Drug response and psychiatric nosology.

Drug response and psychiatric nosology. The possibility that pharmacological response might help to refine psychiatric nosology has been the subject of recurrent speculation, but few clear-cut results have been obtained. Only bipolar depressives and several other minor patient subgroups manifest consistent drug responses in association with characteristic psychobiological features. The presence of multiple intervening variables, such as individual differences in drug metabolism, drug-taking behaviour and biological sensitivity to drugs, may mitigate against the reliable identification of clinically distinguishable drug-responding subgroups. Futhermore, the majority of available psychoactive drugs have either multiple or broad spectrum effects inconsistent with hypotheses utilizing the mechanism or site of drug action to argue for a diagnosis-specific biological disorder at such sites. Nonetheless, the successful use of drug-response models in other areas of medicine suggests a rationale for continued exploration in this area, and a number of recent advances make this approach potentially more productive. Pharmacological developments have rendered it possible to assess the biological availability of drugs in potential responders, thus eliminating some of the confounding intervening variables. Further consideration should also be given to the use of drugs with more specific neurochemical effects, even when they themselves are not necessarily therapeutic. The comparison of drug responder and non-responder group has also been made more meaningful by the availability of more reliable methods of assessing clinical phenomena, more sophisticated diagnostic models and the introduction of other biological measures. Combining several of these approaches may allow the use of one to validate the other.


Physical ill-health and psychotropic drug prescription--a review. This review collates evidence of substantial physical morbidity in patients who receive psychotropic drugs, and evidence that these drugs are not infrequently prescribed for patients with known physical illness. Minor tranquillizers are the psychotropic drugs most commonly prescribed, and the category of physical illness most likely to be associated with psychotropic medication is cardiovascular disease.


Effects of LSD and BOL on the catecholamine synthesis and turnover in various brain regions. In the rat, lysergic acid diethylamide (LSD) 0.5 mg/kg and 2-bromo lysergic acid diethylamide (BOL) 0.5 mg/kg increased the rate of the striatal in vivo tyrosine hydroxylation as measured by the DOPA accumulation after decarboxylase inhibition. Neither LSD nor BOL significantly changed the DOPA accumulation in the olfactory tubercle, a dopamine-rich part of the limbic system. LSD but not BOL increased the DOPA accumulation in the cerebral cortex and in the brain stem. LSD and BOL appeared not to alter the rate of alpha-MT-induced disappearance of DA or of NA in the whole brain, nor did they change the rate of the alpha-MT-induced disappearance of DA in the striatum. It is suggested that in the striatum LSD and BOL block autoreceptorss (presynaptic receptors) regulating the tyrosine hydroxylation. These receptors may be DA receptor, but may also be 5-HT- or LSD-sensitive receptors. The regional differences observed between LSD and BOL suggest that LSD in the cerebral cortex and in the brain stem increases the DOPA accumulation by mechanism other than that functioning in the striatum. One possible explanation is that LSD and BOL may differ in their effects on 5-hydroxytryptaminergic systems in the cerebral cortex and in the brain stem.


Cocaine as a discriminative cue in rats: interactions with neuroleptics and other drugs. Rats were trained to discriminate between the effects of 4 mg/kg of cocaine HCl and saline (1 ml/kg) in a T-shaped maze. When the animals reliably differentiated the imposed training conditions (cocaine vs. no drug), test sessions were interspersed in between the regular training sessions. Test trials resulted in a median effective dose (ED50) of 1.6 mg/kg of cocaine, and the duration of the discriminable effects of cocaine in producing 50% cocaine-appropriate responding was 57.9 min postinjection. Pretreatment with neuroleptics (pimozide, haloperidol, and chlorpromazine), but not with propranolol, phenoxybenzamine, alpha-methyl-para-tyrosine, or physostigmine, attenuated the cocaine discrimination. Data are discussed with reference to previous results from amphetamine discriminations.


The use of percutaneous nephrostomy and urinary alkalinization in the dissolution of obstructing uric acid stones. Two patients are described who presented with complete urinary obstruction secondary to nonopaque uric acid stones. They were treated with percutaneous nephrostomy for urinary diversion and urinary alkalinization by local irrigation and oral sodium bicarbonate therapy with complete dissolution of the stone after 16 and 21 days of therapy. Percutaneous nephrostomy with urinary alkalinization is a reasonable, relatively safe alternative to surgical stone removal for patients with obstructing uric acid stones.


Bile duct cysts secondary to liver infarcts: report of a case and experimental production by small vessel hepatic artery occlusion. Hepatic bile duct cysts were demonstrated on an abdominal CT scan and confirmed at autopsy in a patient with polyarteritis nodosa. The cysts developed in close proximity to hepatic artery aneurysms and occlusions visualized at hepatic arteriography and confirmed postmortem. The development of similar bile duct cysts following hepatic artery occlusion was demonstrated in 13 Rhesus monkeys.


Cytochrome P-450 dependent irreversible binding of 6-thiopurine to rat liver microsomal protein in vitro and protection by glutathione. 6-Thiopurine when incubated in the presence of rat liver microsomes and reduced nicotine adenine dinucleotide phosphate (NADPH) binds to microsomal protein. Data support a mechanism involving initial metabolic activation via a cytochrome P450 mediated reaction to an intermediate which binds to protein. Glutathione protects against protein binding of the 6-thiopurine metabolite.


The effects of some stimulants and anti-psychotic drugs on urinary unconjugated tyramine levels in the rat. The effects of intraperitoneal injections of amphetamine and methylphenidate (ritalin) at relatively low and high doses, the anti-psychotic drugs chlorpromazine and haloperidol and combinations of haloperidol with methylphenidate and amphetamine on the urinary excretion levels of unconjugated meta and para tyramine in the rat have been investigated. With the exception of a high dose of methylphenidate, none of the drug treatments changed significantly the urinary excretion level of para tyramine. meta Tyramine was significantly reduced by a low dose of amphetamine and a high dose of methylphenidate but significantly increased by a high dose of amphetamine. Such effects are different from those reported by Juorio (1977a, b) and Danielson, et al (1976) with respect to the rat striatum and mesolimbic systems where para tyramine was decreased and meta tyramine increased. The effect of adding anti-psychotic drugs in these latter studies was to potentiate their differential effects. Such differences indicate perhaps variations in the metabolism of the tyramines in peripheral tissues as compared with certain brain regions.


Some physiological effects of ketamine in sheep. The effects of intravenous injections of ketamine in sheep on the cardiovascular and respiratory systems are compared with the effects of intracerebroventricular injections of the same drug and also with the effects of intravenous barbiturate and steriod anaesthetics. Intravenously administered ketamine caused an initial fall in arterial blood pressure the extent of which was dose dependent. This depression was short lived and was occasionally followed by a mild pressor phase. Intracerebroventricular injection of the drug provoked only a mild transient rise in mean arterial blood pressure. The intravenous injection of ketamine gave a brief period of respiratory depression which was mirrored in the PaO2 and PaCO2 levels followed by a period of respiratory stimulation with elevated PaO2 levels. The comparison of the three injection anaesthetics showed that the blood gas tensions with ketamine showed there was a brief period of respiratory depression similar to that seen with the steroid anaesthetic but that the barbiturate caused a much longer depression similar to that seen with the steroid anaesthetic but that the barbiturate caused a much longer depression. The blood gas tensions following the steroid anaesthetic soon returned to normal while the tensions following ketamine indicated an elevated PaO2 after the initial depression. The blood gas tensions following intracerebroventricular injection of ketamine were difficult to evaluate due to the variable period of apnoea which followed the injection.


Structural studies on calcium fluoride formation and uptake of fluoride in surface enamel in vitro. The structural changes in human enamel during exposure to an acetate buffer, pH 4, containing 150 parts/10(6) fluoride have been studied using scanning electron microscopy and polarized light microscopy. After exposure for 2 h the enamel surface was covered by a fine-granular layer of calcium fluoride. The underlying enamel was highly eroded with an increased pore volume in the outer layer. Following an equilibration period of 3 months the uptake of fluoride in the apatite lattice had resulted in a highly mineralized, 100-micrometer-thick surface layer rich in fluoride covering a subsurface porous zone with an unchanged fluoride content. The deeply located, caries-like porous zone may have provided calcium and phosphate for saturation of the liquid.


Food-stimulated acid secretion measured by intragastric titration with bicarbonate in patients with duodenal and gastric ulcer disease and in controls. Gastric acid secretion stimulated by a normally eaten beefsteak meal was measured for 4 h in 16 patients with duodenal ulcer disease (DU), in 9 patients with gastric ulcer disease (GU), and in 14 controls by intragastric titration with bicarbonate to a constant pH 5.5. Reproducibility of the method investigated in 6 DU and in 5 controls gave similar acid secretory values (var. coeff. = 7.5%). DU produced acid on a higher level and with longer duration after food than controls and GU (p less than 0.001). Apart from the second half of the first hour after food, when the acid secretion was higher in controls than in GU (p less than 0.025), there was no significant difference in acid output after food between GU and controls. Maximum gastrin values and 'total gastrin output' after food were significantly higher in GU than in controls, but these differences were not significant between GU and DU and between DU and controls. Fasting gastrin and gastrin levels after food were not correlated to basal acid output or acid output after pentagastrin or food in any of the groups. The maximal acid output after food was higher than the peak acid output after pentagastrin in controls, DU and GU. The relation between food- and pentagastrin-stimulated acid output was not statistically significantly different between the three groups. Instead, acid secretion after food was well correlated to acid secretion after pentagastrin in controls, DU and GU (r = 0.85).


Serum group I pepsinogens and gastrin in relation to gastric H+ and pepsin outputs before and after subcutaneous injection of pentagastrin. A conventional pentagastrin test was carried out in 25 patients with dyspeptic complaints, and gastric H+ and pepsin outputs were determined. Blood was drawn before the intubation and 5 and 30 min after subcutaneous injection of pentagastrin, and serum group I pepsinogens (PG I) and serum gastrin were determined by radioimmunoassay methods. A significant correlation was found between serum PG I, on the one hand, and basal gastric pepsin, output as well as pentagastrin-stimulated gastric H+ and pepsin outputs, on the other. Basal serum gastrin was also significantly correlated to pentagastrin-stimulated gastric pepsin output as well as to serum PG I. Pentagastrin failed to induce an increase in serum PG I during the first 30 min.


The influence of salicyl-azo-sulfapyridine on the immune response to antigenic tumour cells inoculated into the coecal lumen of C3H mice. Pretreatment of C3H mice with salicyl-azo-sulfapyridine (SASP) was found to increase the susceptibility of the intestine to malignant ascites cells inoculated into the coecal lumen. The response to intestinal immunization was radically changed by prior treatment of mice with SASP. In non-treated animals protection against a subsequent graft followed the intracoecal inoculation of ascites tumour cells. By prior treatment of the mice with SASP the protective immune response was suppressed and some of the treated animals showed enhanced tumour growth of the challenging graft. The immunological enhancement induced in SASP-treated animals was transferable by spleen cells to untreated mice. In sera from SASP-treated and intestinally immunized animals were found factors which in a competitive manner interfered with the binding of antibodies to antigenic sites on the tumour cell membrane. It is proposed that treatment with SASP modifies the intestinal immunity by suppressing antibody production and increasing production of antigen-specific factors lacking some of the immunoglobulin determinants.


The use of bacteria for the functional characterization of human lymphocyte subpopulations in various lymphoid organs. In a haemolytic plaque assay staphylococcal strain Cowan 1 was shown to induce polyclonal antibody secretion in human blood lymphocytes, whereas Haemophilus influenzae and Escherichia coli gave low responses. Diplococcus pneumoniae and haemolytic streptococci generally did not activate blood cells. All five bacteria could activate spleen, tonsil and adenoid cells both to polyclonal Ig secretion and increased DNA synthesis. Thus blood cell reactivity does not necessarily reflect the response pattern in other lymphatic organs. The adenoid was shown to contain lymphocytes more responsive to bacteria normally residing in nasopharynx than cells residing in other lymphatic organs. On the other hand, spleen and mesenteric lymph node contain a subpopulation of cells highly responsive to bacteria such as Escherichia coli normally residing in the bowel. Therefore, we conclude that there exists a functional compartmentalization of lymphocytes in distinct secondary lymphoid organs.


The role of small rodents and patterns of living in the epidemiology of nephropathia epidemica. The epidemiological role of small rodents and certain human patterns of living for contraction of nephropathia epidemica (NE) was studied by interviewing 46 NE patients and 52 control subjects. The occurrence of small rodents in dwellings and cupboards was significantly commoner among NE patients than among control subjects. The results suggest a connection between NE and small rodents.


Myocardial protection during aortic valve replacement. Physiological and metabolic effects of selective coronary perfusion on the fibrillating heart. The physiological effects and certain aspects of cardiac metabolism were studied in 14 patients undergoing primary aortic valve replacement. The operations were performed under moderate hypothermia (30 degrees +/- 2 degrees C) and blood for coronary perfusion was taken from a sidebranch of the arterial line. The majority of the hearts went spontaneously into ventricular fibrillation at some stage of the operation. In spite of the high resistance measured in the coronary perfusion cannulae, an intraluminar coronary blood flow of 380 ml/min was recorded. The myocardial oxygen uptake decreased to 6.0 ml/min at 29 degrees C compared with 20.0 ml/min at 36 degrees C. The elevated coronary sinus lactate throughout the period of coronary perfusion and the increasing level of ASAT-enzyme indicated that this technique could not fully protect the myocardium from ischaemic changes. One patient died of myocardial infarction and two others needed vasopressor support postoperatively, in spite of documented effective coronary perfusion throughout the procedure. Cannulation of the coronary sinus is a valuable adjunct for the study of cardiac metabolism during ECC and it was accomplished without complications.


[Therapy of headaches. Apropos of 87 cases]. The action of tiapride on headaches has been studied in several neurological departments, both in hospitalized and ambulatory patients. A favourable result was obtained in 63,3% of cases (nearly 2 out of 3). A dosage of 400 mg/day is adequate for an opinion of the efficacy of the product to be made, with the average dosage is about 150 mg/day (1/2 table x 3 times a day). Tolerance  is excellent. Side-effects, wich were noted in 18% of the patients, consist mainly of somnolence and more rarely akathisia. The good results obtained, and the excellent tolerance, enable its use in debilitated alcoholics, the elderly, and those with vascular disorders.


ECT in the treatment of recurrent psychotic depression. Two cases of recurrent psychotic depression are reported in which ECT (electroconvulsive therapy) was administered with good results for previous episodes of depression, but treatment of the current episode with combined drug therapy (antidepressant and antipsychotic drugs) in one case and antidepressant chemotherapy in the other resulted in failure to improve. The patients were transferred to another facility, and improved when ECT was administered. Pertinent literature on ECT and drug treatment of depression is reviewed, and the conditions for which ECT is probably the treatment of choice are enumerated.


Gastric ulceration after a fundoplication operation for gastroesophageal reflux. Gastric ulceration following an antireflux fundoplication procedure is the result of bile reflux into the stomach and not a consequence of gas bloat, antral distention or hypergastrinemia. Whether the bile reflux was present prior to the fundoplication or was a result of fundoplication is not known.


The electron microscopy of "fibrinoid necrosis" in pulmonary arteries. Fibrinoid necrosis was induced in the pulmonary arteries of five male Wistar albino rats by feeding them on a diet adulterated by the addition of 0.07% ground Crotalaria spectabilis seeds by weight. Electron microscopy of the arteries affected by the process showed fibrin in the thrombus occluding their lumens and in the arterial intima, held up from further penetration of the media by the inner elastic lamina. Naturally occurring gaps in this lamina were found, and it is postulated that they determine the characteristic histological configuration of fibrinous vasculosis. The smooth muscle cells of the media of the pulmonary veins showed clear evaginations, devoid of myofilaments and organells, indicative of sustained constriction compatible with viability of the cells. In contrast, the smooth muscle cells of the media of the pulmonary arteries showed loss of myofilaments leading to frank necrosis. Other cells seen in the media include fibrocytes and "vasoformative reserve cells." The authors consider that the latter have considerable and varied potential. Once liberated during the process of fibrinoid necrosis in the arterial media they may play an important part in pulmonary vascular pathology as, for example, in the formation of the plexiform lesion.


HLA-Bw52 in Takayasu disease.

HLA-Bw52 in Takayasu disease. Takayasu disease is characterized by a pulseless condition which most often occurs in young females from Asian or South American areas. The cause of this disease remains obscure. Recently we encountered monozygotic, Japanese identical twin sisters, both of whom were diagnosed as having Takayasu disease. A genetically related factor was considered and HLA analysis was carried out. A population study on HLA typing analyses of 65 patients with Takayasu disease revealed a high frequency of HLA-B5 as compared with 128 healthy Japanese (chi2 :17.0, P less than 10(-4)). Subgroups of B5, Bw51 and Bw52 were successively studied in 82 patients with this disease. Bw51 antigen was found in 12.2% of patients with Takayasu disease and in 19.5% of 128 healthy Japanese. Contrarily, Bw52 antigen was confirmed in 43.9% of patients, a statistically significant frequency with the level of 26.5 in the chi2 test (cP less than 3 x 10(-4)) when compared with 12.5% in normal Japanese. Thus a genetically related factor in the pathogenesis of Takayasu disease has to be considered.


New substrates for the radioassay of angiotensin converting enzyme of endothelial cells in culture. To develop means of measuring angiotensin converting enzyme of endothelial cells in culture, we have synthesized benzoyl-Phe-Ala-Pro-OH (I), benzoyl-Pro-Phe-Arg-OH (II) and benzoyl-Gly-His-Leu-OH (III), each bearing a 3H-atom on the para-position of its benzoyl moiety. All three of the acylated tripeptides are substrates for the enzyme. Substrate I exhibits the lowest Km (12.5 micrometer) and yields the most sensitive assay: the enzyme of 10(6) cells can be measured in a 30 min incubation at 37 degrees C. Radiolabelled reaction product is separated from substrate by extraction of acidified reaction mixture with an organic solvent, and the rate of formation of product can be quantified by liquid scintillation counting of the organic phase. Substrate III can also be used to measure angiotensin converting enzyme of cells but requires longer incubations (180--240 min) and high salt concentrations (0.75 M Na2SO4). Substrate II is not specific: it is hydrolyzed by more than one enzyme of endothelial cells.


Ocular effects of beta-blocking therapy. A survey of 192 patients receiving beta-blocking drug therapy has been carried out. An ophthalmological examination was performed on each patient with particular reference to the clinical status of the cornea and conjunctiva, and to lacrimal function. A selected control group of 52 patients was similarly investigated. The results indicate that the beta-blocking drugs administered to the survey group did not produce any significant adverse effect on the cornea, conjunctiva, or tear secretion when compared with the control group. The findings did not provide any evidence to incriminate the non-practolol beta-blocking agents with the production of ocular pathology.


Relationship of physical symptoms, ECG, free calcium, and other blood chemistries in reinfusion with citrated blood. Changes in ECG, free calcium (CaF), and other biochemical parameters were measured during reinfusion of citrate anticoagulated blood in 12 subjects undergoing plateletpheresis. Physical symptoms during the procedure were also monitored. The CaF was found to correlate best with the Q-oTc interval as compared to the Q-oT, Q-Tc, or Q-T interval. While the correlation was significant (r = 0.592, p less than .001), the Q-oTc could not predict the CaF. A number of other blood constituents were found to change during plateletpheresis, with most directly related to either citrate administration or hemodilution. Severe physical symptoms were found in one subject and no symptoms in three. In the subjects without symptoms the changes in Q-oTc, Pi, alkaline phosphatase, and glucose through the plateletpheresis procedure were different from changes in all subjects. The decrease in glucose level was the most striking single factor correlating with the lack of physical symptoms during the citrate-induced hypocalcemia associated with plateletpheresis. It is concluded that monitoring of the ECG cannot substitute for direct measurement of free calcium in citrate-induced hypocalcemia, that the physical symptoms associated with similar levels of hypocalcemia are variable, that glucose level may be a marker for the effects of citrate-induced hypocalcemia, and that lowered citrate loads during plateletpheresis appear warranted.


[Effect of papaverine on H+ transport in suspension of cat brain mitochondria]. The intravenous administration of papaverin (3 mg/kg) under conditions of acute experiments showed that it is able to induce a considerable increase in intensity of H+ release from mitochondria of the cat brain tissue cells. Taking into consideration the data of previous researches testifying to the fact taht under the papaverine influence there occurs H+ accumulation in cells due to metabolism intensification, it may be suppose that an intensified release of H+ from the mitochondria plays a definite role in vasodilation of the brain by stimulation of the vessels H+-sensitive receptors.


[Effects of oxygen deficiency on rat brain peptide-hydrolase activity with and without hypothermia]. The effect of acute oxygen deficiency on the rat brain peptide-hydrolases (EC 3.4) activity was studied under conditions of acute hypoxic hypoxia (the pressure in altitude chamber 240 mm Hg) with concomitant hypothermia (--5.8 degree C) and without it. The activity of neutral peptide hydrolases decreases by 29% in rats with hypothermia, in animals with normothermia remains unchanged. The activity of acid peptide hydrolases was the control level. The data obtained are compared with those relative to preservation of the content of soluble proteins under hypoxia with hypothermia.


Orchiopexy in prepubertal boys. Five-year survey. A series of 141 prepubertal boys with undescended testes operated on in a provincial teaching hospital has been analyzed five years after operation. The main features noted at presentation were the mature age of the patients and the small number of boys referred by pediatricians. The incidence of unsatisfactory results was 36% in unilateral and 35% in bilateral operations. The majority of the patients (81%) were referred for surgery after the age of five years, commonly regarded as the most suitable time for surgical correction. Three patients required a primary orchiectomy for a small atrophic testis, while 2 patients had an orchiectomy done on a previously operated testis. The complication rate for the series was 4.5%. Testicular biopsy was not done at the time of operation, and no patients were referred for semen analysis. Eight patients underwent a second orchiopexy after the first operation failed. In 6 patients an atrophic testis developed after the second procedure. The need for more than one postoperative examination is stressed in view of the fact that an initially favorable result may not persist since the testes may be found, at a later date, to have retracted into an unsatisfactory position. The reasons for the poor results are discussed and compared briefly with previous reports.


Torsion of undescended testis.

Torsion of undescended testis. Torsion of an undescended testis is uncommon. When encountered, this entity represents a surgical emergency and must be dealt with immediately. A report of 2 cases, one in a five-month-old child and the other in a twelve-year-old mentally retarded child, is made and the pertinent literature is reviewed.


[Peculiarities of amino acids transformation in brain under conditions of acute hypoxic hypoxia]. Acute 15, 30 and 60-minute hypoxia induced in a rabbit placed in the altitude chamber at the atmospheric pressure of 260 mm Hg was an experimental model for a hypoxic state. An increase in the amount of aspartate in the brain under conditions of 15-minute hypoxia and its decrease with prolongation of the hypoxia period up to 1 h may be explained by different mechanisms of amino acids metabolic transformations under these conditions. Changes in the content of aspartate are adequate to these in the activity of aspartate aminotransferase. An increase in the glutamate content in the brain the 30- and 60-minute hypoxic effect is accompanied by a rise of the activity in the glutamine synthesis enzyme (glutamine synthetase). Dynamics of the aspartate quantitative changes in the brain in different periods of acute oxygen deficiency affecting metabolic shifts in amino acids metabolism may serve as an index of the hypoxic effect gravity.


[Determination of carboanhydrase activity in blood erythrocytes]. A simple method is suggested for accelerated determination of carboanhydrase activity (in 0.01 ml of blood or other biological liquid for 3.0--4.0 min). The method is based on the ability of erythrocytes carboanhydrase to induce specifically carbonic acid gas hydration accompanied by formation of carbonic acid. The latter changes the medium reaction from alkaline (pH9,0) to slightly acid (pH 6.0). The reaction end is fixed by an acid-alkaline indicator (or automatically) according to the time of the solution color changes. A simple design is developed for the device to obtain the substrate which removes the factors affecting negatively the reaction course; the optimal concentration of reagents are selected and a new indicator-buffer mixture having no inhibitatory effect on the carboanhydrase activity is used.


Selective testicular venography for localization of nonpalpable testis. Selective testicular venography is a safe, accurate outpatient procedure for preoperative localization of a nonpalpable testis. It may obviate surgery if testicular agenesis is identified or expedite surgical exploration by precise preoperative localization of the undescended testis.


The metabolites of procaterol HCl in urine and faeces of dog and man. 1. The metabolites of procaterol HCl in dog urine and faeces and in human urine were qualitatively analysed by an improved g.l.c.-mass spectrometric method. 2. Trimethylsilylated derivatives of procaterol metabolites were identified by mass fragmentography as procaterol glucuronide, 5-(2-amino-1-hydroxybutyl)-8-hydroxycarbostyril (desisopropylprocaterol), 5-formyl-8-hydroxycarbostyril, 8-hydroxycarbostyril and unchanged procaterol. 3. The metabolic pattern of procaterol HCl was species-independent in rats, dogs and man.


Effect of generalized graft-versus-host-reaction on B- and T-lymphocytes and a benzpyrene-induced murine sarcoma. The investigations of 400 adult hybrids from A/Jax fem. BALB/c male were aimed at answering the following questions: 1. What is the influence of a generalized graft-versus-host-reaction (GVHR) on the induction and growth of benzpyren-induced sarcoma? 2. What is the behavior of B- and T-lymphocytes during GVHR, and during induction and growth of benzpyren-induced sarcoma? 3. Which are the deductions to be drawn with regard to the effect of B- and T-lymphocytes during tumorigenesis and tumor growth? 1. The number of tumors was significantly greater in the GVHR animals (74.5%) than in the controls (49.5%). 2. A significant decrease of T-lymphocytes and increase of B-lymphocytes during GVHR were found in the peripheral blood. 3. The examination of the tumor marginal zone showed a marked decrease of the total round cell count and the T cells, while the count of B-lymphocytes remained uninfluenced. These results are discussed and compared with results of other authors.


Purification and properties of rennin-like enzyme from Aspergillus ochraceus. An active milk-clotting enzyme was purified some 40-fold from culture supernatant of Aspergillus ochraceus. The purification steps included ammonium sulfate precipitation, G-100 Sephadex gel filtration, and ion exchange chromatography, using DEAE Cellulose column. The enzyme exhibited milk-clotting activity and proteolytic behaviour, an optimum at pH 6.0 and in the range of 7--8.5, respectively. The purified enzyme was actively proteolytic against casein, haemoglobin, and bovine serum albumin at pH 8. The milk-clotting activity was greatly enhanced by manganous ions and by increasing concentrations of calcium chloride. Copper, zinc, and ammonium ions were potent inhibitors of the milk-curdling activity of the purified enzyme. Significant inhibition was also noted with sodium chloride at concentrations of 3% or more. Under the specified reaction condition, maximum rate of proteolysis against casein was obtained at 0.4% substrate concentration, whereas the milk-clotting time was linear proportional to dry skim milk concentration in the range of 8 to 24%. The results are discussed in comparison with other microbial milk-clotting enzymes, and limitations of applicability are also presented.


Dynamics of microbial population in soil as influenced by simazine and ecological factors. Simazine, even at normal rates of application, showed toxicity to bacteria fungi. It was less toxic to actinomycetes, since toxicity up to 20 ppm of the herbicide was not observed. On the contrary, the normal rate of simazine stimulated both Azotobacter and actinomycetes population. The interaction of simazine with soil ecological factors, such as temperature, moisture, pH, and organic matter, affected soil microbial population differently. Simazine was relatively less toxic to bacteria under acidic and alkaline conditions of soil; they were not affected at 15 degrees C. Actinomycetes were comparatively not adversely affected even with 200 ppm of simazine under high soil moisture regime. The stimulatory effect of simazine on Azotobacter was also confirmed under different ecological conditions. The incorporation of 2 per cent of organic matter in soil mitigated the toxicity of simazine in respect to soil fungi. Simazine also appeared to be less toxic to soil fungi at lower temperatures, under acidic and alkaline conditions of soil, as well as under high moisture regime.


L-Histidine ammonia-lyase activity of axenically grown Hartmannella culbertsoni. 1. Histidine ammonia-lyase (EC 4.3.1.3) activity in the cell-free extracts of Hartmannella culbertsoni has been partially purified and the optimum activity is found at pH 9.0--9.2. 2. The enzyme required sulphydryl groups for its activity. L-2-Thiohistidine and EDTA competitively inhibit the enzyme. 3. Its molecular weight, as determined by gel filtration technique, is 131,800 daltons and the energy of activation for this enzyme is 15,205 cals/mole. 4. Certain amoebicidal drug and divalent cations have marked inhibitory effect on the enzyme. Co2+ has a profound stimulatory effect.


[Role of B-lymphocytes in inactivating allogenic stem cells]. Antisera to membrane antigens of B lumphocytes eliminated the capacity of lymphocytes to inactivate allogenous stem cells by 60%; however, lymphocytes from the lymph nodes of B mice possessed no inactivating capacity. T-lymphocytes were the main criteria inactivating allogenous stem cells. Cooperating with T-lymphocytes, B-lymphocytes probably contributed to inactivation of precursor cells realized by T-lymphocytes. However, the presence of B-lymphocytes in the killer cells population was not a determinant, since T-lymphocytes were capable of inactivating allogenous stem cells without any participation of B-lymphocytes.


Effects of bile acids, antacids, and cholestyramine on transmural electrical potential difference in man. The effect of glycocholic acid (GCA) on functional changes of the gastric mucosal barrier was examined by measurement of transmural gastric potential difference (PD) in humans in the presence and absence of cholestyramine and of A1(OH)3-containing antacids possessing potent bile acid binding properties. Intagastric instillation of GCA induced reduction of PD which could be prevented by the more potent buffering Mg-A1(OH)3-containing antacid, but not by cholestyramine or the less potent A1(OH)3-containing antacid. It is concluded that for the prevention of bile acid induced damage of gastric mucosa potent antacids are superior to potent bile acid binding agents loosing the binding properties at low pH-values.


Effect of histamine-H2-receptor antagonists on the exocrine pancreatic secretion. Pancreatic exocrine secretion has been studied in 10 patients with documented duodenal ulcer before and after 4 weeks of cimetidine treatment (1 g/die). This chronic 'short term' cimetidine administration did not result in any substantial modification of exo-pancreatic response stimulated by Secretin and Caerulein. From this point of view the drug could be employed in the treatment of pancreatic insufficiency in order to obtain a better utilization of pancreatic enzyme supplement. It is, however, questionable if such a 'long-term' therapy may be responsible for the appearance or the relapse of a peptic ulcer.


Effects of acute hypercapnia and hypocapnia on plasma and red cell potassium, blood lactate and base excess in man during anesthesia. In order to test the relationship between changes in plasma potassium concentration and pH changes of respiratory origin, we produced hypercapnia (mean PaCO2 71 mmHg = 9.5 kPa) in a group of 17 patients and hypocapnia (mean PaCO2 21 mmHg = 2.8 kPa) in another 20 patients during neurolept analgesia and intraabdominal operations. A control group of 19 patients was studied under normocapnia but otherwise identical conditions. During hypercapnia, serum potassium rose, deltaK/deltapH amounting to -0.82, -1.05 and -1.34 after 30, 60 and 90 min, respectively. During hypocapnia, serum potassium decreased, deltaK/deltapH being a little more negative than during hypercapnia (mean values -1.62, -2.44 and -1.60). Red cell potassium concentration decreased in all three groups to a similar extent. Blood lactate levels during hypercapnia decreased to 75% of control and during hypocapnia rose to a maximum of 186% of control. In order to obtain reasonable values for base excess in primarily respiratory acid-base disorders, it is necessary to use nomograms based on in vivo ECF-CO2-titration curves. With this premise, hypercapnia or hypocapnia in our patients was not associated with significant changes in base excess.


Influence of morphine anaesthesia on the endocrine-metabolic response to open-heart surgery. Twelve patients scheduled for aortic valve replacement during extracorporal circulation were randomly allocated to either morphine anaesthesia or fluroxene anaesthesia. Morphine in a total dose of 4 mg/kg was administered before skin incision. At the start of extracorporal circulation all patients received 25 g glucose intravascularly. The endocrine-metabolic response to surgery, as expressed by changes in plasma ACTH, cortisol, insulin, growth hormone, cyclic adenosine-3',-5'-monophosphate (cyclic AMP), glucose, free fatty acids, blood b-hydroxybutyrate and cumulative nitrogen balance was measured before and during anaesthesia and surgery, and on the first five post-operative days. It was found that morphine anaesthesia blocked the increase in ACTH, cortisol, growth hormone, cyclic AMP, and glucose during surgery. However, after initiation of extracorporal circulation only ACTH, cortisol, and, to a lesser degree, the glucose and insulin response to glucose were lowered by morphine anaesthesia. From the first to the fifth days after operation no differences between the two groups could be demonstrated in any parameter. Cumulative nitrogen balance was similar in the two groups. It is concluded that morphine in large doses administered before skin incision inhibits the initial endocrine-metabolic response to open-heart surgery, but that the effect is short-lasting and without effect on overall postoperative protein catabolism.


Pressure passive cerebral blood flow and breakdown of the blood-brain barrier in experimental fetal asphyxia. Cerebral blood flow (CBF) was studied in non-exteriorized near-term sheep fetuses using the radioactive microsphere technique. By partially occluding the umbilical vessels for a period of 1--1 1/2 hours a progressive and severe asphyxia with a final arterial pH of 6.90 was achieved. Varying the mean arterial blood pressure in the fetuses by blood withdrawal or infusion in this state, CBF was measured at different perfusion pressures (mean arterial blood pressure (MABP) minus central venous pressure (CVP)). A passive flow/pressure relationship--loss of autoregulation--was found, with hyperemia reaching CBF values up to 6 times normal at normal MABP of about 60 to 70 mmHg, and severe ischemia reaching CBF values close to zero in large cortical areas at MABP of 30 mmHg. CVP remained essentially unchanged at 10--15 mmHg. The severe and prolonged asphyxia rendered the blood-brain barrier leaky to the albumin tracer Evans blue. In four other fetuses umbilical cord clamping was omitted. However, only in one of these cases was acidosis completely avoided, and CBF autoregulation maintained. The three other fetuses were acidotic at the end of the surgical procedure and had impaired autoregulation.


More on cross-reactions of Pneumococci and Klebsiella. Earlier studies are extended to the higher-numbered K-types of Klebsiella, several of which may now be fitted into the previously found groups. Additional correlations between chemical structure and serological specificity are given, not only among the higher K-types, but also for several which were previously uninterpretable because structures were not known at the time. K1, K5, K6, K7 and K56 are shown to form a related group, although the reasons for their cross-reactivities are not always the same.


California encephalitis group viruses isolated from mosquitoes collected in Southern and Arctic Norway. Three virus strains serologically related to the California encephalitis group (Bunyaviridae) of arboviruses were isolated from 7331 mosquitoes collected in Norway in June-August 1975. Two of the isolates (S 548 and S 618) seemed to be closely related and the third, S 568, more distantly related by serological techniques to Tahyna virus. Viruses were found in the mosquito species Aedes sticticus, A. diantaeus and A. hexodontus colllected (in order) from Oyern (59 degrees N, 11 degrees 12' E), Trandum (60 degrees 08' N, 11 degrees 10' E) and Masi (69 degrees 26' N, 23 degrees 39' E). The Masi isolate seems to be the northernmost arbovirus isolate in the world so far. Strain S 568 was from 16 male A. diantaeus, indicating transovarial transmission of the virus. An accidental infection demonstrated the potential human pathogenicity of one of the newly-isolated strains (S 568), and the ability of CE viruses to persistently infect suckling mouse brains was indicated by in vivo findings. The biological characteristics of the new strains so far investigated are consistent with those of the California encephalitis group. During this work the Aerosil absorption method for production of haemagglutinating antigens proved useful for Tahyna virus and the newly-isolated strains. Trypsinization of erythrocytes improved the haemagglutinating capacities of these viruses.


New evidence that demonstrates that L-pro-L-leu-L-gly-NH2 might be the natural MIF. A wide range of doses was used to study the effect of Pro-Leu-Gly-NH2 (MIF) on the MSH release in rat pituitaries incubated in vitro. The Pro-Leu-Gly-NH2 was added to one half of the gland, and the other was used as control. The MSH released into the medium was measured by a bioassay and the activity of the samples referred to a standard of synthetic alpha-MSH. Pro-Leu-Gly-NH2 in doses of 10 to 30 ng/ml inhibited the MSH release in about 60%. Doses between 10(3) to 10(4) ng/ml induced neither release nor inhibition of the release of MSH. Dose of 10(5) ng/ml clearly induced release of MSH. The results of the additional experiments presented, although they represent no proof, are in line with the contention that Pro-Ley-Gly-NH2 in the natural MIF.


Effect of intraantral pH on basal gastrin release into the circulation and antral lumen in anesthetized cats. In acute experiments on cats antral pouches were perfused with solutions of different pH (1-13). After antrum passage the gastrin levels in the perfusates were measured with radioimmunoassay and the amounts of gastrin released into the antral lumen per minute calculated. The venous gastrin levels were determined concomitantly. Small amounts of gastrin (1,000--1,500 pg/min) were released into the antrum during perfusion with 0.1 M HCl. Subsequent perfusion with 0.15 M NaCl (pH 6.8) did not significantly increase the release of gastrin. On the other hand, 0.1 M phosphate buffer (pH 7.4) caused a dramatic augmentation of the gastrin output into the antral lumen (approximately 17 fold). A concomitant increase of peripheral gastrin levels was observed. Also other alkaline solutions such as 0.15 M NaHCO3 (pH 8), 0.15 M Tris buffer (pH) or 0.01 and 0.1 M NaOH (pH 12 and 13) promoted the release of gastrin. It is discussed whether the gastrin release at alkaline pH is induced by the alkaline pH itself or by anions such as HPO-4, HCO-3 and OH-. The apparent effect of pH could then be due to the formation of these ions at higher pH.


Cottonseed protein derivatives as nutritional and functional supplements in food formulations. Cottonseeds contain protein with desirable food functional and nutritional properties. Storage globulins make up most of the protein stored in cottonseed and can be separated into five fractions by gel filtration chromatography. Each fraction is distinguishable from the other by its amino acid and polyacrylamide gel electrophoretic properties. Proteins of cottonseed contribute greatly to the functional properties of emulsions, co-isolates, and texturized derivatives. For example, increasing the amount of high protein cottonseed flour in wheat suspensions from 2% to 10% improved the capacity (54-97 ml of oil) and viscosity (5,000-100,000+ cps) of emulsions. The 10% suspension formed emulsions with increasing oil capacity (84-100 ml) and viscosity (28,000-100,000+ cps) as the pH was adjusted from 4.5 to 9.5. Consistencies of the products ranged from that of salad dressing (low percent suspensions, or acid pH) to that of mayonnaise (high percent, or basic pH). These data were utilized to derive a multiple regression model to predict optimum use of cottonseed proteins in emulsions of varying consistencies. A coprecipitated isolate containing greater than 94% protein was prepared from a blend of cottonseed and peanut flours. Amino acid content of the co-isolate reflected that of the protein in the two flours of the composite. The co-isolate has lower gossypol level and improved color and functional properties than a cottonseed protein isolate. Storage protein isolate of cottonseed suspended in aqueous solution and heated with constant stirring forms a texturized product; the quality of the product depends on heat, pH, salt, and the quantity of nonstorage proteins. Protein and amino acid content of meat products were improved by the addition of the texturized protein of cottonseed.


Thermal and vortical stability of purified human fibroblast interferon. The loss of biological activity upon heating or agitation of human interferons is markedly altered by changing their aqueous environment. Low pH significantly stabilizes liquid fibroblast interferon at 68 degrees C and 37 degrees C whereas chaotropic salts stabilize at 68 degrees C but not at 37 degrees C; this anomalous result may be due to reactivation of biological activity at the higher temperature. The concentration of extraneous proteins influences the apparent thermal stability at any temperature and pH; thus, interferon was not stable even at low pH at protein concentrations less than 5 microgram/ml. Solutions of partially purified fibroblast interferon can be inactivated by mechanical stress; the addition of proteins or nonionic detergents prevents such inactivation. Freeze-dried preparations show the greatest thermal stability. The use of high-temperature, accelerated storage tests makes it possible to predict the shelf-life of freeze-dried interferon.


Growth of infective forms of Trypanosoma (T.) brucei on buffalo lung and Chinese hamster lung tissue culture cells. Infective cultures of Trypanosoma (T.) brucei (strain 427) have been initiated and maintained on Chinese hamster lung tissue culture cells and buffalo lung tissue culture cells. By changing daily one-third of the RPMI-1640 plus 20% fetal bovine serum medium, the cell numbers can be maintained at 2--4 X 10(6) cells/ml. The cultured trypanosomes on these two tissue culture cell types were infective to mice and morphologically similar to bloodstream slender trypomastigotes in having a subterminal kinetoplast and a surface coat. In addition, they possessed the L-alpha-glycerophosphate oxidase, the predominant steady state terminal oxidase identified in bloodstream trypomastigotes.


The in vitro interaction of Trypanosoma cruzi bloodstream forms and mouse peritoneal macrophages. The uptake and further development of bloodstream forms from T. cruzi Y and CL strains in mouse peritoneal macrophages have been investigated. Parasites from the Y strain (which present predominance of slender forms) are 20 to 30-fold more infective to macrophages than those from CL strain in which stout forms highly predominate. A complete amastigote-trypomastigote cycle is observed in normal or thioglycollate-induced macrophages infected with parasites from both strains.--Opsonization significantly increases the uptake by normal macrophages of parasites from both strains. The fate of the opsonizated parasites is, however, different: the Y trypomastigotes present a normal cycle which culminates with the release of newly formed trypomastigotes whereas CL parasites are extensively destroyed by normal macrophages.--The differences in the uptake and fate displayed by both T. cruzi populations are not well understood. They are apparently related to parasite membrane components or macrophage receptors differences, which are probably influencing endocytosis and the further intracellular development of the parasites.


The influence of hydroxyurea and colchicine on growth and morphology of Trypanosoma cruzi. Cultures of Trypanosoma cruzi have been exposed to the drugs hydroxyurea and colchicine. We found that hydroxyurea (200 microgram/ml) completely inhibited growth and differentiation of T. cruzi Y strain. Colchicine (200 microgram/ml) reduced the growth of T. cruzi 30% and stimulated cell differentiation from epimastigotes to trypomastigotes. Furthermore it caused anuclear cells with apparently intact kinetoplasts. The possible use of these anuclear forms in studies on kinetoplast DNA organization and expression is suggested.


Generation of free radicals from phenazine methosulfate in Trypanosoma cruzi epimastigotes. A significant growth inhibition of Trypanosoma cruzi epimastigotes by phenazine methosulfate (PMS) was observed in Warren's medium. This toxic activity could be related to the following parameters: a) formation of phenazinium free radical, b) generation of superoxide anion in intact cells incubated with PMS, and c) PMS also increased significantly the rate of O2- generation in epimastigotes mitochondrial and microsomal fractions using NADH as electron donor.


Effect of ethidium bromide on growth and morphology of Leishmania tarentolae promastigotes in vitro. Incubation of Leishmania tarentolae promastigotes in 0.01 microgram/ml ethidium bromide in Neo Ye medium for 96 h resulted in 60% inhibition of cell growth and 91% dyskinetoplasty. After 48 h incubation in ethidium bromide over 50% of the cells were scored dyskinetoplastic by light microscopy although the electron microscopical examination revealed that most promastigotes contained at least a small amount of kDNA. A few of the treated cells undergoing division contained two kinetoplasts--one devoid of kDNA and the other with a reduced amount of kDNA as seen in the electron micrographs.


Excretion of uric acid and amino acids during diuresis in the adult female Glossina morsitans. Radiometric analysis was carried out on the urine collected for one hour following feeding of the adult female Glossina morsitans on day 1 of a pregnancy cycle, which had previously received haemocoelic injections of U-14C labelled arginine, histidine, leucine, lysine, phenylalanine, threonine, tyrosine or valine. Mean radioactivity in the urine was quite high after labelled arginine (17.4% of injected activity) and histidine (21.8%) administration, most of the activity being in the amino acid fractions. With the remaining six labelled amino acids, mean radioactivity in the urine varied between 1.6 and 7.2% of injected activity, most of this activity occurred in a non-amino acid fraction (probably uric acid), though low radioactivity was also detected in a range of essential as well as non-essential amino acids.


Ectopic lesion of schistosomiasis of the penis simulating an early carcinoma. A case of ectopic lesion of Schistosoma haematobium of the penis with extensive tissue destruction, simulating an early carcinoma of the penis and almost resulting in an autoamputation of the crown of the penis, is presented. The penis was surgically repaired and the patient treated with ambilhar. In schistosoma endemic area, it is important to think of ectopic schistosoma lesion by such a presentation. Existing theories to explain the presence of schistosoma eggs in locations outside the portal-caval system were reviewed and another one was advanced: its being sexually transmitted.


Immunological studies on onchocerciasis. Varying skin hypersensitivity and leucocyte migration inhibition in a clinical spectrum of the disease. Soluble antigen was prepared from adult worms and microfilariae of Onchocerca volvulus. In 27 patients clinically characterized as having generalized type (17) and localized reaction type (10) onchocerciasis, the response to this antigen was assessed in vivo by skin testing and in vitro by leucocyte migration inhibition assay. Three varieties of skin hypersensitivity were observed: Immediate, Arthus-type and delayed or type IV hypersensitivity. The first 2 occurred in all patients, but type IV  hypersensitivity was noted only in 10, eight of whom had localized reactive type onchocerciasis, whilst the other 2 had mild generalized lesions which had for the most part healed with treatment. The leucocyte migration inhibition assay showed a spectrum of responsiveness with significant inhibition in the presence of antigen in 8 patients with localized lesions and in 2 others with mild generalized disease which had largely healed.--The specificity of the skin reaction and leucocyte migration inhibition to the antigen used was confirmed by the results obtained when a control group of 18 subjects, with no evidence of previous filarial infection, was similarly tested. 16 of them showed no skin hypersensitivity and 2 had a doubtful immediate reaction. No significant inhibition of leucocyte migration in the presence of antigen was noted in this group.


The use of mebendazole in the treatment of Taenia saginata taeniasis in an endemic area in the Philippines. The successful treatment of Taenia saginata taeniasis with mebendazole is herein reported. 41 subjects ascertained to have taeniasis based on the history of passage of gravid segments and positivity for Taenia egg were treated with 300 mg mebendazole b.i.d. for 3 days without need for fasting. No side-effects were observed. The drug acts as a taeniacide. The worms were expelled either as degenerated boluses or fragmented segments on the 2nd to the 4th day (Mean: 2.4 days) after the initial dose. 33 (84.6%) of the 41 subjects expelled the worm. A follow-up of all the subjects 2--3 months after treatment revealed that all those who expelled the worm following treatment and 6 of those who did not were negative for both Taenia egg and gravid segment, or a cure rate of 95%.


The parotid and the pancreas. V. Effects of a synthetic prostaglandin analog on parotid gland secretion. Effects of a synthetic prostaglandin analog--16,16-dimethyl prostaglandin E2 methyl ester (16-diMe-PGE2)--on parotid secretion were evaluated in eight dogs under anesthesia. Graded doses of 16-diMe-PGE2 (0.3, 0.5, 1.0 and 2.5 microgram./kg.) were administered intravenously with the parotid in the resting state or in response to urecholine (intravenous infusion or subcutaneous injections). Profound and prolonged inhibition of volume occurred. Amylase concentration was increased but output was unchanged. Bicarbonate concentration was increased but output was decreased. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects. Although these studies do not establish a physiologic role for prostaglandins in the regulation of salivary secretion, they do demonstrate a wide-ranging effect of prostaglandins on the gastrointestinal tract.


Cefoxitin sodium compatibility with intravenous infusions and additives. The compatibility and stability of cefoxitin sodium in solution with a series of frequently used intravenous infusion fluids and injectable additives were studied. Cefoxitin sodium's stability in various solutions was measured by ultraviolet spectrophotometry, iodometry, thin-layer chromatography, high-pressure liquid chromatography, ion-exchange chromatography and microbiological assay. Cefoxitin sodium was shown to maintain 90% of its initial concentration in aqueous solution for 40 hours at room temperature (25 C) and about 30 days at 5 C. The stability of cefoxitin sodium in common i.v. infusion fluids was independent of the concentrations (1 mg/ml to 400 mg/ml) and containers used, and was retained after 30 weeks storage at -20 C. Similar stability patterns were demonstrated for cefoxitin sodium in protein hydrolysate solutions and multivitamin formulations. Cefoxitin sodium was chemically and visually compatible with amikacin sulfate, gentamicin sulfate, kanamycin sulfate and tobramycin sulfate when admixed with normal saline or 5% dextrose in water injections. Cefoxitin sodium (397 mg/ml) in 0.5% lidocaine hydrochloride was stable after 26 weeks of storage at -20 C. Sodium cefoxitin is compatible with a wide variety of commonly used infusion solutions. Its stability is independent of concentration or pH within the ranges studied, and of types of common containers.


Effect of oxygen at high pressure on spontaneous transmitter release. The effect of oxygen at high pressure (OHP) on resting membrane properties (effective membrane resistance (Reff) and membrane potential (Vm)) and the spontaneous release of excitatory transmitter were examined at the lobster neuromuscular junction. Pressurization with 100% oxygen to 150 pounds per square inch gauge pressure (psig) or with nitrogen to 150 psig (7,000 mmHg nitrogen and 135 mmHg oxygen) produced a decrease in Reff associated with a hyperpolarization of Vm. These changes, however, returned to control values within 20--30 min after completion of pressurization. Spontaneous release of excitatory transmitter was shown to increase dramatically in the presence of 100% oxygen at 150 psig. The increase in miniature end-plate potential (MEPP) frequency persisted beyond the transient changes seen with Reff and Vm. This effect was selective to oxygen, as pressurization with nitrogen did not produce an increase in MEPP frequency. No change in average MEPP amplitude was seen with either OHP or pressure alone. An OHP-induced increase in MEPP frequency was also seen at the frog neuromuscular junction. The results indicate that both glutamate-mediated and acetylcholine-mediated synaptic transmission are altered by OHP.


Influence of pH on elastic deformability of the human erythrocyte membrane. Fresh human blood was diluted 1:5000 in buffered saline-sucrose solution and titrated to a pH varying from 4.5 to 10.5 with 0.1 N HCl or 0.1 N NaOH. Circular regions of the membrane of individual cells were then deformed at 25 degrees C by aspiration into a micropipette having an internal tip diameter of 0.9-1.4 micron. A membrane surface elasticity modulus, mu (dyn/cm), was computed from the relationship between length of the aspirated membrane and the deforming pressure according to a two-dimensional membrane model. Surface elasticity increases with decreasing pH and with time after the cell suspension is acidified, rising several orders of magnitude with a t1/2 of 1--5 h as pH is lowered from 7.2 to 4.6. This increase in mu is only partially reversible. pH greater than 7.2 had little effect on mu. Membrane surface elasticity is not affected by variations in external [Ca2+] over the range of 0--50 mM, tonicity of the suspension medium from 275--400 mosM, or age of 0--50 h. Addition of 50 mM NaHCO3 to the medium increases the rate of change of mu at a given pH. These results suggest that the elastic properties of the red cell membrane are largely determined by interactions among structural proteins located on the cytoplasmic surface of the membrane and that these interactions are initiated by changes in intracellular pH.


Interrelationship between chloride fluxes in pancreatic islets and insulin release. The role of Cl- in the function of pancreatic beta-cells was studied by using islets of noninbred ob/ob mice. 36Cl- was rapidly taken up by islet cells; apparent isotope equilibrium was reached within 30 min. The apparent distribution ratio was 0.50--0.72 in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) medium and about 1.1 in Krebs-Henseleit medium. Uptake of 36Cl- was inhibited by 2,4-dinitrophenol, increased by ouabain, and not affected by omission of K+, Na+, or Ca2+. D-Glucose increased short-term uptake of 36Cl- but decreased the equilibrium content. Efflux of 36Cl- from prelabeled islets approached first-order kinetics with a half-life of about 5 min, was inhibited by 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid or low temperature, was stimulated by D-glucose, D-mannose, or hydronium ion, and was unaffected by L-glucose or 3-O-methyl-D-glucose; D-manno-heptulose abolished the effect of D-glucose. Insulin secretion in response to D-glucose was reversibly inhibited in Cl- -deficient media. It is suggested that Cl- is nonpassively distributed across the beta-cell plasma membrane. D-Glucose-induced depolarization of  beta-cells may partly be mediated by an increase of the Cl- permeability.


Subcellular distribution of nucleotide cyclases in rat intestinal epithelium. The subcellular distributions of adenylate cyclase and guanylate cyclase were determined for the mature enterocyte from the rat duodenum. Brush-border and basolateral membranes were prepared from isolated cells by an analytical isolation procedure, and multiple linear regression analysis was used to obtain a quantitative estimate of the distribution of recovered cyclase activities between the brush borders and basolateral membranes. Adenylate cyclase was largely confined to the basolateral surface of the epithelium, whereas guanylate cyclase was found on the brush-border and basolateral membrane fractions in the ratio 2.4:1. There was no evidence for the presence of nucleotide cyclases in the cytosol. Guanylate cyclase in both the brush-border and basolateral membranes was stimulated by epinephrine, insulin, and Triton X-100, but not by carbachol. Adenylate cyclase was not influenced by epinephrine, but was markedly stimulated by NaF and vasoactive intestinal peptide. These results are discussed in relation to the effects of hormones on transport across the small intestine.


Pancreatic response to intestinal perfusion with lactic acid or acidified albumin. To test the hypothesis that the permeability of weak acids across the intestinal mucosa affects their ability to stimulate pancreatic bicarbonate output, we compared pancreatic bicarbonate secretion in response to intestinal perfusion with an acid presumed to be permeable to cell membranes, lactic acid (90 daltons), and an acid presumed to be impermeable, acidified bovine serum albumin (about 70,000 daltons). These two substances have similar titration curves from pH 2.00 to pH 4.50. In four conscious dogs with pancreatic fistulas, solutions of these weak acids were perfused at 50 ml/15 min into the intestine at concentrations adjusted to deliver 1, 2, or 4 mmol/15 min of acid titratable to pH 4.50 (threshold pH for bicarbonate stimulation) from an initial pH of 2.00 or 3.50. At both pH 2.00 and 3.50 and at all titratable acid loads, bicarbonate secretory responses to lactic acid and acidified albumin were not significantly different. Equal titratable acid loads of HCl produced much larger secretory responses. The data do not support the hypothesis that permeability of weak acids is a factor, but confirm the observation that weak acids are less potent than strong acids in stimulating pancreatic bicarbonate secretion.


Importance of chloride for acute inhibition of renin by sodium chloride. To evaluate the contribution of chloride to acute renin inhibition by sodium chloride, plasma renin activity (PRA) was measured before and after peripheral venous infusion of NaCl, NaHCO3, NaBr, NaNO3, lysine monohydrochloride, or lysine glutamate in NaCl-deprived rats. In contrast to controls and animals infused with other sodium salts, PRA decreased (P less than 0.01) after infusion with NaCl [from 28.3 +/- 2.8 to 13.3 +/- 1.8 ng/ml per h (SE)] and NaBr (from 40.6 +/- 6.2 to 21.8 +/- 3.9 ng/ml per h), and renal tubular halide reabsorption increased (P less than 0.05). Arterial pressure, plasma volume, inulin clearance, net sodium balance, serum Na+ and K+, and pH were not different among sodium-loaded groups. PRA was also suppressed (P less than 0.01) by infusion with lysine monohydrochloride (from 51.6 +/- 5.4 to 32.4 +/- 5.1 ng/ml per h) but not with lysine glutamate. These results suggest that inhibition of renin by sodium is dependent on an intrarenal effect of chloride. During infusion with sodium salts which suppressed renin, negative free water clearance (TcH2O) increased, whereas infusion with sodium salts that did not inhibit renin resulted in either no change or decreased TcH2O. The association of renin inhibition and increased TcH2O indirectly supports the hypothesis that renin suppression by chloride is related to the magnitude of absorptive chloride transport in the thick ascending limb of the loop of Henle.


Temporal stability and precision of ventricular defibrillation threshold data. Over 200 measurements of the minimum damped sinusoidal current and energy for transchest electrical ventricular defibrillation (ventricular defibrillation threshold) were made to determine the stability and precision of threshold data in 15 pentobarbital-anesthetized dogs. Threshold was determined by repeated trials of fibrillation and defibrillation with successive shocks of diminishing current, each 10% less than that of the preceding shock. The lowest shock intensity that defibrillated was defined as threshold. In three groups of five dogs each, threshold was measured at intervals of 60, 15, and 5 min over periods of 8, 5, and 1 h, respectively. Similar results were obtained for all groups. There was no significant change in mean threshold current with time. Owing to a decrease in transchest impedance, threshold delivered energy decreased by 10% during the first hour of testing. The standard deviations for threshold peak current and delivered energy in a given animal were 11% and 22% of their respective mean values. Arterial blood pH, Pco2, and Po2 averaged change of pH, PCO2 and PO2 were not significantly different from zero. The data demonstrate that ventricular defibrillation threshold is a stable physiological parameter that may be measured with reasonable precision.


Pulmonary capillary pressure in intact dog lungs. We used a gravimetric method to determine the ratio (gamma) of pulmonary venous to total pulmonary vascular resistance in intact dog lungs. From this ratio, pulmonary capillary pressure (Pc) can be calculated. The average value of gamma was 0.50 +/- 0.06 (mean +/- SD) in 10 dogs. We found no correlation between gamma and PO2, PCO2, pH, or hematocrit in the narrow ranges of these experiments. Over the capillary pressure range of 22.4--35.2 mmHg we found no correlation between gamma and Pc. The value of gamma found in this study is not significantly different from the value found in isolated perfused lungs.


Impressions of psychiatric problems and their management: China, 1977. The authors, who visited the People's Republic of China in October 1977, describe the treatment methods used there, particularly in the Shanghai Mental Hospital, a 1,000-bed hospital for acutely ill patients. Psychiatric treatment there appears to be a blend of Western pharmacology, traditional Chinese medicine, and group therapy. The authors also speculate on the possible cultural sources of stress-related and interpersonal problems, provide a review of the literature regarding psychiatry in modern China, and outline the history of psychiatric treatment there.


Factors related to tardive dyskinesia.

Factors related to tardive dyskinesia. The authors found a 31% incidence of tardive dyskinesia among 261 schizophrenic outpatients treated with neuroleptics. Multiple linear logistic regression analysis revealed a higher incidence of tardive dyskinesia among elderly patients, those with longer records of hospitalization, those for whom neuroleptic medication had little therapeutic effect, and those treated with fluphenazine. Patients manifesting tardive dyskinesia tended to have fewer parkinsonian symptoms than those without the disorder, especially when tremors and akathisia were excluded from consideration. Multiple linear regression analysis indicated that brain-damaged patients and male patients were more susceptible to severe forms of the disorder, even though these factors were not implicated in its initial appearance.


Eastern equine encephalomyelitis in upstate New York: studies of a 1976 epizootic by a modified serologic technique, hemagglutination reduction, for rapid detection of virus infections. An extensive outbreak of eastern equine encephalomyelitis (EEE) occurred in upstate New York during the summer of 1976, with 37 cases confirmed in horses by isolation of virus and/or by serologic examination. Other specimens collected in the affected area yielded 16 further isolates: 9 from 818 pools of 33,365 mosquitoes, 5 from tissues of 64 birds and 2 from 4 sentinel pheasants with serologic conversions. EEE antibodies were also detected in 81 of 499 wild birds tested. Our data implicate sparrows, cowbirds, and catbirds in the amplification of EEE virus and Culiseta melanura mosquitoes as vectors among avians. During the course of this epizootic a modified serologic technique involving hemagglutination reduction gave reliable diagnoses of EEE as early as 24 hours after receipt of field specimens.


An evaluation of the hypothesis of transovarial transmission of eastern equine encephalomyelitis virus by Culiseta melanura. Evidence for and against the hypothesis of transovarial transmission by Culiseta melanura was obtained during an ongoing eastern equine encephalomyelitis (EEE) surveillance and control program. Evidence inconsistent with transovarial transmission included failure to isolated virus from 1,047 larvae, from 2,140 first-brood adults, or from 8,919 males collected at the same time as 3,977 nonblooded females which yielded 12 EEE isolates. Evidence supporting the hypothesis was the isolation of virus from both blooded and nonblooded adults simultaneously and also from a population with a parity rate so low that the infection rate for parous specimens would have been 1:8. Two alternative hypotheses which assume transovarial transmission are advanced to explain these results, but they seem so unlikely that the data are interpreted as opposing the concept.


Protection of gastric mucosa against acute ulceration by intravenous infusion of sodium bicarbonate. The influence of intravenous infusion of sodium bicarbonate on gastric mucosal injury induced by topical sodium taurocholate and hemorrhagic shock was assessed in a canine ex vivo model. As expected, exposure of the gastric mucosa to sodium taurocholate and acid resulted in excessive back diffusion of hydrogen ions (H+) and mild mucosal damage. This mucosal injury was enhanced by hemorrhagic shock in the control dogs. The degree of mucosal injury was significantly less in the test dogs that received intravenous infusions of sodium bicarbonate. The protection afforded by intravenous bicarbonate was not due to a reduction in the amount of H+ entering the tissue, since the net H+ loss from the lumen was not significantly different between the control and the test dogs. The protection effect of intravenous infusion of sodium bicarbonate is probably secondary to an enhancement of mucosal tolerance to H+. These results support the hypothesis that the enhancement of mucosal injury during hemorrhagic shock may be a result of a decrease in the ability of the gastric mucosa to buffer the influxing H+.


Release of vasoactive intestinal peptide in the central nervous system in man. Recent work has shown that vasoactive intestinal peptide (VIP), one of the many candidate hormones of the gut, also occurs widely in neurones. To determine whether the neuronal peptide may have a neurotransmitter function, we studied changes in immunoreactive VIP in dog plasma and human cerebrospinal fluid after the infusion of choline esterase inhibitors (neostigmine and physostigmine, respectively). Immunoreactive VIP was released in both situations. The systemic changes (in VIP levels) were enhanced five weeks after portacaval shunting in dogs. Our results demonstrate that the immunoreactive VIP level increases as a result of choline esterase inhibitors. The plasma "release" may originate either from peripheral peptidinergic nerve terminals or from APUD cells of the gastroenteropancreatic system. The increase in immunoreactive cerebrospinal fluid VIP may very well originate from central neurons, since the peptide does not apparently cross the blood-brain barrier.


The pancreatic duct mucosal barrier.

The pancreatic duct mucosal barrier. The main pancreatic duct in cats possesses a relatively strong barrier to the diffusion of bicarbonate ions (HCO3-). We studied some of the characteristics of this barrier by perfusing the duct with a solution similar in composition to pancreatic juice before and after exposing the duct mucosa to various test agents. The difference in net flux of HCO3- across the duct before and after exposure to the test agent reflected damage to the barrier. The barrier was damaged by infected bile, aspirin (pH 2.3), hydrochloric acid (pH 2.3), ethanol (5 to 10 per cent), and secondary bile acids. It was not damged by sterile bile, aspirin (pH 6.5), and primary bile acids. These data indicate that the barrier to back diffusion in the pancreatic duct has unique properties, different in some respects from the properties of the gastric mucosal barrier. Furthermore, the barrier is vulnerable to some agents thought possibly to have a role in the pathogenesis of pancreatitis and pancreatic cancer.


Clinical and in vitro analysis of determinants of gastroesophageal competence. A study of the principles of antireflux surgery. The analysis of esophageal manometry and 24 hour esophageal pH monitoring in 266 consecutive patients indicates that the competency of the cardia depends upon the amplitude of the distal esophageal high pressure zone and the length of the abdominal esophagus. These two determinants of competency were examined using human esophagi in a unique in vitro model which allowed control of these parameters, as well as intraabdominal, intragastric, and intrathoracic pressures. The following principles of the function of the abdominal esophagus were graphically illustrated: (1) Competency of a segment of intraabdominal esophagus without intrinsic tone occurs only when intraabdominal pressure is equal to or greater than intragastric pressure. (2) Competency of a segment of intraabdominal esophagus without intrinsic tone is directly related to its length. (3) The length of intraabdominal esophagus necessary to maintain competency is indirectly related to variations in intraabdominal pressure. (4) Competency of a segment of intraabdominal esophagus is augmented by the presence of intrinsic tone, and the shorter the length, the greater the intrinsic tone needed. (5) Competency of a segment of intraabdominal esophagus is augmented by negative intrathoracic pressure. These findings beautifully illustrate the mechanical valvelike function of the abdominal esophagus and the objectives to be accomplished in the surgical treatment of gastroesophageal reflux.


[New aspects of tumor genesis (author's transl)]. The author reports on the molecular biological site of action for cancerogenic substances. He shows how UV-radiation may lead to malignomas of the skin in the hereditary disease xeroderma pigmentosum and how ionising rays may cause changes of the DNA, the place of the genetic information. Since the virus genesis of malignant diseases has become more important lately, the author tries to point out the molecular biological connections of an eventual involvement of virus in the development of malignant diseases.


[Precancerous skin lesions in the aged (author's transl)]. The term "precancerous" needs a new definition since it includes still malignant diseases like Morbus Paget of the nipple, Morbus Bowen and Erythroplasie Queyrat. The degree of malignancy of these disorders is analyzed. Precancerous conditions in the sense of benignant disorders which necessarily develop into malignant tumors are Melanosis circumscripta praeblastomatosa Dubreuilh and actinic keratoses. Potential precanceroses may be X-ray-atrophy, Leukoplakia and oral papillomatosis. Some actinic, chemic and cytostatic cancerogens are mentioned. Reference is made to the diagnosis, differential diagnosis, prognosis and treatment of precancerous skin lesions. The problem of potential malignancy of nevi is considered in detail. Prevention of cancer needs regular careful clinical control of skin and mucous membranes at least after the 50th year of life.


[The rehabilitation therapy for older aged neoplastic patient (author's transl)]. The advances in modern neoplastic therapie are benefitting more and more even older aged patients. The equality of chances for these patients is reached by general rehabilitation. The special problem of the therapy for older aged patients is their multi-morbidity. Besides the cancer exist for instant: malcirculation, emphysema, neurologic diseases and psychical defects. For all those diseases one has to take care within the rehabilitation. Beside consequently treated immuno-chemotherapy, modern surgical treatment, extinction of pain and mobilisation of the patients, the therapy of the patients psychical conditions is very important. For this the modern knowledge of group-therapy has it's special orientated engagement.


[New results on ageing of connective tissue (author's transl)]. Some new results on ageing of connective tissue are demonstrated, regarding not only mesenchymal, but also parenchymal organs of human and rat (both sexes). These results show that ageing of connective tissue is more a dynamic process (with measurable metabolic parameters of the several connective tissue cells and their products) than a passive or so-called degenerative connective tissue process. The bradytrophy concept of connective tissue cannot be accepted any longer. Then connective tissue cells can produce metabolic rates of the same level like parenchymal cells. The different organs possess partly common basic processes partly differences in connective tissue ageing, dependent on the composition and patterns of proteoglycans resp. of GAG and collagen types, furthermore dependent on localisation, structure and function. The results on ageing of connective tissue are useful for better understanding of ageing processes of parenchymal organs. Then their ageing is influenced essentially by the ageing of the own connective tissues. The turnover, more than the number of mesenchymal and parenchymal cells, decreases with ageing. More old than young cells seem to exist in old tissues and organs. The performance of ageing connective tissue cells can be constant or increase or decrease. Many mesenchymal and parenchymal organs develop a so-called "ageing-fibrosis".


Age dependence of mechanical parameters in rat skin following repeated strain. The mechanical parameters of rat skin repeatedly strained with increasing elongation or repeatedly strained with a constant elongation was studied and the hysteresis behaviour was analyzed depending on age. Male Sprague Dawlely rats of an age of 1,2,4, 12, and 24 months were used. Ultimate strain of skin showed a maximum at early adulthood (2 months) whereas the other ultimate values (ultimate load, tensile strength and ultimate modulus of elasticity) exhibited their maxima in late adulthood (4 months). All these ultimate values increased due to maturation and decreased due to senescence. At medium extensions the stress uptake and the elasticity modulus showed a minimum in adulthood. Likewise, in hysteresis experiments both energy dissipation and energy loss at medium extensions exhibited a minimum in adulthood. The ratio between these two parameters, i.e. the relative energy loss was almost independent from age. Residual extension had a minimum at 2 months of age. Therefore, in rat skin the reversibility of deformations had a maximum at early adulthood, stiffness at late adulthood. All those parameters were reversed due to the senescence process.


[Influence of age on biochemical parameters of the rat liver following partial hepatectomy (author's transl)]. In the present paper measurements of DNA and protein content and lysosomal enzyme (beta-glucuronidase, beta-acetylglucosaminidase, cathepsin D) acitivities were performed in the rat liver following partial hepatectomy. The rats were divided into three age groups: 6 weeks, 10 months and 18 months. The regenerating liver of the 6 week and 10 month old animals disclosed significant higher concentrations of DNA than the controls. The 18 month old rats revealed no differences of the DNA content. In all age groups the protein content of the regenerating liver was significant diminished. There were age dependent differences of the activities of the three lysosomal enzymes. In comparison to the controls the beta-glucuronidase activity of the regenerating liver was significantly decreased in the 6 week and 18 month old animals, but significantly increased in the 10 month old rats. Refering to the protein content there were no differences of the activities of beta-acetylglucosaminidase and cathepsin D between the regenerating and control livers. Refering to the liver fresh weight the beta-acetylglucosaminidase activity of the regenerating liver was significant diminished in the 10 and 18 month old rats.


Cumulative dose-response curves for early evaluation of bronchodilator drugs. SM 220, a new beta-receptor agonist, was compared with terbutaline by construction of dose response curves for FEV1, heart rate and blood pressure. The pharmacological profile of SM 220 after preclinical studies was that of a potent and highly selective bronchodilator. In this study the beta2 selectivity of SM 220 was poorer than that of terbutaline. The importance of commencing clinical evaluation of bronchodilators with a dose-response test is stressed.


Cardiovascular, acid-base, electrolyte, and plasma volume changes in ponies developing alimentary laminitis. Twelve Shetland ponies were fed a high-starch ration. Seven ponies which had a transitory metabolic acidosis developed laminitis 56 hours (+/- 3.5, SEM) after overfeeding. These ponies also developed persistent hypokalemia, hyperthermia, and increased heart rate 24 hours before the onset of lameness. Serum sodium, serum chloride, hematocrit, plasma volume, and blood volume were unchanged. At the onset of clinical signs of laminitis, cardiac output and blood pressure increased, but total peripheral resistance was unchanged. None of the measured or calculated values predicted the onset of laminitis. Hypertension appeared to be a response to, rather than a cause of, lameness. Three of the remaining ponies apparently died of shock 29.3 +/- 2.7 hours after overfeeding. All 3 had severe metabolic acidosis; decreased cardiac output, systemic arterial pressure, and plasma volume; and increased hematocrit, total peripheral resistance, and pulmonary vascular resistance. The 11th pony was unaffected and the 12th pony was euthanatized.


Failure to propagate equine infectious anemia virus in mosquitoes and Culicoides variipennis. Laboratory-colonized mosquitoes, Culex tarsalis, aedes aegypti, Culiseta inornata, and Anopheles free-borni, and the biting gnat, Culicoides variipennis, were exposed to equine infectious anemia virus. Exposure to the virus was by intrathoracic inoculation for  mosquitoes and by oral ingestion of an infective blood meal through a membrane for C variipennis. After various intervals, groups of 15 to 20 insects were homogenized and inoculated into susceptible ponies. Positive immunodiffusion test results were used as criterion for equine infectious anemia infection in ponies. Virus was not detected in the 4 species of mosquitoes at 3, 6, 12, and 18 days after inoculation, or in C variipennis at 6, 8, 12, 14, 21, and 26 days after oral exposure to the virus.


[Distribution of oleandomycin between the native broth and butylacetate depending on the biosynthesis conditions]. Distribution of the active substance contained in the fermentation broth of Act. antibioticus between the acqueous phase and butylacetate depended on the fermentation conditions and the procedure for the fermentation broth treatment before filtration. Increase in pH values during the fermentation process resulted in lower antibiotic distribution coefficients which may be explained by the presence of oleandomycin-X, a biologically active substance in the fermentation broth filtrates. This substance differed from oleandomycin and did not pass into butylacetate from the acqueous alkaline solution. For transference of oleandomycin-X into oleandomycin exposition of the fermentation broth filtrate at pH 5.0--5.5 is required.


[Lysozyme activity of pneumococci].

[Lysozyme activity of pneumococci]. Examination of 329 pneumococcal strains showed that 41.2 per cent of the cultures had lysozyme activity. The frequency of the lysozyme feature depended on the method used. The lysozyme active strains were more frequently isolated from patients than from healthy persons and characterized by antibiotic resistance. The lysozyme feature correlated with the pneumococcal virulence with respect to albino mice, capacity for capsule formaiton and resistance to phagocytosis.


HR 756, the syn isomer of a new methoxyimino cephalosporin with unusual antibacterial activity. HR 756, the syn derivative of 7-[(2-(2-amino-4-thiazolyl)-2-methoxyimino)acetamido]cephalosporanic acid, is a new semisynthetic cephalosporin. It was 80 times more active than the anti derivative against beta-lactamase-producing strains of gram-negative bacteria. The range of inhibitory concentrations of HR 756 against gram-negative bacteria, including Haemophilus influenzae, susceptible or resistant to penicillins and cephalosporins was from 0.01 to 0.1 mug/ml. This activity was consistently higher than those observed with cephalothin, cephaloridine, cephalexin, and cefazolin. Nevertheless, some strains of Enterobacter cloacae were resistant. HR 756 showed very similar activity to that of ampicillin against group A streptococci and Streptococcus pneumoniae.


Deodorization of pig feces by actinomycetes. Peg feces, a malodorous substance causing environmental pollution, were completely deodorized within 2 days by Streptomyces. The optimum conditions for deodorization were as follows: pH, 8.6 to 10; temperature, 35 to 40 degrees C; moisture content, 42 to 63%; and minimum amount of inoculum, 2 g of seed culture per 10 g of fresh feces. Many kinds of microorganisms were isolated from the deodorized feces, of which only actinomycetes were found to have the ability to deodorize. Two strains with strong deodorizing activity were identified as Streptomyces griseus and Streptomyces antibioticus. The low-molecular-weight fatty acids, which are the specific malodorous agents of pig feces, scarcely could be found in feces deodorized by the isolated strains. Chemical analysis showed that the deodorized feces are useful as manure.


Prevalence and distribution of Aeromonas hydrophila in the United States. The abundance of Aeromonas hydrophila was measured in 147 natural aquatic habitats in 30 states and Puerto Rico. Viable cell counts were used to estimate density at all sites by using Rimler-Shotts medium, a differential presumptive medium for A. hydrophila. Temperature, pH, conductivity, salinity, and turbidity were measured simultaneously with water sample collection. The density of A. hydrophila was higher in lotic than in lentic systems. Saline systems had higher densities of A. hydrophila than did freshwater systems. A. hydrophila could not be isolated from extremely saline, thermal, or polluted waters, even though it was found over wide ranges of salinity, conductivity, temperature, pH, and turbidity. Of the water quality parameters measured, only conductivity was significantly regressed with density of A. hydrophila.


Infectivity titers of adenovirus type 5 suspensions after exposure to cigarette smoke. Suspension of adenovirus type 5 in 2.0 ml of cell culture fluid at 37 degrees C were subjected to smoke from four cigarettes over a 4-h period. The cigarettes were smoked in a normal manner, and the inhaled smoke was exhaled through glass tubing into the virus-containing fluid. The virus suspensions were then titrated, using monolayer cultures of HEp-2 cells. Smoke from filter-tipped or regular cigarettes caused a 2- to 3-log drop in titer of tissue culture infectious doses of adenovirus type 5 per 0.1 ml of virus suspension. No reductions in titers were observed with parallel suspensions of the virus subjected to normal inhaled and exhaled air.


Behavior therapy, supportive psychotherapy, imipramine, and phobias. In a  controlled outcome study of phobias, 111 adult patients (69% women, 31% men) received a course of 26 weekly treatment sessions consisting of (1) behavior therapy and imipramine hydrochloride (2) behavior therapy and placebo, or (3) supportive psychotherapy and imipramine. Patients were classified as agoraphobic, mixed phobic, or simple phobic. The great majority of patients in all groups showed moderate to marked global improvement (70% to 86%, depending on rater). In agoraphobics and mixed phobics (both groups experiencing spontaneous panic attacks), imipramine was significantly superior to placebo. There was no difference between behavior therapy and supportive therapy, both resulting in high improvement rates (76% to 100%, depending on rater). In simple phobic patients, there was a high rate of improvement with all treatment regimens (72% to 93%, depending on rater), with no significant difference between imipramine and placebo or between behavior therapy and supportive therapy. Of 88 moderately to markedly improved patients followed up for one year after completing treatment, 83% maintained their gains and 17% relapsed. No patients showed symptom substitution. Eighteen percent of the patients receiving imipramine hydrochloride showed marked stimulant side effects on from 5 to 75 mg/day.


[Problem in the management of arterial hypertension resistent to drug treatment. Study of 28 cases]. The antihypertensive effect of the following therapeutic regimens: diuretic alone (DA), diuretic plus sympathetic inhibitor (DSI), diuretic plus betablocker (DB) and diuretic plus, betablocker plus vasodilator (DBV) was studied for 34.1 +/- 5.4 months in 28 patients with resistant essential hypertension (REH). Depending of treatment tolerability and the optimal antihypertensive action of drugs 21, 24, 26 and 10 cases were treated continuously or alternately with DA (9.9), DSI (15.0), DB (4.8), and DBV (14.6), respectively (in paragraph average duration of treatment in months). On admission the 89.3% and 42.8% of population had electrocardiographic signs of left ventricular hypertrophy or past-history of cardio-vascular complications, respectively. Arithmethic average and standard deviation of individual changes of systolic and diastolic blood pressure obtained during DA, DSI, DB and DBV treatment were -32.4 +/- 31.8, -19.3 +/- 27.2, -18.9 +/- 15.9 and -18.2 +/- 21.3 for systolic and -35.8 +/- 20.2, -12.3 +/- 17.2, -15.1 +/- 16.9 and -15 +/- 13.1 (mm. de Hg.) for diastolic blood pressure respectively. Average blood pressure before treatment was 222.4 +/- 30.3/128.0 +/- 20.8 (mm of Hg) and under the most effective treatment was 175.5 +/- 21.8/106.5 +/- 12.1 with a p less than or equal to 0.001 for either sistolic and diastolic pressure. There were not significant regressive electrocardiographic changes during the therapeutic period, neither significant changes in urea and creatinine blood values. 46.4% and 25% of cases exhibited collateral drug symptoms and cardio-vascular no fatal complications, respectively. Three of the last group patients died outside of the Hospital (2 sudden deaths and 1 renal insufficiency death). RH still constitutes a challenge to medical therapy. Nevertheless individualized therapy may modify the natural history of this hypertensive variety.


Minor tranquilizers: clinical correlates of use in an urban population. Rapid growth in the production and prescription of minor tranquilizers has stimulated increasing concern that we live in an "overmedicated" society. Data regarding drug use from a health survey in Oakland, Calif, show that (1) 20% took a minor tranquilizer or sedative during the previous year, 10% daily for a week or more; (2) use was related directly to the amount of distress and dysfunction, to psychologic more than to other types of disturbance, but not to situational stress alone; and (3) taking tranquilizers was only one aspect of a complex pattern of coping behaviors including the almost universal use of some medication, most often a "nonpsychotropic" type.


[Principles and 1977 concept of cancer multistep therapy. Physiological fundamentals of the new timing. Selectotherm local hyperthermy (author's transl)]. A report is given on the further development of the Cancer Multistep Therapy (CMT) Concept. With a clinically applied blood glucose concentration of 5 . 10(-3) g ml-1 the pH value in tumour tissue reduces to about 6.0 which, in turn, causes an increase in thermal sensitivity of cancer cells by approximately 2 degrees C. At the same time, their proliferation ceases almost completely. In addition, the pH value at the venous end of capillaries in tumour tissue increases to about 6.5 so that the flexibility of the erythrocytes gets lost in a selective mode. From this it follows that, under CMT conditions, there will be a total decrease of microcirculation in tumour tissues. All the aforementioned facts have been considered by a new timing: applying cancerostatic drugs and/or ionizing radiation prior to the said drop of microcirculations and of cancer cell proliferation rate. The begin of the hyperthermy step is then planned to take place immediately after the decrease of microcirculation in tumour tissue since the action of the discussed local hyperthermy then becomes very strong (pronounced selective reduction of convection cooling by the blood stream; further enhanced thermal sensitivity of cancer cells). Local hyperthermy then is performed by superposing the Selectotherm Process on 40 degrees C whole-body hyperthermy which allows high power densities also with deep-seated tumour tissues. Finally calculated temperature profiles in tumour tissue of various diameters are discussed together with the practice-considered parameters used in the respective equations.


Periventricular leukomalacia complex.

Periventricular leukomalacia complex. At autopsy in the past three years, a new complex of CNS lesions has appeared in 54% (50/93) of the brains of premature infant cadavers that have come from our neonatal intensive care unit. This complex consists of necrotizing lesions in the periventricular white matter and in the gray nuclei of the cerebral hemispheres, the hippocampus and subiculum, cerebellar folia and white matter, and basis pontis. This entity is called the periventricular leukomalacia complex, since the distribution of lesions is similar, yet much more severe, than that described by Banker and Larroche in 1962. Clinical studies have indicated that these lesions may be related to long periods of time at high blood oxygen or prolonged periods in which PO2 and pH fluctuated widely.


Cimetidine in the management of metabolic alkalosis induced by nasogastric drainage. Metabolic alkalosis resulting from nasogastric drainage is a well recognized and potentially serious clinical problem. In the postoperative patient with acute renal failure, the management of the metabolic alkalosis is particularly difficult, and established modalities of therapy are sometimes ineffective and can be hazardous to the patient. In this article, we report on the successful use of cimetidine (an H2-receptor antagonist) as an adjunct in the treatment of severe metabolic alkalosis in a postsurgical renal failure patient. To our knowledge, this is the first reported successful use of cimetidine in the treatment of metabolic alkalosis due to gastric acid loss.


The effects of agents modifying sympathetic nerve function on the response of the isolated rat tail artery to etilefrine and tyramine. The effects of etilefrine on the ventral caudal artery of the rat have been examined in the presence of agents modifying sympathetic nerve function. Catecholamine levels were also measured in adjacent segments of artery to those studied pharmacologically and an attempt made to relate vascular response to etilefrine (and tyramine) with catecholamine content. Both guanethidine and reserpine produced significant attenuation of the vascular effects of etilefrine and tyramine. Pre-treatment with a monoamine oxidase inhibitor caused an increase in tissue catecholamine levels but, paradoxically, depressed the vascular response to etilefrine. The significance of some of the findings in terms of an indirect component to etilefrine's action are discussed.