apparently linear fashion with the mean concentration in the study segment (up to 20 mM) but reached saturation at the higher concentrations present in the mixing segment. Water and sodium absorption increased slightly during butyrate absorption. The flow rate of fasting intestinal contents did not increase during SCFA perfusion. SCFA's are readily absorbed and do not exert a diarrheogenic effect in the normal human jejunum.


Effects of alcohol on ion transport by isolated gastric and esophageal mucosa. The effects of ethyl alcohol, 20%, were measured on steady state rates of ion transport by isolated mucosa. Luminal, but not serosal, addition of alcohol altered ion transport. Alcohol caused a sustained reduction in apparent basal acid secretion by fundic mucosa. These tissues were resistant to ordinarily effective stimulants of acid secretion (histamine, theophyline, dibutyryl cyclic AMP, and gastrin) by rabbit mucosa. Across antral mucosa, net Na transport was inhibited, and net Cl transport was reduced in the presence of alcohol. The unidirectional fluxes of both ions were increased as was permeability to erythritol. These effects of alcohol did not require the presence of acid in the lumen. The rate of luminal acid loss by antrum was increased by alcohol. Addition of ouabain alone, which inhibits net Na and Cl transport, did not alter the rate of luminal acid loss by antrum. Alcohol, however, still increased the rate of luminal acid loss by antral mucosa treated with ouabain. Alcohol reduced the electrical resistance of fundic and antral mucosa but had no effect on the rate of luminal acid loss or electrical resistance of esophageal mucosa. Luminal application of alcohol inhibits active ion transport in addition to increasing cation and anion permeability. However, inhibition of active transport per se is not necessarily associated with an increase in mucosal permeability.


Gastric pacemakers.

Gastric pacemakers. Gastric electrical control activity (ECA) controls the sequence of occurrence of contractions in the gastric wall. Normally, the direction of phase lag among control waves is aborad, and hence a ring of contraction originates in the corpus and moves distally. This study was undertaken to determine if a reversal in the direction of phase lag among control waves by an electronic pacemaker  surgically implanted near the pylorus in dogs would reverse the sequence of contractions and hence delay gastric emptying. Electrical stimulation was applied at 5.8 to 6.0 pulses per min, 50 to 80-msec pulse width, and 10 to 14-v pulse amplitude. Liquid gastric emptying was measured by introducing 400 to 600 ml of phenol red or phenol red plus barium sulfate by a nasogastric tube through an esophagostomy into the stomach and withdrawing the remainder after 5- and 15-min periods. Solid emptying was measured by means of radiological image intensifier observation of the gastric emptying of small barium-filled balls. The study shows that an electronic pacemaker implanted in the antrum reverses the normal aborad direction of movement of contractions and delays the gastric emptying of both liquid and solid meals.


The potential role of protein in the absorption of fat. Stabilization of triglyceride emulsions by proteins was studied in vitro using either chemical or optical methods to measure to amount of fat emulsified under standard conditions of emulsification. Concentrations, pH, and degree of digestion of protein emulsifiers were varied to determine how such manipulations affected emulsion stabilization. Proteins from endogenous as well as exogenous sources were capable of stabilizing triglyceride emulsions, and this effect varied with protein concentration. Peptic digests of a prototype protein retained the efficacy of the undigested protein, while further digestion of the protein in pancreatic proteases decreased, but did not abolish, the emulsifying power of the protein. Emulsion stabilization by peptic digests of protein still persisted despite alterations in pH from 1 to 7. Such emulsions were capable of being hydrolyzed by pancreatic lipase and could be absorbed from the gut of bile-deficient rats. These emulsions also speed the initial rates of fat absorption from animals with an intact bile supply. We conclude that stabilization of luminal emulsions by dietary or endogenous protein may facilitate fat absorption similar to the way that detergent-stabilized emulsions have been previously shown to have these effects.


The biliary system in primary biliary cirrhosis. A study by endoscopic retrograde cholangiopancreatography. Endoscopic retrograde cholangiograms from 23 patients with primary biliary cirrhosis (PBC), 10 controls with either normal livers or hepatocellular disease, and 4 patients with sclerosing cholangitis, were compared. Of the PBC group, 39% had gallstones. The calibers of the common bile duct and left and right intrahepatic ducts were comparable in the PBC and control groups. The small intrahepatic ducts, while normal in the control group were abnormal in 7 of the 23 PBC patients. These small ducts were irregular in caliber and had a tortuous course. The changes were not related to the presence of gallstones or the duration of the disease, but all the patients had histologically proven cirrhosis. Two patients with cirrhosis had normal intrahepatic ducts. We conclude that whereas the major bile ducts are normal in PBC, there is a high incidence of gallstones (39%), and the changes that do occur in the intrahepatic ducts are probably related to the distorted hepatic architecture due to cirrhosis and may be used as a sign that cirrhosis has supervened.


Reduction of gastric ammonia by ampicillin in normal and azotemic subjects. Ampicillin was tested with regards to its capacity to reduce gastric ammonia production in basal and betazole-stimulated gastric secretion. A 7-day course of oral ampicillin (4 g per day) reduced basal gastric ammonia concentration from 5.5 +/- 1.4 to 1.8 +/- 0.3 mM and postbetazole ammonia from 4.7 +/- 0.9 to 1.3 +/- 0.3 mM (P less than 0.01) in 7 control subjects. Similar results were obtained after oral neomycin (4 g per day) or intramuscular ampicillin (4 g per day), each given to a separate group of 7 control subjects. In 5 azotemic patients, oral ampicillin treatment resulted in a reduction of ammonia concentration from 16.3 +/- 4.7 to 3.1 +/- 0.7 mM in basal secretion and from 18.3 +/- 8.1 to 2.3 +/- 0.6 mM in betazole-stimulated gastric juice (P less than 0.01). Antibiotic therapy did not alter volume of gastric secretion. Gastric acidity appeared lower in azotemic patients and increased significantly after treatment, indicating that the higher ammonia content could account for at least part of the hypoacidity. Because ampicillin is active orally as well as parenterally and can be readily used in renal failure, it may be of value for the treatment of hepatic encephalopathy, especially in the azotemic patient in whom neomycin is toxic.


Selective hepatic uptake and biliary excretion of 35S-sulfobromophthalein in marine elasmobranchs. The hepatic metabolism of 35S-sulfobromophthalein was studied in the free-swimming Elasmobranchs, Squalus acanthias (spiny dogfish shark) and Raja erinacea (small skate), to evaluate the physiological significance of biliary excretion of organic anions in marine vertebrates. Twenty-four hours after intra-arterial injection, 85.8 +/- 15.7% of the administered dose was recovered in bile and liver in dogfish and 78.4 +/- 9.9% in skates. More than 85% of BSP in bile was in unconjugated form in both species. Furthermore, selective hepatic uptake and biliary excretion of 35S-sulfobromophthalein occurred despite very little specific binding protein (Ligandin). These studies demonstrate that transport systems for biliary excretion of organic anions evolved before migration of marine life from the sea and independent of conjugation and organic anion binding proteins which facilitate biliary excretion of compounds such as 35S-sulfobromophthalein in higher vertebrates.


Ménétrier's Disease. Serial morphological, secretory, and serological observations. Serial morphological, secretory, and serological observations of a patient with Ménétrier's disease disclosed hypergastrinemia, antibodies to parietal cells and dietary substances, and an acute reduction of gastrointestinal protein loss after atropine administration. Transformation of the gastric mucosa from hypertrophy to atrophic gastritis was associated with disappearance of the protein-losing gastroenteropathy and serum antibodies and reduction of the serum gastrin concentration.


Acute dilation of the colon in malignant lymphoma. Acute dilatation of the colon with signs of systemic toxicity developed in an elderly man with malignant lymphoma. Although barium contrast X-rays taken previously were interpreted as consistent with granulomatous colitis, rectal biopsy had revealed features characteristic of malignant lymphoma, poorly differentiated lymphocytic type. Bone marrow and lymph nodes were also involved. The onset of dilatation was temporally related to therapy with opiates and anticholinergics, and the acute episode was resolved with nasogastric suction, intravenous fluids, albumin, and antibiotics.


Pneumatic ileal perforation: an unusual complication of colonoscopy. Pneumatic perforation of the bowel is a rare complication of colonoscopy. Pneumatic ileal perforation complicating this procedure has not been reported. We describe a case of pneumatic ileal perforation during colonoscopy in an elderly lady who also had adhesions from previous abdominal surgery. A relative lack of symptomatology, the finding of a clean ileal perforation at surgery, and a benign postoperative period characterized her course. Possible etiological factors are discussed with reference to the literature dealing with intraluminal pressures in the bowel. Pressure much higher than the physiological pressure is likely to be reached during colonoscopy, with reflux of air across the ileocecal sphincter acting as a safety mechanism. Bursting pressures differ for different layers of the bowel and from segment to segment. This report calls attention to certain risk factors which might lead to a remote perforation during colonoscopy.


Gastroesophageal (GE) scintiscanning to detect and quantitate GE reflux. To evaluate the gastroesophageal (GE) scintiscan, a technique which detects and quantitates GE reflux, 30 patients with heartburn and a positive acid-reflux test and 20 normal control subjects were studied. Conventional diagnostic tests including barium esophagography, fluoroscopy, esophagogastroscopy, esophageal biopsy, acid perfusion testing, and esophageal manometry were performed on each patient with GE reflux. None of these techniques was sufficiently sensitive in detecting GE reflux. In contrast, GE reflux was visualized by scintiscanning in 27 out of 30 (90%) of patients. The GE reflux index was significantly greater in reflux patients, 11.7 +/- 1.8%, compared to controls 2.7 +/- 0.3%. These studies suggest that GE scintiscanning can detect GE reflux accurately, rapidly, noninvasively, and with greater sensitivity than other diagnostic techniques. In addition, it can be employed to quantitate GE reflux.


Serum group I pepsinogen levels and their relation to gastric acid secretion in patients with and without recurrent ulcer. Serum group I pepsinogen (PG I) levels have been determined by radioimmunoassay in 15 patients without, recurrent ulcer after vagotomy and either a gastric resection or a drainage procedure. The mean (+/-SE) levels were 151.8 +/- 16.9 ng per ml in the patients with recurrent ulcer and 79.7 +/- 9.8 ng per ml in those without recurrence (P less than 0.001). A recurrent ulcer was present in 6 of 7 patients with an elevated serum PGI (greater than 175 ng per ml) but not in any of 10 patients with a low serum PGI (less than 50 ng per ml). The correlation between serum PG I and peak acid output (PAO) was statistically significant in patients with recurrent ulcer (pi=0.815, P less than 0.001) and in those without recurrence (r= 0.540, P less than 0.025). In patients with recurrent ulcer, a serum PG I level within the normal range (50 to 175 ng per ml) was uniformly associated with a PAO of more than 10 mEq per hr. In contrast, of 10 patients without recurrent ulcer and a normal serum PG I, eight had a PAO of less than 10 mEq per hr. The reason for the discordant results in the two groups of patients is not certain.


Complications of endoscopic retrograde cholangiopancreatography (ERCP). A study of 10,000 cases. Of 402 United States owners of side-viewing duodenoscopes surveyed, 222 (55%) responded, reporting 10,435 endoscopic retrograde cholangiopancreatograms. Procedure failed occurred in 30%, complications in 3%, and death in 0.2%. Complications included pancreatitis, cholangitis, pancreatic sepsis, instrumental injury to the gastrointestinal tract, and drug reactions. Pancreatitis was associated with injection into the pancreatic duct, sepsis with injection into an obstructed duct or pseudocyst, and injury with abnormal gastroduodenal anatomy. Experienced workers had a 15% incidence of complications, whereas inexperience gave 4 times the failures (62%) and twice the complications (7%). The causes of complications and their prevention are discussed.