Tritiated Uridine Uptake in the Retinal Ganglion Cell Layer of the Cat during Normal Development and after Visual Cortex Ablation

The short-term metabolic response of immature retinal ganglion cells to destruction of their target cells in the dorsal lateral geniculate nucleus (dLGN) was assessed in newborn cats. Retrograde degeneration of virtually all dLGN cells was induced by ablation of the 13 contiguous areas of visual cortex on the day of birth. The metabolic response of retinal ganglion cells to this loss of target cells in dLGN was determined by exposing the ganglion cell layer to tritiated uridine, a precursor of RNA. Control measurements were made from unoperated littermates. Following sectioning and processing of the retinae from both groups of kittens for autoradiography, silver grain densities overlying the cellular profiles in the ganglion cell layer were calculated. These calculations revealed levels of uridine incorporation at Postnatal Day 4 in both groups of kittens significantly higher than at either Postnatal Day 2 or 7, but no significant differences between the two groups on any day examined. These results show that the level of RNA synthesis in retinal ganglion cells increases temporarily during the first postnatal week and that this synthesis is unaffected by the death of target cells in the dLGN. The temporary increase may be related to the establishment of synaptic connections on retinal ganglion cells by their afferent bipolar and amacrine neurons in the inner nuclear layer.     

Propofol stimulates nitric oxide release from cultured porcine aortic endothelial cells.

Propofol, an intravenous anaesthetic agent, causes marked vasodilatation in vivo. In the present study the effects of propofol on the release of nitric oxide (NO) from vascular endothelial cells was determined in vitro. Application of propofol to co-cultures of porcine aortic endothelial and smooth muscle cells resulted in a rapid increase in cyclic GMP formation. This increase was significantly inhibited following pretreatment of the cells with either NG-nitro-L-arginine (L-NOARG) or in the presence of haemoglobin. When applied to smooth muscle cells alone, propofol did not result in an increase in cyclic GMP levels. These results demonstrate that propofol stimulates the production and release of NO from cultured endothelial cells and suggest that the vasodilatation and hypotension observed when propofol is given in vivo may be due to NO release.     

Attitudes toward prevention of cardiovascular diseases among first-year students at eight American medical schools, 1983-1985

First-year medical students at eight U.S. medical schools were surveyed by written questionnaire in 1983-1985 to determine their attitudes toward cardiovascular diseases prevention at medical school entry. An overall response rate of 92% was achieved (2,654 questionnaires), and 97% of responders provided complete and analyzable survey data. Response rates at five of eight medical schools were 98-100%, and one school each had rates of 67, 84, or 90%. Differences in mean attitude responses from school to school were small, as were differences between men and women or between blacks and whites. This survey found that entering medical students have generally positive attitudes toward the effectiveness of preventive cardiology practice as well as toward the importance of research efforts in cardiovascular disease prevention. Students frequently indicated, however, that it is "extremely difficult" to change patients' unhealthful habits and that "physician encouragement" may not be sufficient to help patients achieve more healthful behaviors. These findings could be helpful in directing educational efforts for medical students. The data suggest that major emphasis should be placed on conveying facts regarding the physicians' efficacy in clinical preventive cardiology and on teaching the skills of preventive cardiology practice. Less emphasis appears to be necessary on encouraging positive attitudes about the importance of prevention since current students' attitudes appear to be already positive in this dimension.     

The effects of carbamazepine on stuttering.

No pharmacological treatment protocol has proven generally useful for all patients who stutter. Various medications, behavior therapy, relaxation, suggestion, and social-based therapies have been used. For this drug treatment study, two groups of adult stutterers were followed in an 8-week open label protocol. All subjects had in the past received speech therapy; none had been treated previously with medication for stuttering. The first group (N = 12) received a maximum dose of 800 mg of carbamazepine; the second group (N = 8) received a maximum dose of 400 mg of carbamazepine. Each patient served as his or her own control. A series of systematic speech tests was given weekly to determine the variability of fluency for each subject. A statistically significant change occurred for a number of "expectancy to stutter" characteristics. Subjects felt that they stuttered less often while taking carbamazepine. Subjective effects began before medication and continued after patients discontinued the medication. Struggle characteristics also subjectively decreased. However, no objective improvement was found. No change was found in percentage of words stuttered, reading improvement, or improvement in spontaneous speech rate. Interrater reliability showed a correlation of .996. Three carbamazepine serum level therapeutic windows were inspected with negative results. Interestingly, naive listener ratings did show a statistically significant improvement on carbamazepine versus placebo. Future anecdotal reports of pharmacological improvement of stuttering should be subjected to rigorous objective testing before general acceptance.     

Immunopathogenesis of infection with the visceralizing Leishmania species

Human leishmaniasis is a spectral disease that includes asymptomatic self-resolving infection, localized skin lesions, and progressive visceral leishmaniasis. With some overlap, visceral and cutaneous leishmaniasis are usually caused by different species of Leishmania. This review focuses on host responses to infection with the species that cause visceral leishmaniasis, as they contrast with species causing localized cutaneous leishmaniasis. Data from experimental models document significant differences between host responses to organisms causing these diverse syndromes. The visceralizing Leishmania spp. cause localized organ-specific immune responses that are important determinants of disease outcome. Both the Leishmania species causing cutaneous and those causing visceral leishmaniasis require a Type 1 immune response to undergo cure in mouse models. However, during progressive murine infection with the visceralizing Leishmania sp., the Type 1 response is suppressed at least in part by TGF-beta and IL-10 without type 2 cytokine production. This contrasts with the cutaneous species L. major, in which a Type 2 response suppresses type 1 cytokines and leads to murine disease progression. Population and family studies are beginning to elucidate human genetic determinants predisposing to different outcomes of Leishmania infection. These studies should eventually result in a better understanding of the immunopathogenesis and the spectrum of human leishmaniasis.     

DNA probe analysis for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy: a standard diagnostic procedure.

Thirteen marker loci localised on the short arm of the X chromosome are available for use in genetic studies for Duchenne muscular dystrophy (DMD). This large number of probes detecting about 20 RFLPs encouraged us to set up a standard procedure using a sequence of selected probes and restriction enzymes for the diagnosis of DMD families. The application of DNA probe analysis for carrier detection and prenatal diagnosis, involving 61 pedigrees of both familial and isolated cases, has yielded the following results. Carrier detection using flanking markers was possible in more than 75% of the cases (104 out of 136 females) with a reliability of better than 98%. Prenatal diagnosis was possible in 95% of the cases (65 out of 68 proven carriers or women at risk). Twenty-three prenatal diagnoses were performed on male fetuses; 13 appeared to have a low risk for DMD (less than 1%) and thus the pregnancies continued. Seven have since come to term and the male infants have normal CK levels. The genetic distances of the loci relative to the DMD locus and their order on the short arm of the X chromosome were deduced from our total DMD family material and are not significantly different from those reported earlier. For 754 (DXS84) we found a genetic distance of 5 cM with a lod score of +12.4 and 95% confidence limits between 2 and 12 cM. Similar data were obtained for pERT87 (DXS164), suggesting that in our family material both loci are tightly linked. Multiply informative recombination showed that both 754 and pERT87 map proximal to the DMD mutations in the cases studied. The high frequency of DMD mutations and its relation to the observed instability in this part of the genome will be discussed. Unequal crossing over is proposed as one of the mechanisms contributing to the high mutation frequency.     

Is semiquantitative culture of central vein catheter tips useful in the diagnosis of catheter-associated bacteremia?

Semiquantitative culturing of catheter tips has been used as an index of catheter-related bacteremia. As the sensitivity and predictive values of this test have not been determined, we studied 780 tips from central vein catheters inserted into 440 critically ill patients in an intensive care unit. The results were correlated with clinical data for 30 bacteremic episodes which occurred in these patients, 14 of which were catheter related. When five or more colonies per plate were taken as a positive result, the sensitivity of the method was 92%, and the specificity was 83%. Although the predictive value of a negative result was excellent (99.8%), the predictive value of a positive result was low (8.8%) in our patient population, which had a relatively low incidence of catheter-related bacteremia (2%). We conclude that a semiquantitative culture technique is useful in the diagnosis of bacteremia associated with central vein catheters.     

Reovirus-like agent (rotavirus) from lambs.

Rotavirus particles were demonstrated by electron microscopy in the feces of lambs with diarrhea. Rotavirus antigen was synthesized in cell cultures infected with filtrates of the diarrheic feces, but the virus was not adapted to grow serially in cell cultures. An antigenic relationship between rotaviruses from lambs, pigs, and calves was demonstrated by immunofluorescence. Colostrum-deprived lambs were infected with the lamb rotavirus, and the virus was passaged in lambs. Viral replication occurred in the villous epithelial cells of the small intestine, and the virus was excreted in the feces up to 78 h postinfection. Diarrhea was not observed in the experimentally infected lambs.