Some studies in an institution for the mentally retarded. Patient characteristics and psychotropic drug use in a hospital for the mentally retarded were studied. The majority of patients appeared permanent, 80 percent having been there five years. Ages ranged from 2 to 71 years. Most were mildly or moderately retarded. Fifty-five percent had been originally domiciled within two hours driving time of the hospital. Visiting was proportional to time in hospital, degree of retardation and distance of domicile from hospital. Forty percent of patients were on some kind of psychotropic medication for behavioural control, the majority of these receiving two or more antipsychotic drugs in moderate dosage (phenothiazines or butyrophenones). Despite their long acting nature, drugs were given several times a day. Average time on present medication was about one year. A subgroup of patients was taken off medication and observed by staff. Almost all deteriorated behaviourally but the study was not double blind so these findings must be treated with caution.


New Zealand Committee on Adverse Drug Reactions: eleventh annual report 1976. Under the voluntary reporting scheme 499 cases of adverse drug reaction or reactions were reported. Noteworthy items included immediate hypersensitivity-type reactions to anaesthetic agents, a number of life-threatening reactions to anti-inflammatory drugs, paradoxical increase in blood pressure with high-dose pindolol and rebound hypertension after cessation of clonidine. A further 904 reactions were reported during an intensive survey in general practice and 342 from the ongoing hospital monitoring studies in units at the Auckland and Hutt hospitals. Data from numerous sources are now being channelled through the Committee's administrative centre. During the 11th year of operations 499 reports were received under the spontaneous reporting scheme. Additionally 342 reactions derived from the established hospital monitoring programmes at the Auckland Hospital and School of Medicine and the Hutt Hospital were notified to the Committee, and a further 904 reactions were received as a result of the intensive monitoring survey of drug reactions in general practice carried out in October and November 1975. The significance of each of these sets of data is substantially different and they will be discussed separately.


Flight muscle ultrastructure of susceptible and refractory mosquitoes parasitized by larval Brugia pahangi. On parasitization with larval Brugia pahangi the infected flight muscle fibres of "resistant" Anopheles labranchiae atroparvus undergo the following ultrastructural changes. The fibres become almost totally devoid of glycogen, their sarcoplasmic reticulum becomes elongate and closely associated with muscle fibrils. These fibrils degenerate and vesicles appear both within the degenerate fibril and within elements of the sarcoplasmic reticulum. Vesicles accumulate around the worm and degenerate to a uniform mass which eventually becomes melanized from its inner edge (next to the parasite) outwards. The infected flight muscle fibres of both "resistant" Aedes aegypti and "susceptible" Aedes togoi are almost totally devoid of glycogen granules, but show no other ultrastructural change from the uninfected state.


Multiple leukocyte abnormalities in chronic granulomatous disease: a familial study. A variety of leukocyte enzyme activities were studied in an 11-year-old female with chronic granulomatous disease (CGD) and several members of her family. Leukocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity was 17 nmol/min/mg protein in the patient; two brothers with symptoms of recurrent bacterial infections have G-6-PD activities of 58 and 37 nmol/min/mg protein; the activites of this enzyme in both parents, maternal grandmother, and one additional brother were within normal limits. Storage at 4 degrees or heating at 37 degrees over a 120-min period revealed a marked lability of G-6-PD activity in the patient's cells which could not be stabilized by the addition of NADP and 2-mercaptoethanol; this lability was not seen in other family members tested. Activities of leukocyte glutathione reductase were reduced in both parents and the two affected male siblings with values of 18, 23, 23, and 24 nmol/min/mg protein, respectively. Activities of leukocyte glutathione peroxidase were reduced in all of the immediate family members tested, with values ranging from 11.2 to 43 nmol/min/mg protein; the activity of this enzyme in the patient was 38.5. Leukocyte NADP content in the patient, father, and two affected male siblings were 16.5, 23.4, 22.2, and 28.2 nmol/15 min/10(7) leukocytes, respectively.


Fluoresceinylthiocarbamyl-tRNATyr: a useful derivative of tRNATyr (E.coli) for physicochemical studies. Fluoresceinylthiocarbamyl-tRNATyr (FTC-tRNATyr) is prepared from tRNATyr and fluoresceinisothiogyanate (FITC) under mildly alkaline conditions. Labelling occurs specificly at the base Q of tRNATyr. The modified tRNA is fully active in the aminoacylation assay; when aminoacylated it is recognized by the elongation factor Tu (EF-Tu). Codon-anticodon interaction, however, is severely affected by the modification.


[Perspectives of use of genetic methods of control of bloodsucking Diptera - vectors of the diseases of man]. This paper presents genetic methods of control of bloodsucking Diptera, mosquitoes. The perspective of the use of various control methods, first of all those tested under field conditions in application for bloodsuckers which are of medical importance throughout the USSR, is regarded. The opinion is suggested that the method of X-ray sterilization of pupae taken from nature and the translocation and chemical sterilization methods can be successfully used for the control of An. m. sacharovi, malaria vectors resistant to DDT. The male sterilization method and the use of males cytoplasmatically incompatible with translocations are suggested for the control of synanthropic populations of C. pipiens.


A 31P-NMR study of the interaction of Mg2+ ions with nucleoside diphosphates. The interaction of Mg2+ with nucleoside disphosphates : ADP, GDP, CDP and UDP has been studied by phosphorus magnetic resonance spectroscopy in aqueous solution. The results show that these four nucleotides behave similarly, the Mg2+ ion binds to the alpha but not to the beta phosphate moiety. The strength of the interaction of Mg2+ ions with nucleoside diphosphates is weaker than with nucleoside triphosphates. The association of Mg2+ on the phosphate chain is stronger in a neutral than in an acid medium.


High-dose treatment with neuroleptics in the acute phase of mental disease. More than 300 patients have been observed during treatment with either flupenthixol, haloperidol, fluphenazine enanthate or perphenazine enanthate in high doses, whilst suffering from severe mental disease, usually of psychotic nature. Used correctly, high-dose treatment gives a rapid control of psychotic symptoms, an earlier discharge from the ward, and (when using long-acting neuroleptics) pharmacological control even during a follow up period. This means a social availability gain of 30-50%. We have not seen any severe somatic effects except those of parkinsonian type which can be treated successfully by the well trained psychiatrist and a skilled staff.


Competitive inhibitors of renin. A review. This review describes some of the characteristics for renin's substrate specificity and also some features of its species specificity. It describes how competitive inhibitors were synthesized and how the solubility was increased in order to make them effective at physiological pH. Their use for in vitro and in vivo inhibition of renin is discussed and their use for purification of renin demonstrated.


Interaction of salicylic acid with adenosine and adenosine triphosphate. Potential mechanism of intensifying acetylsalicylic acid-induced GI blood loss. Complex formation between salicylic acid and adenosine or adenosine triphosphate in 0.2m phosphate buffer at pH=7 was investigated as a potential factor contributing to the prolongation of acetylsalicylic acid-induced GI blood loss. Spectrophotemetric techniques were used to evalute the complexation. Concerntration dependency of the absorbance decrease was measured at 27 and 37 degrees C. The addition of salicylic acid to either adenosine or adenosine triphosplate solutions appeared also to cause a decrease in surface tension which may play a role in reducing platelet aggregation induced by adenosine diphosphate. The results obtained seem to support the opinion that the mechansim of acetylsalicylic acid-induced GI blood loss is due to a combination of both local and systemic effect.


Kinetics and mechanism of degradation of some 5-allylbarbituric acid derivatives. Part 3: Kinetics of solvolysis of major intermediates of 5.5-diallylbarbituric acid degradation. Solvolysis of N-diallylacetylurea and 5.5-diallylmalonuric acid was investigated in the pH range ca. 8--12 by means of spectrophotometric and t.l.c. methods. Their log k--pH profiles were constructed from the experimental results obtained by degradation at 70 degrees C. Therefore, specific catalytic rate constants and pKa's were derived. The kinetic mechanism of N-diallylacetylurea solvolysis, resulting among other things from the so-called kinetic salt effect, depends on hydroxyl-ion attack on its undissociated and monoanionic forms. However, the degradation of alpha.alpha-diallylmalonuric acid in the pH range 10--12 is an example of specific base catalysis which can be explained by hydroxyl-ion attack on its monoanionic species. The degradation of alpha.alpha-diallylmalonuric acid below pH=10 does not follow a theoretical equation postulated, because the spectrophotometric method does not allow monitoring the formation of N-diallylacetylurea in the presence of the above acid. Thin-layer chromatography was used to check different pathways of transformations of the intermediate studies.


Effects of hypolipidemic agents on lipid synthesis in subcellular fractions from Tetrahymena pyriformis. Lipid synthesizing systems have been prepared from subcellular fractions of Tetrahymena pyriformis, GL. These fractions, the mitochondrial fraction, the microsomal fraction and the soluble cell fraction, have been characterized as to cofactors and cations required for optimal lipid synthesis. The effects of hypolipidemic agents on lipid synthesis by all fractions are presented.


Analgesic, heart rate, and temperature effects of delta8-THC during acute and chronic administration to conscious rats. Acute and chronic effects of delta8-THC on tail-flick, heart rate, and rectal temperature responses in conscious, unrestrained male rats were studied. In the acute experiment unidirectional dose-dependent analgesic, hypothermic, and negative chronotropic cardiac effects were observed within the dose range employed. Of the three variables, heart-rate decreases were most sensitive to the effects of THC, reaching significance at 2 mg/kg. Rapid development of tolerance occurred for all three measures, with complete tolerance developing within 13 days only to the heart-rate decreases. The results discussed in the context of previous data.


Efficacy of loxapine in the treatment of paranoid schizophrenia. A combined analysis of data from 11 controlled studies of loxapine versus either chlorpromazine or trifluoperazine in acute schizophrenia (5 studies) and chronic schizophrenia (6 studies) showed statistically significant superiority of loxapine on several items and factors of standardized psychiatric rating scales. Upon review of these findings, it was observed that the rating scale symptoms for which loxapine appeared superior to the reference compounds could, in the main, be considered a broad paranoid "cluster". The data were then reanalyzed to detect possible differences in efficacy of loxapine versus the reference compounds in those patients with a clinical diagnosis of schizophrenia, paranoid type and in those patients of any diagnostic subtype other than paranoid. Results of these analyses demonstrated clear superiority of loxapine in paranoid schizophrenic patients; nonparanoid patients responded at least equally as well to loxapine as to the reference compounds. Findings could not be attributed to inadequate dosages of the references compounds or inequality of treatment groups at baseline.


[Psychopharmacological influence on the prey catching behavior of ferrets (Putorius furo L.) (author's transl)]. The prey-catching behavior of ferrets (Putorius furo L.) consists mainly of instinctive behavior patterns, which can be elicited only through their releaser. Then they are performed stereotypically. To get information concerning the central background and the hierarchical structure of this behavior the neuroleptics Haloperidol (0.14 mg/kg), Clozapine (10 mg/kg) and Chlorpromazine (4 mg/kg) were injected i.m. under controlled conditions. In a conditioning experiment the reactivity of the animals was examined. This conditioned reaction was strongly decreased by the drugs. The reaction to the natural stimulus the prey was changed, but not suppressed. The modification of the predatory behavior was manifedsted in an "improvement" of orientation reactions when pursuing the prey and in a better placement of bites. This effect, most evident with Haloperidol, is possibly due to the specific neuroleptic component of the substances. A delay in approaching the prey, or even the total suppression of the prey-catching behavior is suggested to be due to a sedative component which was most obvious in some experiments with Clozapine. On the other hand, there are behavioral elements like the use of paws which are not effected by the neuroleptics. From these and other observations, it is concluded, that the predatory behavior of the ferret has a hierarchically organisated structure. Further it is suggested that some functional connected parts of the behavior have distinct central representation, for they are not influenced in the same way by these drugs.


Effect of flupenthixol and butaclamol isomers on prolactin secretion in rats. Cis (alpha)-flupenthixol and (+)-butaclamol are effective anti-psychotic agents but trans (beta)-flupenthixol and (-)-butaclamol are not. alpha-Flupenthixol was found to be 245 times more active in elevating rat plasma prolactin than the beta-isomer. The discrepancy between (+)-butaclamol and (-)-butaclamol was even greater. These results support the hypothesis that the dopamine receptors that mediate the effects of dopamine on prolactin secretion are similar to those that mediate the anti-psychotic effect of neuroleptic drugs.


Changes in dopamine synthesis rate in the supersensitivity phase after treatment with a single dose of neuroleptics. The changes in 14C-dopamine accumulation formed from 14C-tyrosine in mice after treatment with three neuroleptics, cis (Z)-flupenthixol, fluphenazine, and haloperidol, were followed for 6 days. The neuroleptics all changed DA synthesis rate in the same way, initially causing an increase which was followed by a decrease after approximately 3 days. The results are compared with pharmacological results (Christensen et al., 1976) and there seems to be a very close correlation between receptor blockade and increase in DA synthesis on the one hand and on the other hand receptor supersensitivity and decrease in DA synthesis, as was also shown previously for teflutixol (Hyttel, 1975). It is concluded that the changes in receptor activity are always followed by compensatory changes in DA synthesis rate.


The biosynthesis of dimethyltryptamine in vivo. The in vivo formation of dimethyltryptamine was studied in rabbits, rats and monkeys. When C14-labelled N-methyltryptamine was administered by intravenous injection to rabbits, C14-dimethyltryptamine was found in lung, the principle site of the methyltransferase that biosynthesizes this psychotogen. Unequivocal evidence for C14-dimethyltryptamine formation in rat tissues was not obtained. When rabbits were given non-radioactive N-methyltryptamine intravenously, dimethyltryptamine appeared in carotid arterail blood, peaking within the first minute after injection of the precursor. USing this assay procedure we could not demonstrate dimethyltryptamine synthesis in the rhesus monkey.


An improved technique for the preparation of chromosomes from cattle whole blood. The method of preparation of chromosomes from cattle whole blood is described in detail and has been tested by use on more than 1000 different animal samples. It is shown that elevated levels of glutamine and 1-cystine increase the mitotic index and improve the keeping qualities of the medium 199. The recipe for whole medium is modified, describing the inclusion of heparin for the first time and recommending the exclusion of fetal calf serum. The optimum pH 7-3 is confirmed. The reported conditions of transport show that the best results pertain where air transport is used and the worst after prolonged journeys by car.


Blood respiratory properties in the naked mole rat Heterocephalus glaber, a mammal of low body temperature. Respiratory properties of whole blood and Hb solutions have been studied in Heterocephalus glaber, a fossorial rodent, having a low body temperature (30.0-32.0 degrees C) and poor thermoregulatory ability. For comparison similar, measurements were made on laboratory mice, Mus musculus. Whole blood showed a distinctly higher O2 affinity for Heterocephalus at both 30 and 37 degrees C.P50 values were 23.3 mm Hg and 33.0 mm Hg at 37 degrees C for Heterocephalus and Mus, respectively, while at 30 degrees CP50's were 18.8 mm Hg and 24.9 mm Hg, all values at pH (b) 7.4. deltaH values (expressive of the effect of temperature on P50) were -5.8 kcal-mol-1 for Heterocephalus and -7.5 kcal-mol-1 for Mus. The CO2 Bohr effects (omega) were -0.43 and -0.50 for Heterocephalus at 37 and 30 degrees C. Corresponding values for Mus were -0.65 and -0.56. Both species had a Hill's n-value of 2.6. Red cell concentrations of 2,3-DGP were closely similar in the species being 7.3 mmol-L-1 rbc for Heterocephalus and 7.4 mmol-L-1 rbc for Mus. Stripped Heterocephalus Hb had a very high O2 affinity, at pH 7.25, 37 degrees C,P50 was 8.0 mm Hg whereas the corresponding value for Mus was 11.3 mm Hg. Addition of DPG to stripped Hb from the two species decreased O2 affinity to the same degree. The high O2 affinity of Heterocephalus blood is viewed as a possible adaptation to its burrowing habits. Its basis is inherent to the hemoglobin molecule itself and not dependent upon cofactor influence or the temperature sensitivity of the O2-Hb binding.


The role of brief hypocapnia in the ventilatory response to CO2 with hypoxia. In conscious cats the ventilatory response curve to physiological range of CO2 is displaced upward by hypoxia (about 45 torr), but it rises, either parallel with, or convergent on, the normoxic curve. Thus, a positive interaction of hypoxia and hypercapnic stimuli is not observed under these circumstances. However, if during the hypoxic exposure, hypocapnia is allowed to develop, the subsequently determined CO2 ventilatory response curve will shift to the left, rise steeply, particularly in the early phase, and demonstrate a positive hypoxic hypercapnic interaction. A demonstrable interactive effect was dependent on a conditioning period of hypocapnia, and this was shown to be associated with an elevated level of lactic acid to a greater degree in cerebral venous blood than in CSF or arterial blood. The interpretation is discussed without reaching a firm conclusion of mechanism, but the results emphasize how a minor change of experimental protocol affects a basic phenomenon in the chemical control of breathing.


Ventilatory and circulatory O2 convection at 4000 m in pigeon at neutral or cold temperature. Awake domestic pigeons, either maintained at 22 degrees C (series I) or acutely exposed at 2 degrees C (series II), were studied in a hypobaric chamber at 140 m and at various stages during a 4-week exposure to 4000 m. Steady-state pulmonary ventilation (Vg) and breathing pattern (VT, fr), oxygen consumption (MO2), O2 concentrations and pressures in the arterial (a) and mixed venous blood (v), hematocrit (Ht) and acid-base status in arterial blood, systolic blood pressure and heart frequency (fH) were measured. From these data cardiac output (Vb) and stroke volume (Vs), ventilatory and circulatory requirements (Vg/MO2, Vb/MO2), extraction of O2 from inspired air (EgO2) and blood EbO2), and capacitance coefficient of blood for oxygen (betabo2) were calculated. At 140 m, by comparison with predicted values for mammals of same body weight, pigeons at 22 degrees C extracted more O2 from the inspired gas, with lower fR, larger VT, similar Vg; they extracted O2 from the blood like mammals, with lower fH, larger VS, greater Vb, similar betabO2=70 mumol-L-1-torr-1. Acute exposure to 2 degrees C provoked a two-fold increase in MO2 which was achieved by doubling Vg and increasing O2 extraction from the blood. At 4000 m, in both series, pigeons hyperventilated within the first 30 min, with a resultant hypocapnic alkalosis comparable to that in mammals. Further hyperventilation with consequent greater hypocapnia and increase of arterial PO2 was complete beyond 3 hr. After a few weeks, the pH remained 0.07 above control normoxic value, Ht increased from 45 to 52%, betabO2 reached about 172 mumol-L-1-torr-1. At 2 degrees C, Vb also increased, mainly due to tachycardia.


The CSF HCO3 increase in hypercapnia relationshp to HCO3, glutamate, glutamine and NH3 in brain. To study the role of carbonic anhydrase in the CSF [HCO3] increase in respiratory acidosis and its effect on brain ammonia, anesthetized rats were subjected to hypercapnia (7% CO2) for 2 hours. The animals received periodic intraventricular injections of either 'mock' CSF or 'mock' CSF and acetazolamide for 45 minutes prior and during hypercapnia when: (a) plasma [HCO3-] was allowed to increase normally and (2) plasma [HCO3] increase was prevented by i.v. HC1 infusion, CSF [HCO3] increased 8.5 mM/L after 2 hours of hypercapnia (delta PCO2 40) in the rats with intraventricular 'mock' CSF injections, and only 6 mM/L in the animals with acetazolamide injections. CSF [HCO3-] increased 7 mM/L during hypercapnia and HCl infusion with intraventricular 'mock' CSF injections, but only 2 mM/L with acetazolamide injections. Changes in total brain CO2 (increase) and brain glutamic acid (decrease) in hypercapnia were not affected by intraventricular acetazolamide and i.v. HCl. The increase of brain NH4+ and glutamine in hypercapnia was reduced in these conditions. It is concluded that there are at least two sources for the CSF [HCO3-] increase in hypercapnia; one formed in the CNS and dependent on carbonic anhydrase, and the other derived from plasma [HCO3-] increase.


Preparation of 125I-labeled synthetic porcine secretin for radioimmunoassay. Synthetic porcine secretion was labelled by the conjugation-labelling method of Bolton & Hunter, the lactoperoxidase method, the gaseous diffusion method, and the chloramine-T method. The chloramine-T technique was adapted as routine method. Ten mug (3.27 nmol) peptide was reacted with 5 mCi of Na125I at a concentration of chloramine-T of 1.3 mmol/l. Synthetic secretin was suitable for labelling for at least eight months when stored as dry matter in nitrogen-filled glass ampoules. Purification and separation of labelled from unlabelled hormone was carried out by gel-permeation chromatography on Sephadex G-50 superfine. The labelled preparation had a specific radioactivity of 405 +/- 33 muCi/nmol (mean +/- SEM., n = 9) and was unable for six days. 6-tyrosyl-secretin took more iodine compared to porcine synthetic secretin but had lower immunoreactivity with all antisera tested.


Microbial and salivary conditions in 9- to 12-year-old children. The prevalence of S. mutans and lactobacilli, the salivary secretion rate, and salivary pH and buffer capacity were examined in 655 children 9-12 years old. Some of these factors were correlated with the frequency of caries. Positive correlations were observed between for example S. mutans and lactobacilli, between S. mutans and incipient smooth surface caries, and between lactobacilli and open carious lesion. A high proportion of the children showed large numbers of S. mutans and lactobacilli.


Oral complications in anorexia nervosa.

Oral complications in anorexia nervosa. Anorexia nervosa (AN), a psychosomatic disease mainly affecting young women, is characterized by conscious starvation, periods of excessive carbohydrate intake and often deliberate vomiting. Medical history, dental examination, and saliva tests of 39 patients aged 14 to 42 years, having suffered from AN for periods of 1 to 20 years, showed dental caries, due to excessive carbohydrate consumption, in all subjects, often in a rampant form. In patients with a history of intense vomiting (27 cases) severe lingual-occlusal erosion (perimylolysis) was nearly always present. Buccal erosion, mainly due to high consumption of acid fruits and drinks to relieve thirst caused by dehydration, was more frequent in vomiting than in non-vomiting patients. Subnormal values of saliva properties, owing to dehydration or xerostomia-inducing medication, were present in the majority of cases; the lowest values occurred in those vomiting. The association AN - vomiting - perimylolysis is discussed, as well as prophylactic and therapeutic measures. A medical, psychiatric, and dental survey of AN is presented.


Phenylethanolamine: a new putative neurotransmitter in Aplysia. Phenylethanolamine is present in the Aplysia nervous system in concentrations similar to that of octopamine. These are receptors that are very specific for phenylethanolamine, which on different neurons mediate sodium, chlorine, or potassium conductance increase responses. These observations indicate that phenylethanolamine may act as a neurotransmitter in Aplysia.


Denture stomatitis-yeast occurrence and the pH of saliva and denture plaque. The study comprised 30 denture wearers with generalized simple or granular inflammation in the palate and 30 without (controls). )easts, mostly Candida species, were cultivated from the maxillary dentures of all subjects with inflammation and of 23 controls. Hyphae were found in the maxillary denture smears from 28 subjects with inflammation and from 18 controls. Thus it seems unjustified to consider the occurrence of hyphae pathognomonic of denture stomatitis. The pH of whole saliva did not differ in the two groups (inflammation:mean pH 6.5, control:6.6). There was no clear relation between the pH of resting saliva and the amount of fungal cultures. Thirty minutes after a mouthrinse with 10 ml of a 25% sucrose solution, the mean saliva pH had dropped equally in both groups. With regard to the denture plaque, samples taken 40 min after the rinse indicated a more pronounced acid production in the plaque associated with inflammation. The pH of "resting" plaque was also lower in the inflammation than in the control group (mean maxillary pH 5.7 and 6.3 respectively, a=0.002). No association was found between the pH and the occurrence of hyphae in "resting" denture plaque. This supports the view that the pH is of no major importance for filamentation in vivo.


Possible cyclic nucleotide regulation of calcium mediating myocardial contraction. An inhibitor of adenylate and guanylate cyclases was tested on strips of left atria from rabbits. Effects of catecholamines (cardiotonic) and of acetylcholine (cardiodepressive) were blocked, and positive force-frequency was converted to negative. Ouabain produced only contracture without positive inotropy. The cardiotonic effect of increased calcium remained. Data suggest that cyclic nucleotides modulate calcium associated with these stimuli.


Glutamine synthetase: glial localization in brain. Light microscopy immunohistochemical techniques were used to examine the distribution of glutamine synthetase in rat brain. Glutamine synthetase was found to be localized in the glial cells. Neuronal cell bodies, endothelial cells, and choroid epithelium contained no enzyme. The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.


Massive skeletal trauma in renal transplant patients. A review of 251 renal transplants done at the Vanderbilt University Medical Center since October 1962 revealed three patients who had suffered subsequent skeletal injuries sufficient to cause hospitalization. In a 37-year-old woman, a closed fracture of the pelvis healed satisfactorily in the usual period of time. In a 30-year-old man, closed fractures healed well, but there was prolonged delay in the healing of massive open wounds resulting from crushing injuries of the lower extremities. He required prolonged hospitalization, but satisfactory result was achieved after early amputation and close cooperation between orthopedic and renal teams. No significant alterations in the function of either patient's transplanted kidney occurred. It is postulated that severe trauma in transplantation patients may become more common in the future, and certain guidelines for its management are set forth. With close cooperation between the orthopedic surgical and medical renal teams, a successful outcome can be expected.


Pathophysiology of propranolol in hypertension. Only recently approved for use in the treatment of hypertension in the US, the beta-adrenergic receptor blocking compound propranolol has been used elsewhere for this purpose since 1964. The exact mechanisms to explain why and how "beta-blocking drugs" reduce arterial pressure are not known with certainty, but possible explanations include: (1) "resetting" of the baroreceptors, (2) reduction of cardiac output, (3) adaptation of circulation ("autoregulation"), (4) inhibition of renin release, (5) central nervous system effects, (6) possible antihypertensive metabolites, and (7) other unknown mechanisms or a combination of known mechanisms. Propranolol alone has been demonstrated to be extremely effective in reducing arterial pressure. In addition, the combination of propranolol and vasodilator and diuretic drugs would be expected to reduce vascular resistance without reflexive cardiac stimulation and with prevention of sodium and fluid retention.


Clottability and cross-linking reactivity of fibrin(ogen) following differential release of fibrinopeptides A and B. Human fibrinogen was treated at pH 6.0, 7.3 and 9.0 with thrombin, batroxobin (thrombin-like fraction of Bothrops atrox venom) or an extract of the venom from Ancistrodon contortrix contortrix. These three enzymes released the NH2-terminal fibrinopeptides A and B at different rates. Thrombin-free, preactivated factor XIII (factor XIIIa) was added to incubation mixtures to stabilize resulting fibrin(ogen) aggregates. Cross-linking of gamma-chains and the size of covalently linked fibrin-fibrinogen oligomers were studied in an early stage of fibrinopeptide cleavage using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Batroxobin (pH 7.3) and thrombin (pH 6.0) preferentially released fibrinopeptide A, and resulting fibrin aggregates became rapidly insoluble. However, when fibrinopeptide B was removed with the contortrix enzyme, soluble cross-linked oligomers appeared initially. The opaque fibrin clots, produced by thrombin (pH 6.0) or contortrix procoagulant fraction (pH 7.3), were found to be devoid of alpha-polymers even after prolonged incubation with factor XIIIa. Our data suggest that the solubility and opacity of fibrin networks are not primarily related to the type of the cross-link (gamma-gamma versus alpha-alpha interactions).


Soluble fibrin complexes: separation as a function of pH and characterization. 1. The influence of the pH on the separation of high molecular weight derivatives obtained by a limited action of thrombin on fibrinogen was studied by agarose gel chromatography. When the pH of the elution buffer was 8.5, non crosslinked associations were easily separated in two peaks eluted prior to the fibrinogen peak: one contained a dimer, the other several high polymers. At pH 6.5, only the fibrinogen peak appeared: the fibrinogen molecule proteolysed by thrombin formed no stable associations at this pH and was eluted with the intact fibrinogen molecule. In the presence of factor XIII and Ca++, numerous associations were obtained which are independant of the pH. 2. The polypeptide chain composition of the different species separated at pH 8.5 was studied by SDS-polyacrylamide gel electrophoresis. This technic showed Aalpha, Bbeta and gamma chains in the fibrinogen peak, whereas in the chromatographic fractions containing the dimer four bands corresponding to Aalpha, alpha, Bbeta and gamma chains were found. In the peak containing the high polymers, only the presence of alpha, Bbeta and gamma chains was demonstrated. 3. These experimental results concerning the effect of pH on the formation of soluble complexes showed that the presence of fibrin monomers in fibrinogen solution was not sufficient to promote any associations. The formation of such derivatives is strongly dependent on the pH of the solution. This obviously can be explained by an influence of the pH either on the ionization of polymerisation sites and the intermolecular bonds between the complex units or on the unmasking of the polymerisation sites by a hypothetical pH induced conformational change of the fibrinogen molecule.


The host component of the popliteal lymph node graft-versus-host (GVH) reaction. Identification of cells in the node and kinetics of cell proliferation. The cellular composition of rat popliteal lymph nodes undergoing a GVH reaction was examined. The great majority of cells isolated from the nodes were lymphocytes, while the contribution of phagocytic cells was negligible (less than 5%). Both T and B cells were present in GVH nodes. However, the proportion of B cells was higher than in normal lymph nodes (40-50% vs 30%). Cells synthesizing DNA were enumerated autoradiographically in sections of GVH nodes up to day 7 of the response. A significant increase in the proportion of 3H thymidine labelled cells had already been found on the third day of the GVH response, before lymph node enlargement was apparent. Of the differnt days tested a maximum of 6% labelled cells was found on day 7. Liquid scintillation counting of cell suspension from such nodes showed an even higher increase in 3H thymidine incorporation in GVH vs normal nodes. These findings indicate that cell proliferation is a central mechanism behind the lymph node enlargement.


Effects of general anesthetics on search in memory in man. Recovery of search functions in long-term memory following several hours of anesthesia was studied on human volunteers. Verbal as well as visual search was assessed. The anesthetics used, fluroxene and halothane, slowed down considerably the verbal search for the first few hours following anesthesia, but had very little effect on the following day. No effect was observed a week later. Visual search was not affected at all, in accordance with previous findings indicating a selective effect of low concentrations of inhalation anesthetics on verbal memory.


Absorption, metabolism and excretion of safrole in the rat and man. The metabolic disposition of different doses of [14C] safrole were studied in rat and man. In both species, small amounts of orally administered safrole were absorbed rapidly and then excreted almost entirely within 24 h in the urine. In the rat, when the dose was raised from 0.6 to 750 mg/kg, a marked decrease in the rate of elimination occurred as only 25% of the dose was excreted in the urine in 24 h. Furthermore, at the high dose level, plasma and tissue concentrations of both unchanged safrole and its metabolites remained elevated for 48 h probably indicating impairment of the degradation/excretion pathways. The main urinary metabolite in both species was 1,2-dihydroxy-4-allylbenzene which was excreted in a conjugated form. Small amounts of eugenol or its isomer 1-methoxy-2-hydroxy-4-allylbenzene were also detected in rat and man. 1'-Hydroxysafrole, a proximate carcinogen of safrole, and 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat. However, in these investigations we were unable to demonstrate the presence of the latter metabolites in man.


[Radiation response of mitochondria in dependence on their metabolic status (author's transl)]. The influence of the metabolic status of mitochondria upon their radiation response was studied. It turned out that the reduction of pyridine nucleotides by addition of beta-hydroxybutyrate (BOH) and the decrease through respiration were distinctly impaired in mitochondria with a substrate deficit by an irradiation with 2.7 krd already. The evolution of the lesion depends on the incubation conditions following irradiation, a presence of BOH having protective effects. The general redox level seems to be essential for radiation response of mitochondria. An exit of NAD from mitochondria has proved to be the main cause for inhibition of the respiratory BOH-consumption.


Chemiluminescence microanalysis of substrates and enzymes. Extracts from bioluminescent organisms are increasingly used for analysis of small amounts of substrates and enzymes. The light emission is in some organisms related to the conversion of substrates and cofactors of central metabolic importance. Extracts from such organisms are particularly valuable for analytical applications. This is quite obvious in the firefly where the energy, required for light production, is derived from ATP and in a couple of strains of luminescent bacteria where reduced pyridine nucleotides through reduction of flavine mononucleotide is utilized in the light reaction. It deserved to be noted that many biochemical reactions can be coupled more or less directly to the conversion of ATP, NAD(H), NADP(H) and FMN(H), thus providing the basis for a great variety of analyses. Special kinds of bioluminescent reactions are also of considerable interest, as for instance the relationship between "active sulphate" and PAP, which participate in the formation of light in the sea pansy (Renilla reniformis). High sensitivities are often reached in chemiluminescence analysis making the technique suitable for samples composed of a small number of cells. How bioluminescence has been employed in these kinds of microanalyses is examplified in studies of nucleotides, metabolites and enzymes with low activities.


A contribution to the formation mechanism of calcium oxalate urinary calculi. II. In vitro experiments concerning the theory of the formation of Whewellite and Weddellite urinary calculi. In vitro investigations of the formation of Whewellite or Weddellite are described. By means of different precipitation models the influence of cationic minerals on the formation of Weddellite could be observed. The possible conversion of Weddellite into Whewellite in vivo is demonstrated by in vitro experiments. A theory of the formation of Weddellite or Whewellite urinary calculi is developed on the basis of the results obtained.


A contribution to the formation mechanism of calcium oxalate urinary calculi. III. On the role of magnesium in the formation of oxalate calculi. The influence of magnesium in vitro on the precipitation of calcium oxalate was investigated. Even at maximum physiological magnesium concentrations a litholytic effect could not be observed, but the retardation of the calcium oxalate crystallization caused by magnesium might be decisive for a reduction in calculi formation. The enlargement of the calcium oxalate crystals and aggregates caused by the retardation of crystallization, however, should be regarded as a contraindicating factor for Mg therapy in oxalate calculous disease. It is safe to say that high magnesium concentrations prevent the conversion into Whewellite of the calcium oxalate calculi substance primarily formed as Weddellite.


[Age-dependence of catecholamine effects in man. IV. Effects of specific inhibitors on the lipolytic action of alpha and beta adrenergics]. In order to characterize age differences in the lipolytic effect of catecholamines on tests of subcutaneous adipose tissue of test persons aged from 0.1 to 10 years, from 20 to 40 years, and from 60 to 75 years the influence of propranolol, phentolamine and theophyllin on the release of glycerol by isoprenalin and adrenalin was investigated. Propranolol (10(8) and 10(5) mol/1) inhibits the lipolysis in the adipose tissue of all age groups stimulated by isoprenalin (10(6)and 10(5) mol/1). The following Ki-values were calculated: 2x10(6) mol/1in the tissue of adults, 0.5 x 10(6) mol/1 in the infantile adipose tissue, 0.2 X 10(6) mol/1 in the tissue of old persons. Phentolamine (10(5) mol/1) increases the lipolytic effect of adrenalin (10(5) mol/1), there are no age differences. Theophyllin (10 (2) mol/1) increases the release of glycerol induced by isoprenalin (10(5) mol/1) in infantile and adult adipose tissue, however, it has no influence on them in the adipose tissue of old man. The findings suggest the higher sensitivity of the fat cells of the ageing organism to beta-adrenergics underlies a higher affinity of the adrenergics to the specific beta-adrenoceptors in the cytoplasm membrane of the adipocytes. The more intensive lipid mobilization in old age by beta-adrenergics is explained by a low activity of the cAMP-phosphodiesterase of the fat cells and by the higher and possibly longer lasting increase of intracellular cAMP in this age group.


[Stability in drinking and surface water of nine virus species from different genera (author's transl)]. The stability of nine viruses, Aujeszky, Sindbis, Vesicular Stomatitis, Newcastle Disease, Vaccinia, FMD, HCC, Reo and Teschen virus in drinking and surface water was investigated comparatively at temperatures of 9 and 15 degrees C as well as the influence of water factors like seasonal difference in temperature, pH value, hardness and sort of water. The results can be summarized as follows: 1. At temperatures of 9 to 15 degrees C the majority of the viruses remained stabil in natural water for an astonishing long time. 2. Starting with virus concentration of about 10(4) infectious units per ml Teschen, Vaccinia, Reo, HCC and ND virus could mostly be demonstrated in water longer than 200 days and FMD, Aujeszky, Vesicular Stomatitis and Sindbis virus for 20 to 50 days on average at 9 degrees C. The stability of the viruses investigated decreased in water in the named turn. 3. Based on these results it can be assumed that under natural conditions with very low virus content of some particles the labile viruses such as Toga, Herpes, Rhabdo and pH labile Picorna remain infectious in water for some days. They should not have any importance as water contaminants. More resistant viruses like Paramyxo may keep infectious for weeks and very stabile viruses such as Entero, Reo, Adeno and Pox viruses several weeks to months. 4. As to factors temperature, pH, hardness and sort of water-within the naturally differing range-only the temperature and only in the case of less resistant viruses showed significant influence on the virus stability in water.


[Gamma-glutamyltranspeptidase in chronic polyarthritis. I. Comparison with a control group and relationship with alkaline phosphatase]. Gamma-GT, alcaline phosphatase and other parameters of abnormal liver functions were estimated in 54 consecutive in-patients having active RA but without a previous history or clinical signs of liver disease, and compared with a matched control group, suffering from degenerative rheumatic disease. There was a slight to moderate elevation of gamma-GT in 40.4% of the RA-patients (mean value 27.2 IU/l) and in 32.1% (mean value 22.3 IU/l) of the control group, respectively. The difference was not significant. Abnormal values in the control group occurred mainly in patients with peri-arthropathia of the shoulder, before mobilisation under anaethetic (3 of 5) and - coxarthrosis before total hip replacement (4 of 12). Alkaline phosphatase was elevated in 25.9% of the RA-patients (mean value 41.3 +/- 21.9 IU/l) and in 14.8% of the control group (mean value 34.3 +/- 15.9 IU/l). The difference was significant. There was a correlation between gamma-GT and alcaline phosphatase in the RA-group (r = 0.549, p less than 0.001) but not in the control group (r = 0.102). Abnormal values found in the control group were mainly found among patients with osteoporosis, following fractures, and coxarthrosis. The frequency of abnormal results and the value of the means increased with raising disease activity. Two groups of 30 and 32 patients, respectively, were examined at intervals of 2 or 4 weeks over a period of 6-10 and 18 months, respectively, and showed temporary elevations os gamma-GT in 3/4 of all patients, of GOT in 2/3 of alcaline phosphatase in 1/2 and of GPT in 1/3. Compared with other parameters of liver disease gamma-GT did not react in a different but in a more sensitive way. In our opinion it is the most sensitive indicator of reactive changes of the liver in RA.


Relationships between chemical structure and antiviral activity of some biguanide derivatives. The aim of this report was to indicate the correlation between chemical structure and antiviral activity of some biguanide derivatives obtained according to Monsanto Chemicals Ltd. Neth. Appl. 289. 283. The studies were carried out on the culture of monkey kidney cells infected with parainfluenza Sendai virus and on the mice infected with influenza virus. The increase of antiviral activities of N-Phenylbiguanide and N-p-Ethoxyphenylbiguanide was estimated.


[Gamma-glutamyltranspeptidase in chronic polyarthritis. II. Influence of drugs]. Thirty outpatients with active RA were treated with Sudoxicam, a nonsteroidal antirheumatic drug, for periods of 6-10 months. Gamma-GT, alkaline phosphatase and transaminase were estimated at 2 week intervals. During treatment, the frequently elevated values showed a significant tendency towards normality (time trend analysis). During a second drug trial with Piroxicam in 32 RA outpatients over a period of 18 months, the mean value of gamma-GT and alkaline phosphatase did not decrease significantly. With regards to liver function tests, there was no significant difference between 19 patients receiving and 13 patients not receiving simultaneous gold therapy. During gold treatment periods of 26 patients with a total dose of 3.8 g Fosfocrisolo (0.8 g Au) the mean value of gamma-GT decreased from 26 to IU/l. Cyclophosphamide treatment of 13 patients, with daily doses of 50-150 mg to a total dose auf 48 g, had no significant influence on gamma-GT and alkaline phosphatase. Our results indicate that the very frequent elevations of gamma-GT and of other liver data in RA are caused by the rheumatoid process itself and not induced by drugs.


[Changes in the acid-base condition and gas composition of the blood in meningoencephalitis of meningococcal etiology]. A study of the acid-base state in meningococcous meningoencephalitis demonstrates that there are different metabolic changes: metabolic acidosis, metabolic alkolosis, respiratory alkalosis and metabolic and respiratory alkalosis. These studies also detected a significant correlation between the character of these changes and syndromes of brain lesions. Deep lesions are characterized by metabolic acidosis, basal-stem lesions by respiratory alkalosis, multiple lesions--by metabolic alkalosis. These data give ground to speak of the significance of brain pathology in the pathogenesis of general metabolic disturbances in meningococcus infections.


[Purification and various properties of NADP+-dependent alcohol dehydrogenase from Acinetobacter calcoaceticus]. The constitutive NADP+-dependent alcohol dehydrogenase from Acinetobacter calcoaceticus can be accumulated about 50 fold in 3 purification steps. The end-product shows in the analytical polyacrylamide gel electrophoresis only one active enzyme band. The molecular weight of the enzyme was determined to be 235,000 by gel chromatography on Sephadex G 200, the smallest subunit shows a molecular weight of 61 000 on SDS electrophoresis. The isoelectric point is at 5.84. The KM values determined with primary aliphatic alcohols diminish in the range of the homologous order (C2--C10) with growing chain length. The KM value for hexanal is about 20 fold less than that for 1-hexanol.


Synthesis, turnover and compartment analysis of the free fatty acids in the placenta of rats. The in vivo tracer method and in vitro acetate incorporation experiments were used to investigate the metabolism of placental free fatty acids. Analysis of data revealed that free fatty acids pass into the fetus from maternal plasma through a small placental compartment, which accounts for only 5 percent of all of the placental free fatty acids. The turnover time of this compartment is 0.57 min. The rate of placental fatty acid synthesis evaluated by both methods is very small and amounts to 0.003 mumols fatty acids/min/all placentas of one litter.


[Antihemolytic effect of various benzodiazepines on human erythrocytes]. The benzodiazepines, medazepam, chlorodiazepoxyde, and oxazepam, act antihemolytically just as chloropromazine in hypotonic NaCl solution on human erythrocytes. The effect depends on concentration and is biphasic with the exception of oxazepam. The maximal antihemolytic concentrations are for medazepam 9.1-10-5 M, for chlorodiazepoxyde 4.6-10-4 M and, respectively, 9.1-10-4 M for diazepam and oxazepam. No linear correlation exists between the concentration at maximal hemolytic protection and the lipid solubility.


Studies on ligand binding of kidney bean leghemoglobin. Absorption spectra of different ligand derivative;s of kidney bean leghemoglobin alpha have been recorded. The effect of pH on the absorption spectra of kidney bean leghemoglobin alpha has been studied. The pK of the acid-alkaline transition of the heme-linked water molecule is 8.25 and the pK for the acid dissociation of the heme group is 4.03. Affinities of kidney bean leghemoglobin for two different types of ligands have been studied in comparison with soybean leghemoglobins alpha and c and sperm whale myoglobin. All these leghemoglobins have similar affinities for the small anionic ligand fluoride ion, and they are only slightly more accessible to this ligand than is sperm whale myoglobin. Differences in the primary structure or in conformation of these proteins are reflected in the affinity for the bulky ligand imidazole. The accessibility to imidazole increases in the order sperm whale myoglobin less than soybean Lbalpha less than soybean Lbc less than kidney bean Lbalpha, and also low spin Lbalpha less than high spin Lbalpha. The results are discussed with respect to the amino acid sequences of the leghemoglobins.


Relative value of beta blockers and thiazides for initiating antihypertensive therapy. Beta blockers or thiazides in hypertension. Fifty-five patients with mild to moderate, renal or essential hypertension were admitted to a double blind cross-over trial of 18 weeks, involving treatment periods with placebo, the thiazide bendrofluazide (15 mg daily) and the beta blocker atenolol (600 mg daily). Compared to the placebo period (190/117 mm Hg) the hypotensive effect of atenolol (-24/16 mm Hg) was more pronounced than the hypotensive effect of bendrofluazide (-17/6 mm Hg). Arguments in favor of initiating antihypertensive drug therapy with beta blocker were its more powerful hypotensive effect, the quicker onset of its action, less metabolic disturbance, decreased frequency of complaints and patient's preference. On thiazides body weight and the frequency of swollen ankles decreased. Plasma renin concentration was not found to have a strong predicting power for the hypotensive effect of atenolol or bendrofluazide but low renin patients showed a more pronounced blood pressure decrease on bendrofluazide and high renin patients, especially essential hypertensives, on atenolol. While these points can be a guide to therapy today, the preference of one drug over the other must eventually be based on their relative efficacy in decreasing morbidity and mortality from the hypertensive disease.


Stabilization and assay of a 17beta-hydroxysteroid dehydrogenase in the serum of pregnant women. Up to the present the activity of the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in the blood of pregnant women has not been accurately measured because of its great instability. The enzyme was stabilized by mixing fresh serum with an equal volume of potassium phosphate buffer (100 mM, PH 7.4), containing 40% (v/v) glycerol, 40 muM oestradiol-17beta (Oe2) and 0.4% (v/v) ethanol. Under these conditions the 17beta-HSD was stable for several days at -20, +4 and +20 degrees C and resistant to heat denaturation at 60 degrees C. The Km-value for Oe2 with NAD or NADP as cosubstrate was 5 X 10(-6) or 2 X 10(-6) M, respectively. In the presence of NAD, Oe2 was oxidized twice as rapidly as with NADP. The Km-value for NAD was 10(-5) M. Under the conditions of assay [3H]oestrone formation was linear with time (3 h) and with protein concentration. Serum enzyme activities in normal pregnancies (between 20 and 60 muU/ml serum at the end of gestation) were nearly twice as high as those reported by other investigators. In normal single and twin births highest activities were obtained at the expulsion of the placenta which in all cases was followed by a rapid decrease in activity.


Glucose-6-phosphate dehydrogenase Velletri. A new variant of red cell glucose-6-phosphate dehydrogenase (G6PD) has been found in a Caucasian man with congenital non-spherocytic haemolytic anaemia. This variant has reduced activity, increased thermolability, increased Michaelis constants for glucose-6-phosphate and NADP, slightly increased electrophoretic mobility, and a biphasic pH-activity profile. The red cell adenine compounds and ATP, are in normal limits. The increased activity of red cell NADP-glutathione reductase is probably the expression of a mechanism of compensation for the decrease of G6PD and a consequence of the decrease of NADPH.


Acid-base status before and after arterial clamping. The necessity of providing alkalizing therapy after re-establishment of the local circulation was studied in 10 otherwise healthy patients with intermittent claudication. No such necessity was found in providing stable peroperative circulation, normo- to slight hypothermia, adequate infusions, and normal acid-base values prior to arterial clamping. It is pointed out that alkalosis can cause circulatory problems that are just as serious as those occurring with acidosis; therefore the routine use of alkalizing agents during vascular surgery is inadvisable. Should unstable circulatory parameters occur and hypoperfusion be suspected, then repeated control of the acid-base values is indicated.


The pathogenesis of acute selective necrosis of the granular layer of the human cerebellar cortex. PH determinations by means of a sturdy, spear-electrode inserted in the cerebellar tissue immediately after necropsy were carried out in 60 patients suffering from different disorders and dying in hospital, and from 25 individuals killed instantly by violent accidents. A correlation was found between the presence of NGL and low pH levels in the cerebellum (average pH 5.56); subjects without NGL changes showed an average pH OF 6.08. No correlation was found between the pH levels and the time after death, or between pH and any specific disease. The so-called acute selective necrosis of the granular layer of the human cerebellar cortex (NGL), is considered from the present studies to be a phenomenon of postmortem origin. Its relationship to certain specific diseases can be explained by the fact that in these conditions there is a higher postmortem acidity, known to promote autolysis.


Infantile periarteritis nodosa or mucocutaneous lymph node syndrome. A report on four cases and diagnostic considerations. Coronary artery aneurysm in childhood is a rare disease and has in most cases been ascribed to infantile periarteritis nodosa (IPN). In recent years a mucocutaneous lymph node syndrom (MLNS) has been found almost exclusively in Japan first described by Kawasaki 1967; this disease frequently involves the coronary arteries and myocardium. Four cases with coronary aneurysms are presented from Sweden and seem to be first described from Scandinavia. Three of these patients died a sudden death with cardiac arrest. Since MLNS and IPN have identical clinical and pathological features, we suggest that MLNS and IPN constitute a pathologic entity and that to separate them on a clinical or histological basis is nonsensical. The risk of coronary aneurysm and possible sudden death must be considered in patients with uncharacteristic symptoms including prolonged fever, conjunctivitis, exanthema, lesions in the oral mucosa, elevated sedimintation rate, and leukocytosis.


Human interferon and cell growth inhibition. II. Biological and physico-chemical properties of the growth inhibitory component. Human leukocyte interferon (IF) inhibits the growth rate of homologous cells in culture. The growth inhibitory component, formerly separated from the antiviral component of human leukocyte IF by adsorption chromatography on albumin-agarose, is investigated. The properties of the component are compared with the accepted characteristics of IF. The growth inhibition is caused by a small molecule, unstable to pH 2 treatment with HCl, but stable to trichloro-acetic acid (TCA) and to proteolytic enzymes. The siolated growth inhibitor seems to be a dimer of molecular weight (mol wt.) approximately 2300. It is activated by heat treatment and lacks species specificity. The discrepancies in the properties of the growth inhibitor before and after separation from IF are discussed.


C1 subcomponents in acute pneumococcal otitis media in children. Twenty children with acute pneumococcal otitis media were studied. In 6 children the infection ran a normal course and healed after the first episode and in 14 it relapsed. The serum levels of the immunoglobulins IgG, IgA and IgM were normal in all 20 children. Specific antibodies to pneumococcal polysaccharide were found in all cases, with no differences in the titers between the relapsed cases and those that healed. The complement components were quantitated with electroimmuno assay. G1q proved depressed in 60 per cent of the relapsed cases and in 16 per cent of the healed cases. C1r and C1s were disproportionally high compared with the C1q levels. Furthermore, crossed immunoelectrophoresis revealed abnormal complexes composed of C1r and C1s, and complexes composed of C1r, C1s and C1 IA. These complexes were more pronounced in sera from the children with relapsing otitis media.


Digestive enzymes of three teleost fishes. The activity of amylase, sucrase, protease and lipase has been examined in Wallago attu, Clarias batrachus and Labeo rohita. The optimum pH value for carbohydrases ranges from 5.0 to 7.0 and that for trypsin between pH 6.8 and 7.8. Lipase is active at a slightly more alkaline medium. The optimum pH for a given enzyme varies in different sections of the alimentary canal of the same fish and also from species to species. Variations are also found in the optimum substrate concentration for a given enzyme in the different sections of the alimentary canal. The activity of carbohydrases is higher in the herbivorous fish Labeo, than in the carnivorous fish Wallago, and the omnivorous fish Clarias. As for protease, maximum activity is found in Wallago. The difference is not so well marked for the activity of lipase. There is a correlation between the normal diet of the fishes and the relative activity of the digestive enzymes.


Myocardial noradrenaline uptake after coronary occlusion in the rat. Coronary ligation produced a marked increase in labelled noradrenaline uptake by the myocardial tissue of rats. The peri-ischemic zones showed an elevated accumulation of noradrenaline on the 4th day but the intact zone had returned to normal values. At the 14th day of observation, both the ischemic and per-ischemic tissue exhibited a subnormal accumulation of radioactivity. The role of the acidotic state in the changes of noradrenaline uptake was studied in vitro. Noradrenaline accumulation in the myocardial tissue was higher at pH 6.8 than at 7.4 or 7.1 Competition studies revealed that unlabelled noradrenaline had occupied the binding sites in the same quantity at pH 6.8 and at 7.4. It is assumed that intracellular acidosis was involved in the enhanced accumulation of noradrenaline in the damaged myocardium, and that an increase of noradrenaline concentration in the myocardium may be considered a risk factor in supporting heart function.


Effects of carbachol and calcium on the cyclic guanosine-3',5'-monophosphate (cyclic GMP) metabolism in intestinal smooth muscle. In a submaximal concentration carbachol contracted the rabbit colon muscle and increased the cyclic GMP level. The cyclic AMP level was reduced. In a Ca++-depleted muscle carbachol reduced the cyclic GMP level while the effect on the cyclic AMP content of the muscle was unchanged. Carbachol had no effect on the guanylate cyclase activity of the "plasma membrane fraction" (the 35-45% fraction). In the homogenate and the microsomal fractions Ca++ had no effect on the guanylate activity while it stimulated the enzyme in a soluble fraction. In the "plasma membrane fraction" cyclic GMP released Ca++ from the preloaded fraction and inhibited the Ca++ accumulation. These effects were not found in the vesicular microsomal fraction (the 35% fraction). In both fractions, however, cyclic GMP counteracted the stimulating effect of cyclic AMP. These results indicate that cyclic AMP and GMP may have antagonistic roles on the Ca++ metabolism in the colon muscle. It is suggested that cyclic GMP may act as some kind of positive feedback mechanism which may have a modulating effect on the release of Ca++ from one pool to another in rabbit colon.


The analysis of organic water pollutants by gas chromatography and gas chromatography-mass spectrometry. Four methods for the analysis of trace levels or organic compounds in water have been discussed: direct aqueous injection, vapor stripping, solvent extraction, and lipophilic adsorption. Table 6 presents a comparison of these techniques. Direct injection is applicable to compounds having a wide range of polarities and volatilities, but it is not a very sensitive technique. For applications in which low sensitivity is acceptable, direct injection offers a very rapid and potentially accurate means of measuring organics in water. Vapor stripping is a factor of 10(6) more sensitive than direct injection, but this is achieved at the expense of simplicity. This method is applicable to compounds of volatilities less than that of eicosane. A subtle operational problem with most vapor stripping techniques is that the contents of the trap are consumed with one analysis; if anything goes awry, the analysis of that trapped sample cannot be repeated. Solvent extraction has a respectable sensitivity (about 0.5 ppb) and operationally it is very simple. Furthermore, aliquots of the resulting extract can be analyzed many times with different techniques if necessary. Because of the evaporation step, very volatile compounds (greater than that of decane) cannot be measured effectively with solvent extraction. The introduction of a solvent into the water carries with it the potential for contamination. Thus, ultrapure solvents must be used and all glassware should be carefully cleaned [96]. Lipophilic adsorption has the unique property of sampling many hundreds of liters of water. Thus, the method is quite sensitive (potentially in the ppt range) and, in addition, it can provide several milligrams of an isolated component. This latter feature is of considerable advantage if one wants to complement GC-MS analyses with infrared or NMR for difficult structural identifications. As a solvent extraction, the evaporation of the final solvent limits the applicability of adsorption methods to compounds with volatilities greater than that of decane. Finally, the importance of avoiding contamination should be emphasized. Many of the compounds encountered in environmental samples are also common laboratory artifacts, for example plasticizers and antioxidants. When one finds such compounds in a water sample, it is absolutely essential to demonstrate that they are indeed present in the water and are not the result of laboratory contamination. The best such demonstration is procedural blank analyses that are indeed blank.


[Comparison of the effects of oxazepam and oxypertine in treatment of anxious depressive neuroses]. The author has treated with the double blind method 38 neurotic patients, hysterical or obsessionnal type, in a state of anxious depressive relapse. Some patients received oxazepam (3 X 15 mg per day), others received oxypertine (3X 10 mg per day); this chemotherapy was completed with supportive psychotherapy. Patients were examined at least once a week for one month. At the end of the treatment, results obtained with both drugs were found to be beneficial. Statistical analysis indicates a more both drugs were found to be beneficial. Statistical analysis indicates a more rapid action for oxypertine, which effects are more pronounced than those of the control medication after two weeks of treatment.


Renin and age as determinants of a predominantly betablocker-based antihypertensive drug program. Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%) or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall in two categories: younger patients with fairly mild hypertension and older patients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of betablocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, betablockers normalized blood pressure (less than or equal to 95 mm Hg diastolic) in three-quarters of the younger-than-40-year-olds, in about half of those 40-60 years of age but in only 20% of those over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state whereas those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the betablockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, although not exclusively, to renin suppression.


The importance of bites by the saw-scaled or carpet viper (Echis carinatus): epidemiological studies in Nigeria and a review of the world literature. The incidence of Echis carinatus (saw-scaled or carpet viper) bite and its mortality have been investigated in the Nigerian savanna region. A geographical area was defined in which the snake was particularly abundant and bites were frequent. Perennial and seasonal fluctuations in incidence and mortality, the circumstances in which bites occurred and the types of people bitten were studied at Bambur, Zaria, Kaltungo and Gombe hospitals. Peak incidence coincided with the increase in farming during the rains whereas percentage mortality seemed to be greatest during the cold dry season. The majority of the patients were young males bitten on the foot while walking or farming. A review of the world literature indicated that E. carinatus was the principal cause of snake bite morbidity wherever data were available throughout its wide geographical range. Official statistics have seriously underestimated this important rural health problem.


Etiological determinants of protein calorie undernutrition in a rural child community. Two groups of randomly selected underweight and well-nourished preschool children residing in study villages of Punjab, Ludhiana district were examined with respect to their socioeconomic background, birth weights, dietary intakes, quality of received mother care, blood biochemistry, parasite load, psychomotor development and past illness prevalence. It was found that underweight children showed significantly less favourable indices in all of the above categories except stool parasitology suggesting an extremely intricate and complex interaction of a host of ecological variables in the causation of undernutrition. Using the discriminate analysis on readily available social variables, it was found that caste affiliation and, less so parental income were the two most significant variables distinguishing between the two groups. A model for the interaction patterns of ecological variables in their effect of protein calorie malnutrition for the given area is suggested.


Salivary Secretion in wild Glossina pallidipes Austen. (Diptera, Glossinidae). The salivation behaviour of wild G. pallidipes obtained from Lambwe Valley and Kbwezi was studied. Salivation was measured by counting the number of salivary drops secreted per minute and measuring the sizes of the stained saliva after drawing them with a camera lucida. The results confirmed observations obtained from laboratory bred flies. The quantity of saliva secreted by tsetse flies was significantly increased as the flies became hungrier. The proportion of flies salivating also increased with intensity of hunger. Female G. pallidipes secreted significantly more saliva than the males. There was no significant difference between the quantities of saliva secreted by infected and free tsetse flies; thus there is no evidence to support the suggestion that the presence of trypanosomes in the tsetse fly stimulated it to salivate copiously. Flies having trypanosome infection in their salivary glands discharge large numbers of mature parasites in their saliva. Flies with trypanosomes in their proboscis discharged relatively few mature and immature parasites in their saliva.


Nuclear coat and viruslike particles in the midgut epithelium of Glossina morsitans sspp. The ultrastructural aspects of the nuclear coat formation in midgut epithelial cells of pupae and adult flies of G. morsitans sspp. are described. Out of four different species of Glossina examined, this peculiar structure was only found in G. morsitans sspp. Three different types of viruslike particles were found in midgut epithelial cells. One type which is of the same kind of particle found in the salivary glands, lies inside of cytoplasmic vesicles. Two other types of particles were detected in the nuclei.


Comparative study of the postoperative flow in the saphenous vein and internal mammary artery bypass grafts. Postoperative coronary bypass flow was evaluated in two groups of randomly selected patients with grafts to the left anterior descending artery (LAD). Saphenous vein bypass grafts were placed in 27 patients and internal mammary artery grafts in 25 patients. Postoperative flow studies were performed in both groups with roentgendensitometric methods based on the transit time of radiopaque media along the graft plus the mean graft diameter. There was no significant difference between the two groups of patients for age, duration of symptoms, or the frequency of hypertension, diabetes mellitus, prior myocardial infarction, or cardiomegaly. Intraoperative bypass flows were 75+/-27 and 77+/-24 ml. per minute for the saphenous vein group (SVG) and internal mammary artery group (IMAG), respectively. There was no significant difference in the heart rate or mean aortic pressure at the time of the roentgendensitometric flow study. The mean graft diameters were 3.0+/-0.5 and 1.9+/-0.3 mm. for the SVG and IMAG, respectively (p less than 0.001). The ratios of graft diameter to LAD diameter were 1.9+/-0.3 and 1.2+/-0.2 for the SVG and IMAG, respectively (p less than 0.001). The roentgendensitometric postoperative flows were 68+/-27 ml. per minute in the SVG and 46+/-16 ml. per minute in the IMAG (p less than 0.01). The present study indicates that flow in significantly higher in saphenous vein than in internal mammary artery bypasses and that the difference in flow may in part be explained on the basis of the graft diameter.


The essential action of propranolol in hypertension. The unique action of propranolol and other beta blockers in lowering raised arterial pressure is discussed. Although the onset of the antihypertensive effect is not immediate, many trials have confirmed the efficacy of these drugs. Animal experiments have thrown little light on the mechanism of action of beta blockers in hypertension: this may be because in animals, especially the rat, peripheral beta adrenoceptor vasodilatation is relatively more important than in man. Five principal theories have been advanced to explain the antihypertensive effect. None of these, the renin, central nervous system, cardiac, baroceptor or metabolite theory, is totally satisfactory. A new theory is proposed suggesting that the essential action is to diminish sympathetic nerve output by damping sensory input to the central nervous system from a heart whose capacity to respond to exercise and stress is blunted by beta adrenoceptor blockade.


Acute and long-term studies of the mechanisms of action of beta-blocking drugs in lowering blood pressure. The antihypertensive effect of intravenous (acute) and oral (long-term) beta-adrenergic blockade with propranolol or pindolol was evaluated in 46 male patients with either borderline (group I; 23 patients) or sustained (group II; 23 patients) essential hypertension. Arterial pressure, plasma renin activity and plasma concentration of aldosterone were determined during continuous recumbency overnight every 30 minutes before and after treatment. Patients of group I exhibited a marked variation of their recumbent plasma renin activity with relatively low values before midnight and large increases early in the morning. In contrast, low plasma renin activity values and only minimal fluctuations in renin were observed in patients of group II. Plasma renin activity had a consistent relationship with blood pressure both after acute (r = 0.79) and long-term (r = 0.4) beta-blockade. In four patients of group I, who had high plasma renin activity and had responded to intravenous propranolol, infusion of angiotensin II inhibitor did not lower pressure. In group I following beta-blockade, day-night profiles of renin were similar to those observed in group II before treatment. Thus in this latter subgroup, low renin profiles might reflect reduced beta-adrenergic activity. Acute as well as long-term beta-blockade consistently eliminated the day-night rhythm of plasma renin activity, but it did not change rhythm of plasma concentration of aldosterone. Plasma concentration of aldosterone was lower in group II but appeared to be inappropriately high relative to renin levels. These observations suggest that in hypertensive patients classified according to blood pressure and recumbent plasma renin activity profiles a significant relationship exists between changes in plasma renin activity and arterial pressure responses. Thus, patients with high renin levels respond better to treatment than patients with low renin levels. We conclude that in the patients studied, sympathetic nervous system activity mainly determined renin levels as well as antihypertensive effectiveness of the beta-blocking drugs.


Renin and aldosterone secretion in pheochromocytoma. Effect of chronic alpha-adrenergic receptor blockade. Patients suffering from pheochromocytoma characterized by an exclusive or almost exclusive excess of norepinephrine showed no (one patient) or only a moderate increase (two patients) in renin and aldosterone secretion. In those three patients with concomitant distinct hypersecretion of epinephrine, renin release (and aldosterone secretion except in one patient) was markedly enhanced. Similar results were obtained in a patient with excess norepinephrine and dopamine secretion. Renin release was markedly reduced in all patients during preoperative long-term alpha-adrenergic receptor blockade. With the exception of one patient, increased renin and aldosterone secretion was abolished. The results indicate that augmentation in renin release depends on the ratio of the different catecholamines secreted by the pheochromocytoma and their different effe-tiveness in stimulating beta-adrenergic receptors. Even in the presence of excess catecholamine secretion, there is evidence that renin secretion is predominantly mediated by beta receptors rather than by renal vascular alpha-adrenergic receptors. Normalization of catecholamine-induced enhanced renin release in patients with pheochromocytoma during chronic alpha-adrenergic receptor blockade supports the assumption that (alpha-) adrenergic blocking agents inhibit renin secretion distal to their blockade of specific adrenergic receptors. However, contrary to beta-adrenergic blockade, circadian rhythm of renin release seems to remain intact during alpha-adrenergic blockade.


Experience with pindolol, a betareceptor blocker, in the treatment of hypertension. Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, were studied at rest and during work before and after an average of two and 16 months of oral treatment with the beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, both at rest and during work. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: (1) a negative chronotropic effect on the heart, (2) a decrease in peripheral vascular resistance, and (3) an increase in venous capacitance affecting the venous return. However, the significance of these mechanisms seems to differ when the situations after two months of treatment are compared with those after 16 months of treatment. In the beginning, a decrease in cardiac output seems to be the main cause of the lowering of the blood pressure; later, a decrease in systemic vascular resistance might be of greater importance.


Beta-adrenoreceptor blockade in hypertension. There is good evidence from many sources that beta-adrenoreceptor blockade is an effective form of therapy in mild, moderate and severe hypertension either alone or in combination with other antihypertensive agents. Although a number os such beta blocking compounds are now available, they appear to have a hypotensive effect of approximately equal magnitude. This hypotensive effect is obtained in both the supine and standing positions thus avoiding postural hypotension. The maximum hypotensive effect may take some time to become apparent. Despite considerable work the mode of action remains uncertain, reduction in cardiac output, resetting of baroreceptors, reduction in plasma renin and a central nervous system effect have been suggested but remain unproved. There is evidence to suggest that these compounds can control, to some degree, the surges in blood pressure resulting from either mental or physical stress. A low incidence of serious side effects has been reported by many workers. Only the long-term use of these compounds in comparison with other antihypertensive agents will determine their place in the management of hypertension.


Rapid identification of patients with essential hypertension sensitive to acebutolol (a new cardioselective beta-blocker). Acebutolol, a new cardioselective beta-blocking agent, was administered for 48 hours to 44 patients with essential hypertension at a total dosage of 2.0 g (2,000 mg). The slowing down of their pulse rate and the decrease in blood pressure were highly significant, whereas eight subjects treated with placebos had no change in either the pulse rate or blood pressure. Plasma renin activity decreased from 2.26 +/- 2.11 ng/ml/hour to 0.87 +/- 1.04 ng/ml/hour. The decrease in blood pressure was correlated with the initial plasma renin activity and with the decrease in plasma renin activity. These results demonstrate that a rapid decrease in blood pressure can be obtained in patients with essential hypertension treated with acebutolol and that the decrease in blood pressure is related to the initial state of the renin-angiotensin system.


Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension. The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents.


Gastric emptying and secretion in the rhesus monkey. The volume and composition of the gastric contents as well as the rates of gastric emptying and secretion were determined simultaneously in conscious chair-adapted monkeys. These determinations were made during fasting and after a liquid meal, thereby allowing studies of the physiologic variables which regulate gastric emptying and gastric secretion. Administration of a water meal is followed by a complex pattern of changes in rates of secretion as well as the fractional rate of emptying. During administration of a 100-ml water meal (pH 7.4), intragastric volume increased while acid concentration decreased; both then returned to fasting values 50 min later. The fractional rate of emptying increased fivefold during administration of the water meal, returned to basal values after 30 min, and then increased again, indicating that gastric emptying cannot be characterized as a simple first-order process with a constant coefficient. The pattern of the change in the rate of water secretion was similar to that for fractional gastric emptying. In contrast, after the meal, gastric acid secretion increased steadily and did not become maximal until 20 min.


Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs. When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired.


Mechanism of intrarenal blood flow redistribution after carotid artery occlusion. Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.


A smooth muscle active factor isolated from renal cortex of the rabbit. Homogenates of rabbit renal cortex contained a water-soluble material with striking activity on smooth muscle derived from the rabbit aorta, rat stomach, and guinea pig ileum--but not rat colon or chick rectum. Evidence derived from the spectrum of its pharmacologic activity, the influence of specific competitive antagonists on the smooth muscle responses to the factor, the influence of proteolytic enzymes and its elution position during molecular sieve filtration on Sephadex G-10 made it unlikely that the factor was a prostaglandin, renin, angiotensin, a catecholamine, serotonin, bradykinin, a nucleotide, a small organic product of local metabolism, or a small ion. The agent was not found in extracts of renal medulla, spleen, myocardium, or lung. The smooth muscle response to the factor was blocked by phenoxybenzamine. The renal cortical factor in subthreshold concentration also potentiated responses of the rabbit aorta to angiotensin and norepinephrine. The factor's intrinsic activity and ability to potentiate the smooth muscle actions of endogenous vasoconstrictors make it a candidate as a mediator of smooth muscle responses in a number of states.


Specific desensitization (tachyphylaxis) of the guinea pig ileum to angiotensin II. Tachyphylaxis to [Ile5]angiotensin II (angiotensin) in the isolated guinea pig ileum was found to be more severe when the Ca2+ concentration or the temperature of the medium were lowered, or when glucose was absent. Incubation with indomethacin or prostaglandin E2 did not affect the onset of tachyphylaxis or recovery from the tachyphylactic state. The angiotensin dose-response curves of tachyphylactic organs were shifted to the right, and the maximum responses were depressed in proportion to the conditioning doses of the hormone. The recovery from tachyphylaxis followed zero-order kinetics and was not affected by Ca2+ concentration or pH. The temperature dependence of the rate of recovery yielded a value of 14.6 kcal/mol for the activation energy in the physiological temperature range. It is concluded that tachyphylaxis results from the tight binding of angiotensin to superficial calcium-binding sites in the smooth muscle cell membrane. Recovery from tachyphylaxis appears to involve displacement of angiotensin by calcium in a process that is dependent on active transport.


Effect of nicotine on gastric acid secretion: evidence of electrogenic pump theory. In vitro studies on H+ secretion, potential difference (PD), short-circuit current (Isc), and resistance across stripped mucosa of frog stomach in Cl-medium have shown that addition of nicotine in the serum bathing fluid caused a marked inhibition of the H+ secretory rate and an increase of PD and Isc without change of the transmucosal resistance. A dose-response correlation was indicated. During the first 8 min, the changes in the measured parameters, namely, PD versus Ih and Isc versus Ih, were linear. After 8 min, a deviation from linearity was observed. From the slope of the regression lines, the resistance of the electrogenic Cl- pump on the mucosal membrane (Rcl) was calculated to be 127 omega cm2 and the resistance of the chloride pathway on the serosal side (Rcl) was 407 omega cm2. The resistance of the H+ pump on the mucosal membrane (Rh) in Cl- medium was estimated to be  385 omega cm2. The sum of the emf's of the Cl+ pump on the mucosal membrane and of the Cl- gradient across the serosal membrane, namely Ecl + Ecl, was found to be 35 mV. The presence of such linear relationships between measured versus the H+ rate and Isc versus Ih lends support to the electrogenic theory of HCl secretion.


Consequences of ventromedial hypothalamic lesions on metabolism of perfused rat liver. Metabolism of perfused livers from control and ventromedial hypothalamus (VMH)-lesioned rats has been studied. To eliminate the possibility that observed metabolic abnormalities could be realted to hyperphagia, VMH-lesioned rats were placed on restricted diet matching that of controls. Ten days postoperatively, VMH-lesioned rats had hyperinsulinemia, hypertriglyceridemia, increased blood urea nitrogen levels, together with decreased plasma free fatty acid (FFA) and glucose levels. Insulin release produced in vivo by a glucose load was much higher in VMH-lesioned than in control rats. Perfused livers from VMH-lesioned rats secreted more triglycerides and produced more urea than controls, whereas production of glucose and ketone bodies was reduced. Lipogenesis, newly synthesized triglyceride secretion, and the activity of acetyl-CoA carboxylase and fatty acid synthetase were greatest in livers from VMH-lesioned rats. Fasting abolished hyperinsulinemia and most of these observed metabolic alterations. After treatment with anti-insulin serum, the high rate of lipogenesis observed in livers from VMH-lesioned rats was restored toward normal. It is suggested that hyperinsulinemia may be partly responsible for the metabolic disorders observed in livers from nonhyperphagic VMH-lesioned rats.


Uptake of K+ by frog gastric mucosa from submucosal side and acid secretory rate. The K+ content in frog gastric mucosa (K+) was measured as a function of the submucosal K+ concentration ([K+sm]) in the absence of K+ on the mucosal side. The (K+) in HCO3- buffer with 95% O2-5% CO2 gas showed that the removal of external K+ induced a  27% K+ loss from the control value of 5 mM K+sm, that there was no linear relation between (K+) and [K+sm, and that the change in the (K+) versus the [K+sm] was hyperbolic, indicating that there are two different types of K+ in the mucosa: bound and free K+.


Intracellular pH in hypoxic smooth muscle. Hypoxia impairs contractility in canine tracheal smooth muscle (TSM). This is attributed to intracellular lactacidosis. The present studies were undertaken to confirm this. Lactate was found to be significantly increased in hypoxic TSM (65.36 +/- 7.37 mg/100 g wet tissue), compared to normoxic (29.83 +/- 5.05). Intracellular pH (pHi) was, however, significantly increased in hypoxic active TSM to 7.71 +/- 0.05 as compared to 7.30 +/- 0.03 in normoxic active muscle. pHi of resting normoxic muscle (7.20 +/- 0.04) was statistically not different from that of resting hypoxic muscle. The pHi's of resting normoxic and active hypoxic muscles were significantly different. These results show that under in vitro, hypoxic conditions: 1) an increase in glycolysis in TSM is indicated by the increased lactate production, 2) there is a surprising, concomitant rise in pHi rather than a decrease as previously expected, and 3) it is mechanical activity of the muscle which leads to this paradoxical result, inasmuch as pHi is unaltered in the resting hypoxic muscle.


Neuroleptic drug levels and therapeutic response: preliminary observations with red blood cell bound butaperazine. The authors studied neuroleptic concentration-therapeutic response curves for butaperazine (BPZ), a piperazine phenothiazine, in 10 schizophrenic patients during the first 12 days of treatment. BPZ bound to red blood cells (RBC) was more strongly correlated with therapeutic response than was plasma BPZ. RBC BPZ concentrations could be used to define a "therapeutic window", an optimun concentration for therapeutic response, above and below which favorable response diminishes. The authors emphasize the preliminary nature of the data but suggest that levels of RBC-bound neuroleptic may provide an important guide for dosage regulation in schizophrenic patients.


Systemic artery--pulmonary artery communication in Takayasu's arteritis. Four cases of Takayasu's arteritis in which systemic artery-pulmonary artery communication is demonstrated on thoracic aortography are presented. Pulmonary arterial involvement in Takayasu's arteritis seems to be more frequent than generally appreciated (12% in the present series). Demonstration of the communication in the absence of evidence of other causes of a shunt is strongly suggestive of pulmonary artery involvement. It is not necessary to perform pulmonary angiography to confirm the involvement unless clinically indicated. It is also stressed that the presence of pulmonary artery involvement is useful to differentiate Takayasy's arteritis from arteriosclerosis.


[Effect of run-training and run-stress on glucose assimilation and insulin release in rats of different age (author's transl)]. 82 male rats of different age have been investigated after a definitive run-training, after a run-training with subsequent run-stress and after a run-stress without run-training. An intravenous glucose tolerance test has been done measuring glucose and insulin serum levels before and after i.v. glucose application. Data obtained in this study demonstrate that: 1. adult rats have a better glucose assimilation and higher insulin serum levels after i.v. glucose than older ones. 2. run-stress leads to a deterioration of glucose assimilation and diminution of insulin release in rats of any age. 3. run-training improves glucose tolerance and saves insulin at the same time. 4. in old rats, which have never done any training before, run-training improves glucose assimilation, too. 5. run-stress after run-training has a different effect on adult and old rats: In adult rats there is nearly no effect on glucose assimilation and insulin release in comparison to control animals, while old rats show a significant deterioration of glucose assimilation in comparison to control rats of the same age. Obviously the effect of run-training is less distinct in old rats despite of similar running work.


[Investigations on LH and FSH serum levels before and after application of synthetic LH-releasing-hormone in healthy men of different age]. 50 male healthy volunteers of different age had measurements of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Basal levels of LH and FSH as well as maximal release of both hormones after i.v. application of 25 mug of synthetical LH-releasing hormone have been done. Results demonstrate an increasing reserve capacity of LH and FSH with age. FSH/LH ratio is altered in favor of FSH with duration of life. Sensitivity of gonadotropin producing cells of adenohypophysis to LH-releasing hormone is diminished in old age that can be recognized from a diminution of the relative rise of serum LH and FSH after LH-RH application. Correlations and partial correlations of absolute and relative body weight with age and basal LH and FSH serum levels demonstrate that age and not body weight plays a main part for increasing gonadotropin serum values. Causative responsibility for the increased LH serum concentrations is a decrease of testosterone production with age. Data obtained in this study and reports presented in literature give no convincing explanation for the increase of FSH serum levels with age.


[Sexual hormones in ageing males (author's transl)]. Alterations of sexual hormones in plasma of ageing males occur between the 50th and 60th year of life with individual variations: 1. Decreased values of testosterone in plasma and a poor response to gonadotrophins demonstrate a diminished synthesizing capacity of the testes in old men. 2. The decreased testosterone plasma values are followed by an increase in LH. The response of the anterior pituitary gland to LH-RH stimulation in old men is normal. 3. Under basal conditions estrone as well as estradiol plasma concentrations increase significantly with age because of increased conversion from androgens. 4. Parallel to estrogen plasma values an increased concentration of the sexual hormone binding globulin (SHBG) is found, resulting in a steep decrease of the free (= active) testosterone fraction. 5. Decreased testosterone, which is more strongly bound to SHBG and increased estrone and estradiol plasma values result in an androgen/estrogen imbalance in old men.