Radiation-induced interference with postnatal hippocampal cytogenesis in rats and its long-term effects on the acquisition of neurons and glia.

The long term consequences of graduated interference with the acquisition of hippocampal neurons and glia during early infancy were examined with quantitative histology and 3H-thymidine autoradiography. the head region containing the hippocampus was irradiated from day two on with either two (2X), four (4X), six (6X) or eight (8X) doses of 150-200r X-rays. The animals were killed at 30, 60, 90 and 120 days of age. The morphology of the hippocampus was normal in all irradiated groups with the characteristic interlocking flods of the pyramidal and granular layers. While the number of pyramidal calls of Ammon's horn was unaffected, the number of granule cells of the dentate gyrus was progressively and permanently reduced from control levels by the different dosage schedules (2X, 59% reduction; 4X, 77%; 6X, 83%; 8X, 84%). Incidental observations in control animals indicated a 20% increase in granule cells between 30 and 120 days of age in agreement with earlier observations of granule cell labelling after 3H-thymidine injections in adult rats. The time of origin of tha approximately 15-16% of the granule cells surviving irradiation in the 8X group was determined by injecting either pregnant females (gestation days 19-20) or pups (days 0 and 1) with two successive dosed of 3H-thymidine; the animals were irradiated from day two on the eight X-ray doses. The granule cells surviving in the postnatally injected group were all unlabelled and comparable in number to the unlabelled cells in control animals that were given five successive postnatal injections of 3H-thymidine. This established that the radioresistant complement of granule cells is formed prenatally. In the prenatally injected group, over half the surviving cells were labelled; it was assumed that those not labelled were formed befor gestation day 19. In contrast to the permanent reduction in the number of granule cells, there was some reestablishment of the number of cells in the dentate molecular layer and the Ammonic stratum oriens; in the fimbria, recovery in cell number was complete by 60 days. In a supplementary autoradiographic experiment, cell proliferation in the granular layer and in the fimbria was determined at 60 days of age after a single postnatal injection of 3H-thymidine on either day 15 or day 20 in the control, 2X, 4X and 6X groups. The number of labelled cells in the irradiated groups was always well below control levels in the granular layer, but it was wither above or at the same level as controls in the fimbria. Tentative interpretations were offered for the differential long-term effects of variable X-ray schedules on the neuronal and glial populationf of the hippocampus.


A quantitative analysis of the cat retinal ganglion cell topography.

A retinal ganglion cell distribution map has been prepared for the cresyl violet stained cat retina. It differs from previously published maps in revealing the visual streak to be more substantial and in showing a higher peak density of 9-10,000 ganglion cells/mm2 at the presumed visual pole. The map was used to obtain a minimum estimate of the retinal ganglion cell population as 217,000 cells, more than double the total previously reported. The problem of classifying the cells of the ganglion cell layer is discussed in detail and examples of criterion cells illustrated. The paper also includes an account of retinal mensuration (dimensions, area, etc.) and a discussion of the visual streak orientation.


Species differences in mechanosensory projections from the mouth to the ventrobasal thalamus.

To determine whether the largely ipsilateral, inverted representation of mouth parts in the ventrobasal thalamus of sheep was unique to that species or an expansion of a general mammalian pattern, the corresponding thalamic projections were mapped electrophysiologically in a selected series of mammals (oppossums, agoutis, squirrel monkeys, cats, raccoons, and sheep) representing major branches of evolution among therian mammals. In mapping, tungsten microelectrodes were used to record multi-unit discharges in the thalamus in response to mechanical stimulation of oral surfaces. The pattern of projections seen in sheep is not a general mammalian pattern; there is extensive variability among mammals in the laterality and internal orgainzation of the projections from the mouth. In spite of the great variability, the results suggest an hypothesis concerning phylogenetic trends: descendants of palaeoryctoid insectivores (cats, raccoons, and sheep in our sample) have extensive ipsilateral projections from the mouth, in other therian mammals (opossums, agoutis, and squirrel monkeys in our sample) the ipsilateral component is small or absent.


The projections of different morphological types of ganglion cells in the cat retina.

The central projections of the retinal ganglion cells of the cat were examined using the method of retrograde transport of horseradish peroxidase. Peroxidase was injected into the lateral geniculate nucleus and into the superior colliculus by means of a recording micropipette. After injections at retinotopically homologous points in these two structures in separate animals, tha patterns of retinal ganglion cell labeling were compared. We found that there were three populations of ganglion cells: small cells, that projected predominantly to the superior colliculus; medium-sized cells, that projected predominantly to the lateral geniculate nucleus; and large cells, some of which projected to both structures, and some of which projected to the lateral geniculate nucleus alons. Quantitative studies showed that the average size of the cells in each population was smaller at the area centralis than in the periphery. These results could be directly related to physiological classifications of retinal ganglion cells proposed by other authors.


The projections of cells in different layers of the cat's visual cortex.

The projection of cells in different layers of several cortical visual areas in the cat were studied using the method of retrograde transport of horseradish peroxidase. Injections of the enzyme were made through a recording micropipette, making it possible to localize the injection site by physiological criteria. We found that layer VI cells projected to the alteral geniculate nucleus, while a distinct population of cells in layer V projected to the superior colliculus. Cells in layers II and III were tha major sources of ipsilateral cortico-cortical connections. This pattern of projection was consistent from one visual area to another. Pyramidal cells appeared to be the source of cortico-geniculate, cortico-collicular and cortico-cortical projections. The proportion of cells within a layer that terminated in a given site varied from layer to layer: apparently all of the large pyramids in layer V had terminals in the superior colliculus, about half of the pyramids in layer VI had terminals in the lateral geniculate nucleus, while only a small proportion of the pyramids in layers II and III had terminals in any single cortical area. The results indicated a remarkable specificity in the projections of the cortical layers. The cortical connections of the different cell types in layers A and A1 of the lateral geniculate nucleus were also examined: the cells that projected to area 17 were much more numerous and were on the average smaller than those that projected to area 18. Projections to the cortex were also found from the pulvinar, the medial interlaminar nucleus and the posterior nucleus. Direct connections were observed to the lateral geniculate nucleus from several midbrain reticular nuclei. Finally, projections were found to the superior colliculus from the zona incerta, the reticular nucleus of the thalamus and the ventral lateral geniculate nucleus.


Hormonal basis of sexual differentiation in the Japanese quail.

On the 10th day of incubation, Japanese quail eggs either were injected with testosterone propionate (TP), estradiol benzoate (EB), or oil, or were not injected. When sexually mature, all birds were examined for a variety of sexually dimorphic behavioral and physical characteristics, both masculine and feminine. They were then exposed to a short photoperiod (causing gonadal regression), treated with either TP or EB, and examined again. Either androgen or estrogen administered before hatching demasculinized males, but did not masculinize females or defeminize either sex. In contrast, early sex hormones masculinize and/or or defeminize mammals. This difference is discussed in relation to other differences in avian and mammalian sexuality.


Vaginal stimulation in rats induces prolonged lordosis responsiveness and sexual receptivity.

Sexual receptivity to males resulted from stimulation of the vagina with a glass rod in previously unreceptive ovariectomized, estrogen-treated rats. Several minutes of rejection behavior preceded the receptivity. In a second study, manual palpation was used to determine the duration of the lordosis response facilitation. Initially, all females were unresponsive to manual flank-perineum stimulation (palpation). Vaginal stimulation plus palpation, which together elicit lordosis, facilitated subsequent lordosis responses to palpation. This effect persisted for several hours after the vaginal stimulation was applied. Vaginal stimulation alone, which was ineffective in eliciting lordosis, also facilitated lordosis in response to subsequent palpation. Repeated palpation did not facilitate lordosis. These prolonged effects were independent of hormone treatment.


Malpractice law and the dietitian.

The recent increase in lawsuits against health care personnel makes it advisable that dietitians recognize the potential for legal liability as they practice their profession. Whatever the exact nature of a dietitian's daily duties, an awareness and understanding of the concepts governing the law of malpractice will enable him/her to minimize exposure to liability. To accomplish this, the dietitian should exercise at least a standard of care accepted as competence for the profession. By so doing, the dietitian can insure not only less exposure to malpractice suits, but also attainment of an important goal: delivery of high-quality care to patients.


Food choices of obese and non-obese persons.

An observational study of food choices of patrons of a campus cafeteria was conducted to ascertain whether obese and non-obese individuals had the same eating patterns. Subjects were unaware of the monitoring of their food choices. Patrons were categorized by visual appraisal into forty-eight cross-classified groups according to sex (male, female), body build (slender, sturdy, stocky, obese), height (tall, average, short), and age (less than and more than thirty years of age). Servings of food were estimated visually as it was not possible to determine exact amounts. Foods were classified as either protective foods with good contributions of nutrients in proportion to calories (Group B) or as high-calorie, low-nutrient foods (Group A). Significant findings were the tendency for those in the obese category to select more servings of food and more foods from the high-calorie, low-nutrient Group A foods, when compared with selections of persons in the other body-build groups. A more controlled study is suggested for more definitive results. Also pointed out was the importance of recognizing that excessive food intake may be one possibility among many in cases of refractory obesity.


Oral satiety in the obese and nonobese.

Elapsed mealtime, number of mouthfuls per meal, and the time each mouthful was chewed were observed in thirty subjects, fourteen of whom were obese and sixteen, nonobese. Obese subjects consumed their meals and chewed mouthful in significantly less time than did nonobese subjects. There was no significant difference between the two groups in the number of mouthfuls per meal. In obese subjects, oral satiety as assessed in this study, appeared to play a less-than-meaningful role in the attainment of postprandial satiety. The clinical implications of these observations are discussed.


Nutrient menu planning for clinical research centers. Control by computer.

A computer program has been developed for the dietetic service of the Clinical Research Center at the University of Florida. Presently, it is used in menu planning and nutrient analysis for selective, controlled-nutrient diets and for constant diets. The program is able to compute food weights for a patient-selected daily menu which would satisfy up to twenty-three nutrient constraints and which may be optimized with respect to one or more of these. The principal benefit of the program is a saving in the dietetian's time in calculating the nutrient content of the diet and in planning diets with several constrained nutrients. It is also being used as a teaching resource for dietetic interns and dietetic trainees.


Comprehensive evaluation of fatty acids in foods. IV. Nuts, peanuts, and soups.

As part of USDA research to provide reliable and up-to-date tabulations of lipids and fatty acids in foods, representative values have been derived and tabulated for nuts and commercially canned condensed soups. Except for palm-type nuts, unsaturated fatty acids are the major acids in nuts; oleic acid is generally the predominant unsaturated fatty acid. The new fatty acid values indicate greater concentrations of saturated fatty acids than previously reported. The P:S ratios for nuts and peanuts are presented. The fatty acid contents of soups are varied and reflect the lipid composition of the source(s) of fat of the particular ingredients used in the manufacture of these products. These new values for fatty acids in nuts and soups should greatly help nutritionists and dietitians to better assess the total contribution of each particular fatty acid to the diet.


Major nutrients in the Type A lunch. II. Amounts consumed by students.

Plate waste from Type A school lunches was collected during the period that fifth, seventh, and tenth grade students ate lunch. Twelve elementary, three junior high, and seven high schools distributed among three geographic regions of North Carolina were included in the sample. Nutrients served and nutrients in plate waste were determined by laboratory analyses of two five-day composites of meals and of waste from each school. Nutrients consumed were determined by difference. Relative to the Type A goal, protein intake was highest; riboflavin and vitamin A values were consumed in satisfactory (one-third or more of the allowances) amounts. Younger students consumed adequate iron and calcium, and calcium intake approached adequacy among older students. High school students consumed only 69 per cent of their goal for iron and 75 per cent of the goal of energy value; among the three groups, however, this was the highest percentage of the goal for energy value consumed. Ascorbic acid intake was least satisfactory for fifth and seventh grade students. Overall, fifth graders consumed a significantly (P less than .01) lower percentage of the nutrients served than the two older groups. With a few exceptions, students consumed 80 to 90 per cent of the various nutrients which were served: 62 to 66 per cent of the vitamin A value served was consumed; fifth grade students consumed only 77 per cent of the iron served; and the two younger groups consumed only 69 per cent of the ascorbic acid served. Although the most marked regional differences in nutrients consumed occurred with vitamin A and ascorbic acid, overall elementary students in the eastern region consumed a significantly (P less than .01) higher percentage of nutrients served than did those in other two regions.


A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients.

Clinicians whose practice includes elderly patients need a short, reliable instrument to detect the presence of intellectual impairment and to determine the degree. A 10-item Short Portable Mental Status Questionnaire (SPMSQ), easily administered by any clinician in the office or in a hospital, has been designed, tested, standardized and validated. The standardization and validation procedure included administering the test to 997 elderly persons residing in the community, to 141 elderly persons referred for psychiatric and other health and social problems to a multipurpose clinic, and to 102 elderly persons living in institutions such as nursing homes, homes for the aged, or state mental hospitals. It was found that educational level and race had to be taken into account in scoring individual performance. On the basis of the large community population, standards of performance were established for: 1) intact mental functioning, 2) borderline or mild organic impairment, 3) definite but moderate organic impairment, and 4) severe organic impairment. In the 141 clinic patients, the SPMSQ scores were correlated with the clinical diagnoses. There was a high level of agreement between the clinical diagnosis of organic brain syndrome and the SPMSQ scores that indicated moderate or severe organic impairment.


A follow-up longitudinal study of selected physiologic functions in former physical education students-after forty years.

Reported is the continuation of follow-up investigations of certain physiologic functions in former physical education students. The first follow-up study was conducted about 30 years after the initial measurements. The present follow-up study concerned a re-investigation of the same group (23 men and 11 women), 10 years later, i.e., about 40 years after the first examination. Resting values for heart rate, blood pressure and metabolism were determined, as well as values for lung volume, hand-grip strength, and reaction time. During moderately hard exercise, measurements were made of oxygen uptake, ventilatory equivalents, and heart rate. By extrapolation of these heart-rate determinations to "maximal heart rate," the maximal oxygen uptake was estimated and expressed as L times min-1 and as ml x min-1 and as ml times kg-1 x min-1. The data show a general deterioration in practically all the physiologic functions studied, most pronounced during the last 10 years of the 40-year period.


Psychopharmacologic investigations in elderly volunteers: Effect of diazepam in males.

Forty male volunteers over the age of 60 took either a daily dose of diazepam (12 mg) or placebo for a two-week period. Differential responses to these compounds partially depended upon age and the initial symptom level. Diazepam produced sedative side effects, a modest antidepressant effect, and a reduction in memory. Placebo had an antianxiety effect in the relatively older subjects, and was associated with decreased fatique, improved memory and improved motor function. Considerable variability was observed in both drug and placebo responses among the elderly. A self-rating depression scale (D30R) was useful for assessing changes in affective states and in discriminating between the effects of active drug and placebo.


What is a geriatrician?

A geriatrician is something more than a physician who simply cares for old people. The geriatrician should, above all, be well grounded in internal medicine, have a genuine fondness for the elderly and their problems, and be experienced in neurology, psychiatry and rehabilitation medicine. A possible additional role is that of organizer and coordinator of health services for old people.


A psychogeriatric assessment program. I. Social functioning and ward behavior.

Eightly newly admitted psychogeriatric patients were intensively investigated by a variety of disciplines -- medical, laboratory, and psychologic-psychiatric tests, including a Minimal Social Behavior Scale and an Integrative Social Functioning Scale. The sample of patients  and methods of study for this 10-month Geriatric Assessment Program are described. Assessment of present and past social functioning revealed good agreement between ratings made by different staff members. A decline in social functioning with time differentiated organic from functional psychiatric illness. Some of the scales employed may be of value for social screening purposes in the community.


A geriatric functional rating scale to determine the need for institutional care.

This study was carried out to validate a rating scale which could serve as a guide in determining the need for institutional care. The scale assesses the subject's physical and mental disability, balanced against his ability to function and the support available from relatives and community resources. Cut-off points were tested by the use of an 18-month follow-up interval. Initially, 130 aged men and women from three different settings were rated. At the time of follow-up eighteen months later, 83 per cent of the subjects who had obtained an initial score indicative of their inability to function in the community were either dead or in an institution. In contrast, 90 per cent of those who obtained an initial score indicating that they were able to continue in the community, were not in an institution at the time of follow-up. The rating scale can be used not only to help decide the need for institutional care, but also to help determine the most suitable setting for the patient if placement is necessary.


Transitional-cell cloacogenic carcinoma of the anal canal: Case report.

A case is presented of transitional-cell cloacogenic carcinoma of the anal canal in a 66-year-old woman. Eight years previously she had received radiation therapy for early carcinoma of the uterine cervix, but there was no evidence of recurrence. The rectal carcinoma was therefore regarded as a second primary malignant tumor. This point in differential diagnosis was considered important because of its bearing on the plan of treatment. After abdominoperineal resection of the tumor, the prognosis seemed favorable.


Distribution of concanavalin A binding sites on the surface of dissociated rat submandibular gland acinar cells.

The submandibular glands of 4-week-old rats were dissociated by a procedure involving digestions with collagenase and hyaluronidase, chelation of divalent cations and mechanical force. A suspension of single cells was obtained in low yield by centrifugation in a Ficoll-containing medium. Immediately after dissociation and after a culture period of 16-18 hr the dissociated cells were tested for agglutinability by concanavalin A (Con A). Using ferritin (tfer)-conjugated Con A the lectin binding by the isolated acinar cells was also studied. The dissociated cells were agglutinated by low concentrations of Con A and bound Fer-Con A molecules on their entire surface without any indication of polarization of the cell membrane. There was a considerable cell to cell variation in the amount of Fer-Con A binding which was, in general, sparse and patchy. The contact surfaces between agglutinated cells revealed a dense binding of Fer-Con A molecules irrespective of the types of cells participating in the agglutination reaction. Cells cultured for 16-18 hr were no longer agglutinated by Con A. As compared to the freshly dissociated cells the cultured acinar cells revealed a more uniform and denser binding of Fer-Con A molecules. Furthermore, there were more lectin molecules bound to the cell surface corresponding to the basal part of the cell, where the nucleus and most of the rough surface endoplasmic reticulum were located, than to the apical cell surface. It is suggested that the higher density of lectin-binding sites on the cell surface in the vicinity of the cisternae of the rough endoplasmic reticulum indicates insertion sites of newly synthesized membrane glycoproteins.


Retention of antimelanoma effect of polyinosinic-polycytidylic acid in neonatally thymectomized, irradiated, leukopenic mice.

Polyinosinic-polycytidylic acid (PIC), a synthetic polyribonucleotide, inhibits the growth of B16 malignant melanoma in C57BL/6 mice. Since PIC has been reported to augment immune responses, we tested the hypothesis that the antitumor effect of PIC against B16 melanoma is via immune stimulation. Mice were neonatally thymectomized or neonatally thymectomized and subsequently irradiated to suppress their immune reactivity. In such animals PIC retained its ability to inhibit the growth of B16 melanoma, in the face of profound leukopenia and lymphopenia, suggesting that its antimelanoma effect is probably not mediated by augmentation of the host's immune antitumor response.


Mouse model for protoporphyria. I. The liver and hepatic protoporphyrin crystals.

Outbred albino mice were rendered protoporphyric by a diet containing 2.5% (weight) of griseofulvin. There was a 5-fold increase in liver weight, hepatocellular degeneration and necrosis, cholestasis, ductular proliferation and cirrhosis. Liver protoporphyrin values were elevated and brown pigment granules were present in hepatocytes, Kupffer cells, and bile ducts. The granules showed red fluorescence, birefringence, and, at the ultrastructural level, consisted of aggregates of needle-like crystals. Crystals isolated from such livers showed solubility and absorption characteristics of protoporphyrin; in vitro recrystallization of protoporphyrin, extracted from protoporphyric mouse livers, yielded crystals identical with those observed in vivo, and commercial protoporphyrin exhibited similar morphologic features. The liver pathology and protoporphyrin crystals observed in these animals are identical to the liver pathology and crystals observed in the human disease, erythropoietic protoporphyria. In this mouse model, protoporphyrin crystals are intimately associated with hepatocellular injury and it appears that their accumulation within hepatocytes leads to hepatocellular destruction. A similar pathogenesis is postulated for the hepatic damage that occurs in some cases of erythropoietic protoporphyria.


Mouse model for protoporphyria. II. Cellular and subcellular events in the photosensitivity flare of the skin.

Acute phototoxic reactions were induced by long-wave ultraviolet light (UV-A) in mice with griseofulvin-induced protoporphyria. The clinical response was characterized by erythema, pronounced edema, and purpura. Tracer experiments and electron microscopy revealed pronounced vascular damage and leakage of vascular contents, whereas the epidermis and all other dermal components were intact. There was selective destruction of endothelial cells and damage of the basal lamina of the vessels. This striking vascular injury was absent from nonprotoporphyric UV-A-irradiated mice and from protoporphyric and nonprotoporphyric mice exposed to short-wave ultraviolet light (UV-B). Patients with erythropoietic protoporphyria (EPP) exhibit an identical, selective damage of blood vessels when irradiated with UV-A or sunlight but not with UV-B alone. It is hypothesized that in both murine protoporphyria and EPP, endothelial cells are photosensitized by protoporphyrin circulating in the serum and that photosensitized endothelia represent the primary cellular target of the photochemical reaction induced by UV-A.


Elastic fibers in fetal dermis.

Dermal elastic tissue in fetal skin was evaluated by light microscopy using three different staining techniques. Postmortem skin was obtained from the abdominal wall of 45 fetuses ranging in age from 8 to 42 weeks. Elastic fibers were first detected in skin from fetuses of 22 weeks and, with increasing gestational age, appeared to increase in quantity and complexity. Skin from fetuses older than 32 weeks had a well-developed network of elastic fibers throughout the dermis. There was no diminution of dermal elastic tissue during the latter part of the sixth lunar month as had been reported in a previous study.


Further studies on the isolation of ribosomes from normal and methylcholanthrene-treated mouse epidermis.

Ribosomes from normal or hyperplastic mouse epidermis have been isolated from the postmitochondrial supernatant and from the entire cytoplasm using either the postnuclear supernatant technique or the Redman technique which permits isolation of ribosomes separately from the nuclear, mitochondrial, and postmitochondrial fractions. In contrast to liver, the yields of ribosomes from skin are similar irrespective of what technique is used. Increasing the centrifugation force from 105,000 gav to 253,000 gav results in highly significant increases in the yields of ribosomes, from both normal and hyperplastic epidermis.


Epidemic keratoconjunctivitis: a community outbreak of mixed adenovirus type 8 and type 19 infection.

During the fall and winter of 1973, 145 cases of epidemic keratoconjunctivitis were diagnosed in Nashville, Tennessee. Of the 74 cases studied virologically and/or serologically, 62% were caused by adenovirus type 8, and 28% were caused by adenovirus 19. Whereas adenovirus type 8 was isolated only from conjunctival scrapings, adenovirus type 19 was isolated from nose and throat swabs as well as from conjunctivae. The two viruses produced clinically indistinguishable eye disease and household secondary attack rates that were not statistically different. Regardless of etiology, the secondary attack rate in households was significantly higher among the contacts of those patients who had severe disease for greater than 28 days than among the contacts of patients who had milder disease of shorter duration.


Further evidence for cross-linking as a protective factor in experimental cholera: properties of antibody fragments.

Enzymic fragments of IgG antibody were tested for their protective abilities in the infant mouse cholera model. F(ab')2 retained the full protective activity of the parent IgG molecule despite losses in complement fixation and opsonic functions. Fab' and Fab fragments also contained significant protective activity but at a level of only 10% of the intact IgG or F(ab')2. Self-recombinant univalent F(ab')2 also contained about 10% of the protective activity of the divalent F(ab')2 parent molecule. These results are interpreted as evidence that cross-linking is an important mechanism by which specific antibody protects mucosal surfaces against experimental infection with Vibrio cholerae.


Antibody cross-linking as a factor in immunity to cholera in infant mice.

Several antibody preparations were tested for their ability to reduce adsorption of Vibrio cholerae to isolated intestinal epithelial cells, and this ability was related to agglutination and protective activity in infant mice. The results demonstrate that (1) the reduction in adsorption of V. cholerae to epithelial cells correlates with the degree of agglutination for given antibody preparation; (2) intact tantibodies protect infant mice from cholera only at concentrations that agglutinate the bacteria; and (3) purified antibodies to flagellar antigens protect infant mice from cholera. These results indicate that cross-linking of bacteria by antibody causes a reduction in the number of organisms adsorbed to the intestinal wall. Thus antibody cross-linking plays an important role in immunity to cholera in infant mice.


Relationship between the transport and toxicity of cephalosporins in the kidney.

Large doses of cephaloridine cause acute necrosis of the proximal renal tubule that can be prevented by probenecid and other organic anions. Although there is little or no net secretion of cephaloridine by the mammalian kidney, the degree of cephaloridine uptake by the cortex of the rabbit kidney is substantial; this uptake is also prevented by probenecid and other organic anions. Cortical concentrations of cephaloridine were measured in control and probenecid-treated animals of different mammalian species. Evidence of cephaloridine trnsport was found in the guinea pig  and the rat as well as in the rabbit. The degree of reduction of cortex-to-serum ratios by probenecid (control cortex-to-serum minus probenecid-treated cortex-to-serum ratios) correlated with the sensitivity to the nephrotoxicity of the drug. This degree or reduction was greatest in the rabbit, intermediate in the guinea pig, and least in the rat. In addition, the newborn rabbit, which is more resistant to the toxicity of cephaloridine than the adult, also had significantly lower cortical concentrations of cephaloridine. Finally, the acute tubular necrosis produced by extremely large doses of cefazolin in the adult rabbit was prevented by probenecid. It was concluded (1) that the nephrotoxicity of cephaloridine is related to its renal cortical transport with high intracellular concentrations of drug; and (2) that this relationship between transport and toxicity exists for cefazolin as well, although the toxicity is of a different order of magnitude. The unusual mechanism of cephaloridine transport in the proximal tubule was contrasted with that of the other cephalosporins in an attempt to explain its greater degree of nephrotoxicity.


Therapy of murine rabies after exposure: efficacy of polyriboinosinic-polyribocytidylic acid alone and in combination with three rabies vaccines.

A murine model simulating human street rabies virus infection was used to evaluate the efficacy of polyriboinosinic-polyribocytidylic acid (poly I-poly C), three rabies vaccines, and combinations of these modes of therapy administered after exposure. One or two doses of 100 mug of poly I-poly C, injected into the same intramuscular site as the challenge virus, significantly reduced the mortality rate when therapy was initiated 3 hr after challenge; however, the same quantity of poly I-poly C injected into the opposite leg did not reduce the mortality rate. The muscle injected with poly I-poly C invariably contained four to eight times more interferon than a similar noninjected muscle from the same animal. Mice treated 3 hr after challenge with each of the three vaccines produced significant levels of antibody but were not protected, whereas treatment with combinations of poly I-poly C and vaccine resulted in significant protection. These results suggest that the combination of induction of local interferon and an immune response contributes to the protection of mice after exposure to street rabies virus infection.


Cutaneous sensitivity and in vitro responsiveness of lymphocytes in patients with disseminated coccidioidomycosis.

Sixty-eight of 74 patients with disseminated coccidioidomycosis demonstrated cutaneous reactivity to intradermal injectionof coccidioidin. Lymphocytes of all patients with positive skin test results underwent blast transformation in vitro in response to coccidioidin. No correlation was found between the size of skin test induration and the magnitude of in vitro lymphocyte response. Six patients with disseminated disease failed to demonstrate cutaneous reactivity to coccidioidin; however, lymphocytes of three of these patients responded with blast transformation in vitro. The lymphocyte reactivity of two of these three patients was abrogated by addition of autologous plasma to the culture medium. Autologous plasma did not block the patient's in vitro response to phytohemagglutinin or allogeneic lymphocytes, and blocking did not appear to be attributable to direct neutralization of coccidioidin.


Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus.

Children immunized with inactivated (Tween 80 and diethyl ether, TE) measles vaccine, attenuated live vaccine, or a combination of the two types were studied with regard to the production of hemagglutination-inhibiting (HAI), hemolysis-inhibiting (HLI), and nucleocapsid complement-fixing (CF) antibodies. For identification of antibodies to envelope components distinct from hemagglutinin. HLI tests were done both before and after removal of HAI antibodies with TE-treated virus antigen. Immunization with three or four doses of TE vaccine led to the production of HAI antibodies and, in some cases, of nucleocapsid CF antibodies. Non-HAI HLI antibodies were not detected. In contrast, live vaccine caused the appearance of non-HAI HLI antibodies and, in the majority of cases, nucleocapsid CF antibodies. After combined immunization with TE vaccine and attenuated vaccine, non-HAI HLI antibodies were absent from 25 of 29 children. Most children exposed to wild measles virus after immunization with TE vaccine alone developed a poorer non-HAI HLI antibody response than children who had had normal measles. The latter infections resulted in a more pronounced non-HAI HLI and nucleocapsid CF antibody response than that observed after infections with vaccine virus. An even more accentuated response involving these antibodies was seen in patients with subacute sclerosing panencephalitis. Thus the failure of inactivated measles vaccines to prevent infection may be due to the absence of an envelope component responsible for the production of non-HAI HLI antibodies.


Gentamicin sulfate pharmacokinetics: lower levels of gentamicin in blood during fever.

The effect of fever on serum concentrations and urinary excretion of gentamicin sulfate was studied in humans and dogs. Endotoxin-induced fever in dogs resulted in a decrease of approximately 25% in levels of gentamicin in serum 30 and 60 min after intravenous injection of the antibiotic (1.5 mg/kg) when compared with corresponding afebrile values. In six volunteers with etiocholanolone-stimulated fever, serum concentrations of gentamicin was reduced by an average of 40% in all measurements made 1.2, and 3 hr after intramuscular injection (1.5 mg/kg) as compared with afebrile control values in the same subject. Fever was thought to be the principal factor associated with lower levels of gentamicin, although the half-life of gentamicin in serum and renal clearance of the antibiotic were not significantly affected. These findings emphasize the need for frequent measurements of gentamicin in serum as a guide to adjustment of gentamicin treatment in febrile subjects, and perhaps in all patients receiving the antibiotic.


Antimicrobial therapy of experimental intraabdominal sepsis.

Septic complications of colonic perforation involve miltiple bacteria derived from the intestinal flora. This type of mixed intraabdominal infection was produced experimentally by insertion of a standardized inoculum of rat colonic contents into the  peritoneal cavity of male Wistar rats. The respective roles of coliforms and anerobic bacteria were then studied by use of selective antimicrobial therapy (with gentamicin and clindamycin). Untreated rats had a two-stage disease. Initally, there was an acute peritonitis associated with a 37% mortality rate; all animals that survived developed indolent intraabdominal abscesses. Treatment with gentamicin reduced the acute mortality rate to 4%, but 98% of the survivors had abscesses. Clindamycin acute mortalherapy was associated with a 35% mortality rate, but the incidence of intraabdominal abscess was only 5%. A combination of gentamicin and clindamycin yielded the salutary effects of each agent--7% mortality and 6% incidence of abscesses. These studies, in concert with bacteriological findings, suggest that coliforms caused early mortality while anaerobes were primarily responsible for the late complication of intraabdominal abscess formation.


Coxsackievirus B5 infections in acute oliguric renal failure.

Six patients with acute oliguric renal failure were studied for detection of acute viral or mycoplasma infection. Precipitating causes, such as streptococcal infection, use of nephrotoxic drugs, etc., were ruled out. Tests for neurtralization and complement fixation antibodies, in which 19 viral and mycoplasma agents were used as antigens, demonstrated a recent coxsachievirus B5 infection in five of six patients. Rises in titer to other antigens tested were not noted. A group of control patients showed no significant rises in titer of antibody to coxsackievirus B5. These studies strongly suggest that an association exists between coxsackievirus B5 infections and acute oliguric renal failure. Whether this association is etiologic is not known.


Bacteremia at Boston City Hospital: Occurrence and mortality during 12 selected years (1935-1972), with special reference to hospital-acquired cases.

The cases of all patients hospitalized at Boston City Hospital during 1972 who had blood cultures positive for a clinically significant, aerobic bacterial pathogen or for Candida were analyzed with respect to incidence and mortality, sex, age, admission to medical or surgical services, and the causative organism. Similar data were obtained for 11 years between 1935 and 1969 selected to reflect the introduction and general use of various effective antibacterial agents. Comparisons were also made between hospital-acquired bacteremic infections (defined as those in which the first positive blood culture was obtained on or after the third day in the hospital) and community-acquired infections (defined as those with positive blood cultures on admission or within the first two days in the hospital). In 1972, the incidence of bacteremic infections (but not the case-fatality ratio) was significantly higher in males than in females. Bacteremic infections were more than twice as frequent on the medical than on the surgical services, but the case-fatality ratio was slightly but not significantly higher on the surgical services. Bacteremia wasteremia was most frequent in the youngest (birth through nine years) and the oldest (greater than or equal to 60 years) age groups, whereas the case-fatality ratio was lowest in the youngest group and increased with each decade of life. Streptococcus pneumoniae was the most frequent organism causing bacteremia; next were Escherichia coli, Klebsiella-Enterobacter, and Staphylococcus aureus, in that order...


Trans-chest ventricular defibrillation of heavy subjects using trapezoidal current waveforms.

Effectiveness of four truncated exponential waveform defibrillators for transchest ventricular defibrillation was evaluated in 27 human-sized animals. With all waveforms, effectiveness was virtually 100% for small subjects, but decreased as body weight increased. These data confirm the electrical dose concept for ventricular defibrillation and demonstrate that the truncated exponential waveform is effective only when adequate current is delivered through the subject's chest.


Overdrive suppression in diagnosis of sick sinus syndrome.

A criterion to determine the indication for pacemaker implantation in the sick sinus syndrome by overdrive suppression is proposed. Overdrive suppression was performed in 10 patients with the sick sinus syndrome (SSS) and another 10 patients with normal sinus rhythm (NSR) who served as controls. In the SSS group, 9 patients had complained of such severe symptoms as Adams-Stokes attack and/or congestive failure and were referred to our laboratory for pacemaker implantation. One other patient, an apparently robust young man (20 years old) referred for detailed cardiac examination, had no remarkable symptoms except for arrhythmias, but was found dead two months later. Atrial pacing for overdrive suppression was carried out at first at various rates ranging from 60 to 180 beats/min for 15 sec, and then at a rate of 100 beats/min for various durations ranging from 5 to 180 sec. After cessation of the atrial pacing, asystolic pauses were measured and the maximum (maximum pause) among the pauses obtained was used as a parameter indicating depression of cardiac automaticity. The maximum pause in the SSS group ranged from 5.6 to 9.0 sec (mean +/- SD = 7.0 +/- 1.2), WHILE THOSE IN THE NSR group ranged from 0.7 to 1.5 sec (mean +/- SD = 1.2 +/- 0.14). Therefore, the maximum pause was considered not only to reflect the severity of the symptoms necessitating pacemaker implantation in the 9 patients of the SSS group but to have warned us of sudder death in another patient. We concluded that overdrive suppression is useful as a supplementary challenge to determine indications for pacemaker implantation for the sick sinus syndrome, and that prolongation of the maximum pause beyond 5.0 sec is the critical level for pacemaker implantation.


The electrocardiogram of burros.

Electrocardiograms of two burros are presented. Compared to those seen in humans, amplitudes were lower, especially in lead I, and marked prolongations were observed in P-Q and Q-T intervals. The QRS axes were craniad.


Electrocardiographic studies in the stumptail macaque (Macaca arctoides).

Our study has defined normal electrocardiographic standards for Macaca arctoides. It appears that certain species differences exist in the electrocardiogram (ECG) in monkeys and that different criteria for normality may be necessary. Thus, in apparently normal Macaca arctoides a high frequency of Q waves and ST segment elevations of the J point type are present compared to Macaca mulatta. It is suggested that normal ECG criteria be established for each species of monkeys to allow accurate interpretation.


A device for producing high frequency electrocardiograms on a conventional direct writing electrocardiograph.

A device has been developed which can be used in conjunction with a direct-writing electrocardiograph to record the high frequency electrocardiogram (ECG) including notches and slurs in the waveform. The device operates on the principle of temporarily storing the QRS complex and then reproducing it at a rate 10 times slower than real time. Increasing the ratio to 80 to 1 permits registration of pulse artifacts from implanted cardiac pacemakers.


His bundle electrogram in congenitally corrected transposition of the great vessels.

His bundle electrogram was recorded in a young adult male with corrected transposition of the great vessels and single ventricle. Prolonged PA and AH intervals, wide diphasic His spike, and normal HV intervals were found. These findings are suggestive of the diffuse nature of conduction delay in this congenital lesion involving intra-atrial, AV nodal, and intra-His regions.


Transient ST segment elevation occurring without anginal pain. Correlations with Prinzmetal's angina.

Two cases presenting with episodes of marked ST segment elevation occurring with, but most often without, anginal pain are reported. The changes were recorded through continuous ECG monitoring during Prinzmetal's angina and in the course of myocardial infarction. Such transient asymptomatic ECG abnormalities reveal silent acute myocardial ischemia and are often unrecognized. However, they may lead to severe arrhythmias or myocardial infarction, and sudden deaths occurring in the course of ischemic heart disease are likely to be explained on this basis. Transient episodes of silent ST segment elevation similar to those occurring in Prinztal's angina have been reported in various circumstances. They bring into discussion the delimitations of variant angina pectoris.


Sinus and A-V nodal dysfunction following myocardial infarction.

A patient in whom syncopal episodes occurred following an inferior myocardial infarction is described. Electrocardiographic monitoring revealed periods of profound sinus bradycardia and AV block during syncope. In addition, transient spontaneous prolongations of the PR interval due to AV nodal delay and episodes of atrial fibrillation also occurred. Sinus node recovery time following atrial overdrive was within normal limits. Symptoms disappeared following the insertion of a permanent, demand pacemaker. The onset of symptoms following myocardial infarction suggests that dysfunction of the sino-atrial and AV nodes may have been the result of ischemic damage during the infarction.


Pacing techniques in the management of supraventricular tachycardias. Part 1. The use of high frequency stimulation (HFS) in the management of paroxysmal supraventricular tachycardia.

Using techniques for programmed electrical stimulation of the heart, seven patients with paroxysmal supraventricular tachycardia have been studied and shown to have a reciprocal mechanism as the most likely basis for the tachycardia. In four patients it was found that the tachycardia could be terminated by single right atrial premature beats and in three patients two right atrial premature beats were required. A variable zone for tachycardia termination was found when single or double stimuli were used and so a system for introducing high frequency stimuli at 100 or 1000 stimuli/sec for a given duration is described. Using this system a wider range of the cardiac cycle could be covered, thereby increasing the likelihood of producing correctly timed premature beats. The results of using this system are presented and its practical usage discussed.


Patterns of activity in the antennular motoneurones of the hermit crab Pagurus alaskensis (Benedict).

1. Using electromyogram recordings from the antennular muscles of intact animals and recordings from the antennular nerves of partially dissected preparations, the patterns of activity in specific antennular motoneurones have been described during antennular flicking and antennular withdrawal. 2. The slow extensor motoneurone A30S is active during flicking in addition to the phasic component of the antennular motor system (A30F, A31F and A32F). 3. The flexion phase of a flick is the result of a burst of variable duration and number of spikes within flexor motoneurones A31F and A32F. 4. The extension phase of a flick is the result of a burst of variable duration and number of spikes in extensor motoneurones A30F and A30S. 5. Extension-withdrawal and slow flexion-withdrawal reflexes, tonic flexion withdrawal and maintained flexion at the MS-DS joint usually result from activity in part of the tonic component of the antennular motor system:moto-neurones A30S, A31S and A32S. 6. Fast flexion-withdrawal reflexes result from a burst of spikes in motoneurone A31F-S which constitutes the phaso-tonic component of the antennular motor system. 7. During high-frequency activity (15-60/sec), reciprocity exists between the slow flexor motoneurones A31S and A32S and slow extensor motoneurone A30S.


The effect of progressive hypoxia on respiration in the dogfish (scyliorhinus canicula) at different seasonal temperatures.

1. Dogfish were acclimated to 7, 12 or 17 degrees C and exposed to progressive hypoxia at the temperature to which they had been acclimated. During normoxia, the Q10 values for oxygen uptake, heart rate, cardiac output and respiratory frequency over the full 10 degrees C range were: 2.1, 2.1, 2.1 and 2.5 respectively. Increased acclimation temperature had no effect on cardiac stroke volume or systemic vascular resistance, although there was a decrease in branchial vascular resistance, pHa and pHv. 2. Progressive hypoxia had no effect on heart rate or oxygen uptake at 7 degrees C, whereas at 12 degrees C and 17 degrees C there was bradycardia, and a reduction in O2 uptake, with the critical oxygen tension for both variables being higher at the higher temperature. Cardiac stroke volume increased during hypoxia at each temperature, such that cardiac output did not change significantly at 12 and 17 degrees C. Neither pHa nor pHv changed significantly during hypoxia at any of the three temperatures. 3. The influence of acclimation temperatures on experimental results from poikilotherms is pointed out. Previously-published results show quantitative differences. 4. The significance of the present results with respect to the functioning and location of oxygen receptors is discussed. It is argued that as the metabolic demand and critical oxygen tension of the whole animal are increased at high acclimation temperatures the same must be the case with the oxygen receptor. This would raise the stimulation threshold and could account for the bradycardia seen during hypoxia becoming manifest at higher values of PI,O2, Pa,O2 and Pv,O2 as the acclimation temperature is raised.


The effect of caffeine on calcium efflux and calcium translocation in skeletal and visceral muscle.

1. KCl-induced depolarization resulted in a large stimulation of the 45Ca efflux from both cockroach skeletal muscle and rat ileal smooth muscle. 2. Caffeine (10 mM) induced a large stimulation of 45Ca efflux from skeletal muscle, but a fall in the efflux from ileal muscle, especially if the efflux was previously stimulated by KCl depolarization. 3. Caffeine inhibited calcium uptake by skeletal muscle mitochondria and sarcoplasmic reticulum, was without effect on ileal muscle mitochondria, but significantly increased caclium binding by ileal muscle membrane vesicular preparations. 4. The induction of contractures and stimulation of 45Ca efflux in skeletal muscle by caffeine are clearly related to inhibition of intracellular calcium binding by the sarcoplasmic reticulum and mitochondria. 5. The relaxation of ileal muscle by caffeine and the inhibition of fibre calcium efflux correlate well with caffeine enhancement of intracellular calcium binding. These experiments suggest that the membrane vesicular compartment may be the main agency centrally involved in fibre calcium regulation in this muscle during the contraction-relaxation cycle.


Hormonal control of integumentary water-loss: evidence for a novel neuroendocrine system in an insect (Periplaneta americana).

An accelerated water-loss was observed in decapitated individuals, no equivalent increase being obtained following severance of the nervous connectives in the neck. Injection of brain and, to a lesser extent, corpus cardiacum extract resulted in a significant reduction in the rate of loss of water from decapitated individuals. The accelerated water-loss observed following decapitation appeared not to result from significant increase in excretory output or loss of water through the spiracles. It is suggested that integumentary transpiration may be affected by a blood-borne factor, or factors, which originate in the brain and corpus cardiacum.


Peripheral specialization for fine analysis of doppler-shifted echoes in the auditory system of the "CF-FM" bat Pteronotus parnellii.

Pteronotus parnellii uses the second harmonic (61-62 kHz) of the CF component in its orientation sounds for Doppler-shift compensation. The bat's inner ear is mechanically specialized for fine analysis of sounds at about 61-62 kHz. Because of this specialization, cochlear microphonics (CM) evoked by 61-62 kHz tone bursts exhibit prominent transients, slow increase and decrease in amplitude at the onset and cessation of these stimuli. CM-responses to 60-61 kHz tone bursts show a prominent input-output non-linearity and transients. Accordingly, a summated response of primary auditory neurones (N1) appears not only at the onset of the stimuli, but also at the cessation. N1-off is sharply tuned at 60-61 kHz, while N1-on is tuned at 63-64 kHz, which is 2 kHz higher than the best frequency of the auditory system because of the envelope-distortion originating from sharp mechanical tuning. Single peripheral neurones sensitive to 61-62 kHz sounds have an unusually sharp tuning curve and show phase-locked responses to beats of up to 3 kHz. Information about the frequencies of Doppler-shifted echoes is thus coded by a set of sharply tuned neurones and also discharges phase-locked to beats. Neurones with a best frequency between 55 and 64 kHz show not only tonic on-responses but also off-responses which are apparently related to the mechanical off-transient occuring in the inner ear and not to a rebound from neural inhibition.


Central patterning and reflex control of antennular flicking in the hermit crab Pagurus alaskensis (Benedict).

1. The effects of altering sensory input on the motoneuronal activity underlying antennular flicking have been tested. 2. Removal of the short segments of the outer flagellum results in a reduction of the number of spikes/burst in the fast flexor motoneurones A31F and A32F. 3. During a flick the delay between the burst in motoneurone A31F and the burst in motoneurone A32F is insensitive to alteration of sensory input. 4. Sensory feedback from the flexion phase of a flick is necessary for the activation of either extensor motoneurone. Evidence is presented to suggest that this feedback is primarily from joint-movement receptors at the MS-DS and DS-OF joints. 5. The results are incorporated into a model in which the patterns of flexor activity result from some specified properties of three components: a trigger system, a follower system, and the spike initiating zone of the flexor motoneurones. The trigger system determines when a flick will occur. The follower system determines the number of flexor spikes during a flick. Properties of the spike initiating zone determine the spike frequency and the timing between bursts in the flexor motoneurones. Extensor activity in the model is reflexively elicited by feedback from phasic, unidirectional receptors sensitive to joint flexion. 6. The functional significance of reflex control of extensor activity is discussed in relation to the form and proposed function of antennular flicking. It is suggested that this form of control is adapted to the function of antennular flicking because flexion at the MS-DS joint is not always necessary for the fulfilment of the fuction of a flick.


Oxygen consumption, ventilatory frequency and heart rate of lampreys (Lampetra fluviatilis) during their spawning run.

1. The standard rate of oxygen consumption, ventilatory frequency and heart rate of adult Lampetra fluviatilis were measured during the light phase of the photoperiod and at times corresponding to various stages in the upstream migration. 2. All three parameters increased during the spawning run but only in mature individuals were significant differences found between the sexes. 3. The regression coefficients for the logarithmic relationship between oxygen consumption and body weight of immature animals were 0.912 and 0.925 at 9.5 and 16 degrees C respectively. 4. Both the standard rate of oxygen consumption and the amount of oxygen taken up during activity increased greatly during the hours of darkness. 5. Oxygen consumption, ventilatory frequency and, to a lesser extent, heart rate increased significantly at 9.5 degrees C over the 100-20% range of saturation with air. 6. Below 20% saturation with air, lampreys no longer remained attached by their oral disc for prolonged periods and the ventilatory frequency rose even more rapidly to reach a maximum of 175 beats/min at 12.5%. Exposure to 7.5% resulted in death within 5-8 h.


A technique for repeated sampling of the blood of individual resting fish.

A dorsal cannulation technique is described. It has been employed for repeated blood sampling in unanaesthetized rainbow trout (Salmo gairdneri) kept singly in special receptacles described in the paper. The level of the studied haematological parameters (Haematocrit, Hb, glucose, lactate, K+, Na+, Ca2+) differed between fish kept in receptacles for 1 week and free-swimming fish, most probably owing to differences in the motility of the fish. The receptacle seems to minimize visual and handling disturbances, and permits both the standardization of experimental conditions and quick and easy sampling via the dorsal aorta cannula. The general variation in the blood parameter values was very small compared with the previously reported variation in such values for rainbow trout.


Patterns and bilateral coordination of scaphognathite rhythms in the lobster Homarus americanus.

The bilateral patterns of forward and reversed scaphognathite (SG) pumping are described for the American lobster. During forward pumping the two SGs usually function synchronously, but may also function independently. The nine muscles of one SG are arranged into four functional groups which are sequentially active during forward pumping. During reversed beats, motor neurones to one group of muscles are inactive while bursts to another are either delayed or missing. Reversal beats do not appear to alter the phasing of the central oscillators that generate the basic SG rhythm. Phase analysis of bilateral SG beating demonstrates two types of relationship: phase coupling or phase drifting with a tendency to couple. An animal may remain in one state for long periods of time or may alternate between states. Coupling can occur at more than one phase indicating phase multistability. The coupled state may remain constant at markedly different frequencies of beating, indicating phase rather than latency coupling between SGs. During the drifting state each SG tends to assume its "intrinsic" rate of oscillation. The drift state reflects the inherent asymmetry of the two SG systems. The influence of several parameters of sensory stimulation on phase and frequency of SG beating are analyzed.


The removal of sulphate by the excretory apparatus of the blowfly Calliphora vomitoria.

The excretion of sulphate by the isolated Malpighian tubules of Calliphora vomitoria has been investigated. Contrary to expectation, it was found that the isolated tubules are freely permeable to sulphate. The rate of sulphate secretion is comparable to the rates of secretion of both phosphate and chloride. The excretion of sulphate by the intact fly has also been verified.


Micropuncture study of the renal responses of the urodele amphibian Necturus maculosus to injections of arginine vasotocin and an anti-aldosterone compound.

1. Necturus maculosus kidney function has been examined using standard clearance techniques and renal tubular micropuncture methodology. 2. Throughout, cyanocobalamin (vitamin B12) has been used to monitor glomerular filtration rate (GFR) and tubular water movements. It was established that this substance was handled by the Necturus kidney in a similar manner to inulin. It can be readily analysed, together with renal electrolytes, by electron microprobe techniques. 3. Profiles of transtubular gradients (TF:P ratios) along the nephron were established for osmolarity, sodium, potassium, calcium and cobalt (of cyanocobalamin). 4. Ureteral urine is always hyposmotic with respect to plasma and the site of dilution of the plasma ultrafiltrate is within the distal segment. 5. Up to 30% of the filtrate is isosmotically reabsorbed along the proximal tubule; the tubular fluid:plasma ratio for osmolarity and sodium is around 1, and the TF:P for cobalt of cyanocobalamin is about 1.4 by the end of this segment. 6. The renal effects of the neurohypophysial hormone arginine vasotocin (AVT) and an aldosterone antagonist (SC14266; Soldactone) have been examined. 7. AVT was consistently antidiuretic causing both a decreased GFR and an enhanced distal tubular reabsorption of water. 8. SC14266 also increased distal tubular reabsorption of water. Such an effect differs from that found in higher vertebrates, and may indicate a "glucocorticoid-type" of renal action for aldosterone in amphibians.


Central control of feeding in the diapausing adult blowfly Phormia regina.

1. The tarsal acceptance threshold of non-diapausing adult blowflies rises with age. 2. Diapausing flies have a non-significantly elevated tarsal acceptance threshold, but drink significantly less sucrose solution than their non-diapausing counterparts. 3. Removal of diapausing flies to non-diapause inducing conditions resulted in a lowering of the threshold. 4. Failure to demonstrate a significant difference between the input signal from the peripheral receptors of non-diapausing and diapausing flies showed that the inhibition of feeding in diapausing flies was not due to peripheral inhibition but was controlled centrally.


Metabolism during flight in two species of bats, Phyllostomus hastatus and Pteropus gouldii.

The energetic cost of flight in a wind-tunnel was measured at various combinations of speed and flight angle from two species of bats whose body masses differ by almost an order of magnitude. The highest mean metabolic rate per unit body mass measured from P. hastatus (mean body mass, 0.093 kg) was 130.4 Wkg-1, and that for P. gouldii (mean body mass, 0.78 kg) was 69.6 Wkg-1. These highest metabolic rates, recorded from flying bats, are essentially the same as those predicted for flying birds of the same body masses, but are from 2.5 to 3.0 times greater than the highest metabolic rates of which similar-size exercising terrestrial mammals appear capable. The lowest mean rate of energy utilization per unit body mass P. hastatus required to sustain level flight was 94.2 Wkg-1 and that for P. gouldii was 53.4 Wkg-1. These data from flying bats together with comparable data for flying birds all fall along a straight line when plotted on double logarithmic coordinates as a function of body mass. Such data show that even the lowest metabolic requirements of bats and birds during level flight are about twice the highest metabolic capabilities of similar-size terrestrial mammals. Flying bats share with flying birds the ability to move substantially greater distance per unit energy consumed than walking or running mammals. Calculations show that P. hastatus requires only one-sixth the energy to cover a given distance as does the same-size terrestrial mammal, while P. gouldii requires one-fourth the energy of the same-size terrestrial mammal. An empirically derived equation is presented which enables one to make estimates of the metabolic rates of bats and birds during level flight in nature from body mass data alone. Metabolic data obtained in this study are compared with predictions calculated from an avian flight theory.


Potassium exchange between bathing solution and midgut of Hyalophora cecropia and time delay for potassium flux through the midgut.

Exchange between potassium of the isolated midgut of the American silkworm Hyalophora cecropia and the bathing solutions has been determined by different authors, but with contradictory results. Therefore the experiments were repeated with another technique and the exchange determined for varying time intervals. It was found that the exchange was fast-half of the midgut K was exchanged in 2-3 minutes, which confirms the earlier findings by Harvey & Zerahn (1969).


Neurohormonal alteration of integrative properties of the cardiac ganglion of the lobster Homarus americanus.

The spontaneous burst discharges of isolated lobster (Homarus americanus) cardiac ganglia were recorded with a spaced array of electrodes. Small regions (less than 1 mm) of the ganglion were exposed to the cardioexcitor neurohormone in extracts of pericardial organs (XPO) or to 10(-5) M 5-hydroxytryptamine (5HT). All axons were excited (increased mean firing frequency, f) by both substances, but only by applications in the region between the soma (but excluding it) and proximal site of impulse initiation. Units not so exposed changed their f relatively little despite f increases of as much as threefold in exposed units and changes in burst rate and overall length. Regularity and grouping of all impulse activity into bursts was never disturbed. 5HT increases burst rate at any point of application. The increases are larger if small cells are affected than if only large cells are exposed. Burst length decreases except when the pacemaker is affected. In contrast, XPO affects neither burst rate or length unless small cells are affected. Length is increased if non-pacemaker small cells are affected; both rate and length increase if the pacemaker is affected. The pacemaker usually exhibits an f of intermediate value. Rate changes are not simply related to its f. A small cell can "burst" in the absence of impulses from any other cells. XPO may enhance endogenous "driver potentials," while 5HT may excite by depolarizing at limited sites.


The energetics of the jump of the locust Schistocerca gregaria.

The anatomy of the metathoracic leg is redescribed with particular reference to storage of energy in cuticular elements and the way in which the stored energy is used in jumping. The jump of adult male locusts requires an energy of 9 mJ and that of the female requires 11 mJ. The semilunar processes of each metafemur store 4 mJ at a stress of 15 N, and the extensor tibiae apodeme stores a further 3 mJ at the same stress. The total stored energy in both metathoracic legs is 14 mJ. The extensor tibiae muscle produces a maximum isometric force of over 15 N at 30 degrees C and, when loaded with the extensor apodeme and semilunar processes, attains this force in 0.3 sec with a strain of 0.8 mm. The peak power output is 36 mW or 0.45 W.g-1. The peak isometric force is attained when the tibia is fully flexed and the force falls as the tibia extends. The extensor tibiae muscle A band is 5.5 mum long and the peak force is over 0.75 N.m-2. The peak velocity of shortening is 7 mm.sec-1 or about 1.75 lengths/sec at 30 degrees C. The tensile strength of the extensor apodeme is 0.6 kN.mm-2 and Young's modulus is 19 kN.mm-2. The safety factor does not exceed 1.2 and the safety factor of the semilunar processes and tibial cuticle is little higher. The jump impulse lasts 25-30 msec. A velocity of 3.2 m.sec-1 is reached after a peak acceleration of 180 m.sec-2. The peak power output is 0.75 W at close to maximum velocity. Energy losses in rotating the femur and tibia are small and it is shown that the leg is able to extend at 7 times the normal rate with losses of about 20%. Most of the stored energy is converted to kinetic energy as the animal jumps. A model is based on the relaxation of a spring that has the properties of the elastic elements of the locust leg into a lever with the same kinematics as the locust leg produces a force-distance curve similar to that measured for locust jumps. The major part of the jump energy is stored before the jump.


Electrophysiological analysis of potassium and sodium movements in crustacean nervous system.

1. An electrophysiological method was used to estimate the half-times for sodium and potassium entry to, and efflux from, the extra-axonal space in peripheral nerve and central nervous connectives of two species of crustacean. Results from crab (marine) and crayfish (fresh water) were qualitatively similar. 2. Peripheral nerve showed no evidence for diffusion barriers, potassium entry and efflux being rapid, and proceeding at comparable rates. 3. In connective, potassium entry was extremely slow, with a half-time greater than 100 min, while potassium efflux was relatively rapid (T 1/2 = 6 min). Sodium movements were less restricted, but sodium entry was more rapid than sodium efflux. 4. The potassium experiments were compared with the behaviour of a theoretical model system. Evidence is presented for diffusional restriction to potassium at the connective perineurial layer. The mechanism of restriction may involve changes in permeability or activation of an ion pump in the perineurial layer. 5. The physiological significance of these findings is discussed.


Annoyance, type and duration of postannoyance activity, and aggression: the "cathartic effect".

A series of experiments was conducted to elucidate the conditions conductive to a decrease in aggression following annoyance.  The potential capacity of expression of aggression to bring about a reduction in the amount of subsequent aggression was of particular interest. This empirical concern was supplemented by tests of several influential and competing theoretical concepts dealing with the cathartic aspects of human aggressive behavior.  Given the failure of such concepts to account for major portions of the data, an integrative theoretical model was proposed.  experiment 1 evaluated the usefulness of the hydraulic, self-arousal, and dissipation of anger concepts in accounting for the earlier demonstrations of the cathartic effect.  In a 2 x 3 x 2 design, half of the subjects were annoyed by a confederate, while the other half were treated neutrally.  During the next stage (the interpolated period), a third of all subjects gave "shocks" to the confederate, another third simply waited, while the remaining third worked on mathematical problems.  Orthogonal to the first two facotrs was the duration of the interpolated period (7 to 13 min).  The main dependent measure was the number of shocks administered to the confederate in the final stage of the experiment.  It was found that annoyed subjects gave more shocks than nonannoyed ones did, and that only the former were substantially affected by other manipulations.  In the case of the annoyed wait and annoyed math subjects, the anger dissipation hypothesis correctly predicted that the mere passage of time would decrease the amount of subsequent aggression, presumably due to the action of homeostatic processes.  The self-arousal hypothesis correctly predicted that the annoyed math subjects would give fewer shocks than the annoyed wait ones would.  Since the subjects were engaged in an absorbing activity, the likelihood of their arousing themselves by ruminations about the preceding annoying incident was minimized, and the amount of subsequent aggression reduced.  Yet, when annoyed subjects had given the confederate a moderate number of shocks in the interpolated period, they subsequently gave him fewer shocks than the 7-min annoyed wait and annoyed math subjects; this was the only outcome predicted correctly by the hydraulic model.  In contrast, when a large number of shocks had been administered in the interpolated period, the amount of subsequent aggression was relatively high.  The interpretation of the latter result in terms of an "adaption effect" was tested by further experiments.


Sizes of components in frog skeletal muscle measured by methods of stereology.

Stereological techniques of point and intersection counting were used to measure morphological parameters from light and electron micrographs of frog skeletal muscle. Results for sartorius muscle are as follows: myofibrils comprise 83% of fiber volume; their surface to volume ratio is 3.8 mum-1. Mitochondria comprise 1.6% of fiber volume. Transverse tubules comprise 0.32% of fiber volume, and their surface area per volume of fiber is 0.22 mum-1. Terminal cisternae of the sarcoplasmic reticulum comprise 4.1% of fiber volume; their surface area per volume of fiber is 0.54 mum-1. Longitudinal sarcoplasmic reticullum comprises 5.0% of fiber volume, and its surface area per volume of fiber is 1.48 mum-1. Longitudinal bridges between terminal cisternae on either side of a Z disk were observed infrequently; they make up only 0.035% of fiber volume and their surface area per volume of fiber is 0.009 mum-1. T-SR junction occurs over 67% of the surface of transverse tubules and over 27% of the surface of terminal cisternae. The surface to volume ratio of the caveolae is 48 mum-1; caveolae may increase the sarcolemmal surface area by 47%. Essentially the same results were obtained from semitendinosus fibers.


Magnitude and location of surface charges on Myxicola giant axons.

The effects of changes in the concentration of calcium in solutions bathing Myxicola giant axons on the voltage dependence of sodium and potassium conductance and on the instantaneous sodium and potassium current-voltage relations have been measured. The sodium conductance-voltage relation is shifted along the voltage axis by 13 mV in the hyperpolarizing direction for a fourfold decrease in calcium concentration. The potassium conductance-voltage relation is shifted only half as much as that for sodium. There is no effect on the shape of the sodium and potassium instantaneous current-voltage curves: the normal constant-field rectification of potassium currents is maintained and the normal linear relationship of sodium currents is maintained. Considering that shifts in conductances would reflect the presence of surface charges near the gating machinery and that shape changes of instantaneous current-voltage curves would reflect the presence of surface charges near the ionic pores, these results indicate a negative surface charge density of about 1 electronic charge per 120 A2 near the sodium gating machinery, about 1 e/300 A2 for the potassium gating machinery, and much less surface charge near the sodium or potassium pores. There may be some specific binding of calcium to these surface charges with an upper limit on the binding constant of about 0.2 M-1. The differences in surface charge density suggest a spatial separation for these four membrane components.


Avoidance response, house response, and wind responses of the sporangiophore of Phycomyces.

Avoidance response: An object placed 1 mm from the growing zone of a Phycomyces sporangiophore elicits a tropic response away from the object. The dependence of this response on the size of the object and its distance from the specimen is described, as well as measurements which exclude electric fields, electromagnetic radiation, temperature, and humidity as avoidance-mediating signals. This response is independent of the composition and surface properties of the object and of ambient light. House Response: A house of 0.5- to 10-cm diameter put over a sporangiophore elicits a transient growth response. Avoidance responses inside closed houses are slightly smaller than those in the open. Wind responses: A transverse wind elicits a tropic response into the wind, increasing with wind speed. A longitudinal wind, up or down, elicits a transient negative growth response to a step-up in wind speed, and vice versa. It is proposed that all of the effects listed involve wind sensing. This proposal is supported by measurements of aerodynamic effects of barriers and houses on random winds. The wind sensing is discussed in terms of the hypothesis that a gas is emitted by the growing zone (not water or any normal constituent of air), the concentration of which is modified by the winds and monitored by a chemical sensor. This model puts severe constraints on the physical properties of the gas.


Blockage of gallbladder tight junction cation-selective channels by 2,4,6-triaminopyrimidinium (TAP).

The organic cation 2,4,6-triaminopyrimidinium (TAP) specifically inhibits Na+ passive permeation (PNa) across gallbladder, small intestine, and choroid plexus without detectable effect on the Cl(-) permeability, indicating that Na+ and Cl(-) follow different permeation pathways. In bullfrog gallbladder, where it was examined in greater detail, the effect of TAP was shown to be: (a) completely reversible, (b) due only to the protonated form of 2,4,6-triaminopyrimidine, (c) effective when added to either one or both sides of the membrane (the rate limiting for the delay in the response being the diffusion through the unstirred layers), and (d) exhibiting a typical saturation kinetics, best fitted with the parameters "Km" = 2.6 mM and maximal effect = 100% inhibition. These data, along with the fact that the PNa blocking action of chemical analogs of TAP increases with their ability to donate protons to form hydrogen bonds, suggest that TAP blocks the cation permeation of the channels by strongly associating, via hydrogen bonds, with the anionic ligands within the channel.


Properties of visual cells in the lateral eye of Limulus in situ.

Excitatory properties of visual cells in the lateral eye of Limulus, investigated by optic nerve recordings in situ, differ significantly from the properties of cells in the classical, excised eye preparation. The differences suggest the possibility that two receptor mechanisms function in the eye in situ: one mechanism encodes low light intensities and the other responds to high intensities. The two mechanisms enable each ommatidium to respond over an intensity range of approximately 10 log units. This hypothesis was tested by measuring the increment threshold and the spectral sensitivity, by studying light and dark adaptation, and by analyzing the variability of the impulse discharge. Although the results do not conclusively identify two receptor mechanisms, they indicate that a process or a part of a process that functions in the eye in situ is abolished by excising the eye or cutting off its blood supply.


Semliki Forest virus intracellular RNA: properties of the multi-stranded RNA species and kinetics of positive and negative strand synthesis.

Three replicative forms of RNA (RF I, RF II, and RF III) have been isolated from BHK cells infected with Similiki Forest virus. Using analytical and rate-zonal sedimentation the mol. wt. of these replicative forms were estimated to be 8-5 times 10(6), 5-5 times 10(6) and 3-1 times 10(6) respectively. After continuous labelling from 1 to 6 h post-infection, RFI constituted more than 80% of the total replicative forms. Competition hybridization experiments showed that one strand of RFI was 42S RNA which had opposite (negative) polarity to that found in the virus particle. The positive strand of RFI was 42S RNA. The negative strand of replicative intermediate (RI) was also found to be 42S RNA. No evidence was found for an RI with a 26S negative strand. RFI was shown to contain non-hydrogen bounded poly A at or near the 3' end of the component 42S positive strand. Isolation and analysis of the poly A tract from RFI on an acrylamide gel showed it to be of essentially the same average size as the poly A tract from virus particle RNA. About 30% of the RI molecules contained non-hydrogen bonded poly A. No poly U was detected in either RFI or RI. The kinetics of positive and negative strand synthesis were investigated during virus multiplication. These experiments showed that the rate of negative strand synthesis reaches a maximum 2 1/2 post-infection and thereafter rapidly falls. The rate of positive strand synthesis increases rapidly up to 3 h post-infection and then remains constant for a further 3 to 4 h.


The impact of staff suicide on a psychiatric inpatient unit.

A staff nurse on a psychiatric inpatient unit committed suicide.  A retrospective study of patients and staff reactions was conducted.  It showed that the inpatients dealt openly and effectively with grieving.  Staff had a great deal of difficulty with the situation.  One of the nurse's outpatients required rehospitalization.  Recommendations for more attention to the staff mourning process were made.


Editorial: The right to know.  On the freedom of medical information.

Information about health and disease has high social value and is, thus, subject to a variety of controls. These influence the freedom of investigators to generate it; of editors and publishers to transmit it; and of professionals and the public to have access to it. Unconstrained research may threaten the social order and evoke legal or political limit setting. Prominent in the present era are the possibilities of dangerous ethical and biological consequences of new knowledge or, perhaps more important, of procedures for obtaining it. Medical information is transmitted through both the mass media and professional journals. Access to both by potential authors is limited by institutionalized mechanisms of social control and the academic-research subculture. An emerging factor is the editor's possible ethical responsibility for material which he accepts for publication. Access to information is determined by what finally is published, as well as membership in informal communication networks. It is also influenced by dependence, due to cost, time limitation and information overload, on prepackaged material presented in texts, anthologies, busy clinician-oriented journals, or commercial, e.g., pharmaceutical firms. The possibility that governments will, in time, become the major distributors as well as generators of medical information raises new questions as to its eventual freedom and control.


The nature of inhibition of cat brain mitochondrial monoamine oxidase by clorgyline.

In the cat brain the highest monoamine oxidase (MAO) activity is observed in the hypothalamus followed by hippocampus, caudate nucleus, pons and median cortex. Tyramine was the most actively deaminated substrate tested followed by dopamine. Clorgyline was more selective in its inhibitory action and could distinguish between tyramine and dopamine MAO deaminating system. The latter being more resistant to inhibition. The multiple forms of solubilized MAO as separated by polyacrylamide gel electrophoresis have varying phospholipid phosphorus content and sensitivity to inhibition by clorgyline in vitro and in vivo.


Failure of decreased serotonin uptake or monoamine oxidase inhibition to block the acceleration in brain 5-hydroxyindole synthesis that follows food consumption.

The acceleration in brain serotonin synthesis produced by injecting rats with tryptophan or allowing them to consume a carbohydrate diet was not blocked by the prior elevation of brain serotonin levels (by administration of a MAO inhibitor: Lilly 51641) or by a treatment (chlorimipramine administration) that decreases impulse flow along serotoninergic neurons.


Relationship between the preoptico hypophysial system and the vascular system in the teleost Rita rita (Ham.).

In Rita rita the internal carotid artery gives rise to hypothalamic and hypophysial arteries. The hypophysial artery directly enters the pituitary and largely contributes to the interface vasculature lying in between the neurohypophysis and the pars distalis which can be considered as an equivalent of the median eminence. Blood vessels from the interface vasculature enter the pars distalis. The hypothalamic artery gives rise to the primary capillary plexus in the infundibular floor and the portal vessels formed by it irrigate the glandular pituitary. Both, at the level of the hypothalamus and at the interface, neurosecretory material might get access to blood vessels. Thus, in Rita rita, not only the typical teleostean type of hypothalamo-hypophysial vascularization is present, but also an incipient tetrapodal pattern is evident.


The effects of protoveratrine and germines on the release of acetylcholine from the Auerbach plexus of the guinea-pig ileum.

The effect of protoveratrine A and germine-3-acetate (GMA) on the release mechanism of acetylcholine from the nerve terminals of the Auerbach plexus in the longitudinal muscle layer of the guinea-pig ileum was studied. Protoveratrine A, GMA and germine potentiated neuroeffector transmission in Auerbach's plexus in the longitudinal muscle preparation provided the neurons were stimulated at low frequencies (less than 10 Hz). Protoveratrine A and GMA enhanced the release of acetylcholine from the nerve terminals during the resting period and at low frequency of stimulation (less than 10 Hz). At continous stimulation with high frequency they were ineffective (greater than 10 Hz). When trains of 20 stimuli, with a pulse interval of 0.1 s (10 Hz) were repeatedly applied with intervals of 0.1 to 20 s between trains, the effect of GMA to increase ACh release depended on the length of the train interval; the longer the resting period between trains the higher was the output of ACh. This fact indicates that the release of ACh increased primarily during the resting periods following single stimuli or trains. The effect of GMA on ACh release proved to be highly temperature-dependent: in the presence of GMA Q10 increasing from 3.25 to 4.92. A high Ca concentration, removal of Mg or lowering of the Na concentration abolished the effect of GMA to enhance ACh release.


Evidence for endocytotic uptake of cobra neurotoxin in mouse skeletal muscle.

An isolated 3H-labelled neurotoxin from Naja naja siamensis binds irreversibly to the extensor digitorum longus muscle of the mouse in vitro. The binding consists of an adsorption to cholinergic receptors and of a slower temperature sensitive binding mechanism. The slow binding is markedly stimulated by the presence of cationic proteins (protamine, histone and polylysine) and is blocked at low temperature (+4 degrees C). Vinblastine and colchicine inhibit the stimulatory effect of protamine on the slow binding. Unlabelled neurotoxin blocks the adsorption binding but fails to affect the slow binding. The results suggest that the slow binding of neurotoxin is not associated with the presence of cholinergic receptors but is the result of endocytotic uptake into the muscle cell. Unless properly recognized this uptake will give a considerable overestimate of the number of cholinergic receptors present in the muscle.


On the synchronizing effect of amantadine-1-hydrochlorid (Symmetrel) on pathological EEG-activity.

The pathological EEG of a 60 years old lady who suffered from an organic mental syndrome with parkinsonian features, showed diffuse, slow asynchroneous activity. Administration of Symmetrel repeatedly and consistently caused a normalization of the EEG, while its discontinuation immediately led to the reappearance of the original desynchronized pattern. These EEG changes were not accompanied by any modifications in the patients' clinical condition. This discrepancy between the antiparkinsonian and the synchronizing effect of Symmetrel upon the EEG can be explained by a specific activity on the reticulo-thalamo-cortical pathways in addition to that upon the nigro-striatal tracts.


Trial of long-term anticoagulant therapy in the treatment of small stroke associated with a normal carotid arteriogram.

The clinical features of 49 patients who had sustained small strokes in the internal carotid artery territory, who were normotensive, free from cardiac or other relevant disease, and who each had a normal appropriate single vessel angiogram are presented. These were randomized into two groups: group A, 25 patients, who received only supportive treatment; group B, 24 patients who were treated with anticoagulants for an average period of 18 months. There was a reduced incidence of neurological episodes during the administration of anticoagulant therapy but, after treatment was discontinued, there was no significant difference between the two groups. In view of the relatively benign prognosis for this syndrome, unless special facilities exist for the personal control of anticoagulant treatment, the dangers may outweigh the benefits.


Cluster headaches associated with vascular malformations.

A vascular malformation was demonstrated in a migrainous female who had developed cluster headaches. The patient responded well to oral dihydroergotamine 1 mg twice daily.


Responses of isolated human basilar arteries to 5-hydroxytryptamine, noradrenaline, serum, platelets, and erythrocytes.

The isolated human basilar artery suspended in Kreb's solution contracts to 5-hydroxy-tryptamine, noradrenaline, and histamine, which stimulate specific receptors. Normal human serum contains an unidentified contractile substance, and erythrocytes relax the artery. Serum and erythrocytes potentiate 5-HT contractions. This preparation is suitable for studying vasoactive substances released during vasospasm after subarachnoid haemorrhage.


Effects of increased arterial pressure on blood flow in the damaged brain.

The effect of induced arterial hypertension on cerebral blood flow and intracranial pressure was measured before and after the production of a standard cryogenic brain lesion in 10 anaesthetized, ventilated baboons. Before injury the animals were divided into a group with intact autoregulation, having more than 20% increase in cerebrovascular resistance during arterial hypertension, and a group with impaired autoregulation, in which the change in cerebrovascular resistance was much less. The cryogenic injury produced a rapid rise in intracranial pressure and a reduction of cerebral blood flow in the affected hemisphere. Despite this, there was an increase in cerebrovascular resistance during arterial hypertension in all animals after brain injury, accompanied by a further significant rise in intracranial pressure. It is suggested that this response is unlikely to represent normal physiological autoregulation and caution should be exercised in interpreting it as such in the course of studies of cerebral blood flow in patients with acute brain damage.


Concentration gradients of monoamine metabolites in human cerebrospinal fluid.

The monamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), vanillylmandelic acid (VMA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were analysed in CSF from different regions of the CSF system to study the caudocranial concentration gradient of the metabolites. Four consecutive 10 ml fractions of CSF were withdrawn in 17 patients during the course of four minutes. The CSF pressure was monitored through a lumbar cannula because of suspected adult hydrocephalus. A pronounced gradient of the HVA concentration was found with a ratio between the last and the first fraction of 1,7. 5-HIAA showed a slight increase while HMPG and VMA showed no increase at higher levels of the CSF system. The results suggest that lumbar HVA reflects dopaminergic activity in the brain, whereas lumbar 5-HIAA and HMPG/VMA reflect the activity of 5-hydroxytryptamine and noradrenaline secreting neurones in both the brain and the spinal cord.


Single fibre electromyographic studies in myasthenia gravis with repetitive nerve stimulation.

A method is described for repetitive stimulation studies in myasthenia gravis using submaximal stimulation and single muscle fibre recording techniques. It was found that there were no impulse blockings due to neuromuscular transmission factors in normal subjects with 2 Hz stimulation, although there was a decrease or increase in the number of potentials which was caused by axonal stimulation factors. In myasthenia gravis a pathological picture was obtained, consisting of impulse blockings and facilitation at this rate in all of the eight patients studied, even those with only the ocular form of myasthenia and without surface decrement in the ADM. This technique allows study of both the minimally involved motor endplates and those with pronounced neuromuscular disturbances.


Analysis of electrical activity of normal muscle in man at different degrees of voluntary effort.

Electrical activity during voluntary effort was analysed in 33 normal subjects. Parameters of activity measured were number of peaks, mean amplitude, distribution of time intervals and of amplitudes between peaks. Recording from 10 sites evenly distributed over a muscle gave adequate representation of activity; force should be a fixed proportion of maximum rather than constant.


Metastatic carcinoma in a spinal meningioma.

Metastatic mammary carcinoma invaded a spinal meningioma.


Orthostatic hypotension associated with paroxysmal ventricular tachycardia.

Two patients (aged 46 and 49 years) are presented who gave a history of several years' duration of unsteadiness, dizziness, and syncopal attacks on standing. Both had orthostatic hypotension which was associated with the development of a unifocal paroxysmal ventricular tachycardia. There was no evidence of organic heart disease. In one of the patients the symptoms usually developed when standing after working in a crouched position. He responded to treatment with beta-adrenergic blockade. The other patient developed her symptoms on standing, after exercise or other stress. The paroxysmal ventricular tachycardia, which occurred in the upright position only, was accompanied by a marked rise in plasma adrenaline. In this patient one contributory factor was a low blood volume and she responded to plasma volume expansion. We wish to draw attention to the common neurological symptoms with which paroxysmal ventricular tachycardia may present. We suggest that paroxysmal ventricular tachycardia may result from ventricular sensitivity to circulating adrenaline and not due to aberrant innervation of the heart as has been suggested previously.


Temporal lobe epilepsy due to an intracerebral Schwannoma: case report.

An intracerebral Schwannoma giving rise to temporal lobe epilepsy is described. The possible origin of such tumours in the central nervous system in general, and in the temporal lobe in particular, is discussed.


Recovery of adenovirus type 7 from human brain cell cultures.

A  strain of adenovirus type 7 was recovered from cultured brain cells, taken at necropsy from a patient aged 71 years with chronic schizophrenia. This recovery may indicate the reactivation of a latent infection with one of the few adenoviruses that has regularly-if rarely-been associated with clinical encephalitis.


Evaluation and outcome of aphasia in patients with severe closed head trauma.

In this study long-term observation of 12 patients with aphasia secondary to severe closed head trauma took place. The most frequent symptoms were amnestic aphasia and verbal paraphasia. Only one patient with a constant slow wave EEG focus in the dominant hemisphere had severe receptive symptoms. In all other patients the aphasia recovered rather well, though not totally, but the presence and degree of concomitant neuropsychological disorders were most important for the final outcome.


Mechanisms of cell-mediated myotoxicity. Morphological observations in muscle grafts and in muscle exposed to sensitized spleen cells in vivo.

Fragments of rectus abdominis muscle or diaphragm from AKR or Prince Henry mice were transplanted beneath the skin of the anterior abdominal wall of BALB/C mice and were examined by light and electron microscopy 1-23 days after transplantation. Observations were made on the mode of entry of lymphoid cells into grafts, the nature of the inflammatory cells present in grafts and the interactions between mononuclear cells and regenerating muscle fibres during the rejection phase 7-14 days after transplantation. Lymphoid cells were found to migrate through the endothelium of venules and to enter the space between the basement lamina and the plasma membrane of muscle fibres to make contacts of varying degrees of complexity with the muscle cell membrane. Evidence of penetration of lymphoid cells into muscle fibres (emperipolesis) was found and was usually associated with signs of damage to the muscle fibre. Interactions between mononuclear cells and mature muscle fibres were studied after inoculation of sensitized spleen cells into the musculature of the tongue in mice. Both lymphoid cells and mononuclear phagocytes were found to invade muscle fibres by penetrating the basement lamina. The muscle cell membrane was usually broken down in zones of invasion by mononuclear cells but generally remained intact at sites of invasion by lymphoid cells.


Internuclear ophthalmoplegia in progressive supranuclear palsy.

Internuclear ophthalmoplegia has not previously been described in progressive supranuclear palsy. The present report draws attention to the occurrence of varying degrees of anterior internuclear ophthalmoplegia in 4 out of 13 cases of this condition studied over a 4-yr period. This finding suggests that the medial longitudinal fasciculus may be involved in the degenerative process in some cases of progressive supranuclear palsy.