Acinetobacter septicaemia following prolonged intravenous therapy. A 76-year-old man developed septicaemia during the infusion of stable plasma protein solution (SPPS) which was subsequently shown to be contaminated with Acinetobacter anitratus. Septicaemia persisted for four days despite change of the intravenous cannula and administration of an appropriate antibiotic. Clinical improvement occurred only when the entire intravenous line, (infusion bottle, airway needle, giving set and intravenous cannula), all of which grew Acinetobacter, was replaced. Contamination of the SPPS probably occurred in the ward via a contaminated giving set and airway needle, which had been in use for one week. This case illustrates the importance of following accepted guidelines for infection control in intravenous therapy.


Community health in the University of Melbourne. After changes to the curriculum of the University of Melbourne Medical School, a Department of Community Health has been established. Undergraduate teaching will be carried out in the first, third, fourth and sixth years of the course. Although an introduction to primary care will occur in first year, the teaching emphasis in the preclinical years will be in the behavioural sciences, epidemiology and social medicine. Primary care as a clinical subject will be taught in fourth year with electives available in the sixth year.


A study of the effects of hyperbaric oxygen on the experimental spinal cord injury. The degree of motor recovery in sheep with a controlled contusion to the thoracic spinal cord is compared with the recovery in sheep treated with hyperbaric oxygen and confirms the results of a preliminary series previously reported. The degree of central cord cystic necrosis and degeneration in the surrounding white matter is compared in the control and treated animals. The improvement in motor recovery and in the degree of cord degeneration after treatment with hyperbaric oxygen suggests that ischaemia plays a significant role in the experimental animal with a contusion injury to the spinal cord.


Poisoning by carbamate pesticides.

Poisoning by carbamate pesticides. In recent years the number of carbamate pesticides registered for use in New South Wales has increased. Some of the newer carbamates are very toxic and have cholinergic properties similar to those of the organic phosphates, though the effect is of much shorter duration. Because of this, separate tests for plasma and red blood cell levels of cholinesterase should be conducted as soon as possible after exposure in order to obtain meaningful results. A typical case of carbamate poisoning is described in which both plasma and red blood cell cholinesterase values were lowered. The substitution of a liquid pesticide formulation for the original powder formulation has reduced the operator inhalation hazard in the case of methomyl.


Evaluation of the nitroprusside test for the diagnosis of cystinuria. Because of the wide acceptability of the nitroprusside test for the diagnosis of cystinuria, an analysis of 525 consecutive urine tests performed at this laboratory was undertaken, the nitroprusside test result being correlated with the urinary cystine excretion as determined by paper chromatography, high-voltage electrophoresis and chemical tests. It was found that the nitroprusside test clearly separated urine samples into categories of cystine excretion within the normal, heterozygote and homozygote range (P less than 0-001). However, 7 (1-33%) urine specimens from homozygous cystinurics gave a negative nitroprusside result. If properly performed on a concentrated urine specimen, this test is a very accurate means of diagnosing cystinuria (expected error approximately 1%), but it is not infallible.


[Aetiology, diagnosis und therapy of mastopathy and mastodynia. Experiences of treatment with mastodynon (author's transl)]. The aetiology of mastopathy and mastodynia has not yet been fully explained. Hormonal dysregulation with relative or complete hyperoestrogenism, or a deficiency of androgens or progesterones has led to treatment with gestagens or gestagen-active preparations. The treatment of 112 patients with Mastodynon has shown a good result in 78% of cases, the risks and side effects of the treatment being small. Careful diagnosis with all of the possibilities available to us today and clinical supervision during the treatment are necessary in order not to overlook malignant processes.


[Urinary tract infection after gynecologic surgery (author's transl)]. In a prospective research study, 119 (female) patients were examined with regards to the occurence of bacteriuria six days after abdominal or vaginal operations of benignous gynecologic disease. Prior to operation, in 7% of the patients a urinary tract infection was already present. Subsequent to operation, 36% got an urinary tract infection within the first six days. From the correlation between urinary tract infection and age of patient, type and uration of operation, a probability catalogue for post-operative urinary tract infections is deducted. The high infection rates, especially in patients beyond 55 years of age, speak in favour of a chemoprophylaxis, especially for such patients.


[Mycoplasms in the anorectal region of women (author's transl)]. 650 samples of vaginal and anorectal smear from 325 women with fluor were examined. 78 patients (24%) had mycoplasms. 17% of these patients had only rectal mycoplasms and 30.5% women had only vaginal mycoplasm. 51.3% of the women had fluor since years, they had mycoplasms as well in the rectal as in the vaginal region. There were urea cracking and non urea cracking mycoplasms.


Further data on the characters of Listeria strains. The composition of a minimal medium suitable for the demands of modern genetical work is described. The nutritional requirements of some 15 strains of L. monocytogenes were studied on this medium. DL-6,8-thioctic acid was not essential. The organisms also grew without thiamine but for a convenient colony size this vitamin had to be used. The presence of Fe++, Mg++, and Ca++ ions as well as a low redox potential supplied by thioglycollate was necessary. There was some difference in the amino acid requirements of the strains. The most common demand was for leucine, iso-leucine, valine, and cysteine. The serotype, agglutinability, hemolytic effect, virulence, and nutritional requirements of the Listeria were compared. It seems that these properties are not consistently linked. Two 'EMS' mutants were also studied. The arginine, glutamine, and methionine metabolism of the auxotrophic mutant 025/4/4 was damaged and its virulence was lost. Data connected with the virulence markers of Listeria are discussed.


0 antigen distribution and sensitivity to the bactericidal effect of normal human serum of Proteus strains from clinical specimens. 9 antigen distribution and sensitivity to the bactericidal effect of normal human serum were determined in 485 Proteus strains isolated from urine, blood, wounds, and feces. Of all strains, 62% could be grouped according to 25 0 antigens. The most frequent one, 0 3, appeared in 13% of all the strains. In blood cultures this antigen was found significantly more often. No other 0 group dominated. Of all strains, 11% were spontaneously agglutinating but such strains were significantly more common in urinary specimens from children with neurogenic bladder disorders. Strains sensitive to the bactericidal effect of normal human serum were significantly more prevalent in urines than in fecal specimens. Most of the sensitive strains were spontaneously agglutinating and were isolated from the urines of children with neurogenic bladder disorders. This may be an example of 'antigenic drift' of the bacteria as a response to host defense mechanisms in the urinary tract.


An inhibitor to rubella hemagglutination present in bovine albumin preparations: its removal by treatment with kaolin. Certain commercial preparations of bovine albumin, fraction V, show inhibitory activity in the rubella hemagglutination (HA) and hemagglutination-inhibition (HI) tests. This does not appear to be due to albumin per se, but instead to a contaminant (or contaminants) with the properties of a lipoprotein. All inhibitory activity can be removed from albumin preparations by treatment with kaolin, gel filtration, or flotation ultracentrifugation. We have found that, even when there was no inhibition of HA titers, kaolin treatment of the albumins prior to their incorporation into the test diluent resulted in more clearly defined agglutination patterns. Reasons for and against including albumin in the test diluent are discussed. It is concluded that, although not essential, it is a worthwhile additive. Our data suggest, however, that each batch of albumin used for this purpose should be checked for the presence of inhibitor, and that treatment with kaolin might be considered as a routine step prior to its incorporation into the test diluent.


Current problems in cardiology.

Current problems in cardiology. Many achievements in medicine in general, and in cardiology in particular, are the result of joint endeavors by cardiologists, surgeons, research workers and engineers. This paper deals briefly with some of the devices which have been developed as a result of this interdisciplinary cooperation. They included cardiac pace-makers, the use of computers in the analysis of electrocardiograms and echocardiograms in intensive coronary care units (ICCU) and in catheterization laboratories. Finally, the use of an intra-aortic balloon pump and other cardioassist devices will be mentioned. The joint efforts of medical and engineering workers have helped to improve diagnosis of acute myocardial infarction and to improbe techniques and results of cardiac surgery. Finally, it is anticipated that through this combined work, more intensive epidemiologic studies will be made possible, new risk factors uncovered with analysis of their significance - all of which will ad to the prevention of heart diseases.


Surveillance of pacemaker patients by an automatic pacemaker function analyzer. An external, simply operated, fail-safe, automatic pacemaker function analyzer (PFA) has been designed for routine examination of ambulatory patients in local medical clinics and for continual surveillance of hospitalized patients in cardiology units. The instrument provides a comprehensive test of the pacing system, including the battery, pulse generator, and electrodes (leads), during varying heart activity. In the recorded ECG from 92 pacemaker patients, the PFA recognized all but 0.29% of the QRS complexes and 0.21% of the pacing artifacts; no signals were incorrectly attributed to the QRS complex. With the PFA, 1171 pacemaker tests were performed on these patients. In all cases, the PFA judged the performance of the tested pacemakers in accordance with the predetermined criteria. The PFA can be integrated into a pacemaker-patient surveillance system within a general-purpose cardiac care unit.


Impedance rheography: a new method for recording spontaneous arterial section variation. The aim of this work is to define, on the basis of impedance rheography, a method to record arterial section variations without either inertia or the production of wall-strain. High frequency current (2 MHz) is employed to measure the impedance variations of the deforming artery. The modulating envelope is representative of arterial section variations. This method permits the recording of arterial section variations by a peri-arterial method or an external method on superficial arteries (without denudation). A comparison between arterial section variations and arterial pressure variations at the same point shows that the arterial wall behaves as a non-linear pressure gauge: Rheogram-pressure curves are similar to volume-arterial pressure curves. The great precision with which this method describes the chronology of arterial deformations is of great interest in defining viscous properties of the arterial wall and following their evolution during pathologic alterations such as atherosclerosis.


Instrumentation for health care in India: a realistic approach. The health care of 600 million people, belonging to various religions and speaking different languages, is a challenging proposition. Manufacture of X-ray and electromedical equipment is going up. When a comparison is made with 1951 figures, a lot of improvement is noticeable. Rural masses (80% of the population) are yet to receive benefits of modern advancements. A planned and realistic approach fully realizing the momentary limitations can lead to better patient care. Some recent techniques which are safe and clinically useful are economically feasible even in rural hospitals. Instruments have to be classified as essential, useful and optional, to enable progressive precurements in a phased manner. Maintenance of instruments is an important aspect which is receiving due attention. Instruments are bound to play a vital role in health care in the years ahead.


Physical mapping of BglII, BamHI, EcoRI, HindIII and PstI restriction fragments of bacteriophage P1 DNA. A cleavage map of bacteriophage P1 DNA was established by reciprocal double digestion with various restriction endonucleases. The enzymes used and, in parenthesis, the number of their cleavage sites on the P1clts genome are: PstI (1), HindIII(3), BglII (11), BamHI (14) and EcoRI (26). The relative order of the PstI, HindIII and BglII sites, as well as the order of 13 out of the 14 BamHI sites and of 17 out of the 26 EcoRI sites was determined. The P1 genome was divided into 100 map units and the PstI site was arbitrarily chosen as reference point at map unit 20. DNA packaging into phage heads starts preferentially at map unit 92 and it proceeds towards higher map units. The two inverted repeat sequences of P1 DNA map about at units 30 and 34.


Slow UV-recovery and fast gamma-recovery in wild-type Schizosaccharomyces pombe. The time course of recovery in UV- or gamma-irradiated wild-type Schizosaccharomyces pombe has been determined by fractionated dose experiments and by measuring the rate at which the "resistant shoulder" of the survival curve was regained during post-irradiation incubation in growth medium. The kinetics of recovery after UV-irradiation were different from those after gamma-irradiation, and may be described as due to a fasy gamm-repair and a relatively slow UV-repair process. In fractionated dose experiments, for single exposures which gave about 10% survival, gamma-repair was rapid (t1/2 congruent to 2 h), began immediately, and was essentially complete within 3 h. UV-repair, in contrast, showed a lag of about 5h and was relatively show (t1/2 congruent to 10h). The nature of the recovery response was analyzed from the survival curves at intermediate times; recovery was evident as the reappearance of a shoulder. A heterogenous recovery was evident after UV-irradiation; after a 5 h lag, a progressively increasing fraction of the survivors regained UV-resistance, which suggested that some critical event or rate-limiting step was involved. A requirement for post-irradiation protein synthesis for activity of a recombinational repair pathway on UV-damage may be a factor in the UV-recovery lag. A homogeneous recovery response, however, was observed in gamma-irradiaged cells.


Evidence for second "prereplicative G2" repair mechanism, specific for gamma-induced damage, in wild-type Schizosaccharomyces pombe. The major part of the substantial gamma-resistance of wild-type Schizosaccharomyces pombe appears to be due to prereplicative recombinational repair mechanisms. The existence of a second "prereplicative G2" repair pathway, specific for gamma-induced damage, has now been deduced from studies of the effect of the repair inhibitor caffeine on gamma-irradiated G1 phase and G2 phase cells. only G2 cells are additionally inactivated on exposure to caffeine after gamma-irradiation. This shows that both known caffeine-sensitive gamma-repair processes (Gentner and wener, Molec. gen. Genet. 145, 1-5 [1976]) are dependent on the presence of a duplicated genome (2c) at the time of radiation exposure. Pathway I is the known "prereplicative G2" repair process (Fabre, Radiation Res. 56, 528-539 [1973]) which is involved in both UV- and gamma-repair, and which requires post-irradiation protein synthesis for activity. Pathway II represents a second distinct "prereplicative G2" repair mechanism; it differs from the first in that it is specific for repair of gamma-induced damage and appears to be constitutive.


Cytoplasmic and mitochondrial protein synthesis in the "petite-negative" yeast Kluyveromyces lactis. Cytoplasmic inheritance of resistance to tetracycline. The growth of two strains of the "petite-negative" yeast Kluyveromyces lactis is inhibited by Tetracycline in different ways under the same culture conditions. Tetracycline resistant mutants of one strain have been isolated which can tolerate doses as high as 3000 microgram/ml of antibiotic. The segregation pattern of this character obtained by random spore analysis of the ascospores derived from the cross of the two strains strongly suggests that the resistance to tetracycline is under mitochondrial control.


Two modes of loss of the Tol function from Pseudomonas putida mt-2. Some of a set of independently arising Tol- (non toluate-utilising) derivatives of Pseudomonas putida mt-2 have lost the unique plasmid present in the parent strain. In others this plasmid has suffered a deletion of a specific region of about 27 Md.


Circular dichroism of human urinary Tamm-Horsfall glycoprotein. Human urinary Tamm-Horsfall glycoprotein, which contains 28% carbohydrate, has a monomeric molecular weight of about 80,000 but is isolated from urine in the form of intertwining helical suprastructures with molecular weights greater than 10(7). The native glycoprotein was dissociated and denatured with 6 M guanidinium chloride and was subsequently renatured by dialysis against a Tris-HCl buffer. Using sedimetation equilibrium, the renatured glycoprotein was characterized by a Mw cell of 256,800 and a Mz cell of 356,000. The ratio, Mz/Mw, of 1.39 indicates some polydispersity with regard to molecular size. There was no evidence of helical suprastructures in the renatured glycoprotein as judged by electron microscopy. Ca2+ concentrations of up to 50 mM failed to precipitate the renatured glycoprotein; in contrast, the native glycoprotein is precipitated by Ca2+ concentrations between 5-10 mM. The circular dichroic spectrum of renatured Tamm-Horsfall glycoprotein was obtained, resolved, and tentative band assignments made. The spectrum, which is quite similar to that of native Tamm-Horsfall glycoprotein, exhibited negative extrema at 269 nm (due in large part to disulfides and tyrosines) and at 215 nm (due to protein beta-structure and the N-acetylated hexosamines). The alpha-helical content of the glycoprotein was estimated to be no more than 10% and the amount of beta-structure to be about 33%; these values were not affected by the presence of Ca2+ (1 mM). A glcopeptide fraction (ca. 90% carbohydrate), prepared by extensive pronase digestion of the reduced, S-carboxymethylated glycoprotein, exhibited an ellipticity extremum at 212 nm of + 4,750 deg-cm2/dmole, referred to the concentration of (N-acetylated) hexosamines and neuraminic acid.


Stimulation of isocitrate lyase biosynthesis by hydroxylamine and hydrazine. Recently it has been demonstrated that hydroxylamine is an activator of triglyceride catabolism. We have studied the effect of hydroxylamine on isocitrate lyase activity and lipid catabolism and have noted a stimulation of isocitrate lyase biosynthesis by 5 mM hydroxylamine. The specificity of this effect was tested with a number of representative enzymes of other metabolic pathways. In an attempt to study the possible mechanism of action of hydroxylamine we have also tested the effects of two substances that are structural or functional analogues of hydroxylamine, namely, ethanolamine and hydrazine, both on the enzyme level in plant cultures and on the activity of enzyme preparations. From our data we may conclude that "de nove" biosynthesis of isocitrate lyase depends on the reaction of hydroxylamine or hydrazine with glyoxylate to give the corresponding oxime and hydrazone. The removal of glyoxylate from the biological equilibrium in this way could cause extra formation of isocitrate lyase.


Fibrinolytic activity associated with cultured human neoplastic and normal cells. Fibrinolytic activity was studied in a number of different established as well as secondary human cell cultures derived from both malignant and normal tissues. The ability to degrade [25I]-labeled fibrin was found to be characteristic of some malignant cultures as well as some normal cultures, and to be dependent upon the presence of serum. For the most part, this activity was detected in cultures with a relatively short in vitro passage history (less than 30 passages). Low passaged colon and rectal carcinoma cells, HCT-8 and HRT-18, as well as normal rectal, colon and foreskin fibroblasts were positive for fibrinolytic activity, while long established (greater than 100 passages) cultures of malignant cells (colon carcinoma, HeLa, Hep-2, KB) as well as normal cells (HEI, AV3) were negative. It is proposed that although some normal cells synthesize plasminogen activators, the fibrinolytic capability of both malignant and normal cells may be lost on prolonged in vitro cultivation.


[On the syndrome of childhood-hypoglycemia. I. Definition of hypoglycemia in different age-groups and problems of neonatal hypoglycemia (author's transl)]. Hypoglycemia was diagnosed in 118 patients admitted to the University Children's Hospital Basel over 13 years, altogether 137 times. A definition of infantile and childhood hypoglycemia is discussed. Hypoglycemia was accepted as the correct diagnosis in 72 cases (group I), where 2 or more blood sugar values or at least one blood sugar value and one glucose value in the cerebrospinal fluid were below the limit for the age-group. In 46 cases only one abnormal blood sugar value vas documented (group II). In 19 cases no value was found to be definitely below the normal range. 58 patients were newborns up to 10 days of age. 34 patients (43 hospital admissions) were children in the agegroup after the newborn period. 65% of the newborns in group I and 58% of them in group II showed clinical symptoms concomitant with hypoglycemia. Convulsions (62%) were the most frequent feature. In more of the 76 patients was hypoglycemia documented as an isolated symptom. 75% of newborns were premature and/or of low birth weight. 50% had hypoglycemia and 20% verified central nervous system disease. 4 patients (5%) died in the hospital for reasons other than hypoglycemia. 15% (11 patients) had definite neurological symptoms when discharged from hospital. 30 of the 72 surviving neonates could be reexamined at a mean age of 26,5 months. 18% (13 patients) showed evidence of neurological disorders. 4 patients were readmitted with hypoglycemia at a later age, 3 were diagnosed as idiopathic and one as a ketotic hypoglycemia. One child developed diabetes mellitus at the age of 8 years.


[On the syndrome of childhood-hypoglycemia. II. Hypoglycemia in the postneonatal period (author's transl)]. Hypoglycemia (h.) in the postneonatal period was predominantly observed in male infants and children. The incidence was 0,51/1000 hospitalizations. The majority of cases was found in the agegroup around 2 years. Concomitant diseases (mostly infections of the upper respiratory tract or gastrointestinal tract) were found in 30 out of 43 hospitalizations. Convulsions and coma were the most frequent symptoms which were found in 43%. In 30% some degree of somnolence was obvious. Hypoglycemia was not considered in the differential diagnosis in any case by the physician treating first. Only 7 out of 34 cases a complicated biochemical work up resulted in an etiological diagnosis: one leucininduced h.; one ketotic h,; one h. in dystrophy and bronchopneumonia with septicemia; one h. in meningococcic septicemia; one h. in adrenal insufficiency; one h. in isolated ACTH-deficiency; one ethyl-induced h.; one h. in polynesy of pancreas; one h. in insulinoma; one h. in diabetes mellitus under insulintherapy.


[The treatment of renal hypertension with verapamil in childhood (author's transl]. Twenty children with severe renal hypertension caused by renovacular lesions or chronic renal failure were treated with verapamil. The application of the drug as a single intravenous injection (0.1 mg/kg) during hypertensive crisis was followed by a drop of the systolic blood pressure which was highest 30 min after injection (--25% of the original value). In order to normalize the blood pressure during prolonged hypertensive crisis verapamil was used successfully as an intravenous infusion. For the long-term treatment of renal hypertension verapamil was given orally with success, alone or combined with other antihypertensive drugs. Verapamil has a lowering effect on the blood pressure even in the presence of advanced renal failure. Prolongation of atrioventricular conduction time is the most important side effect of the drug when given in high doses and, especially, when combined with digitalis.


[The influence of different feeding regimens on the capacity of lipolysis and ketogenesis during the neonatal period (author's transl)]. The capacity of lipolysis and ketogenesis as well as blood glucose homeostasis is studied in full-term newborn infants on different feeding formulas during the first days of life. Only with the aid of an oligosaccharide compound, carbohydrates can be administered in sufficient quantities, about 7 g/kg X 24 h, so that fat mobilization and ketogenesis are almost completely suppressed. This is not achieved by a regimen mimicing breast feeding in that no milk feeding takes place during the first day, nor by feeding maximal quantities of milk as soon as possible nor by administration of a mixed formula consisting of 10% glucose and milk. Though by early ingestion of large volumes of milk which without introducing tube feeding cannot be further enhanced total caloric intake almost equals the amount attained by the oligosaccharide formula the proportion of carbohydrates in respect to the latter only amounts to one third. In summing up the data reported herein demonstrate that the energy requirements of neonates cannot be supplied by usual dietary regimens, mainly due to the limitation of volume newborn infants can drink voluntarily. As a result of a deficiency in available carbohydrate lipolysis is stimulated in adipose tissue and ketosis arises. These are physiological adaptions resulting in increased availability of free fatty acids and ketone bodies which are easily utilized and thus satisfy the caloric requirements of the newborn infant.


[Vitamin E deficiency and anaemia in premature infants (author's transl)]. The effect of a prophylactic treatment with tocopherol, early iron substitution and administration of polyunsaturated fatty acids in different quantities on the plasma concentration of vitamin E, hemolysis in the peroxide test and hematological parameters during the first two months of life was determined in 23 premature infants with birth weights of less than 1800 gms. In no patient in any of the different treatment groups a tocopherol deficiency (plasma concentration less than 0.50 mg/100ml) was observed and accordingly no hemolytic anemia attributable to E hypovitaminosis was found. The mean concentration of tocopherol at birth (0.51 mg/100 ml) was already above the critical limit, and no single value was found below the latter after the 10th day of life. For that reason, the amount of vitamin E included in formulas generally used in this country and its intestinal absorption have to be considered as adequate even for small premature children. The different treatments of the test groups had no significant influence on the clinical state or the hematological findings. The infants with vitamin E substitution and those without had similar hemoglobin levels. Almost all children had a distinct reticulocytosis and thrombocytosis during the second month of their life. This seems to occur naturally. The peroxide test proved to be no reliable indicator of a tocopherol deficiency in the individual case. It is not yet clear which additional factors cause vitamin E deficiency, infrequently seen in small premature infants.


[T3-thyrotoxicosis in a 12 year old girl (author's transl)]. Isolated Triiodothyronine (T3) hyperthyroidism in childhood is rate. The incidence among hyperthyroid children is about 10%. The authors present a case history of a 12 2/12 year old girl with T3-thyrotoxicosis. Cause, diagnosis and therapy are thoroughly discussed. The importance to estimating serum T3 concentration for establishing the diagnosis of T3 hyperthyroidism is emphasized.


Nitrosated methylcarbamate insecticides: effect on the DNA of human cells. Normal human skin cells were treated with six insecticide esters of N-methylcarbamic acid or their N-nitroso derivatives. The DNA of the cells was sedimented in alkaline sucrose gradients at various times after treatment. The insecticides used were aldicarb, baygon, BUX-TEN, carbofuran, landrin, and methomyl. Numerous single-strand breaks were apparent in the DNA of all the nitroso derivative-treated cells but not in the DNA of those treated with the parent insecticides. Since the effect of the nitroso derivatives on the DNA could be observed for at least 20 h after removal of the chemical from the cultures, the DNA repairing events normally occurring in human cells after damage initiated by these chemical agents was not repaired as UV-type DNA damage or ionizing-type DNA damage in human cells. These observations suggest that the human cellular DNA in vivo is irreversibly altered by nitrosated N-methyl carbamate insecticides resulting in numerous alkali-sensitive bonds.


A collaborative cytogenetics study to measure and minimize interlaboratory variation. Six cytogenetics laboratories joined in a collaborative study of rat chromosome aberrations to measure interlaboratory variation in results of standardized procedures and to devise methods to minimize interlaboratory differences. A preliminary workshop was held to resolve scoring differences, to develop a joint protocol and common glossary, and to reach agreement on uniform reporting methods. Osborne-Mendel rats from a common source were sent to each laboratory. Triethylenemelamine (TEM) was used at doses of 100, 200, 300 and 400 microgram/kg to induce clastogenic effects; results were compared to those of a control group of untreated animals. Femoral bone marrow cells were evaluated with the scorers unaware of the dosage. Final results showed highly significant dose effects with the test compound, and most laboratories showed a similar pattern of dose response. This study illustrates that rat cytogenetic analysis can be an effective test system for evaluation of a compound for mutagenic potential, particularly for the index reflecting the proportion of abnormal cells, but that results should be interpreted cautiously when arbitrary values are assigned for some of the categories being analyzed, as was done in this project for the category of severely damaged cells.


Mutation in continuous cultures of Schizosaccharomyces pombe. I. Dependence of the kinetics of mutation accumulation upon the growth-limiting nutrilite. The rate of spontaneous mutation to resistance to the 12,13-epoxytrichothecene trichodermin has been determined under different growth limiting conditions in continuous cultures of the microbial eukaryote Schizosaccharomyces pombe. In agreement with data obtained in bacterial systems by previous workers the kinetics observed for the accumulation of mutations is found to be dependent upon the nutrient used to limit the growth of the population. Under conditions of glucose-limitation mutation accumulation is directly proportional to the rate of cell division, while under histidine-limitation it is proportional to chronological time. Various possible explanations for these observations are discussed.


Evidence for chemically-induced structural gene mutations at the thymidine kinase locus in cultured L5178Y mouse lymphoma cells. L5178Y mouse lymphoma cells normally appear to possess two functional thymidine kinase alleles (TK+/+). TK-deficient (TK-/-) clonal lines can be derived from these cells by treatment with EMS or other mutagens. Mezger-Freed [12] has argued that such stable phenotypic variants do not arise as the result of gene mutations but instead represent epigenetic events such as normally occur during differentiation without any permanent gene alteration. If this be so, then rare TK+/- revertants arising in TK-/- cultures should possess TK enzyme identical with one of those present in the original TK+/+ cells, since only depression of the TK gene is involved. Our studies show that this is not the case. Among the mutant TK enzymes analyzed in vitro (those from parental TK+/- lines, each derived in turn from separate TK-/- lines) differences were found in (1) solubility in saline; (2) solubility in 3 M LiCl; (3) Km's; and (4) ATP-Mg2+ requirements. These findings were incompatible with a non-mutational model for the production of these stable variants and, in conjunction with reversion-rate data, they tended to favor either direct structural gene modifications or mutations affecting the expression of adult and fetal enzymes.


Inefficacy of immediate node dissection in stage 1 melanoma of the limbs. From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clark's level or Breslow's thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.


Graduate education in primary care: an economic analysis. To determine the financial requirements of an established primary-care educational program for house officers, we studied two prepaid and two fee-for-service Harvard Primary Care Program affiliated practices. Program-wide, each resident saw an average of 112 patients per month, with patient service costs of $2,580. With teaching and administrative expenses included, total monthly costs averaged $3,120 and $3,270 per trainee for prepaid and fee-for-service practices respectively. In fee-for-service practices, resident billings for patient services averaged $2,790, yielding revenues of $2,510 per month, which offset 77 per cent of total program costs. At current reimbursement rates, covering full program costs in the fee-for-service practices would require an increase of more than 40 per cent in resident-provided patient-care volume. By reducing time available for broad ambulatory experiences, such an increase would necessitate substantial program restructuring and limit opportunities for innovation in the Harvard Primary Care Program.


Bayesian analysis of electrocardiographic exercise stress testing. We evaluated the diagnostic accuracy of exercise-induced ST-segment depression in detecting coronary-artery disease by applying the likelihood-ratio formulation of Bayes's theorem to stress-test data, which were partitioned into half-millimeter ranges of depression. The graphic relation between the predictive value of a given test result and the pretest risk of disease in the test subjects was obtained for each of these half-millimeter intervals. This method reveals that the predictive value of testing depends on the degree of ST-segment depression, and that the pretest risk of coronary-artery disease is an important determinant of the predictive value of any test result in the individual patient. These findings suggest that the use of the terms "positive" and "negative" are inappropriate to describe most stress-test results. Instead, the results should be interpreted in terms of a continuum of risk based on the extent of ST-segment depression.


Multicellular origin of parathyroid "adenomas". Most cases of primary hyperparathyroidism are associated with enlargement of a single gland (i.e., an "adenoma") or with chief-cell hyperplasia, but there is controversy about the relative frequency of each of these entities. It has even been postulated that adenomas do not arise spontaneously, bu- result from prolonged hyperplasia in response to unknown stimuli. We studied four parathyroid adenomas from three women with heterozygosity (GdB/GdA) for the X-chromosome-linked enzyme, glucose-6-phosphate dehydrogenase, to determine the number of cells from which the growths arise. Unicellular origin would be compatible with a rare oncogenic event, whereas multicellular origin might be seen with hyperplasia. Both B and A isoenzymes were found in each "adenoma" in proportions similar to those observed in normal tissues, indicating that the lesions have multicellular origin. Thus, parathyroid hyperplasia and adenomas, which at best are difficult to distinguish from one another pathologically, may also be similar biologically.


Socioeconomic factors affecting the utilization of surgical operations. Between 1963 and 1970 public programs were introduced to reduce inequalities in access to medical care. We examined differentials in surgical utilization among socioeconomic groups in 1970 as well as changes between 1963 and 1970. Multivariate analysis of National Health Interview Survey data indicated that large increases in surgical utilization occurred among disadvantaged groups: the aged, lower educated and nonwhites in urban areas. Some differential by race and residence remains, but is strongly related to income. Income had a large positive effect on surgical utilization, but this effect was less strong in 1970 than in 1963. Education had a negative effect on surgical utilization. Eleven surgical procedures were selected and scaled on indexes of "complexity," "urgency" and "necessity." These indexes do not vary among demographic groups that have significant differences in surgical utilization. However, lower-income groups utilized to a lesser extent procedures rated lowest on the necessity scale.


A prospective comparison of current diagnostic tests for pancreatic cancer. In 70 patients suspected of having pancreatic cancer, we prospectively compared results of seven diagnostic tests. Subsequent exploration (of 68) and liver biopsy (of two) demonstrated pancreatic cancer in 30, pancreatitis in seven, nonpancreatic neoplasms in nine and nonpancreatic non-neoplastic disease (or no disease) in 24. For detection of pancreatic disease, the best tests were the pancreatic-function test (cholecystokinin-stimulated enzyme outputs) and ultrasonography. The pancreatic scan was nonspecific (P less than 0.001), and thermography was insensitive (P less than 0.001). Endoscopic retrograde pancreatography and arteriography were significantly more sensitive than cytologic study in diagnosis of pancreatic cancer (P less than 0.001). Therefore, when pancreatic cancer is suspected, abdominal ultrasound should be performed first, and if it is negative, a pancreatic-function test next. A positive result from either test warrants an endoscopic retrograde pancreatography for definitive diagnosis. This sequence identified 88 per cent of patients without pancreatic disease and 89 per cent with pancreatic cancer.


Enhancement of exercise-induced asthma by cold air. To study the possibility that the inhalation of cold air accentuates the bronchoconstrictor response to exercise in asthma, eight subjects exercised while breathing air at ambient or subfreezing temperatures. On a separate day, cold air was breathed at rest so as to isolate the effects of this stimulus. Pulmonary mechanics were measured before and after each experiment. In all subjects acute bronchoconstriction followed the control exercise challenge. With cold-air breathing, however, the magnitude of the response was markedly enhanced. Residual volume increased 158 per cent more than it did previously, and specific conductance and one-second forced expiratory volumes changed an additional 85 and 100 per cent, respectively. The effects of cold air at rest were very small. The results demonstrate a positive interaction of two common naturally occurring stimuli in the induction of asthmatic attacks, and constitute objective verification of a frequent clinical complaint.


Abnormal regulation of ventilation in infants at risk for sudden-infant-death syndrome. To test whether alveolar hypoventilation and an abnormal ventilatory response to inhaled carbon dioxide explains some episodes of sudden-infant-death syndrome, we assessed ventilatory control during quiet sleep in 12 normal infants and 11 infants who had required at least two resuscitations because of prolonged apnea (greater than 20 seconds) during sleep (aborted form of the syndrome). Infants with the aborted syndrome hypoventilated during quiet sleep (alveolar partial pressure of carbon dioxide, 38.9+/-3.5 mm Hg) as compared to normal infants (35.1+/-1.9, P less than 0.01). In addition, the ventilatory response to carbon dioxide breathing during quiet sleep was impaired (mean change in minute ventilation per change in partial pressure of carbon dioxide 22.1+/-8.9, as compared to 63.1+/-19.1 ml per kilogram per minute per millimeter of mercury in controls [p less than 0.001]). Three infants with the "aborted syndrome" subsequently died during sleep at home; autopsy, done in two, revealed no apparent cause of death. We conclude that infants who have had an episode consistent with sudden-infant-death syndrome have a defect in the regulation of alveolar ventilation.


Smoking: a risk factor for spontaneous abortion. We compared cigarette smoking during pregnancy among 574 women who aborted spontaneously (cases) and 320 women with delivery after at least 28 weeks' gestation (controls). Log-linear analysis was used to test the hypothesis that smoking is associated with spontaneous abortion. Several potentially confounding variables--namely, age at last menstrual period and the number of previous pregnancies ending in spontaneous abortion, in induced abortion and in live birth--were controlled in the analysis. Women who had aborted spontaneously reported smoking during pregnancy more often than those with delivery after 28 weeks' gestation: 41% of cases and 28% of controls smoked. The odds ratio for the highly significant association with smoking was 1.8. The association did not vary with age or previous obstetric events. We conclude that smoking during pregnancy is a risk factor for spontaneous abortion.


Lassa fever: response to an imported case. In February, 1976, a Peace Corps worker returned to the United States from Sierra Leone with an undiagnosed illness later recognized as Lassa fever. To assess the risk of transmission and to contain a potential outbreak, we identified 552 contacts as having had exposure to the patient before the start of strict isolation procedures, and maintained intensive surveillance on these contacts for 21 days. At the end of the surveillance period, no illness had developed in contacts. One month later, a serologic survey among 29 of the contacts judged to be at high risk gave no evidence of infection. In response to the importation of this communicable and highly fatal disease, procedures for the isolation of the patient, the identification, surveillance and management of contacts and the handling of laboratory specimens were developed and implemented. These procedures could be adapted to future introductions of highly contagious diseases.


Performance of graduates of foreign medical schools on the examinations of the American Board of Internal Medicine. We investigated the performance of two groups of graduates of foreign medical schools on the 1975 and 1976 certification examinations of the American Board of Internal Medicine. Nearly all their postdoctoral residency training was obtained in the United States. The performance (most of those in this study were born in Asia and Southeast Asia) was much lower than that of graduates of United States medical schools. United States citizens who studied medicine abroad performed no better than alien graduates from foreign medical schools. Approximately half the foreign graduates born in the United States studied in Italy, and 10% in Switzerland, Mexico and Belgium. There were no significant differences in performance associated with the type of postdoctoral training (university, university-affiliated, community or other) undertaken in the United States. A significant inverse relation was observed between the interval from completion of training to first examination and the examination performance.


Comparative recoveries of airborne fungus spores by viable and non-viable modes of volumetric collection. The suitability of viable and non-viable volumetric collectors as prevalence indicators for potentially allergenic airborne fungi was studied during 124 paired exposures of the Burkard (Hirst) spore trap and a modified, wind-oriented Andersen sampler. Overall, viable recoveries of several Cladosporium form species varied directly with microscopic spore counts (p less than or equal to 0.0001). However, as spore levels rose, culture plate data progressively underestimated prevailing concentrations (recoveries falling below 5% at levels above 500 spores/M3). Viable collections yielded low estimates of prevalence (20-40%) even at modest Cladosporium levels (less than 100 spores/M3) and substantially understated the abundance and regularity in air of several additional taxa. Spores typical of Penicillium and Aspergillus form species were not sought in spore trap deposits. Careful examination of these failed to reveal typical arthrospores or Fusarium macrospores despite substantial recoveries of corresponding growth in culture. Correlations in the occurrence patterns of arthrospore-forming and non-sporulating colonies with those of Coprinus and 'other basidiospores' (excluding Ganoderma) were noted.


Studies on the fungal flora in the lung of human necropsy cases. A critical survey in connection with the pathogenesis of opportunistic fungus infections. An ecological study was carried out on the fungal flora in the human lung of 159 autopsy cases. Fungi were isolated from 129 cases (81.1%). Filamentous fungi consisting of 918 strains were isolated from 113 cases, and the dominant genera were Aspergillus and Penicillium. Yeasts were isolated from 58 cases, and the dominant genus appeared to be Candida. With morbid anatomical study, the incidence of the fungus isolation was examined from various points of view. It was concluded that even a healthy respiratory parenchyma of the human lung cannot be assumed as aseptic. However, only a few numbers of a few genera of air-born fungi were isolated. Special stress was laid on the exposure of the respiratory parenchyma of the human lung to air-born fungi in connection with the pathogenesis of opportunistic fungus infections.


Submicroscopic morphology of Trichophyton mentagrophytes grown at different temperatures. Several modifications were observed in Trichophyton mentagrophytes cultivated at 19 degrees and 37 degrees C, i.e. nine degrees below and above the optimum of 28 degrees C. The phenomena included inhibition of the growth rate, changes in the gross aspects of the cultures as well as of the microscopic and submicroscopic morphology of the hyphal cells. At the ultrastructural level, in particular, it was shown that, at the suboptimal temperature, although the organelle structure in both young and aged hyphal cells remained nearly unchanged, unusual bodies of probable storage significance and plasmalemmasomes were formed. At the supraoptimal temperature, the youngest cells showed a normal organization but were richer in glycogen clusters and enveloped by a cell wall thicker than the ones at the optimal condition. In the cells far from the apex, the endomembrane integrity was lost and consequently an autolytic activity occurred. Degradation phenomena were detectable also at cell wall level. The cytological changes observed were tentatively correlated with a possible different sensitivity of the membrane system at the experimented temperature conditions.


[Migration behavior and toxicology of methyltin stabilizers]. With a view to studying the possible use of methyltin compounds as PVC stabilizers in food industry, the authors elaborated a method for the thin-layer chromatographic and subsequent spectrophotometric or polarographic determination of mono-, di- and trimethyltin compounds in the stabilizer and after migration. Monmethyltin compounds are determined spectrophotometrically after reaction with quercetin. Dimethyltin compounds are incinerated by the wet method using sulphuric and nitric acids, and inorganic tin is then estimated polarographically. Prior to identification trimethyltin compounds must be converted into dimethyltin compounds by ultraviolet irradiation or by treatment with triethylamine and bromine. Corresponding to the different conditions of use, the authors investigated the migration of the methyltin stabilizer from PVC into distilled water, 3% acetic acid, 20% alcohol, 50% alcohol und Fettsimulans HB 307. They stated that its tendency to migration into foods is not greater than that of the octyltin stabilizer. The experimentally obtained migration values are discussed in connexion with toxicological data.


[Protein isolation by means of complexing agents. 2. Formation of insoluble complexes of sunflower albumins with alginate or pectin]. The formation of insoluble complexes of sunflower seed albumin and alginate or pectin is studied by means of turbidimetric titration and by determining the pH-dependent precipitability of protein. The complex formation that is based on electrostatic interaction is a function of the pH value and the protein-polyanion ratio. Consequently, it is affected by the neutral salt content of the solutions. 90% and more of the dissolved protein may be precipitated if the proportion of the precipitant amounts to 20%. A sodium chloride content of 0.6% reduces the precipitability by alginate to 74%. In the presence of 0.3% sodium chloride, at most 55% of protein are still precipitated by pectin. The difference in strength between the albumin-alginate and the albumin-pectin complex is also expressed by the dye-binding power. Albumin-pectin complexes bind the same amount of amido black as free protein. On the contrary, albumin-alginate complexes exhibit reduced dye-binding power due to stronger binding of the protein to the polyanion. The results obtained by turbidimetric titration of model systems can, in principle, be extrapolated to the precipitation of albumins from protein extracts. In accordance with the heterogenicity of the protein, the turbidimetric titration of the albumin-alginate and the albumin-pectin complexes exhibits two maxima.


[Heavy metal content of tobacco products and tobacco smoke]. The authors determined by means of square-wave polarography the copper, lead, cadmium and zinc contents in the tobacco and smoke of cigarettes (16 brands), cigars (5 brands) and pipe tobacco (3 brands) and discuss their possible actions on the human organism. A comparison of the amount of heavy metals taken up by an average smoker (at most 20 cigarettes per day) with the MAC values adopted in the GDR conveys the impression that the loading with copper, lead and zinc is unimportant, whereas, according to the findings of other authors, the loading with cadmium is but seemingly insignificant.


Drugs from the sea--fact or fantasy?

Drugs from the sea--fact or fantasy? Drugs from the sea are as much a potential marine resource as cultivated fish, and mineral deposits. The study of the chemical structure and properties of unusual metabolic products of marine life is a subject where marine ecology and the experimental sciences of chemistry, biochemistry, pharmacology and medicine share a common and complementary interest. The development of ad hoc collaboration between specialists has advanced basic knowledge and resulted in a significant feedback to marine biology and ecology as well as in the development of some useful drugs.


Mechanism of acid protease catalysis based on the crystal structure of penicillopepsin. A proposed mechanism for the catalytic hydrolysis of peptide bonds by acid proteases is similar in many respects to the Zn-carbonyl mechanism previously derived for carboxypeptidase A. In the acid proteases the electrophilic component is the proton shared by Asp-32 and Asp-215; Tyr-75 donates its proton to the amide nitrogen of the scissile bond and an OH- ion from a water molecule bound between the carboxyl group of Asp-32 and the substrate attacks the carbonyl carbon atom.


A genetic model for sympatric speciation through habitat diversification and seasonal isolation. Based on studies with natural populations, we offer a genetic model for sympatric speciation that could have broad application to polyphagous animals with habitat differences. The model comprises three steps, each of which includes simple genetic changes and plausible selective forces.


Structure of nucleosome core particles of chromatin. Cystals have been obtained on nucleosome cores and analysed by X-ray diffraction and electron microscopy. The core is a flat particle of dimensions about 110 X 110 X 57 A, somewhat wedge shaped, and strongly divided into two 'layers', consistent with the DNA being wound into about 1 3/4 turns of a flat superhelix of a pitch about 28 A. The organisation of the DNA can be correlated with the results to enzyme digestion studies. A change in the screw of the DNA double helix on nucleosome formation can be deduced.


Inhibition of choline incorporation into brain lipids in rats by urethane, a proposed mechanism of depression of the central nervous system. Concentrations and specific radioactivities of choline, acetylcholine, phosphorylcholine, lipid choline, and sn-glycero-3-phosphorylcholine after i.v. injection of methyl-14C-choline were measured in the brain of untreated controls and of rats anesthesized with urethane. The specific activity was found to be decreased during deep anesthesia by 40% in acetylcholine, 20-30% in phosphorylcholine, 50-75% in lipid choline, and 30-40% in sn-glycero-3-phosphoryl-choline. No significant change was detected in the specific activity of choline. The brain concentration of acetylcholine was increased by 40%, the concentration of sn-glycero-3-phosphorylcholine, however, was diminished by 10% during anesthesia. No change was found in the concentration of the other choline containing compounds investigated. Measuring choline incorporation into 4 subcellular fractions of brain tissue specific activities were found to be decreased by the same percentage, although 2 fractions (nuclei and microsomes) were higher labelled than the 2 other fractions (crude mitochondria with synaptosomes and lysosomes). A correlation between the biochemical and the functional alterations is supported by the dose-effect relationships on both parameters. It is suggested that urethane reduces turnover of lipids and by that mechanism inhibits the exocytotic release of the transmitter from presynaptic nerve endings.


Biotransformation and some effects of 2-dimethylamino-4-(N-methylanilino)-phenol in dogs. 2-Dimethylamino-4-(N-methylanilino)-phenol (MP), an active metabolite of N,N-dimethylaniline-N-oxide in the autocatalytic formation of ferrihemoglobin, reacted quickly in dogs after intravenous injection. A dose of 14C-labeled MP which oxidized 40% of the hemoglobin disappeared from the blood in 20 min. During this period of time MP transferred catalytically electrons from ferrohemoglobin to oxygen, reacted with sulfotransferases to form the sulfuric acid ester, and was covalently bound in blood and other tissues. In the urine, in addition to the sulfuric acid ester of MP (25%), methylamine, dimethylamine, and N-methylaniline were found. Their amount indicated that most of the MP not esterified with sulfuric acid had lost a nitrogen by hydrolysis of the quinonimine. The metabolites which were covalently bound in blood and other tissues disappeared slowly, traces of radioactivity being found in blood and urine 7 days after i.v. injection of MP, 15 mg/kg. The formation of methylamines as well as N-methylaniline from MP in vivo and in blood in vitro proves that the oxidation product of MP, a purple dye, is a resonance hybrid of the two structures 2-dimethylamino-N-methyl-N-phenyl-1,4-benzoquinone-4-imonium and 4-(N-methylanilino)-N,N-dimethyl-1,2-benzoquinone-2-imonium. In addition to ferrihemoglobin MP produced numerous Heinz bodies in red cells and caused hemolytic anemia. After lethal doses necroses in the kidney tubules were found.


Weak electrolyte transfer in the guinea pig jejunum: secretion of trimethoxybenzoic acid. In isolated epithelia of guinea pig jejunum the transcellular permeation of 10(-4) M (carboxyl-14C)-3,4,5-trimethoxybenzoic acid (TMBA) in the direction blood-lumen was more than 10 times greater the transcellular permeation of 10(-4) M (carboxyl-was reduced to less than 2 by anaerobiosis or by increasing TMBA concentrations of up to 10(-2) M. Under aerobic conditions the cellular uptake of TMBA (10(-4) M) from the blood side was twice as high as that from the lumen side. In anaerobiosis the percentage of TMBA taken up into the epithelium was enhanced, when TMBA was administered on the lumen side, while the percentage was unchanged after administration on the blood side; thereby the difference in cellular TMBA concentrations was abolished. Similar results were obtained under aerobic conditions, if the TMBA concentration was increased up to 10(-2) M. The results are consistent with a three-compartment model with an intermediate compartment distinguished by a high pH as compared to that of the outer compartments and by a luminal boundary highly permeable for the ionized form of the substrate in contrast to the contraluminal boundary.


The action of botulinum A neurotoxin on the inhibition by antidromic stimulation of the lumbar monosynaptic reflex. 1. Botulinum toxin type A was injected into gastrocnemius muscles of cats and 2 days later its action on the monosynaptic gastrocnemius reflex and on the recurrent inhibition was investigated. 2. In early local botulism, no significant change in the monosynaptic gastrocnemius reflex was observed. 3. The inhibition by antidromic stimulation of the monosynaptic gastrocnemius reflex was significantly reduced. 4. During the early phases of local botulism an action of botulinum toxin on parts of the soma membrane of the alpha-motoneuron is suggested.


Secretory effects of 6-hydroxydopamine in normal and denervated submaxillary glands of the rat. Injection of 6-hydroxydopamine (6-OH-DA) elicited a marked and sustained secretory response of control and surgically sympathectomized submaxillary glands of rats. These responses were diminished by previous treatment with reserpine 0.1 mg/kg 48 and 24 h before the experiment and almost abolished by 5 mg/kg reserpine 6 h before the administration of 6-OH-DA. The responses to 6-OH-DA were potentiated in control glands by previous preganglionic denervation of either the parasympathetic or sympathetic nerves of the gland. Development of postjunctional supersensitivity in denervated glands also increased the responses to 6-OH-DA, while atropine had a feeble blocking action. For all these responses, the adrenal catecholamines played no role. After two consecutive doses of 6-OH-DA a third dose of the drug still elicited a secretory response that was 50% of that of the first dose. It is concluded that for the responses to 6-OH-DA the leakage of noradrenaline from the degenerating adrengic nerve endings of the submaxillary gland plays a partial role. Noradrenaline released by the drug from other tissues and reaching the gland via the circulation also contributes to the responses observed. A muscarinic component may also participate in the secretory effects of 6-OH-DA.


Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. In order to elucidate the mode of action of the Ca2+-antagonistic inhibitor nifedipine, its effect on Ca2+-mediated action potentials and transmembrane slow inward current in papillary muscles of guinea pigs and cats was studied. Nifedipine (0.5 mg/1 approximately 1.4 X 10(-6) M) depressed upstroke velocity and overshoot of the Ca2+-mediated action potential and reduced the transmembrane slow inward current by about 50%, but the kinetics of inactivation and recovery from inactivation were not affected. The decrease of upstroke velocity was accompanied by a proportional diminution of isometric contractile force. This indicates that nifedipine exerts its Ca2+-antagonistic effect on excitation-contraction coupling in mammalian ventricular myocardium by inhibition of the transmembrane Ca2+ inward current. The inhibitory action of nifedipine on contractile tension development could be neutralized by an augmentation of the extracellular Ca2+ concentration from 2 mM to 4 mM or by beta-receptor stimulation (isoproterenol) that promotes the transmembrane Ca2+ uptake during excitation. Simultaneously, in the Ca2+-rich medium or under the influence of isoproterenol the upstroke velocity of the Ca2+-mediated action potentials rose even above the initial values which were measured prior to the nifedipine administration.


The effects of diphenylhydantoin on mechanical and electrical properties of isolated cat myocardium. The effects of diphenylhydantoin (DPH) (4 X 10(-5) to 2 X 10(-4) M) on contractile activity and electrical properties were studied in isotonically shortening cat papillary muscles exposed to DPH. 1. DPH reduces amplitudes of contraction especially at low stimulation rates (6 to 12/min). At higher, more physiological rates the negative inotropic effect is comparatively small. 2. DPH accentuates the mechanical transients usually following step changes of  frequency. 3. DPH reduces the maximum rate of depolarisation (MRD) of the normal action potential (AP) and slows conduction especially at high stimulation rates. AP duration is shortened especially at low stimulation rates. 4. In Ca-mediated "slow responses" DPH reduces MRD, overshoot and AP duration and abolishes the frequency-dependent alterations of these parameters. 5. The results suggest that the antiarrhythmic potency of DPH is due to a cooperative action on both the fast and the slow membrane channels. 6. It is speculated that DPH leads to an accumulation of Ca2+ within a "limited subsarcolemmal space" thereby decreasing the driving force for the slow inward current.


Biopharmacological investigation of 6,6'methylene-bis/2,2,4-trimethyl-1,2-dihydroquinoline (MTDQ) a radical binding antioxidant of secondary amine type. The evidence of free radicals in tumor tissue and the possibility of their experimental influencing by means of antioxidants justifies the search for new pharmacological groups of tumor inhibiting agents. The authors synthesized a sterically inhibited, heterocyclic, bifunctional, non-toxic radical binding antioxidant of secondary amine type. The structural change is interpreted with the possibility of recombination characteristic for secondary amine groups and the double chain closing effect. The conjugation effect secures mobility of the hydrogen atom. The compound contains 10 to 12 per cent dimer-trimer of higher biological activity than monomers, due to higher molecular weight. An additional pharmacodynamic advantage compared to hitherto known antioxidants consists in its lower vapour volutility and the biradicality.


Effect of "3-oxauracil" (2,3-dihydro-1,3-6H-oxazine-dione) in L1210 leukemia. 2.3-Dihydro-1,3-6H-oxazine-dione ("3-oxauracil") was tested against L1210 leukemia. The compound exhibited significant growth-inhibiting effect against this tumor both in vitro and also in vivo following daily intraperitoneal application.


Chromosomal changes in rat pituitary and bone marrow induced by long-term estogen administration. Pituitary weight, mitotic index and chromosomes were studied in male rats following a single or repeated dose of estradiol-benzoate for a total period of 210 days. Estrogen-induced pituitary hyperplasy eventually resulted in large pituitary tumors in some animals. The mitotic index increased until day 90, when it diminished, with chromosomes partly replaced by chromatin clusters. Most of the cells of the hyperplastic pituitaries maintained a normal diploid karyotype. However, a limited number of abnormal stem-lines with marker chromosomes appeared at a relatively early stage of the hyperplastic reaction of the pituitary. Later the tumors were characterized by an increase of number of aneuploid cells. In the bone marrow estrogens significantly lowered the mitotic index without any detectable change in chromosomal morphology.


Host-tumor relationship. XXXIV. Hyaluronidase activity and hyaluronidase inhibitor in the serum of patients with malignant tumors. Current determinations of the hyaluronidase activity and hyaluronidase inhibitor in the serum of patients with a tumor disease failed to show a correlation between a lowered hyaluronidase activity and increased inhibitor level. The serum fraction that contained the inhibitor and which had been obtained by gel filtration of Sephadex G-200 had no in vitro inhibitory effect on the serum fraction containing hyaluronidase. Hence, the decreased serum hyaluronidase activity in these patients is not due to an increased levles of hyaluronidase inhibitor.


Some data concerning immune processes in concomitant tumor immunity experimental models. Comparative in vivo and in vitro investigation I. In vivo experiments. Concomitant tumor immunity evinced by C57BL/6 mice, bearing a MC-induced sarcoma, was evaluated by graded challenge doses for different primary tumor sizes (2-3,4-6,8-12% tumor weight of the total body weight TW/TBW). 100% of mice bearing tumors, representing 2--6% of total body weight, rejected doses from 0.2--1 X 10(4) cells. The gradual curtailment of the concomitant tumor immunity, depending on increasing TW/TBW ratio, could be evaluated, using adequately increasing challenge doses. The immune equipotency of the whole s.c. body area, the failure to modify the concomitant tumor immunity by drainin node excision and the demonstration of its dependency upon the total challenge-dose and its independency upon fractionated multilocular inoculation of the challenge, showed clearly that the concomitant tumor immunity is a local expression of general immunity. The experimental model allows a valuable biological assessment of the tumor-beareer immune status and represents likewise an adequate tool for immunotherapeutic effects estimation.


Some data concerning immune processes in concomitant tumor immunity experimental models. Comparative in vivo and in vitro investigations II. In vitro experiments. The humoral and cellular immune status of C57BL/6 male mice and "R" male rats bearing MC-induced sarcomas were investigated in vitro, using 51Cr-releasing and mixed hemadsorption assays. Analysis was performed on mice subjected to concomitant tumor immunity (CTI) model experiments or bearing primary tumors of different sizes, that was done also in rats. Chromatographic fractions, assumed to contain tumor specific antigens, antibodies or antigen-antibody complexes were identified by their absorption capacity upon specially prepared syngeneic immune sera. Free antibody and antigen-antibody complexes, accompanied with a weak cell mediated immunity (CMI) were correlated with efficient CTI in 2--3% TW/TBW tumor bearers. Homoral immunity (HI) showed sometimes an important increase after challenge administration. High levels of free antigen and antigen-antibody complexes, lack of antibodies and CMI were correlated with CTI absence in huge tumor bearers, representing 30--37% of total body weight. Conditions determining variability of results reported by different authors and the possible mechanisms by which serum immune factor may impair the tumor bearer's immune status are discussed.


Human urinary bladder carcinoma cell line (T24) in long-term culture: chromosomal studies on a wild population and derived sublines. Karyotype changes of human urinary bladder carcinoma T24 cell line were studied in the course of 5-year in vitro cultivation. It has been found that the modal number of chromosomes gradually shifted from hypotetraploidy to triploidy during long-term cultivation. The number of endoreduplications was decreasing simultaneously and minute chromosomes occurring in a number of 4--5 in early passages appeared only rarely in later passages. Using conventional Giemsa staining, persistent marker chromosomes were detected in the wild population as well as in the eight sublines derived from T24 cells by cloning. The marker chromosomes were: metacentrics, subtelocentrics, telocentrics and long acrocentrics. Occasionally, there were found dicentrics, double-minutes, breaks and pulverization. The most characteristic marker was the metacentric chromosome the length of which corresponded approximately to the arm length of the chromosome No. 1. The metacentric chromosome in a number of 1--3 was present in 100% of T24 cells of the wild population and derived sublines at all passage levels examined.


The toxicity and antitumor activity of three individual fractions of lectins from Ricinus communis seeds. Lectins from Ricinus communis seeds (RCL) have been resolved into three electrophoretically distinct fractions (alpha-RCL, beta-RCL, psi-RCL) by ion exchange chromatography on Watman CM-32 cellulose. The toxicity to mice and antitumor activity against murine lymphoma NK/Ly of pure fractions were compared. Optimal effect was achieved with alpha-RCL, Which possessed the lowest toxicity (1000 micron g/kg) and significant antitumor activity (63% inhibition of tumor growth).


A study of plasma CEA by a direct radioimmunoassay method in 1704 cases. The authors have used an original method of direct radioimmunoassay of plasma CEA for testing plasma of 1704 patients affetected by various neoplastic and non-neoplastic diseases. The percentage of positive results in blood from patients with adenocarcinoma of the gastroenteric tract was 66.8%. The positivity in other non-neoplastic diseases was 2.7%, except for liver cirrhosis and other chronic hepatopathies, which showed 29.6% of positive reactions. The test should be clinically useful in the differential diagnosis of gastro-enteric carcinoma.


Iron absorption in experimental uremia.

Iron absorption in experimental uremia. Gastrointestinal absorption of radioactive iron (59Fe) was studied in uremic rats. Duodenal gut sac transport of 59Fe in a group of 12 rats with a mean BUN of 98+/-24.4 mg%, was 2.29+/-1.16. This was significantly lower (p less than 0.01) than the amount of 59Fe transported (4.88+/-1.87) across the duodenum of a group of control rats, mean BUN 22.9+/-3.2 mg%. We conclude that there is diminished absorption of iron in uremia.


Relationship between serum phosphate concentration and proximal tubular bicarbonate transport. Micropuncture studies were performed in intact and thyroparathyroidectomized (TPTX) dogs to evaluate the relationship between the absolute level of serum ultrafilterable phosphate concentration (SUFP) and proximal bicarbonate reabsorption. In both groups of animals, a reverse linear relationship was noted between the serum phosphate level and the tubular fluid bicarbonate concentration (TFHCO3). For the intact dogs, TFHCO3=32.27 SUFP+/-2.17, r=0.715, p=0.02, and for the TPTX dogs, TFHCO3=35.68-2.39 SUFP+/-2.26; r=0.619, p less than 0.02. Furthermore, when late-proximal tubular values for absolute bicarbonate reabsorptive rate (THCO3)/100 nl single nephron filtrate were plotted against SUFP, a direct relationship was found for both groups; intact dogs: THCO3=205 SUFP-169+/-136, r=0.707, p less than 0.05; TPTX dogs: THCO3=224 SUFP-882+/-221, r=0.625, p less than 0.01. Variations in plasma bicarbonate concentration or PCO2 did not contribute to the relationship between SUFP and bicarbonate reabsorption. The data suggest that extracellular fluid phosphate concentration is an important modulator of proximal bicarbonate transport, independent of the action of parathyroid hormone.


Tubulo-glomerular feedback in the rat.

Tubulo-glomerular feedback in the rat. Using conventional micropuncture techniques in 53 adult Sprague-Dawley rats anesthetized with sodium pentobarbital, single nephron GFR at proximal sites (snGFRprox) averaged 30+/-1 nl/min (76 tubules) and at distal sites (snGFRdis), 33+/-2 nl/min (90 tubules). Thus, in spite of interruption of macula densa fluid flow during its measurement, snGFRprox was not significantly greater than snGFRdis (p less than 0.05). Whole kidney GFR averaged 0.9+/-0.07 ml/min before and 1.0+/-0.05 ml/min during an intravenous infusion of SQ20,881, a substance which inhibits production of angiotensin II. Similarly, snGFRdis was unaffected by SQ20,881; the mean difference between paired snGFRdis (collection during NaCl infusion minus recollection at same sites during SQ20,881 infusion) was 6+/-4 nl/min (p less than 0.5). These results suggest that under the conditions of the experiments, tubulo-glomerular feedback is not operative and that angiotensin II plays no role in controlling filtration.


Serial measurement of vital capacity in patients on chronic haemodialysis. Serial measurements of vital capacity (VC) were performed on nine patients on chronic haemodialysis. In six patients the VC remained stable, they were all adequately dialysed and working full-time. Reduction of dialysis time in one of these patients brought about a gradual onset of left heart failure which was preceeded by a decline of VC. In the three remaining patients a decrease of VC preceeded the onset of heart failure, and a rise of VC values signified improvement of cardiac performance. Serial recordings of VC are recommended as a useful objective guide to evaluation and treatment of patients on haemodialysis.


Time perception and hemodialysis.

Time perception and hemodialysis. Subtle alterations in neurological function are often difficult to identify and even harder to quantitate. The identification of a neurotoxic state existing before overt behavioral changes occur has eluded quantification. It was hypothesized that a challenging signal-detection procedure would be used to assess neurological function of dialysis patients and other subjects, the degree of uremic toxicity occuring during an interdialytic interval, and the effects of neuroactive drugs. A vigilance task demanding the detection of an irregularly flashing light from a matrix of regularly flashing lights was administered to 3 groups of 15 men: patients undergoing maintenance hemodialysis, patients with chronic illness and no kidney disease, and healthy subjects. The procedure was found to yield a reliable measure; average test-retest correlation was 0.93, which differentiated not only within the hemodialysis cycle (p less than 0.001), between groups (p less than 0.001), but was also related to the recency of neuroactive drugs ingested (p less than 0.01).


Period of freedom from relapse as an indication of cure in minimal change nephrotic syndrome in adults. 17 adult-onset nephrotic patients with minimal-change glomerular lesions experienced 39 relapses in all. The relationship between the remission period t (expressed in months) preceding each relapse and the rate of relapse (relapse rate) F (t) was proven to correspond closely to Weibull's distribution function as follows (chi 2 = 1.72, 0.5 less than p less than 0.75): In In (formula - see text) From the equation, the time when 99% of relapsing patients have relapsed is 39.3 months. This means that adult-relapsing nephrotic patients with minimal-change lesions will experience a relapse within 39.3 months of remission. They should be free from relapse and considered cured with a 99% reliability when remission has continued longer than 39.3 months, i.e. beyond the 'period of freedom from relapse'.


Alleviation of anoxic experimental acute renal failure in rats by beta-adrenergic blockade. Acute renal failure induced in Charles River rats by right nephrectomy and left renal artery clamping for 70 min, constantly produced high blood urea and serum creatinine levels 24 h following the experimental procedure. The intravascular administration of propranolol in different doses persistently alleviated the severity of uremia seen on the following day. The optimum dose in this experimental set-up was 1 mg/kg/h. The mean blood urea level was 237 +/- 15.5 (SEM) mg% in the saline-treated controls and 116 +/- 16 mg% in the group treated with propranolol 1 mg/kg/h. P113 alone and prostaglandin A1 alone were not effective in alleviating the ARF. The combination of P113 and propranolol produced the same amount of alleviation in uremia as propranolol alone. The PRA was low in the propranolol-treated rats and high in the group which received both P113 and propranolol, even though alleivation of ARF was produced in both of these groups. The mechanism by which the beta-adrenergic blockade produced by propranolol alleviates the anoxic type of acute renal failure is unknown. However, it does not seem to act through the suppression of renin release from the kidney.


Immediate effect of nephrotoxic serum on kidney function in the dog. Nephrotoxic anitbody rapidly fixes to glomerular basement membrane following systemic injection and immediately initiates histopathologic alterations. We studied the functional changes induced by nephrotoxic serum (NTS) in dogs starting 20 min after injection using three different protocols. By this time the GFR, UNa V and FENa had decreased in each study. Volume expansion resulted in a significantly smaller absolute increase in FENa than in the preinjection control study (1.1 vs. 2.8%, p less than 0.005), while maximum tubular secretion of PAH (TmPAH) and reabsorption of glucose (Tm glucose) stayed constant following NTS; thus TmPAH/GFR and Tm glucose/GFR increased significantly. These studies demonstrate that glomerular function is rapidly affected by NTS while absolute tubular function is relatively well maintained. Since histologic and functional changes occurred simultaneously, it seems likely that the functional changes were the direct consequence of the pathologic alterations.


Intraspinal dermoids.

Intraspinal dermoids. Eight cases of spinal dermoids are presented. Four were in the cauda equina region, 2 were intramedullary, one was in the subdural space in the thoracic region, one was intramedullary and extended into the conus and cauda equina. Two patients had an associated dermal sinus. Intracapsular evacuation of the contents was the treatment of choice.


Spinal dermoid tumours.

Spinal dermoid tumours. The present work is a detailed analysis of 12 cases of spinal dermoid tumours operated on between 1935 and 1976. Of these 11 were medullary (3 intramedullary and 8 subdural extramedullary), representing an incidence of 0-80% of medullary tumours, and 1 was an extraspinal coccygeal tumour. Most of the tumours were located in the spinal canal and conus. Good results were obtained following total ablation in 7 cases and partial removal of the tumour in 5 cases.


Intramedullary epidermoid tumours. Remarks on the radical removal. Three cases of intramedullary epidermoid tumours are reported. Microsurgical technique allowed a radical removal of the growths. The value of extirpation versus the evacuation of the cyst content is stressed.


[Investigation of the c. s. fluid levels of two newer antibiotics; cefazolin and sisomicin (author's transl)]. In ten patients continuous estimations of the C.S.F. and serum levels were performed after the administration of a Cephalosporin derivative (Cefazolin - 4 cases) and a new alpha-amino-glycoside antibiotic (Sisomicin - 6 cases). After the evaluation of the results some doubts must be cast on the value of both these antibiotics for the treatment of meningitis or for per-operative chemo-prophylaxis in neurosurgical procedures. The values found were compared with those well-known in the literature, regarding the cephalosporins and the alpha-amino-glycoside Gentamycin.


Leioblastoma, developing as an hour-glass tumour of the spinal canal. The present paper describes a tumour that developed like an hour-glass tumour, both intraspinally at lumbar level and retroperitoneally. At operation the tumour was diagnosed as a malignant neurinoma. The structure of the tumour, studied by light and electron microscopy, as well as the subsequent evolution of the case, showed it to be a leiomyoblastoma with a retroperitoneal origin, that gradually infiltrated the nerve root (L1) up to the dura mater, epidural and subdural space, where it took on the appearance of a primary tumour of these formations. The author discusses the existence of the so-called primary intracranial rhabdomyosarcoma and its relationship with medullomyoblastoma.


[Comprehensive investigation on fifty meningiomas (author's transl)]. In order to increase the accuracy of preoperative "type-diagnosis" fifty meningiomas in various sites were investigated by brain-scan, and routine angiography. Some cases in addition had external carotid angiography and angioscintigraphy of the external and internal carotid. By tabulating the findings, it is possible in 90% of cases to provide a pre-operative "type-diagnosis" of meningioma. Details are given regarding the influence of the tumour site on the ability to demonstrate the tumour through branches of the external or internal carotid, as well as "filling defects" or isotope uptake in angioscintigraphy. The reasons are discussed for the lack of agreement about the size of the tumour, in angiogram and angioscintigram, as well as in the brain-scan, in 15 out of 34 meningiomas.


[Serum IgC level in myasthenia].

[Serum IgC level in myasthenia]. The level of IgG was determined in the serum of patients with myasthenia using the disc precipitation test. 66 samples of sera were examined. In 24 cases (36.3%) the IgG level was 2SD above the mean value obtained in the control group of healthy subjects. The obtained results were analysed in relation to various clinical parameters. The IgG level +2SD above the mean value of the control group was found in 50% of thymectomized patients and in 12.4% of patients without indications for thymectomy. Taking into account the time from thymectomy the IgG level +2SD above normal value of the control group was found in 60% of patients 1--2 months after the operation. The lowest percent of changes (40%) was observed in patients over 5 years after thymectomy. Taking into consideration the clinical form of the disease according to the classification of Osserman the IgG level 2SD above the mean value of the control group was found in 60% of sera from patients withe the third clinical form -- acute, severe, and in only 26.4% of cases with mild form -- 2a. The serum IgG level in various age groups showed the greatest number of changes in patients past the age of 50 years (57.1%), and lowest in the group aged 10--20 years (11.7%). The IgG level 2SD above the mean value of the control group was found primarily in patients in the 1st year of the disease (42.5%).


[Convulsions in phenylketonuria and the pattern of the bioelectric activity of the brain]. Serial EEC investigations were carried out in 30 children with phenylketonuria aged 8 months to 4 years at the time of dietary treatment. All children had seizures. The results of EEG investigations in this group of children were compared with a preciously observed analogous of 35 children without convulsions. Comparing the results of EEG investigations in both groups it was observed that in the group of children without convulsions the initial EEG tracings were mostly normal while in both groups the abnormalities were mostly of paroxysmal type. On the ground of an analysis of the EEG results of both groups of children during the whole observation period lasting 2 to 7 years no statistically significant differences were observed in the pattern of bioelectric activity of the brain in both groups.  In the light of this material homogenous from the standpoint of aetiology and pathogenesis the asuthors postulated the necessity of verification of the presently accepted principles of diagnosis and classification of infantile convulsions based on diagnostic and prognostic significance of EEG investigations.


[Serum lipids in various polyneuropathies]. Serum lipids were determined in 40 cases of polyneuropathy including 17 cases of Charcot-Marie-Tooth peroneal muscular atrophy, 7 cases of Dejerine-Sot-tas polyneuropathy, 7 cases of Guillain-Barré syndrome, 2 cases of diabetic polyneuropathy, 2 cases of toxic polyneuropathy and 5 cases of polyneuropathy of unclear aetiology. In the studied material shifts were observed in the composition of serum lipids, in particular, sphingomyelin and cholesterol esters. No correlation was found beteen the type of lipid pattern changes and the clinical syndrome, type of histological changes in the sural nerve, the age at onset, as well as the duration of the disease. The probable mechanism of development of changes is discussed.


[Clinico-echoencephalographic-electroencephalographic-angiographic correlations in supratentorial glioma]. The paper contains conclusions from a comparative evaluation of neurological, echoencephalographic, electroencephalographic and angiographic investigations in supratentorial cerebral gliomas. The results of the analysis were based on 55 cases and were related to the whole material as well as to various localization groups. The usefulness of A echoencephalography is discussed from the standpoint of possibility of indicating the cerebral hemisphere involved by the tumour and in comparision with the results of other investigations.


[Changes in peripheral nerves conduction velocity following Guillain-Barré syndrome]. The material reported includes 14 patients with a history of Guillain-Barré syndrome of relatively mild course many years ago. No abnomalities were found in them on neurological examination. Electrophysiological investigations of peripheral nerves revealed, however, changes indicating slight but  persistent subclinical lesions. Conduction changes involved the sensory and motor fibres in the tested nerves and were most evident in the ulnar nerve. Changes of maximal motor conduction velocity were , apart from some cases, parallel to the changes in the minimal conduction velocity. Late subclinical sequelae in this group were compared with those in a group of cases with severe course of the disease and no significant differences were disclosed. It seems thus that the electrophysiological sequelae are not relevant to the clinical pattern of the acute stage and may persist even after the mildest form of the syndrome without evidence of any clinical abnormalities.


[Mesencephalic artery syndrome].

[Mesencephalic artery syndrome]. The authors report a 62-year-old woman, with stroke-like onset of unconsciousness, left oculomotor nerve paresis, slight right-sided paresis with extensor plantar response. On autopsy thombosis at the site of basilar artery bifurcations was found with symmetrical "butterfly type" necrosis of the thalamus, and with necrosis of mesencephalic and pontine midline structures.


Effects of melatonin and an aqueous pineal extract on adrenal secretion of reduced steroid metabolites in female rats. The effects of melatonin and an aqueous extract of bovine pineal glands on adrenal function were studied in pinealectomized, ovariectomized and hypophysectomized rats. Melatonin (50 microgram i.p., twice daily for 1 week) stimulates adrenal 5 alpha-reductase activity in intact animals and after ovariectomy. A corresponding enhancement in the secretion of the principal 5 alpha-reduced metabolites of corticosterone (B), dihydrocorticosterone (DHB) and tetrahydrocorticosterone (THB), occurs in vivo. As a result, proportional output of B declines. In contrast, an aqueous pineal extract (360 mg bovine pineal tissue/day for 1 week) fails to alter reductase activity or to produce the secretory changes associated with increased reductive metabolism of B. Melatonin also stimulates adrenal reductase activity in hypophysectomized rats. The results suggest that melatonin is a potential contributor to the physiologic regulation of adrenal steroidogenesis.


[Diagnostic procedures and therapeutic management in cases of pineal region tumors]. The purpose of the study was an attempt at evaluation of therapeutic results in 10 cases of tumours situated in the pineal region. The diagnosis was based on clinical and neuroradiological findings. Treatment included neurosurgical decompressing procedures (by the methods of Torkildsen, Pudenz Stookey-Scarf) followed in all cases by Co60 radiotherapy. The results of treatment expressed as survival rates were similar to those reported by others.


The effect of anterior cervical ganglionectomy on the seasonal variation in prolactin concentration in goats. Bilateral anterior cervical sympathetic ganglionectomy in castrated male goats had no effect upon the subsequent seasonal variation in the concentration of prolactin (Prl) in plasma when surgery was performed in summer. After ganglionectomy in winter, however, the subsequent rise in Prl concentration associated with season was accelerated.


[Spinal muscle atrophy in the offspring of consanguineous parents]. A child of consanguineous parents (first cousins) has spinal muscular atrophy. Two siblings of the mother are similarly effected. In recessive autosomal type of inheritance such close relation of patents increases greatly the risk of having an affected child.


Ultrastructure of homografts of the rat median eminence into the anterior chamber of the eye. Median eminences (MEs) were transplanted into the anterior chamber of the eye and collected at times varying between 10 and 72 days. At 10 days, all axons had degenerated leaving behind a well-vascularized epitheloid glial organ. With increasing age of the grafts, the characteristic lipid inclusions in the glial cells diminished and even disappeared, and the clear ultrastructural distinction between ependymal (tanycytes) and other glial cells became difficult or even impossible. In both the perikarya and perivascular terminals, an increased number of membrane-bounded, pleomorphic, electron-dense granulated vesicles occurred, the significance of which is unknown. Regrafting of these transplants into various hypothalamic and hypophysial sites is expected to yield information on the function of the glial cells of the ME.


[Diagnostic and therapeutic difficulties in oral apraxia in a 16-year-old girl following severe brain trauma]. Diagnostic and therapeutic difficulties are described in a case or oral apraxia in a 16-year-old girl who had numerous skull vault bone with concussion and crushing of cerebral tissue. The authors point out that the process of rehabilitaiton of speech disturbances in oral apraxia is long and complex.


Neuroticism, extraversion and slow brain potentials. Peak amplitude and area under the curve of average vertex slow potentials recorded during the foreperiod of a reaction time task were found to discriminate between high- and low-neuroticism subjects, defined according to the Eysenck Personality Inventory. High-neuroticism subjects developed smaller peak amplitude, greater area and longer reaction times, presenting a high extinction rate when the imperative stimulus was omitted. Differences between extraverts and introverts were found within the low-neuroticism group and for area values, extraverts exhibiting larger area. A significant interaction effect of extraversion and neuroticism on slow-potential parameters was evidenced. Results are interpreted in terms of heightened arousal and disrupted focused attention in high-neuroticism subjects. Although evolutionary indexes of slow potentials could differentiate between extraverts and introverts, further work using inhibition indicators is needed to further clarify the differences between them. The data reported also suggest that different aspects of overt behavior would be associated diversely with slow-potential parameters.


[Case of Fahr's syndrome].

[Case of Fahr's syndrome]. Convulsions, extrapyramidal-cerebellar syndrome and coma led within 8 weeks to death of a 40-year-old woman. Autopsy demonstrated calcifications in the ganglia of brain base and cerebellum.


Recovery of amnestic effect of alpha-amanitin by post-training administration of d-amphetamine in the rat. alpha-Amanitin, an inhibitor of RNA polymerase II, given intraventricularly 6 or 24 h before training, impaired consolidation of both passive and active avoidance responses in rats. Administration of d-amphetamine sulfate (0.5 mg/kg intraperitoneally) immediately after training produced a clear-cut antiamnestic effect in alpha-amanitin-injected rats without modifying consolidation in control animals. Examination of several parameters of conditioning enabled the authors to rule out an impairment in locomotor performance of alpha-amanitin-treated rats both in training and in test sessions. The amnestic effect of alpha-amanitin and recovery by means of d-amphetamine were discussed in relation to RNA synthesis inhibition and a possible restoring effect of d-amphetamine upon alpha-amanitin-induced decrease of brain RNA content.


MHPG excretion during sleep deprivation in endogenous depression. MHPG excretion of 14 endogenously depressive patients and 5 healthy controls was investigated before, during and after a night of sleep deprivation (SD). Patients having a minimum improvement of 40% in the Cronholm-Ottoson rating scale had shown a significantly higher MHPG excretion in the night before SD ( p less than 0.02) as compared to the non-improved group. The MHPG excretion of the night before SD shows a significant negative correlation, both with the depression score according to Cronholm-Ottoson (p less than 0.05) and with the self-rating score according to von Zerssen (p less than 0.005), on the day after SD. No correlation was found between the motor activity measured by pedometer and MHPG excretion. The results are discussed in connection with values found in controls.


[Prodromal symptoms and manifestations in pontine base infarction]. The authors report a case of diffuse infarction of pontine base confirmed on autopsy. Attention is called to the rich symptomatology of brainstem syndromes and resulting considerable diagnostic difficulties.


Plasma prolactin during lithium treatment. Plasma prolactin was determined in a longitudinal study, where -9 manic-depressive patients were examined before lithium treatment and at various times during the treatment with the aim of unravelling a possible association between initial changes in water and sodium balance during lithium treatment and changes in plasma prolactin level. No significant changes were found, nor could any correlation between serum lithium and plasma prolactin be established. Some reports have indicated association between breast cancer and prolonged elevated plasma prolactin, such as is seen during treatment with phenothiazines and reserpine. In a transversal study, determination of plasma prolactin during long-term lithium treatment in 26 patients did not reveal any elevation compared with 16 controls. Lithium is accordingly not among the drugs which produce prolonged elevation of plasma prolactin.


Annual and daily changes in brain serotonin content in differentially housed mice. The annual and daily variations of brain serotonin and 5-hydroxyindolacetic acid have been studied over a 6-year period in normally grouped and isolated mice. The results obtained indicate that differences exist between normally grouped and isolated animals, especially when referred to the annual changes to which brain serotonin and 5-hydroxyindolacetic acid undergo. The results suggest that the outcome of the experiments on neurochemistry, neuropharmacology and behavior can change according to the month of the year and they can further be modified by differential housing of mice.


[Rare case of brain damage in a primary decompression sickness in a diver]. Pressure disease causes very infrequently multifocal injury to the cerebral hemispheres with resulting organic brain disease. The described case was observed in a diver who after correctly performed decompression without any evident faults in decompressions during several years of diving suffered diffuse, multifocal injury to the cerebral hemispheres and right vestibular nuclei. The authors stress the fact that decompression tables differ in various countries. There is no uniform safety decompression table for the divers. Besides that, such factors as individual sensitivity and resistance of the diver to the effects of raised pressure should be taken into consideration.


Phenelzine in depressed patients. Effects on urinary MHPG excretion in relation to clinical response. Depressed patients' treatment with the monoamine oxidase inhibiting antidepressant, phenelzine, developed marked reductions in urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion. Pretreatment levels of urinary MHPG and platelet monoamine oxidase activity were significantly correlated with each other, but the magnitude of reduction in these measurements produced by phenelzine treatment did not correspond as closely. Similarly, MHPG levels were not significantly different in patients with antidepressant responses to the drug compared to nonresponders.