Neonatal E. coli pericarditis.

A review of the literature reveals only one case of neonatal Escherichia coli pericarditis. This is a case report of Escherichia coli pericarditis occurring in a two day old infant. The infant initially presented with lethargy and jaundice but this rapidly progressed into shock. Despite vigorous resuscitative efforts, the infant succumbed and at autopsy 30 cc of purulent fluid were obtained. Cultures of the admission blood and post-mortem pericardial effusion grew Escherichia coli. The clinical diagnosis of pericarditis is often difficult because of vague, nonspecific symptoms and signs. The symptoms are usually those of sepsis plus those of impaired circulation due to mechanical embarrassment by accumulating pericardial effusion. It is difficult to differentiate pericarditis with effusion from myocarditis and pericardial effusion secondary to congestive heart failure. The use of pericardiocentesis as a diagnostic tool and echocardiography are the most helpful techniques presently available for diagnosis. Management consists of vigorous supportive efforts, antibiotics, and drainage of the pericardial effusion. Because of the very high mortality associated with this disorder, a high index of suspicion with a vigorous diagnostic and therapeutic approach to the patient is indicated.


The evaluation and significance of intrapartum FHR-oscillation patterns.

The last two hours of 342 intrapartum FHR records of high technical quality were evaluated visually with simple tools (compasses, caliper). All data were entered on punched cards (25 pro fetus) and analyzed using an IBM system 370/135. In 253 fetuses with an actual pH in the umbilical artery (UA) above 7.199 the oscillation frequency (OF) during the last 30 min. preceding delivery amounted to 9.5 +/- 4.5 (4615 minutes without decelerations or accelerations). The 5th percentile, the median and the 95th percentile were 2,9 and 18 per minute respectively. OF refers to the number of visually detectable turning points in baseline FHR. There exists a significant association (2 alpha less than 0.001)  between the OF and the oscillation amplitude (OA) per minute: a reduction in OF is followed by a decrease in OA even in vigorous infants. In acidotic fetuses OF is decreased when compared with FHR minutes of equal OA in nonacidotic infants. However this becomes statistically significant only in fetuses with actual pH (UA) below 7.150 i.e. in fetuses with severe acidosis. These findings can explain why the loss of FHR variability as a single symptom may be misleading in individual cases.


The sutureless free gingival graft.

A technique designed to utilize the autogenous free gingival graft without the use of sutures was demonstrated. Necessary objectives were maintained but achieved without unnecessarily piercing the graft, and in less time. The only variance in results would be due to the underlying physical properties of the recipient site. This new approach to grafting avoids the cyanoacrylate from getting between the graft and recipient site, therefore acting as a foreign body. Also shown was the complete coverage of a denuded root surface by this technique using a free autogenous gingival graft. This technique enables the surgeon to achieve the results of a predictable technique (autogenous free gingival graft) even more predictably simple.


Determination of iodide in metabolic studies of 125I-labeled compounds.

Methods capable of measuring inorganic iodide in the presence of other highly polar metabolites were developed in support of studies concerning the metabolism of 125I-labeled compounds. The methods included separation of iodine on a weakly basic resin paper followed by gamma-counting, methyl iodide exchange, and reverse isotopic dilution.


Compound action potentials recorded from mammalian peripheral nerves following ligation or resuturing.

1. Cat hind limb peripheral nerves were fitted with cuff recording electrodes, and their distal portions were later cut and ligated to prevent regeneration. The compound action potential amplitude initially declined with a time constant between 1 and 2 months and then remained relatively unchanged for periods of more than a year. Similar but smaller changes were observed in the conduction velocity of the nerves which also stabilized after a few months. 2. In nerves that were cut and resutured to their distal stumps or sutured directly to nearby muscles, a recovery was observed. The time course was well fitted by an initial exponential decay with a similar time constant to that above, followed by an exponential recovery with a longer time constant (3-4 months). Nerve conduction, muscle potentials and twitch tension often recovered to control values, even when the amplitude of the nerve compound action potential remained depressed. 3. Thus, nerve fibres survive axotomy for long periods of time and continue to conduct action potentials, even if unable to regenerate to appropriate end-organs. When regeneration is permitted, a fraction of nerve fibres may reinnervate nearly all end-organs. The diameter and conduction velocity of these nerve fibres presumably increase toward control values, while other fibres remain subnormal in these parameters. 4. Factors in the design of cuff electrodes which determine the amplitude of compound action potentials are described in an Appendix.


[Calorimetric study of the effect of salicylate in man during heat exposure and exercise (author's transl)].

1. The effect of sodium acetylo-salicylate (2 g per os) on the thermoregulatory responses of 10 male subjects was studied by direct and indirect calorimetry during two tests : heat exposure at 37 degrees C and exercise (50 W) at 25 degrees C. Both test were performed twice : with salicylate treatment and with a placebo. 2. During heat exposure at 37 degrees C for 75 min, the rise in tympanic temperature (Tty) and in mean skin temperature Ts, the time course of heat losses by radiation (R), convection (C) and evaporation (E), and the metabolic rate (M), measured by oxygen consumption, were not altered by salicylate treatment. 3. During exercise, salicylate treatment did not affect the time course of Tty and Ts, (R + C) and M. However, salicylate treatment decreased the delay for triggering the evaporative response (E) to the thermal load; similarly, the increase in cutaneous blood flow was triggered sooner in subjected receiving salicylate than in controls. 4. In conclusion, these results suggest that, during exercise, the thermal controller triggers thermoregulatory responses during passive hyperthermia by heat exposure.


Patient response to variations in denture technique. Part II: five-year cephalometric evaluation.

This study was designed to determine if differences in rates of residual alveolar bone loss could be found in patients wearing dentures made by a complex technique and a standard technique. Cephalometric radiographs were made for each of 64 patients at initial placement of the dentures and for all active patients at five yearly recall visits. These radiographs were measured to determine rates of mandibular bone loss, maxillary bone loss, loss of total face height, rotation of the mandible, and migration of the denture bases over the 5-year period. At the end of the study no statistically significant differences between the two groups of patients could be found. Examination of all participants in this study revealed rates of bone loss that were very similar to those reported by other investigators.


Bilaterally hinged complete denture for a severely undercut maxillary arch. Solution to a problem.

A technique is described for the construction of a complete maxillary denture for a patient with extreme hard tissue undercuts. By means of a three-part impression procedure and buccolabial flanges that were hinged bilaterally with a central latch, a successful prosthesis was attained.


Personal identification using dental prostheses.

A personal identity mark may be added to a metal or an acrylic resin prosthesis. The importance of this technique, particularly in terms of forensic investigation and identification, should make it a compulsory dental procedure. Where metal is involved, engraving is the most desirable method of marking. The heat resistance of various labeling materials indicates that an acrylic resin prosthesis should contain a marked, heat resistant material together with a mark clearly visible from the denture surface.


Maxillary segmental osteotomies for mandibular removable partial denture patients.

The posterior maxillary osteotomy is a versatile and useful treatment alternative for a variety of dentofacial conditions. Its place in the management of bilateral distal-extension removable partial denture construction has been described along with a report of treatment of a patient.


Multiple-abutment fixed partial dentures in maxillofacial prosthetics.

Ten patients were presented to illustrate multiple-abutment fixed partial dentures used in combination with auxiliary prosthetic attachments of a fixed or removable design to solve diverse problems encountered in the rehabilitation of congenital and acquired orofacial defects. While such fixed prostheses have high initial costs, their effectiveness and long-term cost-benefits suggest that, where appropriate, they represent optimum therapy that will prove most economical over the long term.


Modified denture flask for three-piece ear molds.

A method of modifying a conventional large denture flask to accomodate a three-piece ear mold has been presented. The modified flask is useful in producing accurate castings with a decrease in the incidence of stone fracture.


Modification of stone dies for fabrication of porcelain jacket crowns.

This technique affords the use of accurate die materials. The adaptation of matrix foils to a prepared apron will allow its withdrawal, without distortion, resulting in more accurate jacket restorations.


Neurologic sequelae in infants with intrauterine growth retardation.

The literature on neurologic sequelae in infants with intrauterine growth retardation (IUGR) is reviewed. In many studies this term is used for only those infants who have a birthweight (BW) below the 10th percentile and are labeled small for gestational age (SGA). The etiology of IUGR can often be correlated with a characteristic pattern of in utero growth and a subsequently predictable pattern of postnatal growth and/or developmental outcome. The concept that certain premature infants who are appropriately grown for gestational age (AGA) but whose birth weights fall below the 50th percentile may have IUGR is supported by the analysis of data from this study. In attempting to predict the neurologic outcome, it may be more helpful to recognize etiologic factors such as sleep disturbances than to analyze infants by birth weight gestational age groups.


Cardiac surgical research and heart transplantation in Papio ursinus.

The use of non-human primates stems from the concern for employing an animal genetically closely related to man. During a 3 year period over 300 baboons were handled in the Cardiac Research Unit and more than 60 heterotopic cardiac transplantations were performed. The baboon presents multiple advantages if compared with the problems arising from the use of the dog or the pig in cardiac surgical experimentation. This experimental work illustrated these advantages and demonstrated that heterotopic cardiac transplantation is a valuable model for treatment of patients in end stage cardiac failure. The procedure has been performed successfully in 16 patients, 12 being presently alive, 1-36 months following transplant.


The role of laboratory animals in dental research.

In dental research, in common with other forms of scientific research, the use of laboratory animals is necessary to carry out many investigations that may not be undertaken on man, and to control biological variability. In South Africa the main experimental animals used in dental research are rats and vervet monkeys, although other species such as dogs and baboons have been used. This paper lists examples of published dental research carried out in laboratory animals in South Africa in the fields of bone healing, dental caries, dental materials, growth studies, oral cancer, oral mucosa and periodontal disease investigations.


Antimalarials. 4. Trichloronaphthalene amino alcohols.

An improved procedure for the synthesis of naphthalene amino alcohols is described. Four new compounds were prepared and tested by Rane Laboratories for activity vs. Plasmodium berghei in mice. All compounds were active, the most active being 1-[3-(4-chlorophenyl)-5,7-dichloro-1-naphthyl]-3-(di-n-butylamino)propanol hydrochloride (16b). Structure--activity relationships between the naphthalene and quinoline isosteres are discussed.


An economical, semi-automatic system for measuring cellular tree structures in three dimensions, with special emphasis on Golgi-impregnated neurons.

The hardware and software of a semi-automatic system are described for the measurement of cellular tree structures in thick microscopical sections such as the process of Golgi-impregnated neurons. With this system, the morphologist--viewing the neuron directly through the microscope--measures the tree structures using three cartesian coordinates of characteristic points, e.g. centre of cell, origin of processes, bifurcation points, end points, deflection points, etc. The system requires an on-line computer, but does not demand a dedicated computer since a joy-stick generator usually drives the microscopical stage during cell tracking. A digital computer is utilized for acquisition of data, and, when needed, to return the stage to a required position. The microscope stage is coupled to three stepping motors with 0.5 micron as the smallest step. The stepping motor for movement of the stage parallel to the optical axis (z-direction) is coupled directly to a spindle mechanism, replacing the original cog wheel mechanism. This construction shows no measurable backlash. The practical advantages of this new measuring system in relation to the existing digital systems currently in use, its accuracy and its costs, are discussed.


The estimation of neuronal population density by a robust distance method.

A new "nearest-neighbour" or "distance" method of estimating neurone population density is introduced. The method was originally developed for ecological studies but can be imported into histology without significant modification; changes in population density can be estimated by inverting the measure of area per unit cell (the so-called mean area). Its advantages include tests of randomness for the spatial distribution of the cells at issue and a robustness which can tolerate some departure from a random distribution pattern. To illustrate how the method is applied estimates of neurone density, in terms of "mean area" per cell-point, are made on a montage tracing of the human cerebellar dentate nucleus.


Preparation of resin embedded unicellular organisms without the use of fixatives and dehydration media.

A method is presented for processing single cells for conventional ultrathin sectioning without the use of fixatives and dehydration media. The cells were fixed by a physical method--spray freezing--which provides extremely high cooling rates, needs no pretreatment with cryoprotective agents and is therefore assumed to maintain the in vivo morphology of the cell. Hitherto cells prepared in this way have been investigated exclusively by freeze etching. To combine the advantages of this method with those of conventional ultrathin sectioning we have processed spray frozen cells with widely varying water contents (spermatozoa and lymphocytes) by freeze drying at 188 K and vacuum embedding. When compared to conventional chemical fixation the differences found in ultrastructural preservation of spermatozoa using this kind of preparation were confined to the arrangement of spermhead membranes and middlepiece structures. Lymphocyte structure was much closer to that known from chemical preparation, the only differences being a denser cytoplasm, denser mitochondrial matrices and thicker plasma membranes. These differences are probably due to the absence of eluating and dissolving effects present in conventional chemical preparations. The ultrastructural preservation of spray frozen cells is not different after freeze etching or after freeze-drying and vacuum embedding. This indicates clearly that drying and resin embedding does not produce artefacts and that structural preservation is therefore limited by the quality of cryofixation. Therefore this method is considered a contribution to the problem of preservation of the in vivo assembly of cellular substructure. Furthermore it seems to be a potential basis for preparation of soluble or diffusible substances or cellular compounds which would be influenced by fixatives and dehydrating agents.


Vertical plane serial sectioning of identified tissue culture cells.

Identifying marks can be made around specific cells on the culture surface of plastic tissue culture dishes. When the cultures are embedded in situ and the plastic dish is split away, the marks are reproduced around the cells. The marks permit trimming and complete serial sectioning of specific cells in the vertical plane.


Measurement by Quantimet 720 of the proportion of actively growing cells in tissue cultures of human lymphocytes.

The size-distribution of normal human lymphocytes growing in tissue culture was measured with a Quantimet 720 image-analysing computer. The proportion of cells undergoing volumetric growth after phytohaemagglutinin (PHA) stimulation was dervived from a simple mathematical model describing the growth patterns of the cells up to the first mitotic division. The approach may have general application in biology as a method for measuring the proportion of growing cells by microscopy.


Controversy in renal transplantation: antireflux versus non-antireflux ureteroneocystostomy.

A comparison of 118 consecutive nephroureteral allografts suggests that ureteroneocystostomy provides excellent results with (60 cases) or without (52 cases) an antireflex procedure. Reflux was noted in less than 10% of each group after transplantation and no morbidity could be attributed to reflux when it was found. There was no obstruction or anastomotic leakage in either group. The advantages of each procedure are discussed.


Comparison of procarbazine, imidazole-carboxamide and cyclophosphamide in relapsing patients with advanced carcinoma of the prostate.

In this third cooperative chemotherapy trial of the National Prostatic Cancer Project 165 patients with histologically confirmed, relapsing clinical stage D prostatic cancer were randomized to receive either imidazole-carboxamide, procarbazine or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on initial therapy were crossed over or randomized to receive an alternate drug. There were 129 patients available for comparison of treatments. The objective response rates (partial regression plus stable disease) were 26% for cyclophosphamide, 27% for imidazole-carboxamide and 14% for procarbazine. Subjective responses were noted in pain relief, improvement in performance status and weight gain. Procarbazine was associated with excessive toxicity, resulting in many patients (28%) discontinuing therapy within the first 3 weeks and closure of this particular arm of the study. The regimen of initial imidazole-carboxamide therapy with a later cross-over to cyclophosphamide when the disease continues to progress is associated with the longest increase in survival. Imidazole-carboxamide and cyclophosphamide appear to be active agents in advanced prostatic cancer and are worthy of continued use in this disease.


Gallium-67 scanning and conservative treatment in acute inflammatory lesions of the renal cortex.

Three cases of suspected acute suppurative lesions of the renal cortex treated successfully with antimicrobial agents are presented. In support of other reports it appears that selected cases, particularly when diagnosed early, may be managed conservatively without surgical drainage. In those cases of severe sepsis, large intrarenal or perinephric abscesses, resistant organisms or those that are refractory to treatment, surgical intervention may be unavoidable. Gallium-67 nuclear scanning is a safe, non-invasive method of locating rapidly these areas of inflammation and has proved to be a useful tool in earlier diagnosis.


[Basic and clinical examinations of CS-1170 in pediatrics (author's transl)].

1. CS-1170 was administered for the purpose of prophylaxis during cardiac catheterization in patients with heart disease, and its blood levels were measured. 2. The mean blood level (Moni-Trol I standard) after one intravenous shot of 20 mg/kg was 53.6 mcg/ml in catheterized children aged below 6 and 66.9 mcg/ml in catheterized children aged above 10 at 30 minutes, and 1.95 mcg/ml and 5.2 mcg/ml respectively at 6 hours. 3. The mean half life of the blood level was 1.09 hours in catheterized children aged below 6, 1.37 hours in catheterized children aged above 10, and 0.71 hours in infections children. 4. The urinary excretion seemed satisfactorily high although there was a great variation. 5. The clinical efficacy was 88.9%. 6. The bacteriological efficacy was 100% for E. coli, Klebsiella, Proteus mirabilis and Staphylococcus aureus and was 0% for Staphylococcus epidermidis. 7. Although GOT and GPT were elevated in one case as a side effect, they rapidly returned to normal after discontinuation of administration.


[Blood rheological disorders in atherosclerotic lesion of the abdominal aorta and their correction by the use of aspirin].

The initial hemorheologic values and their dynamics in various periods after reconstructive operations were studied in 70 patients with atherosclerosis of the abdominal aorta. The rheologic blood properties proved to be considerably changed in atherosclerotic affection of the abdominal aorta. The causes of the hemorheologic disorders in this pathological condition are marked changes in regional hemodynamics and the character of the blood flow and significant disorders of protein, lipid and carbohydrate metabolism. Study of the effect of aspirin on the rheologic properties of blood in this contingent of patients showed the expediency of its use both in preoperative management and in the postoperative period. Aspirin reduces significantly the degree of blood platelet aggregation and the seeming viscosity of blood.


[Diagnostic value of a method of partial pulmonary rheography in pulmonary hypertension].

In the absence of clinical and X-ray signs of pulmonary hypertension in patients with chronic pneumonia, partial rheography of the lungs revealed symptoms of increased vascular resistance in some pulmonary zones and ventilation disorders with the corresponding discordance of the ventilation-perfusion relations in the early stages, which progressed with the intensification of the stage of chronic pneumonia and the severity of pulmonary hypertension. A decrease in ventilation and perfusion in the pulmonary zones as well as a decrease of the ventilation/blood flow ratio may promote the development of zonal arterial hypoxemia, stable increase of vascular resistance, and development of pulmonary hypertension. The method of zonal rheography of the lungs may be used in the diagnosis of pulmonary hypertension.


Process /prá/,ses/n: the action of moving forward progressively from one point to another on the way to completion.

A rationale for the application of a stage process model for the language-disordered child is presented. The major behaviors of the communicative system (pragmatic-semantic-syntactic-phonological) are summarized and organized in stages from prelinguistic to the adult level. The article provides clinicians with guidelines, based on complexity, for the content and sequencing of communicative behaviors to be used in planning remedial programs.


A study of the central auditory processes in stutterers using the Synthetic Sentence Identification (SSI) Test battery.

The performance of a group of stutters (N = 14) and a group of nonstutterers (N = 14) was compared on the Synthetic Sentence Identification Test (Speaks and Jerger, 1965). The test is designed to assess central auditory function. It was hypothesized that because of subtle neurologically based differences in perceptual processing, the performance of the two groups would differ significantly on one or more of the subtests. An analysis of variance revealed that the performance of the stuttering group was significantly poorer (0.01 level of confidence) than that of the nonstutteres on the Ipsilateral Competing Message Subtest. The results of the investigation were compatible with other studies that suggest a neurological dysfunction within the central auditory apparatus as at least one of the underlying causes of disfluency. It was concluded that further investigations of the central auditory processes in stutterers are warranted to make a more definitive statement about the etiology of stuttering.


Postcardiotomy delirium: a critical review.

The literature concerning postcardiotomy delirium contains confusing definitions and contradictory results. In a critical review of the subject, we conclude that cardiac status, the severity of physical illness, the complexity of the surgical procedure, and preoperative organic brain disease are the determining factors in postcardiotomy delirium. Preoperative anxiety, denial, and depression also have some correlation. Age, sex, time on bypass, and preoperative psychological profile seem to have no influence on outcome. No psychological etiology for delirium has been proven consistently. The therapeutic influence of preoperative interviews in preventing postoperative psychiatric complications remains equivocal as do theories implicating sensory deprivation in the intensive care unit. Long-term follow-up studies suggest that psychological problems impair functional recovery from heart surgery. The suggested treatment of patients with delirium includes chemotherapy, psychotherapy, and environmental support. Finally we suggest that investigation of biochemical abnormalities in delirium may prove to be a model for clarifying the role of neurotransmitters in functional psychiatric illnesses.


Myocardial protection with methylprednisolone. Evaluation of viability of hearts subjected to warm ischemia before transplantation.

Methylprednisolone was given at different intervals before warm ischemia of the heart (37 degrees C. for 60 minutes), and viability of these hearts was evaluated after transplantation into the abdomen of another dog. Animals were divided into four groups: Group 1 received no methylprednisolone: Groups II, III, and IV received 30 mg. of methylprednisolone per kilogram 10 minutes, 60 minutes, and 120 minutes before warm ischemia. In all parameters measured, the animals of Group IV performed better than the other groups. It is concluded that methylprednisolone, when given 2 hours before warm ischemia, exerts a protective effect on the ischemic myocardium.


An unusual case of lymphocele after renal transplantation. Case report.

A patient who developed a lymphocele five years after renal transplantation is presented and discussed.


Analysis of the semantic structures of medical reference languages: part 2. Analysis of the semantic power of MeSH, ICD and SNOMED.

Three medical reference languages, Medical Subject Headings (MeSH), International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine (SNOMED), were compared through an analysis of their structures. They were found to differ in the degrees of complexity and specificity of meaning that they could convey. This variation in semantic power has been correlated with their different functions.


Complete reconstruction of the chin and floor of the mouth.

A method of reconstruction of the entire floor of the mouth and chin is presented, utilizing interdigitated ventral tongue flaps for reconstruction of the floor of the mouth, and a deltopectoral flap for reconstruction of the chin, which, even with loss of bony support of the mandible, provides a watertight, competent oral sphincter with adequate communication and nutrition.


Linolenic acid deficiency.

Linolenic acid deficiency has not been demonstrated clearly in warm blooded animals, yet circumstantial evidence suggests that n-3 fatty acids may have functions in these animals. The fact that several species of fish definitely require dietary n-3 fatty acids indicates that n-3 fatty acids have important and specific functions in these animals and suggests that such functions may also be present in warm blooded animals. It is also true that n-3 fatty acid distribution in tissues of birds and mammals appears to be under strict metabolic control, and that this complex metabolic control mechanism apparently has survived evolutionary pressure for a very long time. So far, attempts to produce linolenic acid deficiency in mammals have not revealed an absolute requirement for n-3 fatty acids. If functions for n-3 fatty acids do exist in warm blooded animals, it seems probable that they may be located in the cerebral cortex or in the retina, because these tissues normally contain high concentrations of n-3 fatty acids.


[Early congenital syphilis (7 cases observed in Bangui Hospital Central African Empire) (author's transl)].

In an infant of good condition, skin changes, anemia, hepato-splenomegalia and more over radiological osseous changes are symptoms of great value which are to be confirmed by a serological test of the baby and its mother. Treatment is very effective but it would be better to protect the foetus by an early detection and treatment of the syphilitic pregnant woman.


[Reliability of the indirect immunofluorescence test in the diagnosis of African human trypanosomiasis (author's transl)].

The reliability of an immunodiagnosis depends on its efficiency, i.e. the possibility of sorting out infected people from uninfected thanks to a good sensibility and a good specificity, and to its reproductibility. The authors have studied the reliability of the Indirect Immunofluorescence Antibody Test (IFAT) for trypanosomiasis diagnosis on 90 sera (30 sera from patients with proven trypanosomiasis and 60 sera from patients free of trypanosome infection). Reproductibility is considered as good when the reading has been done by the same reader. Sensibility approaches 100 p. 100 and specificity varies according to readers: the reader taking the "brillance" into account obtains a specificity of more than 85 p. 100 and the reader reading the immunofluorescence extinction obtains a specificity between 65 p. 100 and 77 p. 100. The IFAT may be taken as a reference to evaluate new immunodiagnosis.


[Culex pipiens fatigans Wiedemann in tropical Africa: its importance and its control (author's transl)].

Improvement in communications, unchecked urbanization and use of inadequate insecticides have promoted widespreading and proliferation of C.p. fatigans in tropical Africa. This mosquito is a pest for man but also a main vector of Bancroftian filariasis. Various sanitation measures and insecticidal control are now available to destroy it; these control methods are indicated.


[Organization of mass screening of human trypanosomiasis in West Africa (author's transl)].

Immunological diagnosis methods appear to be necessary at the occasion of large scale surveys. The authors recommend indirect immunofluorescence antibody test (IFAT) and propose the creation of a mobile team supplied with necessary equipment for immunological tests and parasitological exams to be carried out in the field.


In vitro assay for responsiveness of lymphocytes to transfer factor by a new leukocyte migration inhibitory test.

Transfer factor (TF) causes nonimmune lymphocytes to produce leukocyte migration inhibitory factor (LMIF) in the presence of purified protein derivative (PPD). The activity of TF was measured by leukocyte migration inhibitory test (LMIT). The LMIT was a modification of the conventional agarose droplet method. To express the activity of LMIF quantitatively and simply, LMIF titer was introduced. The LMIF titer was obtained from the combination of two factors, LMIF dilution and cell migration diameter, and therefore this made the LMIT much more sensitive as compared to the conventional LMIT. The responsiveness of lymphocytes from acute lymphoblastic leukemia (ALL) and from cell-mediated immunodeficiency in children to TF was assayed by LMIT. In ALL, the lymphocyte responsiveness was poor in relapse but improved with remission. The responsiveness was remarkably well in 3 patients with cell-mediated immunodeficiency. This method appears useful for the in vitro evaluation of responsiveness of lymphocytes to TF.


[Use of a pyrimidine-dependent mutant for effective labeling of the DNA OF Aspergillus nidulans].

Incorporation of the radioactive label from pyrimidines into RNA and DNA of an Aspergillus nidulans pyrimidine-dependent mutant was studied. The label from [14C2]uridine was incorporated at the highest rate into both fractions of nucleic acids from A. nidulans of the wild type and pyr-mutant. The content of the label in the DNA of the pyr-mutant was several times higher than that in the wild type DNA. Therefore, pyr-mutants can be used in order to study molecular-genetic processes in the cells of A. nidulans. The label from [3H5]deoxyuridine, [14C2]thymine, [14C2]thymidine, [14C2]cytosine and I114C2]uracil was incorporated into the pyr-mutant RNA and DNA at a much lower rate than into the wild type RNA and DNA. Apparently, these pyrimidines cannot maintain the growth of the pyr-mutant. Incorporation of the label from [14C2]uracil into the pyr-mutant DNA increased if growth of the mycelium was stimulated by low concentrations of unlabeled uridine.


[Use of ultrasound to obtain small Escherichia coli cells containing drd plasmids].

Treatment with ultrasound of Escherichia coli K-12 chi 1100 producing mini-cells and containing R factor 100-1 drd depressed in conjugation transfer, prior to defferential and zonal centrifugation, makes it possible to increase the yield and purity of mini-cells. Combination of ultrasound treatment with differential centrifugation produces mini-cells with purity greater than 10(3) per parent cell. Ultrasound has no negative effect on the physiological state of mini-cells and the hydrodynamical characteristics of segregated plasmid DNA.


[Dynamics of the interaction of Bdellovibrio bacteriovorus with the bacterial host under aerobic and anaerobic conditions].

Bdellovibrio bacteriovorus can interact with the host bacterium cells under aerobic and anaerobic conditions. The dynamics of the interaction between the parasite and the host depended on the regime of incubation. The latent period and the time at which Bd. bacteriovorus reached the stationary level became shorter under aerobic conditions. Lysis of the host bacterium cells under aerobic conditions proceeded more effectively, at a higher rate, and after a shorter period of the constant titre than under anaerobic conditions.


[Effect of temperature on the viability of Escherichia coli strains in seawater].

The survival and growth of E. coli strains were studied at different temperatures of sea water. The bacterial number for serotypes 055 and 078 was found to increase with a decrease in temperatue of sea water to 5 degrees C. The bacteria of serotype 015 did not grow in sea water whereas those of serotype 0115 were capable of growth only at 20 and 15 degrees C. The bacteria were able to survive from 4 to 98 days depending on the temperature of water and the strain of E. coli.


[Effect of cell reserve carbohydrates on an increase in the keeping qualities of baker's yeast].

Synthesis of reserve carbohydrates (trehalose and metabolically active glycogen) can be intensified in the cells of Saccharomyces cerevisiae by adding glycerol and magnesium or phosphorus salts to the cultural broth. An increase in the content of reserve carbohydrates in the cells increases their preservation after separation from the substrate.


[Comparative study of the rate of glucose and oxygen consumption by bacteria normally and under the action of low temperatures].

The effect of freezing on the rate of respiration and glucose assimilation in Escherichia coli M-17 incubated in 2 mM phosphate buffer, physiological solution, and media containing 1% and 10% glycerol was studied by potentiometry and delayed fluorescence of bacterial cells. When the cells were frozen to --70 degrees C and the rate of freezing-thawing was 10--15 degrees C per 1 min, the rate of respiration and glucose assimilation was below the stationary level, and the restoration took 20--60 min depending on the incubation medium. The low activity of the cells is attributed to the disturbed permeability of bacterial membranes, in particularly, for H+ ions.


Prolactin suppression in the treatment of premenstrual syndrome.

Abnormal secretion of prolactin is amongst the many disorders of hormone secretion which have been proposed as potential causes for the common syndrome of premenstrual tension. Eight women suffering from this disorder participated in a five-month double-blind crossover trial of bromocriptine (5 mg per day) given in the luteal phase of the cycle. Significant improvement in most symptoms occurred during active as opposed to placebo therapy, together with objective evidence of a decrease in premenstrual weight gain and breast enlargement. This corresponds with the results of other studies which used bromocriptine in this dosage. The effect may be mediated by suppression of prolactin secretion, but could equally be a direct effect of bromocriptine.


[Effect of raised temperatures on the protein and RNA synthesis rate in yeasts].

The rates of incorporation of labelled precursors of protein (14C-DL-leucine) and RNA (14C-uracil) into the cells of synchronous yeast cultures of Pichia membranaefaciens, Hansenula anomala, Saccharomyces cerevisiae and Saccharomyces (fabospora) fragilis were studied at different temperatures. Synthesis of RNA and then of protein was inhibited in H. anomala if the temperature was increased above the optimal one. This is manifested even more distinctly in Sacch. cerevisiae and P. membranaefaciens. In the thermotolerant yeast Sacch. fragilis, the incorporation of 14C-uracil was inhibited at temperatures above 40 degrees C while the rate of protein synthesis did not decrease.


Bromocriptine, methyl testosterone and placebo for inhibition of physiological lactation: a controlled study.

Lactation occurs when the fully developed breast is released from the inhibitory influence which oestrogen and progesterone exert upon the action of prolactin. The use of oestrogens to suppress lactation depends on a continuation of the peripheral, that is, mammary, inhibition of prolactin. Androgens are also believed to act by inhibition of the action of prolactin on the mammary gland epithelium. Bromocriptine, when compared in a double-blind trial with orally administered methyl testosterone and placebo, gave almost complete relief of breast discomfort and congestion, though a small amount of milk production was seen. Methyl testosterone, in the dosage used in this study, was quite ineffective in suppressing lactation or breast symptoms.


A double-blind trial of bromocriptine in Parkinson's disease.

Twenty-two patients entered a double-blind trial to test the efficacy of bromocriptine therapy in patients with Parkinson's disease who were already stabilized on conventional L-Dopa therapy. Of these, three patients who were receiving placebo withdrew when no improvement occurred and control became complicated. Another four patients taking active drug withdrew because of side effects, but only in one case was the symptom (nausea and vomiting) thought to be a true effect of the drug. Of the 15 patients who completed the trial, nine were taking active drug and six took placebo. Although more than half the patients in each group were subjectively improved, measurement scales of functional disability and physical examination revealed no significant change in either group. Side effects encountered included nausea, dyskinesia, and hallucinations. It was concluded that bromocriptine does not offer any additional benefit to patients with Parkinson's disease who are stabilized on L-Dopa therapy, but may have a place in those patients who encounter side effects due to fluctuations in serum and tissue levels of L-Dopa.


The first man/machine interaction in medicine: the pulsilogium of Sanctorius.

This article, published in lieu of the customary feature, artifact, describes one of the earliest medical devices--a device to measure pulse rate. A close examination of the pulsilogium of Sanctorius of Padua (1561--1636) reveals it to be something more than the first measuring device in medical history; it is also the first man/machine system in medicine. Using a systems approach, pulsilogium and physician interaction is found to contain important dynamic characteristics. The device is operated in a negative feedback mode, employs the concept of transduction, and measures pulse through another dimension--length. More than 100 years after its invention, the pulsilogium found useful application by de la Croix in measurements of cardiac function during "electrification."


Third Myron Karon Memorial Lecture. Resistance of human tumors to cancer chemotherapeutic agents: an important research problem.

The mechanisms whereby malignant cells become biochemically resistant to anti-cancer drugs are surveyed, with emphasis on human tumors. Methotrexate is used as a model to illustrate the mechanisms of resistance that can occur, and how cells can increase their production of dihyrofolate reductase, the target enzyme. Drug resistance remains one of the major impediments to the successful use of chemotherapy for neoplastic diseases.


[Metabolic pathways of exogenous pyrimidines in Aspergillus nidulans].

Studies on the susceptibility of the wild-type strain of Aspergillus nidulans to 6-azauracil suggest that it synthesizes pyrimidines using a by-pass pathway which is induced with 6-azauracil. The effect of a series of pyrimidines on the toxic action of 5-fluorouracil, 5-fluorouidine and 5-fluorodeoxyuridine has been investigated. As the result of these studies, a scheme is proposed for the metabolism of some pyrimidine bases and nucleosides in Aso. nidulans.


In vitro antitumor reactivity of mononuclear leukocytes from cancer patients receiving immunotherapy with BCG.

Mononuclear cell-mediated cytotoxicity (MCMC) against cultured tumor target cells was studied sequentially in melanoma and breast cancer patients before and during BGC administration. MCMC showed temporary fluctuations. In patients with locally advanced melanoma and carcinoma of the breast after tumor load reduction, the administration of BCG may increase the MCMC. This did not always correlate with a favorable clinical course. Potentiating serum factors appeared in 50% of these patients during BCG therapy, while blocking factors were rare. Neither correlated with prognosis. In patients with disseminated melanoma receiving chemoimmunotherapy, increases in MCMC may be related to clinical course. Blocking serum factors frequently developed in this group of patients and potentiating factors were rare. Neither correlated with the clinical course. Significant MCMC among normal donors and the apparent lack of specificity suggest a common nonspecific (? natural) cellular reactivity against cultured tumor target cells.


4-Aminoimidazole-5-carboxamide excretion in acute leukemia.

The urinary excretion of 4-aminimidazole-5-carboxamide (AIC) as been reported to be increased in children with acute leukemia and has been correlated with disease status. Using a modification of the method of Skibba et al [5], determinations were made on urine from 26 children with acute leukemia. The urine from ten normal children served as controls. The effect of chemotherapy on urinary AIC was studied comparing patients on vincristine and prednisone (V+P) with those on 6-mercaptopurine, methotrexate, and cyclophosphamide (Triple Rx). Patients in remission on Triple Rx had lower levels of urinary AIC than did patients on Triple Rx in relapse or patients on V+P in either remission or relapse. Twenty patients had sequential measurements. Values for individual patients were not predictive of disease status. One such patient is described. This study demonstrates that chemotherapy, as well as disease status, affects the urinary excretion of AIC in children with acute leukemia.


EST 0469B--comparison of high- and low-dose cyclophosphamide in human lung cancer.

A controlled trial of high-intermittent vs low-chronic dose cyclophosphamide in human lung cancer failed to show the benefits reported in noncontrolled trials. There were no differences in toxicity observed.


Safety of delayed leucovorin "rescue" following high-dose methotrexate in children.

High-dose methotrexate (HDMTX) with leucovorin (CF) "rescue" is being investigated for treatment of many malignant tumors. CF is usually begun 2 hours after ending the HDMTX infusion. However, since CF and methotrexate compete for the same cellular transport system, at high extracellular methotrexate concentrations it may be impossible to "rescue" cells with CF. A regimen of HDMTX with delayed leucovorin "rescue" was therefore designed. In this program, a 6-hour infusion of methotrexate (7.5 gm/m2) was followed 24 hours later by leucovorin "rescue." Nine patients with osteogenic sarcoma received 115 courses of this treatment. Toxicity was minimal. Plasma methotrexate values were identical to those following early CF 'rescue" regimens. HDMTX with delayed "rescue" is well tolerated. Although theoretically sound, further studies are needed to determine its efficacy in comparison to standard early "rescue" regimens.


High-dose methotrexate for the remission induction of refractory adult acute lymphocytic leukemia.

Six adults with refractory acute lymphocytic leukemia (ALL) were treated with high-dose methotrexate, citrovorum factor, and vincristine. All patients had previously received extensive treatment with standard therapeutic agents, including vincristine, and all but one had received prior methotrexate. Two patients achieved complete remission and one achieved partial remission. Responses were seen at 3--6 gm/m2 of methotrexate. The durations of remission were 7--10 weeks. High-dose methotrexate with citrovorum factor is effective in the treatment of advanced ALL and should be considered for inclusion in initial combination chemotherapeutic regimens for adult ALL.


CCNU, vinblastine, and delalutin therapy in renal cell carcinoma.

Advanced renal cell carcinoma is relatively resistant to most adequately evaluated chemotherapeutic agents. The combination of CCNU and vinblastine, which has antitumor activity in a frog renal carcinoma model system, has demonstrated activity in initial studies in man. The current study investigated this combination of drugs together with a progestational agent, Delalutin. Seventeen patients with metastatic renal cell carcinoma were treated with CCNU, vinblastine and Delalutin. There were no objective responses. Four patients with stable disease had a mean survival of 18 months compared to 13 patients with progressive disease who had a mean survival of 5 months. The survival of the four patients with stable disease was in large part due to the slowly progressive natural history of their disease.


Meiotic recombination and synaptonemal complexes in Saccharomyces cerevisiae.

The course of meiotic recombination, gene conversion and crossing-over, was investigated in Saccharomyces cerevisiae. Gene conversion was used as the selected event by removing cells from a medium inducing and promoting meiosis to a vegetative growth medium selective for convertants. Gene conversion started to increase at the same time as DNA synthesis, and nuclei entered a phase where the chromatin appeared as thread-like structures. Crossing over of linked and unlinked markers also started early but remained at a low level until synaptonemal complexes were formed. However, gene conversion and a limited amount of crossing-over could be completed without synaptonemal complexes. It was concluded that meiotic recombination in yeast can occur as early as during DNA synthesis and does not require the function of synaptonemal complexes. Moreover, the low incidence of crossing-over early in meiosis is attributed to a low frequency of strand isomerization.


Mitotic recombination in the absence of synaptonemal complexes in Saccharomyces cerevisiae.

Mitotic cells of a diploid strain of Saccharomyces cerevisiae with appropriate markers for the detection of mitotic crossing-over and mitotic gene conversion were irradiated with X-rays. Induction of these recombinational events was strong. After irradiation, cells were incubated in a rich growth medium and samples were removed for studying the possible formation of synaptonemal complexes up to a time when most cells had completed the first post-irradiation cell division. No complexes were found during the entire period of sampling, during which mitotic recombination in G1 (mitotic gene conversion), DNA replication and G2 (mitotic crossing-over) had occurred. These results are interpreted to mean that synaptonemal complexes are not required for mitotic recombination.


Major proteins of the outer cell envelope membrane of Escherichia coli K12: multiple species of protein I differ in primary structure.

Protein I, one of the major outer membrane proteins of E. coli in most K12 strains is represented by two very similar polypeptides Ia and Ib. Sequential mutations (involving selections for phage resistance) can lead to loss of proteins Ia and Ib. Among "revertants" of such Ia-Ib- mutants clones exist that instead of Ia or Ib produce a third species of protein I, polypeptide Ic. Ichihara and Mizushima [J. Biochem. 83, 1095--1100 (1978)] have shown that proteins Ia and Ib exhibit differences in primary structure. Here evidence is presented indicating that protein Ic also is not identical in primary structure with Ia or Ib. Thus, 3 very similar structural genes appear to exist for the protein I species known to date, and that for Ic normally is silent. Introduction of a functional Ic locus into a Ia+ Ib+ strain caused expression of all three proteins with a reduced rate of synthesis of protein Ia.


The non-reciprocality of organelle gene recombination in Chlamydomonas reinhardtii and Saccharomyces cerevisiae: some new observations and a restatement of some old problems.

Organelle recombinant genotype frequencies, derived from analysis of individual mitotic zygote clones of Chlamydomonas reinhardtii and Saccharomyces cerevisiae, were subjected to two types of statistical tests in an attempt to detect the occurrence of reciprocal recombination: (i) calculation of correlation coefficients for the frequencies of two recombinant genotypes (reciprocal or non-reciprocal pairs) within individual zygote clones, and (ii) application of the chi-square test for independence to the frequencies of zygotes yielding one or the other, neither, or both of a given recombinant pair. Applying test (i), the strongest correlations are found for non-reciprocal rather than reciprocal pairs. When the data are analyzed by method (ii), some reciprocal as well as non-reciprocal pairs appear to be produced concurrently in zygote clones. However, such deviations from independence are greatest for non-reciprocal pairs. These tests yield comparable results for yeast mitochondrial and Chlamydomonas chloroplast gene recombination, and provide no convincing evidence for reciprocal genetic exchange. Explanations for the observed lack of reciprocality are discussed with reference both to our present understanding of the molecular events responsible for genetic recombination, and to the problems which may be unique to the analysis of organelle gene recombination.


Genetic mapping of a putative temperature-sensitive transcription mutation in Escherichia coli K12.

A putative temperature-sensitive transcription mutant described earlier (Jabbar and Jayaraman, 1976) has been genetically mapped. The locus maps at 38 min to the left of aroD. The mutation is recessive to the wild type and it affects a gene probably other than the genes coding for the alpha and beta subunits of phenylalanine tRNA synthetase and protein synthesis initiation factor IF-3 which also map in the same region.


[Dental implants coated with isotropic carbon].

22 implants have been carried out in the mandibular arches of 5 dogs for the purpose of assessing the usefulness of a special isotropic carbon coating on vitallium cast dental replicas. Clinico-radiological, histopathological and microradiographic data showed the usefulness of the coating. Permucous acceptability, which is hard to obtain with other materials, proved satisfactory. Anchorage of the replicas to the surrounding bone was good, thus confirming the compatibility and usefulness of the isotropic carbon coating.


Evidence for a common mechanism for the insertion of the Tn10 transposon and for the generation of Tn10-stimulated deletions.

Mutations in and near the Salmonella typhimurium histidine transport operon were generated by insertion of the translocatable tetracycline-resistance element Tn10. Deletion mutants affecting histidine transport genes were subsequently isolated in several of the Tn10-containing strains. Tn10 insertions in hisJ occurred preferentially at one site, designated site A. This same site was also the preferential endpoint of deletions originating from Tn10 insertions at two neighboring sites. Thus, Tn10 insertion and Tn10-stimulated deletion formation appear to involve a common DNA-recogition step.


Binding of lac repressor to the secondary lac operator in Escherichia coli.

In the lac operon, the existence of a secondary repressor binding site, inside Z gene, had been inferred from in vitro binding studies (Reznikoff et al., 1974; Gilbert et al., 1975). A series of deletions have been constructed from a lac transducing lambda bacteriophage. Some of those deleted bacteriophages have still the property of derepressing a chromosomal lac operon, even though they do not contain any more the lac operator. This phenomenon is an indication that the secondary repressor binding site is also active in vivo.


Calcium metabolism in intact isolated thymocytes.

Isolated rat thymocytes incubated under proper metabolic conditions extrude Ca2+ previously taken up under metabolically unfavourable conditions. The extrusion can be supported by both respiratory and glycolytic energy but glycolysis seems to be more efficient for this purpose. La3+ (50--200 micron) and the ionophore A 23187 inhibit cell Ca2+ extrusion. Ruthenium Red (1--100 micron) does not influence cell Ca2+ extrusion while it inhibits the in situ mitochondrial cation uptake. All the results are consistent with a cell regulation model of Ca2+ content in which both plasma membrane and mitochondria co-operate, acting in opposite directions, in order to decrease cytosolic Ca2+ concentration. The possibility of Na+-Ca2+ hetero-exchange participation to cell Ca2+ homeostasis regulation is also discussed.


Platelet responses in health and disease.

This article summarizes recent ultrastructure findings from our laboratory and documents some of the information accumulated primarily since 1975 from many laboratories. Special attention is given to documentation by scanning electron microscopy which affords insight into platelet activation (adhesion, aggregation, release/secretion) and especially platelet-vessel wall interactions. Structural physiology of platelets is considered in some detail as a basis for understanding platelet disorders contributing to clinical problems of thrombosis and hemorrhage. The impaired ability of von Willebrand platelets to adhere to injured vessel wall is reported using the human umbilical vein perfusion model. Relationships between platelets and blood coagulation factors focus on the exquisite sensitivity of platelets to minute amounts of thrombin. Unmasking of platelet factor 3 sites is identified on activated platelets, after glutaraldehyde fixation, by their reaction ot latex bearing anti-platelet factor 3 markers. The basis for platelet-collagen interactions is reviewed. Conditions for and possible mechanisms behind platelet interaction with vessel wall are discussed. Ex vivo flowing blood-vessel wall models offer opportunities for improved understanding of the platelets role(s) in vascular diseases.


Staphylococcal nuclease reviewed: a prototypic study in contemporary enzymology. I. Isolation; physical and enzymatic properties.

This is the first of a series of four articles in which the chemical, enzymological, and crystallographic work on Ribonucleate (deoxyribonucleate)-3'-nucleotidohydrolase, EC 3.1.4.7, (Staphylococcal nuclease, Micrococcal nuclease) will be reviewed and correlated. This article discusses the purification of the enzyme and its general physical and enzymological properties. Subsequent articles will deal with specific studies of the nucleotide binding site, crystallographic studies of a nuclease-inhibitor complex, use of the nuclease as a model for protein folding and possible mechanisms for the action of the enzyme.


[Selective binding of oligoribonucleotides by T7 phage induced RNA-polymerase].

It was shown previously that E. coli RNA-polymerase being incubated with the random oligonucleotide mixtures of definite length binds certain oligoribonucleotides with the length greater than or equal to 5 nucleotides. The data presented demonstrate that T7 phage induced RNA-polymerase (T7 RNA-polymerase) also binds selectively oligoribonucleotides beginning from pentaribonucleotides. From the random mixtures of penta-, hexa-, hepta-, octa-, nona- and decaribonucleotides the hepta- and octaribonucleotides are bound most efficiently. The T7 RNA-polymerase bound oligoribonucleotides can be completely extracted from the random mixture by the addition of the redundant enzyme amounts. As far as E. coli RNA-polymerase and T7 RNA-polymerase do not compete for the oligoribonucleotides the conclusion is made that they bind different oligoribonucleotides. The addition of the T7 DNA to the previously formed T7 RNA-polymerase--heptaribonucleotide complex competitively displace the heptaribonucleotides from the complex; the competitive effect of T4 DNA is very low. The data suggest that the oligoribonucleotides which are selectively bound by the RNA-polymerase are attached to the enzyme site responsible for the interaction with the promotor.


The basis of pulmonary edema, with emphasis on ultrastructure.

In the normal lung, a delicate interplay of physical forces and structural devices maintains the gas-exchanging membranes hydrated but unflooded. Liquids leaking from the alveolar capillaries are prevented from interfering with gas-exchange by a combination of mechanisms: the alveolar epithelium prevents easy access of liquids into the alveolar space; glycosoaminoglycan "sumps" in the thick portion of the septum bind excess liquid, thereby protecting the gas-exchanging thin portions of the alveolar-capillary barrier from water-logging; gradients of subatmospheric pressure promote the rapid transfer of liquids from the septal "sumps" into a compliant peribronchial space for further disposal by the lymphatic vessels. "Leaky" pulmonary and bronchial microvessels upset the osmotic forces in the interstitial space and interfere with the capacity of the lymphatic system to reabsorb liquids. Accumulation of excess liquids is limited initially to the interstitum. When the capacity of this space to bind liquids is overcome alveolar edema develops.


The effect of norharman on the metabolism of benzo[alpha]pyrene by rat-liver microsomes in vitro in relation to its enhancement of the mutagenicity of benzo[alpha]pyrene.

The effect of norharman on the metabolism of benzo[alpha]pyrene by rat-liver microsomes was studied. Separation of the metabolites into hydrophilic and hydrophobic fractions showed that norharman inhibited the conversion of hydrophobic metabolites to hydrophilic ones. Analysis of the hydrophobic metabolites by high-pressure liquid chromatography showed that norharman also inhibited the disappearance of benzo[alpha]pyrene itself. However, large amounts of hydrophobic metabolites, such as phenol, quinones and diols, were formed in the presence of norharman, and formation of the strong mutagen 7,8-dihydroxybenzo[alpha]pyrene was increased 10-fold by norharman. The increase in formation of this compound may be one of the chief reasons why norharman enhances the mutagenicity of benzo[alpha]pyrene on Salmonella typhimurium.


Mutagenicities of styrene oxide derivatives on Salmonella typhimurium (TA 100): relationship between mutagenic potencies and chemical reactivity.

The lethal and mutagenic effects of p-methyl-, m-chloro-, p-chloro- and  unsubstituted styrene oxide on Salmonella typhimurium (TA 100) were investigated. At equal concentrations, p-chlorostyrene oxide was more lethal than p-methyl-, m-chloro- or unsubstituted styrene oxide. When the survival fraction was 0.8 or more, the mutagenicities of these compounds increased in the order: m-chlorostyrene oxide = p-chlorostyrene oxide less than styrene oxide less than p-methyl-styrene oxide. The mutagenicities of these compounds depended only on the reactivity of their benzylic site; the reactivity at their primary site and their partition coefficients appeared to have no effect.


Oxidation of inactive trivalent chromium to the mutagenic hexavalent form.

Soluble trivalent chromium compounds (chromium potassium sulfate, chromium nitrate, chromium chloride, neochromium and chromium alum) were inactive for Salmonella typhimurium TA100, even at milligram amounts per plate. No effect could be detected either in the absence or in the presence of rat-liver, lung or muscle microsomal fractions, of rat-muscle mitochondria (with or without ATP), of oxidized glutathione (GSSG), or of human serum, plasma or erythrocyte lysates. Conversely, addition of a strongly oxidizing agent (potassium permanganate) resulted in toxic effects in plates incorporating more than 40--80 microgram of compounds and elicited a dose-effect mutagenic response at 10--40 microgram per plate. These effects could be ascribed to oxidation of chromium from the trivalent to the active hexavalent state. Insoluble chromite, as tested in the spot test, was spontaneously mutagenic, owing to contamination of the industrial product with hexavalent chromium. The results obtained may be useful to interpret the findings of carcinogenicity tests and to predict health hazards linked to chromium.


Mutagenicity to Salmonella typhimurium of some Aspergillus and Penicillium mycotoxins.

17 mycotoxins produced by various Aspergillus and Penicillium species were screened for their mutagenic activity to Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, both with and without metabolic activation. Austdiol, austocystins A and D, kojic acid and viridicatumtoxin were found to be mutagenic after metabolic activation, while austdiol was also mutagenic per se. Aflatoxin B1, sterigmatocystin and versicolorin A, which were used as positive controls were also mutagenic. No mutagenic activity was evident in the case of citrinin, cyclopiazonic acid, fumitremorgen B, griseofulvin, luteoskyrin, O-methylsterigmatocystin, mycophenolic acid, ochratoxin A, patulin, penicillic acid, secalonic acid D and TR2-toxin. A good relationship was found between the mutagenic activity, or lack of it, of most of the mycotoxins with existing data on carcinogenicity. Inadequate information on the carcinogenicity of austdiol, austocystins A and D, kojic acid and viridicatumtoxin precluded correlations with mutagenicity to S. typhimurium. The relationship between chemical structure and mutagenicity of the mycotoxins is discussed.


Mutagenic activity of furfural in Salmonella typhimurium TA100.

The mutagenic activity of furfural was tested in Salmonella typhimurium strains TA98 and TA100. Furfural produced mutations in the TA100 strain, but not in the TA98 strain. A rat-liver microsomal fraction did not increase the mutagenic activity of furfural in either strain. Mutagenic activity of furfural in the TA100 strain was not increased by benzo[alpha]pyrene in the presence of metabolic activation.


The lack of mutagenic properties of patulin and patulin adducts formed with cysteine in Salmonella test systems.

The mutagenic properties of patulin and the patulin adducts formed with cysteine were tested with histidine auxotroph Salmonella typhimurium strains as indicator organisms. The tests were performed by microsomal activation and host-mediated assay. Neither patulin nor patulin--cysteine reaction mixture was mutagenic in these test systems.


Mutagenicity of aliphatic epoxides.

The mutagenicity of 17 aliphatic epoxides was determined using the specially constructed mutants of Salmonella typhimurium developed by Ames. The activity of these epoxides together with those reported in the literature as mutagens in strains TA100 and TA1535 depended on the degree of substitution around the oxirane ring. Monosubstituted oxiranes were the most potent mutagens in both strains. 1,1-Disubstitution resulted in the complete loss or reduction of mutagenicity, trans-1,2-Disubstituted, and tetrasubstituted oxiranes all lacked mutagenicity, while the cis-1,2-disubstituted oxiranes tested were weakly mutagenic in strain TA100 only. For the monosubstituted compounds the presence of electron-withdrawing substituents increased mutagenicity.


Identification of a mutagenic substance in a spice, sumac, as quercetin.

The mutagenicity of a spice, sumac, was demonstrated on Salmonella typhimurium strain TA98. The active principle was purified and characterized by thin-layer chromatography, UV-absorption spectroscopy and mass spectrometry. All the mutagenic activity of sumac was found to be due to quercetin.


Comparative mutagenesis of plant flavonoids in microbial systems.

The plant flavonoids quercetin (3,5,7,3',4'-pentahydroxyflavone), morin (3,5,7,2',4'-pentahydroxyflavone), kaempferol (3,5,7,4'-tetrahydroxyflavone), chrysin (5,7-dihydroxyflavone), fisetin (3,7,3',4'-tetrahydroxyflavone), myricetin (3,5,7,3',4',5'-hexahydroxyflavone), myricitrin (myricetin-3-rhamnoside), hesperetin (3',5,7-trihydroxy-4'-methoxyflavanone), quercitrin (quercetin-3-L-rhamnoside), rutin (quercetin-3-rhamnosylglucoside or quercetin-3-rutinoside), and hesperidin (hesperetin-7-rutinoside) have been assayed for mutagenicity in the Salmonella/microsomal activation system. Quercetin, morin, kaempferol, fisetin, myricetin, quercitrin and rutin were mutagenic in the histidine reversion system with the frameshift strain TA98. The flavonols quercetin and myricetin are mutagenic without metabolic activation, although more effective when a rat liver microsomal preparation (S-9) is included; all others require metabolic activation. Flavonoids are common constituents of higher plants, with extensive medical uses. In addition to pure compounds, we have examined crude extracts of tobacco (snuff) and extracts from commonly available nutritional supplements containing rutin. Mutagenic activity can be detected and is correlated with the flavonoid content.


Genetic activity of chemicals in yeast: DNA alterations and mutations induced by alkylating anti-cancer agents.

The simple eukaryotic organism baker's yeast allows demonstration of primary DNA lesions in parallel with measurement of mutagenicity and lethality after treatment with alkylating chemicals. Several anti-cancer drugs formed cross-linked DNA molecules and were genetically active. The mutagenicity and lethality of these drugs varied substantially and were dependent on the function of some processes of DNA dark-repair.


The mutagenic effect of benzene, toluene and xylene studied by the SCE technique.

In experiments in vitro, neither benzene, toluene nor xylene changed the number of sister-chromatid exchanges (SCEs) or the number of chromosomal aberrations in human lymphocytes. Toluene and xylene caused a significant cell growth inhibition which was not observed with benzene in the same concentrations.


Herbicidal phenylalkylureas as possible mutagens I. Mutagenicity tests with some urea herbicides.

Substituted phenylalkylureas are widely used as herbicides. In the assay system of Friedman and Staub, which measures the inhibition of testicular DNA synthesis (DSI test), most of these substances showed a positive reaction, i.e. they depressed tnymidine incorporation significantly. Bacterial tests demonstrated a weak mutagenic activity, too; but in the micronucleus test the compounds were almost inactive. As one member of this group of chemicals--the herbicide monuron--is a recognized carcinogen, these results seem to indicate a possible hazard, but more investigations are needed to quantify this danger.


Mutagenicity of aliphatic nitrosamines in Salmonella typhimurium.

25 aliphatic nitrosamines were examined in the Ames assay for bacterial mutagens, using rat liver "S-9" for activation. Of them, 8 carcinogens were mutagenic and 5 non-carcinogens were not mutagenic. However, 2 compounds not carcinogenic in rats were mutagenic and 9 carcinogens were not mutagenic, including 6 that are liver carcinogens in rats.


Comutagenic effects exerted by N-nitroso compounds.

Mutagenesis induced by dimethylnitrosamine (DMN) and N-methyl-N-nitrosourea (NMU) in Salmonella typhimurium TA100 and TA1530 is characterized by biphasic dose and time response curves. At low doses or short incubation times mutagenic response is minimal, but increases rapidly when an apparent threshold dose or threshold incubation time is exceeded. Bacteria pretreated with subthreshold doses of DMN or NMU were many times more sensitive to the mutagenic effects of methylating and ethylating N-nitroso compounds than were untreated bacteria. The growth phase of the bacteria had little effect on the percentage enhancement of mutagenesis caused by pretreatment with NMU although exponentially growing cells were more sensitive to mutagenesis induced by NMU or diethylnitrosamine. Mutagenesis induced by methylmethanesulfonate and N-propyl-N'-nitro-N-nitrosoguanidine was not significantly enhanced by pretreatment of bacteria with NMU or NEU suggesting that the former mutagens act by different mechanisms than NMU or NEU.


Mutagenicity tests of diflubenzuron in the micronucleus test in mice, the L5178Y mouse lymphoma forward mutation assay, and the Ames Salmonella reverse mutation test.

Diflubenzuron, one of a new class of pesticides believed to act via inhibition of chitin synthesis in the developing insect cuticle, was tested for possible mutagenic activity using the micronucleus test in mice, the L5178Y mouse lymphoma forward mutation test at the thymidine kinase locus, and the Ames Salmonella/microsome reverse mutation test. No mutagenic effect was found.


Mutagenicity of anthraquinone and benzanthrone derivatives in the Salmonella/microsome test: activation of anthraquinone glycosides by enzymic extracts of rat cecal bacteria.

Approximately 70 anthraquinones and 20 benzanthrones were assayed for mutagenicity in the Salmonella/microsome test, employing 5 tester strains and Aroclor 1254 induced rat-liver microsomes. About one-third of the anthraquinones were frameshift mutagens, particularly phenolic and nitro anthraquinones. The most potent mutagens detected were of plant origin. Lucidin (1,3-dihydroxy-2-hydroxymethylanthraquinone) and its 2-ethyl ether gave values of 70 and 82 revertants per nmol, respectively, with strain TA100 (and microsomes in the case of the ether). A number of glycosides of mutagenic hydroxyanthraquinones were found to be nonmutagenic in the standard assay procedure, but could be activated by incorporation of cell-free sonic extracts of rat cecal bacteria, e.g., alizarin-2-O-beta-D-glycoside, emodin-1 (8)-monoglucoside and lucidin-3-O-primveroside. Over one-third of the benzanthrones tested were frameshift mutagens for Salmonella; the most potent response of 64 revertants/nmol was obtained with 3-p-toluidinobenzanthrone and microsomal activation in strain TA98.


Ineffectiveness of ascorbic acid therapy in nephropathic cystinosis.

Because high concentrations of ascorbic acid (0.57 mM) lower the free (nonprotein) cystine content of cultured cystinotic skin fibroblasts by over 50 per cent, we did a double-blind clinical trial to establish whether this drug would benefit cystinotic children. Sixty-four patients were randomized into the study; 32 received ascorbic acid (200 mg per kilogram of body weight per day), and 32 placebo. The study was terminated after approximately two years because there was no indication that vitamin C was beneficial and accumulating evidence that it might be harmful. Of 11 patients who left the study because of death or the requirement for dialysis or renal transplantation, eight were receiving ascorbic acid. The estimated relative risk (treatment vs. control) of an adverse event was R = 2.7, with a 90 per cent confidence interval of (0.8, 11.5). The serum creatinine concentration increased 0.53 mg per deciliter per year in patients receiving vitamin C and 0.24 mg per deciliter per year in patients receiving placebo (P = 0.08).


Free "small" and IgG-associated "large" hepatitis B e antigen in the serum and glomerular capillary walls of two patients with membranous glomerulonephritis.

Nephrotic syndrome developed in two children who carried hepatitis B virus. Both their serums contained hepatitis B surface antigen and hepatitis B e antigen (HBeAg).  Two physicochemically and immunologically different categories of HBeAg activity were identified in their serums--i.e., small molecular (free) and large molecular (associated with IgG). Their kidney-biopsy specimens disclosed pathologic changes typical of membranous glomerulonephritis. By a fluorescent-antibody technic, HBeAg was found to be deposited in diffuse granular fashion, along glomerular capillary walls together with IgG and beta1C, but no deposition of hepatitis B surface antigen was detected. The presence of HBeAg in association with IgG both in the serum and in the kidneys of these patients suggests that HBeAg caused membranous glomerulonephritis by inducing the formation and deposition of immune complexes.


Causes of the excessive rates of perinatal mortality and prematurity in pregnancies complicated by maternal urinary-tract infections.

The study was undertaken to determine the causes of the more frequent pre-term deliveries, fetal and neonatal deaths associated with maternal urinary-tract infections during pregnancy. The combined perinatal mortality rate for eight common placental and fetal disorders was 42 per thousand births in the infected vs. 21 per thousand in the noninfected, owing to a greater mortality from noninfectious placental and fetal disorders in the gestations with the urinary-tract infections (P less than 0.001). All the mortality excess took place when the urinary-tract infections occurred within 15 days of delivery. Death rates were highest when the urinary-tract infections coexisted with maternal hypertension and acetonuria.Hydramnios, amniotic-fluid bacterial infections and abruptio placentae were responsible for two thirds of the more frequent preterm deliveries in the pregnancies complicated by urinary-tract infections.


Hypertrophic cardiomyopathy and human leukocyte antigen linkage: differentiation of two forms of hypertrophic cardiomyopathy.

To determine whether hypertrophic cardiomyopathy is associated with a human leukocyte antigen (HLA) phenotype, we tissue-typed 70 unrelated afflicted patients and 86 of their asymptomatic family members (from nine separate kindreds). Forty-five per cent of the white patients had B-12 antigen as compared to 23 per cent in matched control subjects; 69 per cent of black patients had a B-5-complex antigen as compared to 33 per cent in matched controls. Patients with a B-12 or B-5-complex antigen were nonhypertensive and had family members with the disease. Patients without these antigens were severely hypertensive and had no affected family members. Linkage analysis of six families revealed a lod score of 7.7 for asymmetric septal hypertrophy and the HLA region of chromosome 6. We conclude that there is a heritable, nonhypertensive form of hypertrophic cardiomyopathy linked to the HLA loci on chromosome 6 and that a sporadic form is associated with severe, systemic hypertension.


Isolation and rapid identification of yeasts from compromised hosts.

In order to improve the isolation and identification of yeasts in a cancer research hospital, a protocol was developed utilizing an improved blood culture methodology and a four-test schema for rapid yeast identification. The blood culturing technique, based upon centrifugation, has shown a ten-fold increase in isolation of fungi from blood and has provided for: quantitation or organisms, unlimited selection of media and atmospheres for primary culturing, and a 1:200 dilution of microorganisms away from serum antimicrobial factors and antibiotics. The four-test schema, which may be adapted for the identification of any unknown yeast in pure culture, consists of a dye pour plate auxanogram (DPPA), Tween 80-Oxgall-Caffeic acid (TOC), a rapid nitrate-reductase test (swab test) and Urea 'R' Broth. Using this protocol, over 95% of the clinical isolates received were correctly identified within 24 hours and 100% by 48 hours. By using DPPA, a 14 sugar assimilation pattern for each isolate was determined within 12 to 16 hours; and in some cases, as little as 6 hours. Growth on TOC yielded one of the following results: (1) Candida albicans and Candida stellatoidea sequentially produced germ tubes and chlamydospores in 3 hours and 24 hours, respectively; (2) Cryptococcus neoformans produced a brown pigment specific for its identification in 12 hours or less. The swab test gave results on nitrate utilization in less than 15 minutes and urease was detected within 4 hours.


Fungal toxins as a parasitic factor responsible for the establishment of fungal infections.

Although the mechanism of fungal infections, particularly that of opportunistic fungus infections, has been studied extensively, much still remains to be clarified. As is the case of certain bacterial infections, it has long been assumed by numerous investigators that some toxins, enzymes and other metabolites produced in vitro as well as in vivo by pathogenic fungi or their cellular constituents might be responsible for the establishment of fungal infections. However, there are very few papers which deal with isolation and/or characterization of pathogenic fungus-derived toxins, particularly those of high molecular weight, to sufficiently meet various criteria for toxins including etiopathological ability. Likewise, it has been speculated that certain enzymes produced by pathogenic fungi are related to the pathogenesis of infections with the fungi implicated, but no direct evidence has been provided. It is commonly held by researchers concerned with medical mycology that the lowering of specific and/or nonspecific resistance of a host to pathogenic fungi is a prerequisite for the establishment of infections, particularly opportunistic infections. However, it is also accepted that if a given fungus possesses no parasite factors (e.g. toxigenicity, invasiveness and others), it would be unable to initiate infection even when the host is in a severe immunodeficient state. This is supported by our recent studies working with Saccharomyces cerevisiae and some other so-called nonpathogenic yeasts (unpublished data). Based on these considerations, the author and his co-workers have attempted to isolate several high and low molecular weight toxins in a pure state from virulent strains of Candida albicans and Aspergillus fumigatus as opportunist. Studies have also been made on the etiopathological roles of some successfully isolated toxins in infections with the fungi implicated (46). In addition to our experimental results, general concepts in fungal toxins, particularly those related to such toxins as isolated in our laboratory are outlined. Since opportunistic fungus infections have created a global problem because of their world-wide prevalence, a sharp demarcation between the so-called pathogenic and nonpathogenic fungi has become vague. Despite this situation, two terms are conventionally used throughout this paper.


Virulence genetics of Aspergillus nidulans Eidam: a review.

Studies of the influence of genotypic alterations on the murine virulence of Aspergillus nidulans Eidam are reviewed to emphasize the potential of this fungus for genetic studies of virulence.


Epidemiology of Cryptococcus neoformans.

The concept of the epidemiology of Cryptococcus neoformans as the causative agent of cryptococcosis and as a basidiomycetous yeast is based on the fact that bird manure has been until now its only known habitat but not plant material which likewise harbours various nonpathogenic Cryptococcus species. It could be shown that the possible influence of nutritional factors on the morphology and morphogenesis earns attention not only in view of the epidemiology of C. neoformans but of its perfect states, too.


Clinical significance of circulating immune complexes detection in chronic glomerulonephritis.

Sera from 168 patients with various types of chronic glomerulonephritis (GN) were assayed for immune complexes (IC) by two independent methods, a modification of the PEG precipitation test (PEG) and the inhibition of complement-dependent lymphocyte rosette formation (RI). Both assays had different reactivities, the RI being more sensitive than the PEG test. Higher percentages of positivity of these tests were observed in the GN groups than in normal controls. However serial measurements demonstrated that IC were present only intermittently in most instances. The presence of IC correlated with disease activity in patients with focal glomerulosclerosis membranous GN and membranoproliferative GN, while in lupus erythematosus it reflected the effects of different treatment regimens although it had no relationship with clinical symptoms. Nevertheless, our results suggest that these tests are of little help to the clinician to appreciate disease activity and monitor therapy in individual GN patients.


High Rates of controlled ultrafiltration combined with optimal diffusion: recent advances in hemodialysis technique.

A system which permits high rates of middle molecule removal while preserving the removal of low molecular weight substances is described. It consists of a high fluid flux hollow fiber artificial kidney and an ultrafiltration controller. When used in combination, high rates of convective transport can be achieved through rapid ultrafiltration and reconstitution of blood with physiologic salt solutions. The theoretical impact of changing from conventional dialysis to this form of therapy on the body burden of middle molecules is estimated.


Interrelationship of time of dialysis-dependent uremia and pretransplant blood transfusions.

In a consecutive series of 167 renal allotransplants, a statistically significant correlation was found between the number of pretransplant blood transfusions and the time of dialysis-dependent uremia. This correlation suggests that one possible explanation for the association of a beneficial effect of pretransplant blood transfusions with allograft survival may be in part due to the prolongation of uremia, which is a well-known immunosupressive factor. This begs the question of whether the transfusion-dialysis time association promotes a further selection factor leaving sensitized patients waiting for longer periods of time for transplants or unable to receive transplants at all. Whether the transfusion and the favorable prognosis association is also related to other specific immunological mechanisms remains to be proven.


Immunologic monitoring of transplant rejection: correlation of in vitro assays with morphologic changes on transplant biopsy.

The assays of lymphocyte-mediated cytotoxicity (LMC), antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were correlated with histopathologic criteria of refection in 35 transplant biopsies. A positive LMC was seen with 6/8 biopsies showing moderate to severe cellular rejection and in 8/17 with mild cellular rejection. Positive ADCC and/or CDC assays were associated with 14/14 biopsies containing rejection vasculitis. These results suggest that selected in vitro assays may be useful in monitoring the immunologic events occurring in the rejecting allograft.


Blood pressure behaviour in patients with malignant hypertension submitted to kidney transplantation.

The authors investigated post-renal transplantation hypertension behaviour in 20 patients with primary malignant hypertension (PMH), in 42 patients with secondary malignant hypertension (SMH) and in 62 controls (without malignant hypertension). All cases of malignant hypertension required removal of primary kidneys, either before or after transplantation. Hypertension was noticed at different periods of the post-renal transplantation phase, in 93% of PMH cases, 90% of SMH cases and in only 31% of the controls. After a period of time following transplantation, a decrease of hypertension incidence in the SMH and control groups was noticed, and persistence of hypertension was observed in the PMH group. The long-term development of PMH patients was worse than that of the other two groups.


Hyperreninemia during renal transplantation.

18 patients undergoing renal transplantation were studied prospectively to determine the incidence and mechanism of blood pressure elevations which sometimes occur after release of vascular clamps from the grafts. No patients became as severely hypertensive as noted in previous reports. A weak, but statistically significant (r=0.56, p less than 0.05) positive correlation was found between changes in plasma renin activity and small incremental changes in blood pressure. 2 patients in whom the greatest change in renin occurred showed little or no increase in blood pressure. In view of the small blood pressure changes seen in the face of significant changes in plasma renin activity, it appears unlikely that acute hyperreninemia alone is sufficient explanation for postdeclamping hypertension which is sometimes observed during renal transplantation.


A longitudinal study of bone disease after successful renal transplantation.

A retrospective study of 100 patients followed for 1-4 years after successful renal transplantation was undertaken to assess the amelioration of previously present metabolic bone disease and to determine the risk factors associated with the development of osteonecrosis. 42% of patients showed some evidence of bony abnormality. Following transplantation, there was slow but progressive resolution in the X-ray changes of hyperparathyroidism but not of osteoporosis. 14% of patients developed osteonecrosis in the posttransplant period with the femoral head the most common site involved (72% of patients). Osteonecrosis could not be related to average steroid dose, number of steroid pulses, or the preexistence of metabolic bone disease.


Nephrology in the tropical setting.

The pattern of renal disease and its basic principles of management are essentially the same in the tropics as in the temperate environment. Glomerulonephritis and pyelonephritis with concomitant hypertension account for most cases of renal failure. Malaria is now well recognised as a cause of the nephrotic syndrome. Economic and manpower factors dictate a conservative approach to therapy. Maintenance haemodialysis and renal transplantation are not realistic in the present context, having regard to the order of priorities in health care delivery.


A clinical and immunopathologic dissection of rapidly progressive glomerulonephritis.

This contribution seeks to illustrate the immunopathogenetic complexities of the syndrome of rapidly progressive glomerulonephritis. As with most of the clinical syndromes of glomerular disease, rapidly progressive glomerulonephritis may be dissected into a number of categories based upon combinations of clinical, morphologic and immunologic observations. It has been demonstrated that such observations have an important bearing on the natural history, prognosis and treatment of this syndrome. Much remains to be learned, particularly with respect to etiological factors, the genesis of extracapillary proliferation and the means of modifying or preventing these diseases.


Metabolism of polypeptide hormones by the normal kidney and in uremia.

Recent work from our laboratory on the mechanism of polypeptide hormone handling by the normal kidney and the pathogenesis of altered hormonal metabolism in renal failure is reviewed. The kidney extracts substantial amounts of low - and medium - molecular weight polypeptide hormones from the renal circulation by a process which probably involves both glomerular filtration plus luminal reabsorption and direct peritubular uptake, although the relative contribution of the two mechanisms under physiologic conditions is not known. The bulk of the extracted hormone is catabolized in the renal parenchyma since urinary excretion is negligible. Renal catabolism contributes an important fraction of the total metabolic clearance of polypeptide hormones, which accounts in part for their increased circulating levels in renal failure. Since certain hormones are heterogenous and a large proportion of their plasma immunoreactivity may consist of components of uncertain biologic activity, simple correlations between circulating hormone levels and endocrine abnormalities in uremia are hazardous.


Distribution and release of adenosine triphosphate in rat brain.

The steady-state level of brain ATP was measured after the tissue had been treated with a focused microwave irradiation system. The brain ATP content (1.50 nmol/mg tissue) obtained by microwave fixation is similar to that observed by others using fast-freezing and microwave fixation techniques. The concentrations of ATP in different brain regions show a rather uniform distribution, ranging from 1.918 +/- 0.059 (brainstem) to 2.393 +/- 0.19 (caudate) nmol/mg tissue; however, insufficient microwave fixation time seems to produce a greater regional variation of ATP. Release of ATP was investigated by placing a cup on the sensory-motor cortex. The rate for basal release of ATP is 1.43 +/- 0.14 femtomole/min/mm(2). A 30-fold increase in ATP release was obtained by direct stimulation of the cortex with 5 mA pulses of 0.2 msec duration at a rate of 20/sec over a period of 10 min. These results, in conjunction with others describing the potent pharmacological action of the nucleotide, seem to suggest that ATP could be a mediator in a "purinergic" system in the CNS.


Vertebrate GABA receptors.

Physiologic-pharmacologic studies in vivo and with tissue cultures have revealed that synaptic GABA receptors exist in the vertebrate CNS. The GABA antagonist, bicuculline, can be used to detect synaptic GABA receptors in both the presence and absence of Na+, even though GABA binding to cerebral subcellular fractions occurs mainly to transport (uptake) receptors in the presence of Na+.


Luteinizing hormone-releasing factor (LRF) and reproductive behavior in male doves exposed to long and short photoperiods.

In order to determine whether the variable degree of nest-building behavior displayed by male doves exposed to different photoregimes is related to differences in luteinizing hormone-releasing factor (LRF) levels, androgen-treated castrates held on long (16L:8D) or short (8L:16D) daylengths were treated with 20 microgram LRF or saline daily. Birds in both groups exhibited higher levels of initial courtship and nest-building when held on long days. LRF treatment had no effect on any of the behavior patterns examined. The results suggest that photoperiod does not affect reproductive behavior in male doves through changes in endogenous levels of LRF.


[Development of therapeutic neuroradiology (author's transl)].

While therapeutic endovascular occlusions date from as early as 1904, it is in the last 20 years that therapeutic neutroradiology has come into its own. Progress has been made in four directions. (1) Embolization has developed from the original technique involving arteriotomy, through percutaneous methods, to present-day superselective catheterization. Concurrently, the materials used have been improved: from nonmalleable muscle and Silastic balls, to malleable Spongel and dura mater, and most recently to polymerizable fluid plastic substances. The possibility of obstructing very narrow vessels extends the range of indications of embolization. (2) Balloon catheters have been developed, first with nondetachable balloons (1971), more recently with detachable ones (1974). (3) Other techniques may be used to produce a therapeutic thrombosis, e.g., endovascular electrocoagulation and thermocoagulation. (4) Foreign bodies may be extracted safely by catheterization. Further development of techniques should ensure a growing importance for therapeutic neuroradiology in the future.


CT studies in patients operated with stereotaxic thalamotomies.

CT has been used in controlling stereotaxic thalamotomies in patients with movement disorders. The results obtained in 12 such patients, with early and delayed scans, are presented.


Stereotaxic exploration in 200 supratentorial brain tumors. Its value in addition to computerized tomography.

The authors emphasize the advantages of stereotaxic methodology in the management of 200 brain tumors. Nowadays computerized tomography is the first stage of radiologic diagnosis. Both CT scan and stereotaxic examination have been carried out in more than 35% of these tumors. Rather than a comparison of the two examinations, the authors' purpose is to attempt to demonstrate their complementarity in the assessment of location, volume, and nature of the lesion and eventually in the choice of a therapeutic attitude. Analysis of topographic data and staged biopsies, gathered from the 'stereotaxic space,' provides the neurosurgeon with accurate information for planned surgical excision or interstitial irradiation.


[Preliminary evaluation of Depakine effects in epilepsy].

Depakine Labaz in doses from 30 to 1200 mg daily was given to 52 patients in an outpatient clinic. In 13% of cases symptoms of drug intolerance developed and the treatment had to be discontinued. In 45 cases treatment was continued. The drug was given usually to patients refractory to previous drugs, with evidence of organic brain disease. The highest degree of clinical improvement was observed in patients with grand mal seizures and seizures without convulsions. The influence of this treatment of partial complex seizures was slightly smaller. The number of patients treated was too small for evaluation of the effects in partial simple seizures. The total proportion of improved patients was about 60%. In EEG curves normalization of background activity was the most frequent findings, without appearance of rapid activity. In some cases manifestation of focal changes was observed. The favourable effect of Depakine on seizure activity manifested itself in later period of treatment and was slight. The drug had a favourable effect on the wellbeing of patients and had no significant toxic effect in the liver or kidneys.


PAM cell assay as a tests for multiple-sclerosis associated agent.

Contrary to previous reports, no evidence for a multiple sclerosis-associated agent (MSAA) was obtained when coded brain samples from multiple sclerosis patients and controls were tested in PAM cells.


Double-blind study of modified neurotoxin in motor neuron disease.

In a double-blind study, we evaluated the intramuscular administration of modified neurotoxin in 48 patients who were treated for 6 months. There was no evidence to support claims that patients receive any benefit from the neurotoxin. A significant number of patients had minor functional improvement, often of a transient nature, but these manifestations were more common in the placebo-treated patients than in those receiving neurotoxin. These variations in the course of motor neuron disease have not been stressed in the previous literature.


Listeria monocytogenes: brain abscess or meningoencephalitis?

A brain abscess caused by Listeria monocytogenes developed in an immunosuppressed renal transplant patient. Meningitis and meningoencephalitis from this organism were encountered in three other renal transplant recipients at this medical center during the past 4 years. Focal neurologic deficits occurred in patients with either Listeria abscess or meningoencephalitis. Computerized tomography was a rapid aid to the diagnosis of abscess. Immunosuppression has increased the incidence of central nervous system Listeria infections, but ampicillin still provides effective treatment, even when immunosuppressive therapy is continued. Limited experience with Listeria brain abscess suggests that surgical intervention improves the prognosis.


Effects of valproate and ethosuximide on thalamocortical excitability.

Sodium valproate and ethosuximide are anticonvulsants employed in the treatment of petit mal epilepsy; both drugs are considered to be thalamically active. Valproate and ethosuximide both decreased the average evoked response following the second of two stimuli delivered to the ventrolateral thalamus at stimulus frequencies in the region of 3 Hz. Ethosuximide, but not valproate, enhanced the average evoked response at high stimulus frequencies an action shared with several convulsant treatments having different modes of action. The clinical effects of valproate and ethosuximide can be related to this differential modulation of thalamocortical excitability.


The transfer of antibiotic resistance by R plasmids in Shigellae.

Forty-five strains of Shigella species isolated at Auckland Hospital from 1972--1974 were investigated for antibiotic resistance. Forty-two strains were resistant to one or more antibiotics and 11 strains transferred antibiotic resistance by conjugation to E. coli.