Activation of carcinogens and mutagens by rat colon mucosa. Colon mucosal cells can catalyze the activation of precarcinogens to mutagenic metabolites without the intermediacy of intestinal bacteria as shown in a mutagenesis assay system composed of Salmonella typhimurium strain TA100 and the 9000 X g supernatant fraction of rat colon mucosal cells. Pretreatment of rats with beta-naphtoflavone increased the activation of 2-aminoanthracene 10- to 20-fold and the activation of benzo(a)pyrene 4-fold. Pretreatment of rats with Aroclor 1254 doubled the activation of 2-aminoanthracene over control but had no effect on the activation of benzo(a)pyrene. The activation of 2-aminoanthracene and benzo(a)pyrene by liver was induced significantly by pretreatment with beta-naphthoflavone and Aroclor 1254. Phenobarbital/hydrocortisone pretreatment did not increase the activation by the colon system of any precarcinogen tested but did increase the activation of 2-aminoanthracene, cyclophosphamide, and isophosphamide by the liver system. The activation of precarcinogens in the bacterial test system is directly correlated with the activities of the pretreated colon and liver preparations toward several drug and polycyclic hydrocarbon substrates assayed in vitro.


An automatic device for freeze-clamping of cardiac tissue within a fraction of the contraction cycle. An automatic quick-freeze clamping device has been developed. Opposed pneumatic pistons filled with aluminium caps previously cooled in liquid nitrogen are used to compress a portion (100 to 200 mg) of the myocardium to a 0.15 to 0.20 mm thick wafer, colling the tissue from 37 degrees C to -15 degrees C within 10 ms. The clamp is triggered electronically from the R-wave of the ECG. This tissue fixation by freezing within 10 ms is sufficiently rapid to study oscillations of myocardial metabolite levels during the contraction cycle of isolated perfused hearts of small mammals such as the rat and guinea pig whose rate is 4 to 5 beats per second.


Gonadotropic cells in the Atlantic salmon, Salmo salar. An experimental immunocytological, electron miscroscopical study. The gonadotropin-producing cells (GTH-cells) in the Atlantic salmon were studied light and electron microscopically before, during and after spawning, and after injections of luteinizing hormone-releasing hormone (LH-RH). The double immunofluorescent technique was applied using rabbit anti-carp GTH as the first antibody. Numerous immunofluorescent cells were observed throughout the pars distalis, but very few in the pars intermedia. These cells are basophilic and PAS-positive, and ultrastructurally classified as globular gonadotropes. Only one gonadotropic cell type could be identified; its size, morphology and fine structure vary considerably. In the same specimen the GTH-cells can be predominantly globular or vesicular in appearance, depending on the reproductive phase of the fish. At spawning and after LH-RH injection, many GTH-cells reach a vacuolar stage; the content of the vacuoles is not immunofluorescent. Another cell type, which resembles GTH-cells in semi-thin sections, did not show gonadotropic properties; its nature and functional significance are unknown. In addition, the present study revealed an increase in the synthetic and exocytotic activity of prolactin cells after LH-RH injections. It is suggested that LH-RH mediates this effect via LH and eventually via estradiol.


Ultrastructural localization of gonadotrophic hormones in the porcine pituitary using the immunoperoxidase technique. Using specific antibodies against beta subunits of porcine LH and FSH, the pituitary cells which produce these two gonadotrophins were identified in the porcine pituitary at the ultrastructural level using the immunoperoxidase technique. It was clearly shown that most of the gonadotrophic cells are responsible for the production of both FSH and LH. However, some cells, only positive for FSH or LH, indicate that the concentrations of FSH and LH vary from cell to cell. At the ultrastructural level, the FSH/LH cells contain one class of secretory granules strongly positive for bvth FSH and LH as well as large negatively stained dense bodies. These findings indicate that the "one cell-one hormone" concept may not apply to gonadotrophic hormones; a FSH/LH cell cannot be distinguished from a LH or FSH cell without immunocytochemical identification of its hormonal content.


Immunocytological localization of LH, FSH, TSH and their subunits in the pituitary of normal and anencephalic human fetuses. Immunostaining with antisera to oLH, hCG, hLH, pLHbeta, hFSH, hFSHbeta, hTSHalpha and bTSH was used to delineate the gonadotropic and thyrotropic cells of the human fetal anterior pituitary. Hypophyses from 29 normal fetuses, 3 newborn infants, and 5 totally ancencephalic fetuses were used. Several controls to check for the specificty of the immunocytological reaction were made. In normal fetuses, observations showed that: 1) the alpha subunit was detected from the eighth week and throughout gestation without sex differences; 2) intact LH was detected during the third month, however, age and sex differences were observed during the fourth and fifth months; 3) intact FSH was detected in female fetuses from the beginning of the fourth month, a sex difference was observed; 4) LH and FSH were detected in the same cells; 5) the thyrotropic cells were detectable from 15 weeks of gestation and their number increased during gestation without sex difference; 6) at birth the gonadotropic cells were scarce and were located in the ventromedian zone of the anterior pituitary, while the thyrotopic cells remained numerous and were located in the dorsomedian zone. In amencephalic fetuses: 1) the alpha subunit existed at each stage studies; 2) the reaction induced by anti-pLHbeta and anti-hFSHbeta sera was alwys very weak regardless of sex or age; 3) the thyrotropic cells were more numerous in comparison to the gonadotropic cells. These data are discussed in terms of the relationship of the hypophysiotropic hypothalamic factors to the appearance and evolution of the glycoprotein hormones and their subunits.


Nonconventional innervation of the pancreatic islets of the teleost fish, Gillichthys mirabilis. The innervation of the pancreatic islets of a teleost fish, Gillichthys mirabilis, was investigated with various techniques including axonal iontophoresis of cobalt, light microscopy, and electron microscopy. Two types of postganglionic neurons, the splanchnic and the vagus, innervate the islet parenchyma. The splanchnic fibers originate from the single coeliac ganglion, situated near the third spinal nerve on the right side, and pass caudally to the islet. Postganglionic vagal fibers reaching the islets arise from ganglion cells located at irregular intervals along the vagus nerve. Iontophoresis of cobaltous chloride revealed that both types of nerves send large numbers of fibers to the islet cells. Electron microscopy showed that the granules of the vagal fibers are polymorphic, large (130 mm diameter) and markedly electron dense, whereas the splanchnic granules are smaller (100 nm diameter) and less electron dense than those of the vagus. These granules do not correspond to those seen in postganglionic autonomic neurons of other vertebrates. Rather, they are more like classical neurosecretory granules. Although their chemical nature is unknown, the extent of islet innervation suggests that it must play an important regulatory role.


Fine structural studies of the islets of langerhans in the Djungarian hamster (Phodopus sungorus). A study of the pancreatic islets of Langerhans in the Djungarian hamster (Phodopus sungorus) was initiated by the observation that 98 percent of the animals of a recently established colony showed ketoacidosis soon after birth, about ten percent of which later developed persistent hyperglycemia. The islets are made up of a centrally located mass of insulin-producing B-cells surrounded by a peripheral rim of A- and D-cells. Most islets are richly supplied by unmyelinated nerve fibers which terminate on all three cell types with cholinergic synaptic endings. Early changes in islet fine structure due to ketosis comprise degranulation of A-cells combined with signs of crinophagia of alpha-granules. After the manifestation of hyperglycemia, degranulation of B-cells is followed by deposition of glycogen which in the late phase of the diabetic syndrome forms large masses obscuring the regular cellular organelles. In six- to nine-month hyperglycemic animals degenerative changes are also observed in D-cells in the form of autophagic vacuoles.


[Current therapeutic indications and possibilities in prolonged respiratory insufficiency (collective review) ]. The article provides a synthetic review of the most current problems of treatment of acute respiratory insufficiency refractory to standard and conventional therapeutic remedies using extracorporal membrane gas exchangers. On the basis of a review of the literature on the subject, the advantages and disadvantages of each main type of oxygenator are considered and critically evaluated with regard to metabolic, haemodynamic and circulatroy activity and the repercussions of each resuscitation technique on haemocoagulation.


Improved approach to sequential addition immunoassay. In the usual sequential addition enzyme immunoassays for drugs, the activity of the drug-labeled enzyme decreases continuously with time as more of it is bound to antibody. Sensitivity also decreases; the activity immediately after mixing is the most sensitive indicator of drug concentration. The reaction of enzyme-drug with antibody can be stopped by saturating the antibody with a larger quantity of unlabeled drug, which reacts with the antibody faster than does the enzyme-labeled drug. When drug is added soon after the reaction starts, the enzyme activity is stabilized and the sensitivity to small quantities of antigen is increased. This approach, with modification, should be applicable to sequential immunoassays in which other kinds of labels are used. The enzyme activity can be measured for a longer time, with the predictable increase in precision, as well as the ability to detect smaller quantities, to use less reagent, and to use end-point rather than kinetic assays.


Coupled reactions of immobilized enzymes and immobilized substrates: clinical application as exemplified by amylase assay. We described a partitioned enzyme-sensor system, which incorporates an immoblized substrate and three or more discrete immobilized enzymes. This instrument measures alpha-amylase activity by passing the solution containing alpha-amylase over a column packed with immobilized starch. The resulting oligosaccharides are successively exposed to a column or columns containing immobolized glucose oxidase, catalase, glucoamylase or maltase, and glucose oxidase. The resulting hydrogen peroxide is detected by a three-electrode amperometric cell. All immobilized reagents were immobilized on a particulate, porous alumina to allow rapid and constant flow rate. With use of less than optimum immobilized reagents, alpha-amylase activity has been measured from about 5 to 200 kU/liter with a 50 microliter sample size. Lack of sensitivity is predominantly attributable to the low activity and low stability of immobilized maltase and glucoamylase. We believe that a clinical test using this system is feasible and desirable because the immobilized reagent system should allow for testing of alpha-amylase with excellent precision, convenience to the operator, and low cost.


The combined use of L-alpha-methyldopa hydrazine and methyldopa in the treatment of hypertension. 1. The combined use of alpha-methyldopa and L-alpha-methyldopa hydrazine (a peripheral decarboxylase inhibitor) has been studied, in a double-blind cross-over comparison, with alpha-methyldopa and L-alpha-methyldopa hydrazine placebo in the treatment of eight patients with essential hypertension. 2. L-alpha-methyldopa hydrazine did not enhance the antihypertensive effect of alpha-methyldopa. This suggests that because methyldopa can inhibit its own decarboxylation, peripheral decarboxylation is not an important metabolic pathway for methyldopa and elevated brain levels of methyldopa do not necessarily result in elevated brain levels of methyldopamine.


Antihypertensive activity of alpha-methyldopa on a twice daily regimen in comparison to metoprolol. A multi-centre controlled clinical trial. 1. The antihypertensive effects of alpha-methyldopa and metoprolol have been compared in 110 patients (fifty-one males and fifty-nine females) with previously untreated essential hypertension (sixty-eight WHO stage 1 and forty-two WHO stage 2). 2. After 2 weeks of placebo, the patients were randomly allocated to treatment with either of the two drugs: alpha-methyldopa up to 500 mg b.i.d. and metroprolol up to 200 mg b.i.d. for 6 weeks. Periodical clinical, biochemical, haematological, radiological and electrocardiographical measurements were performed. 3. The average reduction in blood pressure produced by the two drugs was comparable. 4. In general, side-effects were few and tolerable: mainly bradycardia in the metoprolol group and dizziness and drowsiness in the alpha-methyldopa group. 5. The plasma renin activity was significantly reduced in the metoprolol but not in the alpha-methyldopa group.


Sodium and fluid balance during hypotensive response to alpha-methyldopa. 1. Detailed observations on sodium and fluid balance during treatment with alpha-methyldopa were made in five hypertensive patients. The initial fall in blood pressure concurred with a decline in fluid and sodium excretion. Sodium balance increased 100-300 mEq. In one patient with serve hypertension the sodium balance was incompletely restored, the relationship with blood pressure indicating a negative feedback loop. In the other patients sodium balance reverted to baseline, while the hypotensive response was maintained. This is probably due to a decrease in renal arteriolar tone. 2. Parallel systemic and renal vasodilatation may account for the discrepancy between a significant increase in blood volume and insignificant long-term changes in the fluid and sodium status.


Clinical experiences with methyldopa.

Clinical experiences with methyldopa. 1. The hypotensive effect of methyldopa alone or associated with other hypotensive drugs was evaluated in 155 patients. After 10 days of treatment, the blood pressure was back to normal in 80% and in 50% of the patients with mild and moderate hypertension, and it was significantly decreased in those with severe hypertension. 2. Contrary to other hypotensive drugs, it did not produce a significant increase in BUN and serum creatinine. Occasional or recurrent episodes of orthostatic hypotension were observed in about 18% of the cases, but in none did it produce important symptoms of cerebral or myocardial ischaemia.


Amiloride in the treatment of primary hyperaldosteronism and essential hypertension. 1. Amiloride (40 mg/day) was given to nineteen patients with primary hyperaldosteronism. There were significant falls in systolic and diastolic blood pressure, in total exchangeable sodium and in serum sodium and bicarbonate, while total exchangeable potassium, total body potassium, serum potassium, chloride and urea, plasma renin, angiotensin II and aldosterone all increased significantly. Amiloride was effective in reducing the blood pressure in patients with and without adrenocortical adenoma. No carry-over effect was seen on withdrawing amiloride. Similar changes were associated with amiloride treatment in five patients with essential hypertension; hyperkalaemia was not observed. 2. Only negligible side effects were encountered in the entire series of 24 patients.


Treatment of acute leukaemia in children. As can be seen, there are many problems yet to be solved in the development of optimal therapy for acute leukaemia in children. For patients with ALL we must be able to identify clearly the standard and the varieties of high risk patients. For the patient with standard risk features life expectancy is long and therapy regimens must be designed to provide optimal control of the disease with minimal short and long-term toxicity. For patients with the high risk features of those varieties of ALL associated with poor prognosis methods must be found to circumvent the problem of early acquisition of drug resistance by the leukaemic lymphoblasts. For children with AML the results of remission induction regimens must still be improved to match those obtained in ALL. The major problem awaiting solution, however, is the maintenance of remission once obtained. As disease-free survival in AML is improved then consideration of CNS prophylaxis and the timing of cessation of therapy must be considered.


Treatment of acute leukaemia in adults.

Treatment of acute leukaemia in adults. Although progress in the treatment of adult acute leukaemia has been much less dramatic than that which has occurred in the management of children with ALL, it should be clear from this progress report that significant strides have recently been made in the treatment of both adult ANLL and ALL that are of real benefit to the individual patient. This improvement is equally the result of improved supportive care and antileukaemia treatment. The progress has been of sufficient magnitude to clearly justify the optimism expressed in several recent reviews of leukaemia treatment (Freireich et al, 1976; Holland et al, 1976; Wiernik, 1976).


The effect of methylmethacrylate on the bacterial inhibiting properties of normal human serum. In vitro evaluation of the effect of known concentrations of methylmethacrylate on the bacterial inhibiting properties of normal human serum has been carried out. In low concentrations, methylmethacrylate was found to abolish almost completely the growth inhibition of Staphylococcus epidermidis by normal human serum. Normal human serum did not have an effect on growth of Staphylococcus aureus. It did inhibit growth of Escherichia coli, but there was no reversal of this effect by methylmethacrylate.


Hemodynamic effects of dopamine in patients with resistant congestive heart failure. Twelve patients with clinical and hemodynamic evidence of severe congestive heart failure, unresponsive to the usual therapy of salt restriction, oxygen, bed rest, digitalis, and massive doses of diuretics, were studied during a control period and after intravenous dopamine. Seven patients survived and 5 died with intractable failure and shock despite transiently improved hemodynamic indices. At control period and after optimal dose of dopamine, there were no significant changes in heart rate (HR) and mean systemic arterial pressure. The mean pulmonary artery (PA) and pulmonary capillary wedge (PCW) pressures decreased slightly. Cardiac index (CI), stroke volume (SVI), and stroke work indices (SWI) rose (p less than 0.005) from the control values of 1.4 +/- 0.1, 15.3 +/- 5, and 13.6 +/- 1.7 to 2.2 +/- 0.1, 24.1 +/- 4, and 24 +/- 2.3, respectively; pulmonary arteriolar (PAR), total pulmonary vascular (TPVR), and systemic vascular (SVR) resistances fell (p less than 0.01). Urine output increased from 13.5 ml/hr before to 58.2 ml/hr after dopamine (p less than 0.005). After 24 and 48 hr of dopamine, in addition to the above hemodynamic changes, PA pressure fell from 38 +/- 4 to 33 +/- 3 and 28 +/- 2, and PCW from 30 +/- 2 to 24 +/- 3 and 18 +/- 3 (p less than 0.05). Compared with nonsurvivors, survivors had significant decreases in PA and PCW pressures, PAR, and TPVR and an increase in SWI. These data indicate that dopamine is effective in some patients with refractive congestive heart failure associated with acute oliguric renal failure and that the prognosis may be improved.


Dose response to chlorthalidone in patients with mild hypertension. Efficacy of a lower dose. A multicenter study of chlorthalidone was performed to determine the relative antihypertensive efficacy and side effects of doses lower than those usually recommended for therapy. After a 4-wk placebo control period 100 patients with mild hypertension were randomly assigned doubleblind to 12.5-, 25-, 50-, or 75-mg regimens of chlorthalidone or to placebo for 12 wk. The groups of patients taking 25, 50, and 75 mg had declines in blood pressure which were not significantly different from each other. Serum potassium decreased in the 50- and 75-mg groups but not significantly in the 25-mg group. We conclude that chlorthalidone, 25 mg daily, was at least as effective for hypertension as 50 and 75 mg with less perturbation of potassium. Use of smaller initial diuretic doses may provide equal efficacy with fewer side effects for many patients.


Effect of benzopyranoperidine, a delta-9-THC congener, on pain. In a double-blind, 5-way crossover designed study, single doses of placebo, 2 doses of codeine sulfate (60 and 120 mg), and 2 doses of benzopyranoperidine (2 and 4 mg) were administered orally to 35 patients who required analgesics for chronic pain due to malignancies. Benzopyranopyridine is an analogue of delta-9-tetrahydrocannabinol and was chosen on the basis of its sedative, hypnotic, and analgesic properties in animals. Pain relief scores indicated a degree of relief of clinical significance with 120 mg of codeine but no consistent difference between placebo and any other active agent. On the basis of the data, bezopyranoperidine (2 or 4 mg) is not as effective as codeine (120 mg or 60 mg) and not more effective than placebo in relieving pain due to cancer; indeed, pain perception appeared to be augmented by both doses.


Neurovascular free foot flaps in reconstruction of the mutilated hand. The neurovascular free flap from the first web region of the foot affords unrivalled potential for refurbishing sensibility to the denervated hand. Its greatest application is when no conventional island flap tissue remains for transfer. Its two-point discrimination is only moderate, but when used for thumb reconstruction, its sensibility is adequate because no functional substitute exists. Functionally and cosmetically it is superior to other methods of thumb reconstruction because of its pulp, size, and nail availability. There are no finger identification problems and secondary donor defects are minimal.


Clinical application of free omental flap transfer. In the field of reconstructive surgery, the greater omentum has been used as a transposed flap for the treatment of chronic lymphedema, radionecrosis, and so forth. Its transferable range was limited by the length of its pedicle. Microvascular anastomosis allows for free transplantation of this organ and has vastly expanded its usefulness.


Microvascular bone transplatation.

Microvascular bone transplatation. A technique has been presented for the transplantation of bone with its own vascular system. Microvascular techniques have been developed to the point that this procedure is feasible in both the laboratory animal and in humans. Using this technique or the fibula transplantation technique of Taylor and colleagues, it should be possible to reconstruct many bone dificits that are refractory to free bone grafting.


Diffuse pulmonary abnormalities: clinical correlations. The clinical correlations of diffuse pulmonary opacities, visible on the chest X-ray, are reviewed and the main diagnostic investigations outlined. Clinically the patients are classified into those with fever; those with no symptoms; those with cough, malaise and loss of weight, but no fever; and those with dyspnoea as the main symptom. The possible diseases giving rise to each group of manifestations are reviewed and the differential diagnosis discussed.


Myocardiopathies. A review.

Myocardiopathies. A review. The author offers a critical review of the present knowledge about myocardiopathies and points out discordant opinions of various authors. He presents his own classification of this inhomogeneous group of myocardial diseases, based on the etiological principle. Special attention is given to the present status of diagnostic methods, the author pointing out the nonspecificity of individual signs and symptoms of the disease. It is emphasized that in two thirds of patients even a general practitioner is capable of diagnosing myocardiopathy on the basis of routine cardiological examinations (patient's history, physical examination, ECG and X-ray). This is of great practical importance because the prognosis--although essentially unfavourable--depends to a great extent on an early diagnosis. Finally, principles of therapy at myocardiopathies are presented.


Automated measurements on human C-bands in family studies. An automated system providing quantitative measurements of C-band size has been used, in conjunction with statistical methodology developed for the purpose, in a family study to demonstrate its potential in determining the mode of transmission of C-bands from parent to offspring, and to test the assumption of Mendelian inheritance. The most serious obstacle encountered was the high within-person variance of the normalized band sizes, the large within-slide variance being increased by technical variation between different preparations. Attempts to reduce variance by developing more effective normalization techniques did not prove fruitful. Nevertheless, the ability of the present system to perform a trace using a reasonable number of cells has been demonstrated in an example. In the two families studied we saw no evidence that band size was not transmitted and changes in band size, if any, were less than about 5 micrometer2 X 10(-2) (compared to a typical medium-category band size of about 65 mcirometer2 X 10(-2)).


Lidocaine-induced cardiac asystole.

Lidocaine-induced cardiac asystole. Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine.


Neonatal assessment procedures: a historical review. A historical review of neonatal assessment procedures is presented to demonstrate the trends in advancement of the field and attempts toward collaboration of medicine and psychology in contributions to the area. The literature suggests that the medically oriented neurological examinations have continued  to be altered and improved. The growth of behaviorism within psychology and the view that behavior is closely related to underlying neurological mechanisms have contributed to the development of behaviorally oriented assessment procedures. These trends have combined successfully in the development of the Brazelton Neonatal Assessment Scale, which focuses on assessment of behavioral capabilities reflecting the quality of parent-infant relationships. The most recent contributions are directed toward development of specialized assessment techniques to fulfill specific research needs. Suggestions and cautions for use of available procedures are presented.


The effects of reinforcement and strategy training on impulsive responding. Impulsive second-grade children received strategy training or strategy training combined with primary or secondary reinforcement. All training groups showed significantly longer response latencies and significantly fewer errors on the Matching Familiar Figures test immediately following training. The reinforcement groups had significantly longer latencies than the training-only group, and there was some indication that primary reinforcement was more effective than secondary reinforcement in producing response delay. The 3 training groups did not differ significantly on error scores.


[The Schrudde method of plastic surgery. Results after 15 years use of the method]. After 15 years of experience with Schrudde's slide-swing operation, the results of this method are evaluated. Indication has been examined in 911 cases, both as to localisation and etiology. Since the resulting scars are smaller than the circumference of the defect, this approach possesses considerable advantages over other methods. Its safety enables it to be applied where defects are very extensive. A first attempt is here made to analyse the method geometrically.


[Cardiotoxicity of mianserin, an antidepressant (author's transl)]. The effect of mianserin on cardiac function was investigated on 60 adults with known heart disease, the drug previously having been shown not to influence the action of phenprocoumon. After satisfactory anticoagulation had been established, all patients were given additionally two different dosage regimens of mianserin or a placebo in a double-blind trial lasting three weeks. The dose was gradually increased to a maximal daily level of 30 mg or 60 mg, respectively, on the sixth day. Heart rate, blood pressure and electrocardiogram were obtained before and after mianserin had been added. There was no statistically significant difference between the three trial groups with respect to the three measured variables.


Effects of central cortical EEG feedback training on incidence of poorly controlled seizures. This study examined the clinical effects of central cortical EEG feedback training in 8 patients with poorly controlled seizures. After base-line recordings, patients were trained in the laboratory and then initiated on a double or triple crossover design using portable equipment at home, with bimonthly laboratory test sessions. Performance at home was monitored by a strip chart recorder with the portable unit. Training was based on the simultaneous detection of two central cortical (C3--T3) EEG frequency bands (6--9 Hz and either 12--15 or 18--23 Hz), with reward provided for the occurrence of one in the absence of the other. The design consisted of successive 3 month periods of training, with reward contingencies reversed after each period without the subject's knowledge. Seizure incidence records were compared statistically before, during, and after the design. Six of the 8 patients reported significant and sustained seizure reductions, which averaged 74%, following reward for either 12--15 or 18--23 Hz in the absence of 6--9 Hz. Response to positive reward for 12--15 Hz was specific, with seizure rates returning to base line when reinforcement contingencies were reversed. Reduced seizure rates following positive reward for 18--23 Hz were not altered with contingency reversals. A nonspecific interpretation of these effects is rejected in favor of an EEG normalizing hypothesis.


Non-monoamine oxidase inhibitor antidepressants and epilepsy: a review. The literature dealing with the convulsant effects of the antidepressant drugs of the non-monoamine oxidase inhibitor variety is reviews. It is concluded that most of these drugs do lower the seizure threshold and may precipitate seizures even at normal therapeutic doses. The pathophysiology of antidepressant-induced seizures is discussed, and attention is drawn to biochemical differences in those antideprssants that have the least epileptogenic potential or may even be anticonvulsant. The clinical difficulties regarding administration of antidepressant drugs to epileptic patients are mentioned, and some practical advice is offered.


Determination of phenytoin in plasma: a comparison of procedures using a new radioimmunoassay, gas chromatography, and enzyme immunoassay. A new commercially available radioimmunoassay (RIA) procedure for the anticonvulsant drug phenytoin has been assessed and compared with a gas-liquid chromatographic (GLC) and an enzyme immunoassay (EMIT) procedure. One hundred and thirty-four plasma samples containing phenytoin were analyzed by the three methods and the results were found to be essentially independent of the procedure used and so would indicate similar clinical interpretation. The correlation coefficients were: RIA/GLC = 0.988; EMIT/RIA = 0.978; EMIT/GLC = 0.981. The cross reactivity of 33 drugs and related compounds was tested in the RIA and EMIT procedures and only a few very closely related substances showed significant cross reactivity. In addition, the three methods were compared with respect to the technical difficulties involved as well as time and cost for the assay of single and multiple samples.


Carbamazepine and the electroencephalogram of epileptics: a double blind study in comparison to phenytoin. In double blind crossover 4 month trials, carbamazepine was compared to phenytoin as sole treatment for 45 patients with uncontrolled partial and generalized epilepsy. EEGs performed at the end of these trials revealed that while using carbamazepine the patients manifested a significant overall increase in diffuse slow waves and an increase in generalized epileptiform discharges without significant accompanying changes in seizure incidence. Also, during the carbamazepine trial generalized epileptiform discharges activated by hyperventilation were more frequent in patients with a higher seizure incidence compared to subjects with a lower seizure incidence of patients taking phenytoin. No significant focal EEG changes occurred.


The synthesis of a photoreactive puromycin analogue and its application for labeling proteins in the 50-S subunit of Escherichia coli ribosomes. A photoreactive puromycin analogue, 6-dimethylamino-9-[3-(p-azido-L-beta-phenylalanylamino)-3-deoxy-beta-ribofuranosyl] purine, was synthesized. Biological activity was demonstrated by inhibition of the poly (U)-directed phenylalanine-incorporation system and by decomposition of isolated polysomes from Escherichia coli. The 3H-labeled puromycin analogue was covalently attached to the 50-S subunit of isolated 70-S ribosomes from Escherichia coli after irradiation. More than 90% of the radioactivity was bound to the protein fraction. The 70-S proteins were separated by two-dimensional gel electrophoresis. The proteins labeled primarily were those of the 50-S subunit, identified as L6, L13, L18, L22 and L25. On the basis of the affinity label used and supportive data from the literature, it is concluded that these proteins are at the active center of the 50-S particle and probably belong to the region of the ribosomal A site.


Homologous RNA polymerase binding to Escherichia coli DNA: a study of the distribution of stable binding sites. The number and the distribution of the sites of Escherichia coli DNA that form stable complexes with the homologous RNA polymerase (class A sites according to Hinkle and Chamberlin [3]) have been investigated. Almost all the DNA can bind RNA polymerase, even when fragmented at short (undergenic) size; this general non-promoter-specific binding is highly labile and is not temperature-dependent. The range of RNA polymerase/DNA ratios that give rise to the stable temperature-dependent complexes was examined. The amount and the distribution of class A complexes were studied analysing the dissociation of complexes formed by RNA polymerase on DNA fragments of various length. The E. coli genome appears to form 3.8 X 10(3) stable complexes; the majority of these complexes shows a short-range distribution (800-1200 base pairs). The rest is more widely spaced (1200-6000 base pairs).


Evidence for catabolite degradation in the glucose-dependent inactivation of yeast cytoplasmic malate dehydrogenase. The cytoplasmic malate dehydrogenase of Saccharomyces cerevisiae was radioactively labeled during its synthesis on a glucose-free derepression medium. After purification a sensitive radio-immunoassay for this enzyme could be developed. The assay showed that after the physiological, glucose-dependent 'catabolite inactivation' of cytoplasmic malate dehydrogenase an inactive enzyme protein is immunologically not detectable. Together with the irreversibility of this reaction in vivo this finding strongly suggest a proteolytic mechanism of enzyme inactivation. For this process the term 'catabolite degradation' is used.


Synthesis of lens crystallins in Xenopus oocytes as determined by quantitative immunoprecipitation. Total poly(A)-containing calf lens mRNA was microinjected into Xenopus oocytes and synthesis of alpha, beta, and gamma-crystallins was demonstrated. By a method of quantitative immunoprecipitation the rate of translation of purified 14S alphaA2-crystallin mRNA was compared with translation of 9-S rabbit globin mRNA. Maximal response of oocytes was obtained with virtually the same molar amounts of mRNA, taking into account the larger size of the alphaA2-crystallin mRNA. Kinetics of translation were also very similar and both mRNAs were translated with similar rate and efficiency for at least two days. It was estimated that 20-30 polypeptide chains per hour per mRNA molecule were synthesized.


Interaction of DNA with DNA-binding proteins: protein exchange and complex stability. The competition of the DNA-binding proteins I and II of Escherichia coli and of the phage fd DNA-binding protein for single-stranded DNA was investigated. Their roles in cells might be judged from their binding affinities to DNA and their mutual exchange in the DNA . protein complexes. Strongest binding on single strands was found for the phage protein. DNA-binding protein II displaced half of the protein I in the complex with single-stranded DNA when no double-stranded DNA was present. Protein-complexed single strands were protected against degradation. The protection is less pronounced for protein II which can increase the stability of the fd DNA complex with DNA-binding protein I against nucleolytic cleavage.


Protein synthesis in muscle cultures from patients with myotonic dystrophy. Influence of A23187 ionophore and calcium: preliminary investigation. Muscle samples for cultures were obtained from the tibialis anterior by open biopsy under local anesthesia in 12 patients with myotonic dystrophy and 15 controls. Total protein synthesis in muscle cultures from patients with myotonic dystrophy showed a nonsignificant increase in (3H)-leucine incorporation. Addition of A23187 ionophore significantly stimulated the protein synthesis in muscle cultures from patients with myotonic dystrophy, but had an inhibitory effect in the cultures from controls. Myosin heavy chain synthesis was measured and found normal in all patients with myotonic dystrophy.


Studies on EEG activities in the beta band. A report on first findings of quantitative investigations of beta activity in the frequency domain is presented. Spectral analysis techniques were applied in three parallel still ongoing clinical studies, i.e. (1) an exploration of beta activities in a broad clinical material, (2) a study of the possible use of quantitative beta assessment in antiepileptic drug therapy, and (3) an investigation of special patterns with harmonic components in the beta band. Several clearly distinguishable types of spectral shapes, different coherence characteristics, significant alterations by changes of drug composition and a rich variation of harmonic patterns indicate a large and fascinating new field for clinical EEG research.


Clonazepam, baclofen and placebo in the treatment of spasticity. 25 patients with multiple sclerosis (MS) and other spastic disorders, 33 MS patients and 10 control patients with MS were given clonazepam, baclofen or placebo over a period of 5 days to 20 weeks. Both clonazepam and baclofen were significantly more effective than placebo in the treatment of spasticity (p less than 0.005 or p less than 0.01). A clinical trial of clonazepam versus baclofen was carried out and this showed no significant difference between the two drugs. However, there was indication that clonazepam influenced with better improvement in patients with slight muscle hypertonia mainly of cerebral origin. Patients with more severe forms, mainly of spinal spasticity, benefited rather from baclofen treatment (Fisher's test, p = 0.003). There was suggestion that combination of the two drugs may be more effective in some patients than than clonazepam or baclofen alone.


Level of blood pressure in patients with Parkinson's disease. A case-control study. The comparison of the blood pressures of 273 patients with Parkinson's disease and of controls matched in sex and age revealed that Parkinsonian patients had a lower systolic blood pressure and more rarely suffered from clinical hypertension than did the control subjects. Among the Parkinsonian patients both the systolic and diastolic blood pressures decreased with advancing stages of the disease. The severity of tremor did not correlate significantly with the level of the blood pressure, but with increasing severity of rigidity and hypokinesia the blood pressure lowered significantly.


Effects of slow intravenous administration of endotoxin on blood cells and coagulation in dogs. Endotoxin shock was induced in dogs by slow administration of a lethal dose of Escherichia coli endotoxin. During the 3-hour infusion period a state of disseminated intravascular coagulation (DIC) was noted. The drop in platelets and leukocytes was the most rapid and pronounced effect of the infusion, while consumption of coagulation factors occurred more slowly. Activation of the extrinsic and intrinsic pathways of coagulation appeared to be closely parallel. Concomitantly increasing amounts of fibrin(ogen) degradation products were detected, while soluble fibrin monomers were observed only inconstantly. Intravascular hemolysis was slight and occurred in the late stages of shock, and could not have influenced the development of DIC.


Effect of haloperidol and d-amphetamine on cerebral tyramine and octopamine levels. The administration of d-amphetamine or haloperidol produced a marked reduction in the rat striatum concentration of p-tyramine, an effect that was not observed in the mesolimbic system. However, the administration of d-amphetamine to haloperidol-pretreated animals produced in both brain areas a marked reduction in p-tyramine levels. Furthermore, this latter treatment produced a marked increase in the m-tyramine levels in both brain regions. Hypothalamic p-octopamine levels were reduced by d-amphetamine, but not by haloperidol or haloperidol in the presence of d-amphetamine.


Early effects of vinblastine and vincristine on the rat spermatogenesis: analyses by a new transillumination-phase contrast microscopic method. Male sterility belongs to the recently recognized complications of cancer chemotherapy and has an increasing importance. Therefore, more information about the mode of action of anticancer drugs on mammalian spermatogenesis is needed. We have developed a technique based on transillumination of living, freshly isolated unstained rat seminiferous tubules, where the cells specifically killed by the drugs are recognized as dull zones. Early stages of cell degeneration can be rapidly analyzed by phase contrast microscopy of living cells. Because the transillumination technique, in addition, permits an accurate recognition of the segments of the seminiferous epithelial wave, the cells representing various stages of the mitotic and meiotic cell cycles during spermatogenesis can be isolated in living state for morphological analysis. Vinblastine and vincristine cause an arrest of mitotic and meiotic divisions to metaphase followed by cell death, which was more rapid after vincristine administration. Both alkaloids had a slight damaging effect on the pachytene spermatocytes. Large doses of both drugs primarily affected the Sertoli cells by destroying their microtubules and mitochondria. Vincristine specifically damaged the acrosomic system and the cytoplasmic bridges of the young spermatids.


Auditory processing in anurans.

Auditory processing in anurans. Anurans (frogs and toads) represent an example of peripheral specialization of the auditory systems. Their inner ear contains two distinct auditory organs: the amphibian papilla and the basilar papilla. Each organ is tuned to different species-specific frequency ranges. Because of this peripheral specialization, anurans offer an excellent opportunity to explore neural decoding of complex sounds in the central auditory system.


Antibody and complement modulation of tumor cell growth in vitro and in vivo. Low doses of highly purified anti-TNP (trinitrophenyl) antibody specifically stimulated nucleoside uptake in TNP-substituted L cells and low doses of heterospecific anti-L cell antibody stimulated nucleoside incorporation, DNA synthesis, and cell growth in L cells in vitro. High concentrations of antibody inhibited these processes. Complement activated through C3 augmented the cytostimulatory effects of low concentrations of antibody and activated through C9 augmented the cytoinhibitory effects of antibody. One very early effect of cytostimulatory concentrations of antibody is activation of membrane carrier transport systems as seen with 45Ca2+ uptake. Growth of L cells in tissue culture in the continuous presence of a cytostimulatory concentration of antibody selected for a variant cell line that was less responsive to antibody, thought to be due to a blocking effect of increased amounts of sialic acid. In vivo experiments documented that the same antibody could modulate L cell tumor growth in T cell-depleted mice, depending on whether a low or high concentration of antibody was given passively. In the experimental systems used, therefore, antitumor antibody and complement directly modulate the growth of tumor cells.


Two types of dopamine receptors in behavioral regulation. Evidence has been presented indicating the existence of distinct dopamine receptors in the brain. The experimental proof that two types of dopamine receptors--the excitation-mediating (DAe) receptors and the inhibition-mediating (DAi) receptors--exist in the snail brain is put forward. The functioning of DAi and DAe receptors in locomotor activity and stereotyped behavior is discussed along with implications of dopaminergic involvement in a gratification system.


Clinical aspects of dopamine agonists and antagonists. Dopamine and its specific receptors are widely distributed in man. Body regions where dopaminergic activity is of special pharmacologic interest include the basal ganglions, hypothalamus, chemoreceptor trigger zone, other less well defined areas in the central nervous system, and the renal and cardiovascular systems. The search for dopaminergic agents to modify these systems in disease states has depended heavily on in vitro and in vivo bioassays. These assays involving receptor binding, enzyme activation, smooth muscle and neuronal excitation, and modification of animal behavior have provided physicians with important therapeutic tools. Indeed, the introduction of levodopa for the treatment of Parkinson's disease and of the phenothiazines and related drugs for schizophrenia and psychosis has been a hallmark of neuropharmacologic research. However, the maximal benefits that these drugs may afford have not yet been realized due to an inadequate understanding of disease processes and a relative lack of specificity of drug action.


Two modifications of the intrauterine membrane contraceptive device. The intrauterine membrane (IUM) is an intrauterine contraceptive device designed to be compliant with a range of uterine shapes and sizes and with transient dimensional changes resulting from uterine motility. This compliance was expected to contribute to low rates for removal due to bleeding and pain, but the use of the IUM resulted in heavy bleeding among its early users. Consequently, two modifications of the device were made to decrease bleeding. One group of IUMs was modified by using ethylene vinyl acetate to provide a high level of lateral compliance and another was modified by using a tissue-compatible Hydron coating in order to decrease the inflammatory response of the endometrium. One hundred of each of these modified IUMs were tested along with 100 of the standard IUMs in a double-blind study conducted at the Noi Klinika in Debrecen, Hungary. The findings of this study suggested that these two modifications did not improve the over-all performance of the IUM.


Endometritis and infertility.

Endometritis and infertility. Endometrial biopsy is an essential tool in the evaluation of the infertile couple. Among the various causes of infertility which may be elucidated by such a biopsy, endometritis plays a significant role. In this review endometritis has been subdivided into three distinct pathologic entities: acute, chronic, and fibrotic. Detailed histologic features are discussed separately for each of these varieties. Most of the acute inflammations of the endometrium are cauased by bacteria. They are usually of short duration, respond well to treatment, and only rarely are associated with long-standing infertility. Chronic endometritis, on the other hand, can be caused by a variety of agents such as bacteria, viruses, and parasites. However, in the majority of cases with chronic endometritis the etiology cannot be determined and these are then considered nonspecific. Tuberculous endometritis, which is discussed under the heading of chronic endometritis, constitutes a common cause of infertility in certain countries but much less so in the United States. Other less common conditions such as mycoplasma infection and cytomegalic virus infection, have also been associated with reproductive failure. However, chronic endometritis, especially the most common so-called nonspecific type, is a relatively uncommon cause of infertility. The syndrome of intrauterine adhesions or synechiae has been classified here as fibrotic endometritis because of the pathogenesis and histopathology of this lesion. This entity is commonly associated with infertility and may constitute the end result of a long-standing inflammatory process in the endometrium. The diagnosis of endometritis is not a simple one and necessitates close cooperation between the clinician and pathologist. Pertinent clinical and detailed histopathologic data have to be exchanged between the treating physician and pathologist, especially in cases of infertility, in order for the patient to have benefit from the examination of endometrial tissue obtained.


Pituitary gonadotropin inhibition by a highly active analog of luteinizing hormone-releasing hormone. Chronic treatment with highly active analogs of luteinizing hormone (LH)-releasing hormone (LH-RH) induces "paradoxical" antifertility effects. Intact male rats, a reduction in testosterone production is observed after the administration of [D-Ser(But)6]-LH-RH(1-9)ethylamide (burserelin, Hoe 766), 50 ng/day subcutaneously for 4 weeks. In castrated male rats treated with the same dose of analog, plasma LH levels were reduced from days 14 to 28 and plasma follicle-stimulating hormone (FSH) levels were reduced from days 21 to 28 of treatment. Pituitary LH and FSH concentrations were also decreased. The plasma prolactin level was reduced at 14 days of treatment. The hypothalamic LH-RH content remained unchanged and the adrenal corticosterone content was lowered. These findings indicate a direct inhibitory effect of the analog on gonadotropin secretion in the absence of the gonads, and may explain some paradoxical antifertility effects observed with high doses of LH-RH analogs which exceed the physiologic dose range.


Microsurgical anastomosis of the rabbit oviduct using 9-0 monofilament polyglycolic acid suture. As part of a larger study to determine which factors are important in fallopian tube reconstruction, 9-0 monofilament polyglycolic acid suture on a 145 micron-needle was used for rabbit oviduct microsurgical anastomosis. A 100% pregnancy rate in five rabbits with no disruption of the endosalpingial or muscular layers was noted. Of special note, the suture was totally resorbed, and no suture residuum or surrounging reaction was noted. The suture material appears to fulfill the criteria for an ideal suture described at the beginning of the paper. This is the first report of the use of a 9-0 monofilament polyglycolic acid suture.


Reducing accidents and injuries in the dental environment. This article has dealt with the dental office and potentially hazardous situations that could result in injury or death from electrical, gas, chemical, or mechanical accidents. Industry spends billions of dollars each year on safety considerations for its employees. Many of their safety practices are applicable to the dental office. A safety check list for the dental office is proposed. The dentist must be aware that other possible hazards exist in dental offices including the misuse of ultraviolet light units and ultrasonic scalers. In addition, the dentist must be concerned with unexpected traumas such as interstitial air emphysema, the aspiration or swallowing of instruments, appliances and restorations and self-inflicted puncture wounds.


The metabolism of glucose in pancreatic islets. Some quantitative aspects of glucose metabolism in isolated pancreatic islets are reviewed, with emphasis on the measurement of metabolic fluxes, substrate concentrations and enzyme activities. The influence of the environmental glucose concentration upon the production rate of metabolic end-products, and the intracellular concentration of both metabolites and co-factors is also considered.


Hypothesis: placental membranes produce prolactin. Orthodox views for the origin of the high concentration of prolactin (PRL) present in amniotic fluid suggest it is derived from maternal or fetal serum. However, the data on which these conclusions are based can also be interpreted to indicate that this hormone may be a product of placental or periplacental tissues. Trophoblast or amnion do not appear to produce PRL, while PRL synthesis by decidua-chorion is suggested from experiments in the rhesus monkey and by in vitro incubation of human tissue. Production of PRL by an extrapituitary cell is not without precedent and would be a simple explanation for high amniotic fluid PRL concentrations. Moreover, decidual-chorionic PRL would be strategically placed to mediate local functions of this hormone such as osmoregulation and myometrial inhibition.


Comparison studies on potency tests for rabies vaccines. Eleven laboratories from eight countries and four continents took part in a collaborative study to evaluate experimental procedures to be used in selecting the new standard reference rabies vaccine prepared in human diploid cell cultures. The following procedures were used : (a) the NIH potency test in mice, (b) the antibody binding technique (by either mouse inoculation or the tissue culture method), (c) virus-neutralizing antibody levels in mice used for the NIH test, and (d) antibody induction in human volunteers treated with vaccine alone and in combination with human rabies gamma globulin. The four methods used for determination of rabies antibodies were mouse inoculation, rapid fluorescent focus inhibition, plaque reduction and complement fixation techniques. All results were expressed in International Units as compared to the standard WHO serum and vaccine preparations. In general, a close correlation was noted in results from different laboratories, and it was recommended that the future rabies standard vaccine should be evaluated by three testing procedures, the NIH test, the antibody-binding technique, and antibody levels in mice used for the NIH test.


Questions concerning the potency of rabies vaccine. In pre-exposure immunization the protective effect of rabies vaccines can be correlated with their ability to stimulate the production of neutralizing antibodies and in post-exposure therapy also antibodies would appear to have a major role. Therefore, the potency of the vaccines may conveniently be compared by measuring their antigenicity in animals or by serum blocking tests. Nevertheless, most authorities will license, for human and veterinary use, only those vaccines which reach the required standards in the Habel or NIH tests, both of which depend upon the inoculation of more than 1 dose of vaccine followed by an intracerebral challenge. We have been involved recently in testing batches of vaccine imported into Britain for use in animals and man. Since the U.K. authorities have adopted the NIH test for this purpose we have taken the opportunity to compare some of these vaccines in the NIH test, in a modified NIH test in which the same amount of vaccine was given in a single dose, and in a test in which the production of serum neutralizing antibodies was measured. We have found that one dose of vaccine given on day 0 gave less protection and less neutralizing antibody than the same amount of vaccine given as two separate doses on day 0 and day 7. The greater effect obtained by inoculating the vaccine in two doses could thus be misleading and we suggest the adoption of a test in which a single dose is given.


Use of the antibody assay in immunized mice for the determination of rabies vaccine potency. At present, the NIH potency test is the most widely used method for determining the potency of rabies virus vaccines. The drawbacks of this test are well known and include significant test variability as well as the use of an unnatural challenge route. The antibody assay in immunized mice involves the assay of sera from mice immunized with serial dilutions of rabies vaccine. The amount of antibody in the sera is expressed in International Units per ml (IU/ml). Sera from identical dilutions of different vaccines are compared for potency with serum from the same dilution of U.S. Reference Rabies Vaccine. A "unit ratio" is calculated by dividing the serum potency value for the test vaccine by that for the reference vaccine at each dilution tested. This unit ratio may then be compared to the antigenic value generated by the NIH test performed on the same vaccines. In this study, results are reported for both duck embryo and human diploid cell culture vaccines using the Serum Neutralization Test in mice as well as the Rapid Fluorescent Focus Inhibition Test to assay the antisera. Correlations are presented between the unit ratio and antigenic value for all vaccines tested. Also, practical applications and limitations of the test are discussed.


Studies on candidate reference preparations of rabies vaccine. Two candidate reference rabies vaccines were tested in a collaborative study involving seven laboratories. Using four different testing procedures it was determined that both vaccine preparations were highly potent and demonstrated satisfactory stability in the thermal degradation test.


Comparative study on antibody determination by different methods in sera of persons vaccinated with HDCS rabies vaccine. The comparative studies undertaken by 7 laboratories in 6 countries show that the calculation of I.U.'s did not, as anticipated, minimize but actually enhanced the variability of results of rabies antibody estimations in the sera of HDCS vaccinees. The high biological variance in the method(s) may not have been considered by individual laboratories and any neglect of fundamental biostatistical laws unfortunately diminishes the theoretical advantage of using the "International Standard (I.S.)" as a  "tertium comparationis". Perhaps the intrinsic variability of the I.S. should be re-evaluated and it is conceivable that a pure IgG fraction of rabies antiserum would show less variability. Intralaboratory variation might be reduced by agreeing that only a geometric mean of the I.S., and not a single value obtained in an individual test, should be used for calculation of I.U.'s. Application of the principles of biochemical and pharmacological methods, such as test-to-test control of the I.S. and its analytical variances might well enhance the reproducibility of the results. MNT, RFFIT, PRT and CFT were unable to detect antibodies in HDCS vaccinees until 7 days after the first vaccination. The establishment of methods for detecting early antibody requires further investigation.


Antibody levels following WI38 rabies vaccine. WI38 rabies vaccine lots with varying mouse potency ratios were compared in their ability to induce neutralizing antibody in human volunteers. Three vaccination schedules were used: 0, 7 and 14 days; o,7 and 21 days; and 0,28 and 56 days. Regardless of the mouse potency ratio, antibody was barely or not detectable on the 7th day after the first dose of vaccine. After the second dose, however, there was a very good correlation between mouse potency and antibody level attained. Vaccines with potency ratios above 2 gave comparable results, whether the 0, 7, 14 or 0, 28, 56 schedules were used. The lowest potency vaccine, however, have a much better response when given at 0, 7 and 14 days than at 0, 28, and 56 days. Although the vaccine with the greatest potency ratio produced the highest levels of antibody, very adequate responses were obtained in 100% of recipients after three doses of vaccines having a ratio greater than 2, given at 0, 7, 14 or 0, 7, 21 days.


The advantage and adequacy of the mixed hemadsorption test for rabies antibody determination. The goal of rabies vaccination is an early development of protecting antibodies. The mixed hemadsorption (MH) test is shown to be an adequate test to evaluate the immunization response. It measures antibodies combining with antigens on rabies-infected cells equivalent to the glycoprotein antigen at the exterior of the budding virus (1). Further, the MH test used measures antibodies solely of IgG class, thus avoiding positive results being obtained by IgM antibodies which can be produced during a prolonged period because of antigen persistence due to daily immunization doses (2). Antibodies of IgM class may play only a minor role in the early defence against rabies as probably only antibodies of IgG class can reach a locally introduced virus and, so far, are the only immunoglobulins shown to induce immune lysis in rabies-infected cells (3). The MH test is described. It is a sensitive, reliable and technically convenient method as it has a capacity for testing many sera in the same run. Results obtained are compared with neutralization values obtained from different types of rabies vaccines (4).


Rapid immunoenzymatic technique for titration of rabies antibodies IgG and IgM. This report is concerned with the application of the enzyme immunoassay to measure the antibodies in humans vaccinated against rabies or presenting symptoms of rabies without having been vaccinated. By the same technique we identify the IgG and IgM classes of antibodies. The antigen (5 microgram/ml), purified virus, is readily adsorbed into polystyrene tube by passive adsorption. The use of only one dilution for each serum assay (1/200) is particularly suitable for epidemiological studies. Antibody response of subjects in the course of rabies vaccination was an obvious application. After 5 inoculations of tissue culture vaccine the IgM response was poor and late; it was even negative in two cases. The IgG response appeared early on the 7th day. In the same way we tried to follow antibody response in three cases of rabies in man. Seroneutralisation (SN) antibody were not detected at the beginning of the illness. In case 1 antibodies were found on the 12th day, in case 2 on the 7th day and in case 3 on the 8th day. When we assayed the serum samples for immunoenzymatic test, we found that the sera became positive some days earlier: on the 5th for case 1, already on the 1st day for the two others. In each of these three cases the positivity of the test corresponded to the presence of IgM class globulins since IgG detection remained negative as did the SN test. Our results could have some clinical interest concerning future rabies treatment and early diagnosis.


Long-term survey of the treatment of diarrhoea with loperamide. 42 outpatients with chronic diarrhoea of varying origin received individually adapted doses (2--12 mg) of loperamide for a median time of 543 days (range 140--1,159 days). In most cases, the mean daily stool frequency dropped significantly and stool consistency improved clearly; the beneficial effects of the drug were maintained over the entire treatment period. Also, patients with diarrhoea of organic origin tended to react more favourably to loperamide than patients with functional diarrhoea. No drug-related changes in laboratory parameters could be detected and clinical side effects were virtually nil. No morphine-like effect of loperamide could be evidence by means of the pupil diameter changes after naloxone administration.


A study of the variations in the response regarding duodenal ulcer when treated with placebo by different investigators. Four series of duodenal ulcer patients presenting with pain have been treated with two types of placebos (intramuscular injections or tablets) by 4 different physicians while a fifth group of patients did not receive any treatment. Patients noted the number of days with pain since the beginning of the test by themselves. All patients treated with placebo presented with a significantly shorter duration of pain than untreated patients. There was a significant difference between the actions of the different physicians on the duration of pain. This suggests that some, until now unprecised, character(s) of the physician plays an important part in the relief of duodenal ulcer pain.


Gastric mucosal cell proliferation and immunoglobulin-containing cells in Ménétriér's Disease. The amount of immunoglobulin-containing cells in gastric mucosa from 6 patients with Ménétriér's disease was estimated. Furthermore, the rate of gastric epithelial cell proliferation was sutdied in 4 of the patients. Fluorescent antisera specifically reacting with IgA, IgG and IgM were applied, and accordingly the cells were differentiated and quantitated. Other biopsies were labelled in vitro with 3H-thymidine and autoradiographs were prepared. The percentage of DNA-synthesising cells in the progenitor cell region was estimated. The number of IgM-containing cells in the gastric fundic mucosa was markedly increased, while the rate of epithelial cell proliferation was increased in 2 cases and within normal range in the remaining 2 patients.


Controlled trial of chenodeoxycholic therapy for radiolucent gallstones. A multicenter study. 134 patients with radiolucent gallstones were randomly allocated to receive either placebo or 1 of 3 different doses of chenodeoxycholic acid (CDCA); 750, 1,500, or 3,000 mg). The initial dose was lowered if not well tolerated. 107 patients were treated for more than 3 months. Among them, stones dissolved in 21 and were smaller in 25 patients. Partial or complete dissolution occurred in 4 of the 13 receiving 375 mg/day, 14 of 37 receiving 750 mg, 24 of the 38 receiving 1,500 mg and 4 of 8 receiving 3,000 mg/day. The number of responders to the therapy was significantly greater in the groups of patients receiving 1,500 mg/day or 17-24 mg/kg body weight than in any other group. However, side effects, i.e., diarrhea and transaminase increase, are also dose related. It appears from this study that the optimal dose of CDCA may be between 17 and 20 mg/kg body weight.


Treatment of active duodenal ulcer with oral cimetidine: a multicenter controlled endoscopic trial. A double-blind 4-week trial of cimetidine (1 g daily) versus placebo was conducted in 68 adult outpatients with active duodenal ulceration endoscopically confirmed. 3 of the patient admitted to the study (1 on cimetidine and 2 on placebo) did not complete the trial. After 4 weeks of treatment, 25 of 33 patients (76%) receiving cimetidine had healed their ulcers compared with 15 (47%) of 32 patients receiving placebo (p less than 0.02). Antacid consumption was also significantly decreased by cimetidine when compared with placebo. Tolerability of the drug was good.


Effect of somatostatin on pentagastrin stimulated secretion by isolated canine stomachs, perfused ex vivo with homologous blood. The effect of somatostatin on pentagastrin-induced gastric secretion was assessed on 6 isolated canine stomachs perfused ex vivo with homologous blood. Hormones were given at a constant rate into the gastric arterial circulation. Somatostatin caused inhibition of the HCl concentration and output and reduced the secretion volume in all stomachs studied. The output but not the concentration of pepsin was also reduced.


[A double-blind cross-over trial of a new hypolipidaemic drug (author's transl)]. A double blind cross-over trial has been carried out on the effects of a nicotinic acid compound on 27 patients affected by hyperlipidemia. The subjects have been treated over one year according the following plan: two peroids of 90 days each with the drug and two with placebo. The statistical analysis showed a significant reduction of serum cholesterol triglycerides, phospholipids and total lipids. In 4 patients out of 27, the treatment has not been completed because of drug intollerance.


Chemical and biological properties of the carcinostatic protein fraction of Escherichia coli. A carcinostatic protein fraction (EPF) was separated from Escherichia coli 055 cells by the following procedure: E. coli 055 cells were suspended in distilled water, and extracted by repeater freezing and thawing. The extracts were centrifuged and the supernatant was treated with 1N acetic acid (pH 4.5). Acid precipitate collected by centrifugation was dissolved in alkaline water (pH 8 to 9) and subjected to gel filtration on Sephadex G-200 column. The high molecular weight fraction obtained by gel filtration was collected, freeze-dried, and designated as EPF. EPF was composed of approximately 74.5% of protein, 20.4% of lipid, and a small amount of polysaccharide. The isoelectric point of EPF was pH 5.2 +/- 0.A and the ultraviolet spectrum showed absorption maximum at 278 nm (E1%1cm 4.30) in 0.01M Tris-HCl (pH 7.8) buffer. The antitumor experiment with EPF demonstrated that the daily injection of EPF in a dose of 10 microgram/mouse inhibited sarcoma-180 ascites in 90% of the treated animals and the dose of 100 micrograms/mouse brought about 100% inhibition. In the contact test using C3H2K and C3HW2K cells, 200 micrograms/ml of EPF exhibited about 40% cell destruction. In the ihhibition test of 14C-phenylalanine incorporation into intact sarcoma-180 cells, EPF exhibited 60.5% inhibition at the concentration of 275 micrograms/ml. In contrast, EPF did not show any inhibition of the incorporation of 3H-uridine or 3H-thymidine.


A clinical trial of cell-wall skeleton of BCG in chemoimmunotherapy of acute leukemia. A clinical trial of chemoimmunotherapy using cell-wall skeleton of BCG (BCG-CWS) was conducted in 28 patients with acute leukemia in complete remission. Chemotherapy consisted of monthly intensification therapy for 2 months and bimonthly therafter. Immunotherapy with 200 microgram of oil-attached BCG-CWS mixed with 10(7) autochthonous leukemic cells was given intradermally at either of upper or lower extremities every week, except when the patients were on maintenance therapy. No serious systemic side effect attributable to BCG-CWS was noted. Six patients developed mild and transient temparature elevation. Most importnat side effect was local skin reaction. Indulated papules developed in all patients, resulting in draining ulcerations in 26 patients. Increase of immunological reactivity of the patients receiving BCG-CWS was noted. Skin test response to PPD, Varidase, and candida extract showed definite increase. In vitro lymphocyte blastogenic response to PPD, concanavalin-A, and pokeweed mitogen revealed significant increase.


Immunoglobulin deficiency diseases of the intestine. Marshak has emphasized the role of the gastrointestinal tract as a major immunologic organ and described the radiologic findings of immunoglobulin deficiency diseases of the small intestine. According to his classification the radiologic findings include multiple nodular defects, edema and increased secretions associated with Giardiasis, a sprue-like pattern, and thickened folds. In this report, the role of the intestine in the immune response is briefly reviewed and several of the radiologic features of immune deficiency diseases and those of benign nodular lymphoid hyperplasia are illustrated.


A comparative double-blind study of esophageal barium pastes. To demonstrate esophageal varices barium sulfate suspensions must coat the lower esophagus for as long as 5 to 10 minutes. This study compared the ability of five barium sulfate preparations to resist disappearance by inadvertent swallowing. Three of the special preparations for esophageal examination, Esophatrast, Barosperse Esophageal Paste, and HD-5000 performed satisfactorily. Examiner skill, persistence, and careful technique are the most important factors in examining the lower esophagus. The authors' procedure for examination of the esophagus for varices is described. It takes into account position, time, phase of respiration, occasional use of drugs, and procedures to insure good coating and relaxation of the lower esophagus.


Pneumatosis cystoides coli.

Pneumatosis cystoides coli. Pneumatosis cystoides coli in most cases is a disease of unknown etiology. In a few patients, it is secondary to an infarction or ulcerative colitis. Associated pulmonary emphysema is not uncommon. The gas pockets, whcih may be of varying size, can be identified along the contour of the bowel. The left side of the colon is more frequently involved than the right. The lesion is usually segmental. The rectum is almost always spared. Symptoms are negligible and operation is not required.


Drug-induced gastrointestinal disease.

Drug-induced gastrointestinal disease. The gastrointestinal tract is a common target for adverse drug reactions. The resultant changes are often nonspecific (e.g., mucosal ulceration, intestinal infarction, motility disturbance) and in many cases no radiographically detectable lesion may occur. A comprehensive review of the reported drug-induced disorders of the digestive organs is herein presented and their radiographic manifestations are described.


Complications of gastrointestinal fiberoptic endoscopy. Flexible fiberoptic endoscopes are being increasingly used for direct visualization and biopsy of lesions of the gastrointestinal tract. The spectrum of gastrointestinal complications associated with fiber-optic esophagoscopy, gastroscopy, and colonoscopy is reviewed. Radiologic recognition and evaluation of these iatrogenic incidents is of critical importance.


Iatrogenic problems following gastric surgery. It is difficult to truly define iatrogenic complications in the postsurgical state in that the surgery is a condition originated by physician intervention and thus any problems that occur may be technically considered as physician created. In this article we attempt to demonstrate problems that occur both due to technical errors and the choice of operative procedure. In addition, unusual postsurgical anatomy is illustrated with the hope of avoiding further iatrogenic problems from lack of recognition.


Roentgen manifestations of radiation injury to the gastrointestinal tract. Radiation injury of the gastrointestinal tract requires a minimum dose of 4200 to 4500 rads. The symptoms and signs of radiation injury usually appear within 6 to 24 months following therapy. The radiation induced changes include mucosal atrophy and ulceration associated with an obliterative endarteritis in the supportive vasculo-connective tissue. The roentgen manifestations are those of an ischemic process but may also mimic those of recurrent malignant disease. Obstruction, hemorrhage, and fistula formation are common complications. Surgery is frequently required. The morbidity and mortality is considerable.


[Problems in the evaluation of contraceptives (author's transl)]. For the evaluation of the effectiveness of contraceptives the Life Table method is at present the best method. It is a disadvantage that the original method of Tietze & Potter was restricted to the evaluation of intra-uterine contraception devices. A Belgian team is now in the process of developing a modified life table method for the evaluation of the effectiveness and the side effects of oral contraceptives. The reference to the Pearl-index for the effectiveness of contraceptives is unclear and in the way in which it is at present used scientifically untenable.


[Role of propionic acid, yeasts and ethyl alcohol in regulating the activity of H-factor in Drosophila simulans]. Effects of yeast, propionic acid and ethanol on the activity of H-factor, which sharply increases the frequency of somatic recombination in X-chromosomes of dorsal prothoracal disc cells in Drosophila simulans are studied. The frequency of yellow and singed mosaic spots in heterozygous yw ++/++sn1vHD. melanogaster females, inherited H-factor from the father (the stock sn1v) is estimated. The results of the varience analysis have shown that yeast and propionic acid regulate the activity of H-factor in cells of dorsal prothoracal disc, the interaction of yeast and propionic acid being also observed. Yeasts (or some unknown product of their metabolism) are the activator of H-factor; thus, when larvae eat much yeast, the frequency of yellow and singed mosaic spots in humeral region becomes high. A decrease of mosaic spot frequency under the increase of propionic acid content in nutrition medium is a result of the inhibitory effect of propionic acid on the yeast growth, but not of the direct repression of H-factor activity. So, propionic acid may be considered as a regulator of the second order. Ethanol does not activate H-factor. Changes in the content of yeast and propionic acid in nutrition medium do not affect the frequency of yellow and singed mosaic spots in other regions of D. simulans body, except humeral.


[Incorporation of phi80 phage into unusual chromosome sites and isolation of a specialized transducing bacteriophage]. The mutant strain KS713 of Escherichia coli K-12 deleted for the normal insertion site and secondary preferable one was obtained. The insertion frequency of phage phi80 into the double deletion strain is reduced about 30-fold with respect to integration into the strain H47 with deletion of the primary phi80 attachment site and about 500-fold relative to integration into wild type Escherichia coli. Analysis of the rare abnormal lysogens of KS 713 strain indicates that there are secondary sites on the chromosome, which are utilized for prophage attachment if insertion at preferable secondary att80-II site is eliminated too. The insertion of phi80 phage into the bfe locus was obtained by the appropriate selection technique. Induced prophage excision from the bfe site was rather efficient and lysates contained phi80 phage particles that could specificically transduce the argH+ gene. Upon transduction into a recipient strain carrying recA, heterogenotes harbouring both the wild-type and the mutant argH genes were isolated. These heterogenotes were used for producing high-frequency transducing lysates.


[Intergeneric conjugational crossing of Escherichia coli with Salmonella typhimurium. II. Transfer of a polA1 mutation from Escherichia coli to Salmonella typhimurium and its phenotypic expression in the salmonella genome]. The Escherichia coli structural gene for DNA polymerase I was inserted into Salmonella typhimurium chromosome by conjugal transfer. The genetic analysis of P1-mediated transduction of obtained hybrid showed that polA gene is located in it between metE and rha loci and is cotransduced with metE (about 50%) and rha (12%). The phenotypic properties of polA1 hybrid E. coliXS. typhimurium concerning UV-MMS-NG and gamma-ray sensitivity are similar to the polA1 mutants of E. coli.


[Supersensitivity to levorin and amphotericin B in several Saccharomyces cerevisiae mutants resistant to nystatin]. 104 mutants resistant to nystatin were isolated after UV-treatment of two haploid marked strains of Saccharomyces cerevisiae. The analysis of resistance to three polyene antibiotics allowed to determine 8 phenotype classes of mutants including those resistant to nystatin but in various combinations showing hypersensitivity to levorin and (or) amphotericin B. The analysis of UV absorption spectra of sterolic extracts prepared from cells of different mutants showed that similar quality changes in sterol composition could be associated both with polyresistant an supersensitive phenotype. New type of mutants resistant to nystatin and supersensitive to levorin and (or) amphotericin B seems to be promising for studies on the mechanisms of action of polyene antibiotics, the bases of resistance to them and also in consideration of the possibility to increase the efficiency of antimycotic antibiotic therapy.


[Gene relA function in the expression of amino acid operons. I. Effect of the allelic state of gene relA on phenotypic manifestations of auxotrophic threonine and isoleucine mutations in Escherichia coli K-12]. The substitution of the relA gene mutant allele with wild type allele of this gene in strictly auxotrophic strain of Escherichia coli K-12 GT25, carrying thr B1007 mitation, results in the appearance of the partial dependence of the bacterial growth upon threonine. On the other hand, the introduction of relA mutation into genome of incomplete threonine auxotroph, which was isolated as pseudorevertant from the strict threonine auxotroph CP78, recovered the strict dependency of the growth on the presence of threonine in the medium. The introduction of relA mutation into genome of partial isoleucine auxotroph, carrying a mutation in ilvA gene, reduces the residual activity of threonine deaminase under the conditions of derepression and results in the appearance of strict dependency of bacterial growth on the presence of isoleucine. These data indicate that operons, which control the biosynthesis of threonine and isoleucine, are positively regulated by the product of relA gene. The possibility of using leaky mutations, which lead to incomplete block of these amino acids synthesis, for testing allelic state of relA gene is discussed.


[Gene relA function in the expression of amino acid operons. II. Effect of the allelic state of gene relA on the overproduction of threonine by an Escherichia coli K-12 mutant resistant to beta-hydroxynorvaline]. Mutants, resistant to threonine analogue, DL-alpha-amino-beta-hydroxyvaleric acid, were obtained after the treatment of Escherichia coli K-12 RelA- cells with nitrosoguanidine, and among them the strain with maximal threonine production (about 3g/l) was selected. Genetic and biochemical analysis of the producer has revealed the dependency of the threonine production on at least three mutations. The mutation in the thrA gene disturbs retroinhibition of homoserine dehydrogenase by threonine. The mutation in the ilvA gene decreases the activity of threonine deaminase, and thus results in partial isoleucine auxotrophy, and finally, the reversion in the relA gene restores the stringent amino acid control of RNA synthesis in threonine producer cells. The role of relA gene in threonine production was demonstrated by comparing pairs of strains differing from one another in the allelic state of the relA gene. The level of threonine synthesis (its intra- and extracellular concentrations) during moderate isoleucine starvation in RelA+ cells 2-3 times as high as in RelA- cells. The presence of relA+ allele is found to result in the increase of the cell resistance to DL-alpha-amino-beta-hydroxyvaleric acid.


Canine kidney cells. II. Neutral lipids, phospholipids and fatty acids of Madin-Darby canine kidney cells in suspension and monolayer culture. Differences in lipid composition and the effects of monolayer and suspension culture were studied in Madin-Darby canine kidney cells and their plasma membranes isolated by the Warren fluorescein-mercuric acetate technique. Unesterified cholesterol was the major neutral lipid extracted from the whole cells and plasma membranes of cultures except for suspension-grown whole cells which had triglyceride as their major neutral lipid. Triglyceride increased about 7- to 20-fold and glycerol ethers increased about 3- to 20-fold in suspension grown whole cells and their plasma membranes compared to those from monolayer cultures. Total quantities of phospholipids are similar in whole cells of both cultures. Plasma membranes from monolayer cultures have about 1.4-fold more total phospholipids than those from suspension cultures. The distribution of fatty acids in the plasma membranes and whole cells generally follow the composition of calf serum used in the culture medium. However, the phospholipids of plasma membranes from monolayer cultures had substantially higher values for C18 unsaturated fatty acids and somewhat lower values for palmitoleic acid than the values for the fatty acids in calf serum. Also, the phospholipids of suspension-grown whole cells had substantially higher values for lauric acid and lower values for C18 unsaturated fatty acids when compared to calf serum.


Alpha-1-antitrypsin deficiency: a biological enigma. The association of certain forms of liver disease and a deficiency of alpha-1-antitrypsin is an observation which raises the possibility that other forms of liver disease ultimately will be found to have as their proximate cause a defined metabolic aberration, which may in turn be inherited. Although alpha-1-antitrypsin deficiency is a genetically determined error of protein synthesis, environmental factors, unrecognised at present, are required for the disease to become overt. Thus, this interesting association may herald an increasing number of clinical diseases in which the interaction of environmental stimuli and single genetically determined aberrations are crucially important. The diseases to which we succumb may be largely determined by a genetically determined susceptibility, a point of view which was stated so well by Archibalt Garrod in his essay Inborn Factors in Disease published nearly half a century ago.


Serum bile acids in hepatobiliary disease. We review the estimation of total and individual serum bile acids to detect the presence and nature of hepatobiliary disease. The different methods for measuring serum bile acids are discussed.


Regulation of blood ammonia.

Regulation of blood ammonia. Disturbance of ammonia metabolism is an important but not the only factor in the genesis of hepatic coma. In this review mechanisms controlling the concentration of ammonia in the blood other than disturbed liver function have been discussed. The key function of ammonia in the pyridine nucleotide cyde has been outlined and it is suggested that the function of this cycle in patients with liver disease would repay further study.


Plasma lipids and lipoproteins in liver disease. There are many changes in the plasma, lipids, and lipoproteins in patients with liver disease. They have proved difficult to study but our understanding of these changes has increased greatly during recent years. In obstructive jaundice hyperlipidaemia is a fairly constant finding and this appears to be due to the regurgitation of phospholipid from the obstructed biliary tree. The plasma lipids tend to fall with parenchymal liver disease. The composition of the lipoproteins depends on the activity of the plasma enzyme lecithin: cholesterol acyl transferase. When LCAT activity is high the individual lipoprotein fractions are normal. When it is reduced all of the lipoprotein fractions are affected but the pattern found with obstruction is quite different from that found with parenchymal disease. The changes in plasma lipoproteins appear to be associated with change in the lipid composition of cellular membranes and this may have important functional implications.


Some clinical features of liver cell failure: an appraisal of their causes. The mechanisms underlying the cause of the major clinical features of liver cell failure are reviewed. These include jaundice, fluid retention, hepatic encephalopathy, bleeding tendency, etc.


Liver biopsy in chronic hepatitis: 1968-78. The classification of chronic hepatitis introduced in 1968 is still current, but has been modified. The concept of bridging hepatic necrosis has been incorporated, and is recognised as an important feature of both acute and chronic aggressive (active) hepatitis (CAH). In the pathogenesis of the latter, piecemeal necrosis is, however, thought to be the more important factor. The histological picture of CAH varies widely. Several causes of CAH have been identified, including hepatitis B virus. Recognition of surface and core components of the virus in tissue sections has facilitated study of the relationship between host response and pathological lesion in chronic hepatitis. CAH and primary biliary cirrhosis share histological features, and a mixed form has been postulated. Staining for copper sometimes helps to distinguish the two lesions. A third histological category, chronic lobular hepatitis, comprises patients with histological lesions like those of acute hepatitis, but with a chronic or recurrent course.


Hepatosplenic schistosomiasis: a great neglected disease of the liver. Schistosomiasis mansoni and japonica, helminth infections involving the livers of 100 million people, are among the 'great neglected diseases of mankind' on the basis both of their prevalence and the relative lack of interest shown in them by clinicians and biomedical investigators. Schistosomiasis is not only an interesting disease in itself but has the added advantage of providing unique human and animal models of hepatic pathophysiology, immunopathogenesis, and collagen metabolism.


Trials and tribulations with artificial liver support. This paper reviews the experience gained over the past few years in two techniques of liver support, charcoal haemoperfusion and polyacrylonitrile membrane haemodialysis. Problems with charcoal haemoperfusion have centred around platelet aggregation and hypertension, and new carbon preparations with a variety of different coatings to overcome these problems are described. Haemodialysis using the PAN membrane has caused fewer side-effects and current results show that 33% of patients so treated recover consciousness. The new techniques for liver support currently being developed, including combined dialysis/perfusion systems and those based on plasma separation, are also described.


Low dose steroids and clinical relapse in Crohn's disease: a controlled trial. The long-term effect of prednisone in Crohn's disease has been examined in a double-blind controlled trial. Clinical relapse, recurrence, and extension of the disease were examined in 64 patients followed-up for up to three years. Fourteen patients were withdrawn because of severe symptoms (eight on prednisone and six controls); the withdrawal rate in both groups was 30% at three years. Nine other patients had radiological recurrence or extension of disease (five prednisone and four controls). Prednisone did not improve the relapse rate, nor did it affect recurrence or extension of disease.


Peliosis hepatis in recipients of renal transplants. Peliosis hepatis, an uncommon liver lesion characterised by blood-filled cavities bordered by hepatocytic plates, was found in 12 patients three to 17 months after renal transplantation. Hepatomegaly and portal hypertension were present in five of the six patients with major peliosis hepatis, and were absent in the other six with minor hepatic lesions. Alterations of centrilobular vein walls in some of these patients suggest that peliosis hepatis could be the result of a blockade or liver blood outflow at the junctions of sinusoids and centrilobular veins. The cause of these alterations might be azathioprine.


The effects of xenopsin of endocrine pancreas and gastric antrum in dogs. Effects of synthetic xenopsin on endocrine pancreas and gastric antrum in anesthetized dogs were studied. Synthetic xenopsin was administered into the superior pancreaticoduodenal artery and plasma insulin, glucagon and gastrin in the superior pancreaticoduodenal vein and gastrin in the right gastroepiploic vein were measured radioimmunologically. Administration of 10 microgram of xenopsin per kg of body weight brought about a hyperglycemic response and rapid and sharp elevations of the hormones in the pancreatic vein. Plasma gastrin level in the gastric vein also showed an immediate and sharp increase following xenopsin administration. Xenopsin appeared more potent inducer of the glucagon. It is concluded that xenopsin acts directly on endocrine pancreas and gastric antrum to secrete their hormones.


Carbohydrate metabolism in thyrotoxicosis: studies on insulin secretion before and after remission from the hyperthyroid state. The effects of thyrotoxicosis on insulin secretion were studied in 11 patients with Graves' disease and compared with the results obtained in 6 of the patients after they had attained clinical remission. Constant glucose infusion (CGI) and acute tolbutamide infusion (AIT) tests were chosen to investigate beta-cell function. For similar means of fasting plasma glucose, basal plasma insulin mean was significantly higher during thyrotoxicosis. During AIT, mean peak insulin was obtained earlier in the hyperthyroid state (2 min) than after remission (4 min), being its level higher in the hyperthyroid state. During CGI, early insulin responses to similar plasma glucose increments, were comparable for both hyper and euthyroid subjects. After 10 minutes of CGI, insulin concentrations in the hyperthyroid state did not increase as in the euthyroid state in spite of comparable increments of plasma glucose, being similar plateau insulin levels attained thereafter. These results suggest the presence of an insulin-resistant state in hyperthyroidism which may either disappear during a chronic glucose infusion and/or be accompanied by a deficient late glucose-induced insulin release.


Effects of protein synthesis inhibitors on the negative feed-back effect of estrogen on LH release. Ovariectomized female rabbits were pretreated with actinomycin D (80 microgram/100 g body weight) cycloheximide (300 microgram/100 g body weight) or chloramphenicol (300 microgram/100 g body weight) 4 h before an intravenous injection of 25 microgram of estradiol benzoate. Actinomycin D, cycloheximide and chloramphenicol decreased basal gonadotropin levels, but actinomycin D was less active than chloramphenicol and cycloheximide. Despite this effect on basal levels, such treatment did not prevent the effect of estradiol benzoate on LH release. Moreover, no significant impairment of the LH response to LH-RH was found. The interpretation of experiments using drugs such actinomycin D, cycloheximide or chloramphenicol requires caution; however, one cannot disregard the possibility that the negative feed-back effect of estrogen, in contrast to the positive effect, may not be mediated by RNA-dependent DNA and the protein-synthesizing systems.


Immunoglobulin deposition in membranous glomerulonephritis: immunofluorescence and immuno-electron microscopy findings. In a series of 250 renal biopsies (transplants excluded) the diagnosis of membranous glomerulonephritis was made in 22. This was done on light microscopy in 17, while the addition of immunofluorescence enabled the diagnosis to be made in a further five. Electron microscopy confirmed the diagnosis in all cases. Immunoperoxidase studies emphasized the basement membrane distribution of the deposits of immunoglobulin and relative sparing of the mesangium. They showed at an ultrastructural level the presence of IgG in the deposits.


The histological preparation of bronchial brushings--a reliable and satisfactory method. A method for improving the diagnostic yield of fibreoptic bronchoscopic bronchial brushings and tiny biopsies has been developed. This technique has proved reliable giving a high positive yield of malignant cells and tissue in the 232 specimens examined.


Percutaneous needle biopsies of renal allografts: the relationship between morphological changes present in biopsies and subsequent allograft function. In the Cambridge renal transplant unit percutaneous needle biopsies of renal transplants have been extensively used to help identify the cause of impaired allograft function. During the period 1966--1973, 154 of the 269 renal allografts transplanted were biopsied at least once during the first 90 days after transplantation. In this survey the relationship between morphological changes in these biopsy specimens and allograft function 1, 3 and 5 years after transplantation is assessed. A highly significant direct relationship exists between early graft failure and the presence of medial necrosis of arteries, acute glomerular lesions and interstitial haemorrhage. Less than 10% of grafts with one or more of these changes and none in which all three types of lesion were present were capable of supporting life at 1 year. There is a significant association between poor subsequent graft function and mononuclear cell infiltration of the intima of arteries. No clear relationship exists, however, between the function of grafts at 1 and 3 years and the degree of mononuclear cell infiltration of the interstitial tissue. Tubular necrosis was frequently observed and future graft performance is related to the extent and cause of the tubular damage.


Morphological aspects of the endocrine pancreas in a prednisolone-treated infant. The endocrine pancreas of a corticosteroid-treated infant during the course of nephrotic syndrome was morphologically studied. Islet cell hyperplasia and dispersed endocrine cell aggregates between acinar tissue were observed. A marked numerical increase of B cells was identified by using cytochemical and immunofluorescent methods. Morphometric data support the morphological observations. The findings suggest that corticosteroid treatment induces endocrine cell replication and neogenesis.