Bleeding time in laboratory animals I. Aspirin does not prolong bleeding time in rats.

A ‘template’, semiauthomatic device, recently developed for measuring bleeding time in man, has been reliably applied to evaluate the bleeding time in rats.This technique allows repeated measurements on the same animal. Following oral or intraperitoneal administration of acetylsalicylic acid (at various dosages), no significant variations of bleeding time were observed, although collagen-and Thrombofax - induced platelet aggregation, measured ex vivo in the aggregometer, was strongly inhibited. These results suggest that platelets might not play a fundamental role in the primary haemostasis of rat, as challenged by the bleeding time technique used in this study.     

Chronic low-level lead exposure in monkeys does not affect simple reaction time

Simple visual reaction time was measured in a group of adult monkeys (Macaca fascicularis) dosed continuously with lead from birth onward, and in matched controls. Blood lead concentrations had been stable for 6 years at 33 micrograms/dl at the time of testing. The monkey was required to make contact with a stainless steel bar to initiate a trial, and release it at the onset of a visual cue. Delays between one and 13 sec were interposed between the initiation of the trial and the onset of the cue light in a semi-random manner over the course of each session. Reaction times did not differ between groups. Reinforcement was then made contingent upon progressively shorter reaction times until performance deteriorated to a specified level. Treated monkeys were able to respond as rapidly as controls. Simple reaction time proved insensitive to impairment by lead exposure, in contrast to other measures of performance tested in this group of monkeys.     

Non‐compliance does not impair qualitative evaluation of colonic transit time

Background Measurement of colonic transit time (CTT) by using radiopaque markers with the “Multiple ingestion‐Single film” technique is a simple, reproducible technique to measure total and segmental CTT. However, it requires good compliance of the patients, who must ingest the capsules containing radio‐opaque markers for 6 consecutive days. The purpose of this study was to estimate the error in CTT measurement if they fail to do this. Methods The protocol tested was to ingest 12 markers per day during 6 days and take a plain film of the abdomen on day 7. The study was done by simulation using a 3‐compartiment model (right colon, left colon, rectosigmoid area). There was a set of 67,525 possibilities with possible single or double failure of markers ingestion for 6 days either 238,266 combinations for one omission, or 312,375 combinations for two omissions; the absence of omission was the reference. The analysis focused on two complementary aspects of the evaluation of omission: quantitatively, the absolute and relative error on the CTT measured and qualitatively, the diagnostic error (a delayed transit is defined by a total CTT > 65 hours). Key Results Total and segmental CTT measured when omission occurred were greater than the reference time. The difference is particularly important, when omission occurs early during the study for all segments. Qualitative analysis showed that, for one omission of markers ingestion, a correct diagnosis of delayed colonic transit time and of the main site of delay could be obtained by the 3‐compartment model in 100% of cases. For two failures of markers ingestion, “delayed” colonic transit could be regarded as normal in only 9.59% of cases; furthermore, the site of delay was correctly recognized in 83% of the cases. Conclusions & Inferences Despite omission of markers ingestion for one or two days, measured CTT overestimates the absolute value of colonic transit time, the formulated diagnosis (delayed transit and site of delay) is perfectly acceptable clinically.     

Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18–24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n?=?56); group 2 had CD4 >350 and were not initiating ART (n?=?66); group 3 initiated ART with CD4 <350 (n?=?59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.     

Neurometrics does not detect 'pure' dyslexics

Thirty-eight severely dyslexic boys and 38 good readers were evaluated with neurometrics, a diagnostic procedure based on the application of numerical taxonomy to EEG spectra obtained during resting conditions, supplemented by selected evoked potential features. This procedure generates deviance scores for the EEG spectra by comparing each individual's values to those obtained from a normative population and has been reported to discriminate learning disabled children from normal controls (Ahn et al. 1980). In the present study, all subjects, dyslexic and control, passed stringent screening to assure normal intellectual, neurological, sensory and emotional status. The false positive rate obtained in our control group was comparable to that reported earlier. However, none of the deviance scores significantly discriminated dyslexics from controls; most subjects from both groups were classified as normal. Severe dyslexia per se is thus not associated with the specific neurometric abnormalities reported previously in more heterogeneous learning disabled populations.     

Deep-brain-stimulation does not impair deglutition in Parkinson's disease

ObjectiveA large proportion of patients with Parkinson's disease develop dysphagia during the course of the disease. Dysphagia in Parkinson's disease affects different phases of deglutition, has a strong impact on quality of life and may cause severe complications, i.e. aspirational pneumonia. So far, little is known on how deep-brain-stimulation of the subthalamic nucleus influences deglutition in PD.MethodsVideofluoroscopic swallowing studies on 18 patients with Parkinson's disease, which had been performed preoperatively, and postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off, were analyzed retrospectively. The patients were examined in each condition with three consistencies (viscous, fluid and solid). The ‘New Zealand Index for Multidisciplinary Evaluation of Swallowing (NZIMES) Subscale One’ for qualitative and ‘Logemann-MBS-Parameters’ for quantitative evaluation were assessed.ResultsPreoperatively, none of the patients presented with clinically relevant signs of dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor symptoms measured by the UPDRS III, no clinically relevant influence of deep-brain-stimulation-on swallowing was observed using qualitative parameters (NZIMES). However quantitative parameters (Logemann scale) found significant changes of pharyngeal parameters with deep-brain-stimulation-on as compared to preoperative condition and deep-brain-stimulation-off mostly with fluid consistency.ConclusionIn Parkinson patients without dysphagia deep-brain-stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase but has no clinically relevant influence on deglutition. Further studies are needed to test if deep-brain-stimulation is a therapeutic option for patients with swallowing disorders.     

Post-ischemic diazepam does not reduce hippocampal CA1 injury and does not improve hypothermic neuroprotection after forebrain ischemia in gerbils

The hippocampal CA1 sector is especially vulnerable to brief forebrain ischemia. Excitotoxicity is widely thought to contribute to this cell death. Accordingly, drugs that presumably counteract excitotoxicity, such as GABAergic agonists, have been repeatedly tested and found to reduce CA1 cell loss. Post-ischemic diazepam reduces CA1 injury. However, diazepam also causes hypothermia, which by itself is neuroprotective. Most studies fail to adequately control for this confound. In this study, we tested whether diazepam reduces injury in temperature controlled gerbils subjected to brief forebrain ischemia. Furthermore, we tested whether diazepam augments hypothermic neuroprotection. All gerbils were implanted with a core temperature telemetry probe and a cannula for the subsequent insertion of a thermocouple probe to measure ischemic brain temperature. Subsequently, they were given a 5-min normothermic ischemic insult. In Experiment 1, two groups of gerbils were given 10 mg/kg doses of diazepam (i.p.) at both 30 and 90 min post-ischemia. Temperature was maintained in one group by heating lamps. Another group was administered saline. Diazepam reduced cell death at 7 days post-ischemia when the drug-induced hypothermia was permitted, but not when it was prevented. In Experiment 2, four groups of ischemic gerbils were treated starting at 12 h post-ischemia with prolonged hypothermia, diazepam and the combination or saline treatment. Hypothermia, but not diazepam, provided partial neuroprotection and diazepam did not augment hypothermic neuroprotection. Thus, neuroprotection with diazepam is solely due to hypothermia. These data do not support the clinical use of diazepam as a neuroprotectant after global ischemia.     

Measles vaccination does not prevent multiple sclerosis

Twenty-seven young patients with multiple sclerosis (MS) were studied to determine if they had received prior measles vaccination. Fourteen patients whose immunization records were available had received measles vaccine in childhood. Eight other patients gave a history of receiving measles vaccine. These results suggest that infection by measles virus is probably not the sole cause of MS and that, unlike subacute sclerosing panencephalitis and postmeasles encephalitis, MS may not be preventable by measles vaccination given at an appropriate age.     

Intrathecal bicuculline does not increase formalin-induced inflammation

Intrathecal (i.t.) administration of the γ-aminobutyric acid (GABA)_A receptor antagonist bicuculline enhances pain behaviors in the formalin test. This study examined whether bicuculline also increases the peripheral inflammation induced by formalin. Subcutaneous injection of 0.25 to 5.0% formalin in the plantar surface of one hindpaw of the rat produced a concentration-dependent increase in plasma extravasation as measured by the Evans Blue method. Pretreatment with 0.3 μg i.t. bicuculline neither enhanced nor suppressed formalin-induced plasma extravasation. This dose of bicuculline also did not affect plasma extravasation induced by injection of 3% kaolin/3% carrageenan in the knee of the rat. These data indicate that the enhancement of formalin-induced pain behaviors by i.t. bicuculline is not secondary to enhanced peripheral inflammation, but more likely reflects enhancement of nociceptive transmission in the spinal cord.     

Prophylactic stretching does not reduce cramp susceptibility

Introduction: Some clinicians advocate stretching to prevent muscle cramps. It is unknown whether static or proprioceptive neuromuscular facilitation (PNF) stretching increases cramp threshold frequency (TF_c), a quantitative measure of cramp susceptibility. Methods: Fifteen individuals completed this randomized, counterbalanced, cross‐over study. We measured passive hallux range of motion (ROM) and then performed 3 minutes of either static stretching, PNF stretching (hold–relax—with agonist contraction), or no stretching. ROM was reassessed and TF_c was measured. Results: PNF stretching increased hallux extension (pre‐PNF 81 ± 11°, post‐PNF 90 ± 10°; P < 0.05) but not hallux flexion (pre‐PNF 40 ± 7°, post‐PNF 40 ± 7°; P > 0.05). Static stretching increased hallux extension (pre‐static 80 ± 11°, post‐static 88 ± 9°; P < 0.05) but not hallux flexion (pre‐static 38 ± 9°, post‐static 39 ± 8°; P > 0.05). No ROM changes occurred with no stretching (P > 0.05). TF_c was unaffected by stretching (no stretching 18 ± 7 Hz , PNF 16 ± 4 Hz , static 16 ± 5 Hz ; P = 0.37). Discussion: Static and PNF stretching increased hallux extension, but neither increased TF_c. Acute stretching may not prevent muscle cramping. Muscle Nerve 57 : 473–477, 2018