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.     

Formation of cyclic 1,N2-propanodeoxyguanosine and thymidine adducts in the reaction of the mutagen 2-bromoacrolein with calf thymus DNA

The interaction of the mutagen 2-bromoacrolein (2BA) with DNA and thymidine was studied in vitro by reaction of [3-3H]2BA with thymidine, RNA, single-stranded DNA, and double-stranded DNA in phosphate buffer (pH 7.4). After purification of the nucleic acids, they were incubated at alkaline pH to convert any (hydroxybromo)propano(deoxy)-guanosine adducts to their dihydroxy analogues. After acid or enzymatic hydrolysis, the hydrolysates were analyzed by reversed-phase high-performance liquid chromatography. At a concentration of 1.6 mM, the fraction of 2BA that became covalently bound to DNA was 2.3% of the amount added. Only 3% of the radioactivity bound to DNA after extensive purification could be accounted for as cyclic 1,N2-(6,7-dihydroxy)-propanoguanine adducts. More 2BA became covalently bound to single-stranded DNA and RNA as compared with double-stranded DNA. However, high-performance liquid chromatographic analyses showed that formation of cyclic 1,N2-(6,7-dihydroxy)propanoguanine adducts was also a minor reaction with these macromolecules. Because these data showed that other type(s) of reaction(s) are more important in the reaction of 2BA with nucleic acids, we have investigated the reaction of 2BA with other nucleosides. It was found that 2BA reacted well with thymidine in vitro, and the major product was identified by 500 MHz 1H and 75.43 MHz 13C nuclear magnetic resonance and thermospray mass spectrometry as 3-(2"-bromo-3"-oxopropyl)thymidine. This adduct was unstable and decomposed upon storage. After enzymatic hydrolysis of [3H]2BA-modified double-stranded DNA and subsequent analysis of the hydrolysate by high-performance liquid chromatography, 22% of the covalently bound radioactivity to DNA coeluted with decomposition products of the 3-(bromooxypropyl)thymidine adduct. This indicates that reaction of 2BA with this nucleotide in DNA is a major reaction.     

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.     

The use of linked DNA polymorphisms for genotype prediction in families with Duchenne muscular dystrophy.

Two DNA restriction fragment length polymorphisms show genetic linkage to the Duchenne muscular dystrophy locus on the short arm of the X chromosome. Examples are given of families in which these polymorphisms can be used in the prediction of genotype for this disorder.     

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.     

CONSISTENCY OF PERFORMANCE CHANGE AND AUTONOMIC RESPONSE AS A FUNCTION OF EXPRESSED ATTITUDE TOWARD A SPECIFIC STRESS SITUATION

A persistent problem in stress research has been that some individuals may show impairment, while others show improvement or no change in performance under stress. Attempts to relate this variance in performance to general anxiety or other personality variables have generally not been too successful. Based upon responses to a fear of shock item in an attitude questionnaire, Ss were classified as “high fear of shock” or “low fear of shock” types. Half of the Ss in each group were assigned a perceptual-motor task; the others were assigned a cognitive-interference task. After training, all Ss were informed that they would be required to maintain their training performance levels in a situation in which they would be shocked if performance declined. Performance and heart rate measures taken during training were compared with the same measures taken under the threat-of-shock conditions. Results indicate significant differences between groups in both performance and physiological activity with “high fear of shock”Ss exhibiting relatively greater performance impairment and increased heart rate.     

Fictive motor patterns in chronic spinal cats.

1. Fictive motor patterns were recorded in hind leg nerves of 10 adult chronic spinal cats (spinalized at T13). Four of these animals had been trained to step with their hind legs on a treadmill (late-spinal animals), whereas the remainder received no training and were examined a short time after spinalization (early-spinal animals). 2. A fictive pattern resembling the locomotor pattern for stepping was evoked in all animals in response to stimulation of the skin of the perineal region. (2-[2,6-Dichloroaniline]-2-imidazoline) hydrochloride (Clonidine) at doses ranging from 100 to 500 micrograms/kg iv facilitated the production of this pattern, particularly in early-spinal animals. 3. The fictive locomotor pattern in late-spinal animals was more complex than that occurring in early-spinal animals. In the latter the pattern consisted of an alternation of activity in flexor and extensor nerves, and changing leg position did not qualitatively alter the pattern, whereas in late-spinal animals the relative durations of the bursts in different flexors were usually not the same, and the pattern of flexor activity was dependent on leg position. 4. Moving the legs from extension to flexion progressively decreased the duration of flexor bursts, increased the cycle period, and decreased the ease with which the pattern could be evoked in both early- and late-spinal animals. 5. 1-beta-3,4-Dihydroxyphenylalanine (DOPA)/Isonocotinic acid 2-[(2-benzylcarbamoyl)ethyl]hydrazide (Nialamide) treatment following Clonidine in early-spinal animals increased the complexity of flexor burst activity. This, and other observations, indicates that DOPA and Clonidine do not have strictly identical actions on the locomotor pattern generator. 6. Stimulation of the paws in late-spinal animals produced two patterns of activity distinctly different from the locomotor pattern. of activity distinctly different from the locomotor pattern. One was a short sequence of high-frequency rhythmic activity (at approximately 8 c/s) in response to gently stimulating one paw with a water jet, and the other was a slow rhythm in flexor nerves in response to squeezing the paw. 7. The main conclusion of this investigation is that three distinctly different fictive motor patterns can be generated in chronic spinal cats depending on the method and site of stimulation. These patterns correspond to three different behaviors (locomotion, paw shake, and rhythmic leg flexion) that can be elicited in behaving chronic spinal cats in response to the same stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)