Prenatal detection of cri du chat syndrome on uncultured amniocytes using fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) with a chromosome-region-specific DNA probe was used prospectively on uncultured amniocyte interphase cells to detect an unbalanced chromosome abnormality that resulted in cri du chat or 5p – syndrome. Confirmation was performed by routine cytogenetics.     

Mycobacterium avium binds to mouse intestinal mucus aldolase

SETTING: Mycobacterium avium complex (MAC) is known to colonize the gastrointestinal tract of human immunodeficiency virus (HIV) infected patients before causing bacteremia and disseminated disease. However, the mechanism involved in the gastrointestinal colonization is not known. OBJECTIVE: To identify putative intestinal mucus receptors which serve as anchor for MAC colonization. DESIGN: C57BL/6 mouse intestinal mucus was subjected to single and two-dimensional electrophoresis and blotted on nitrocellulose membranes. MAC specific mucus proteins were identified by probing the mucus western blots with biotinylated proteins derived from M.avium strain 101 (MAC101). RESULTS: Biotinylated MAC 101 proteins recognized a 39 kDa intestinal mucus glycoprotein. The protein displaying an isoelectric point (pI) of 9.0, was found to be periodate sensitive but resistant to sialidase, heparinase I and chondroitinase ABC. The internal amino acid sequence of the 39 kDa protein displayed homology with fructose-1-6-bisphosphate aldolase B (aldolase). The proclivity between MAC adhesins and aldolase was confirmed by probing rabbit muscle aldolase with MAC proteins. Furthermore, both 25 and 31 kDa MAC adhesins, superoxide dismutase and heparin binding protein, respectively, were found to bind to aldolase. CONCLUSIONS: MAC binds to intestinal mucus aldolase, conceivably facilitating intestinal colonization of the organism.     

Controlled, comparative study of moxalactam and cefazolin for prophylaxis of abdominal hysterectomy

Moxalactam was compared with cefazolin and a control group to determine the efficacy and value of a third generation cephalosporin in abdominal hysterectomy antibiotic prophylaxis. One hundred patients were prospectively randomized in a double-blind manner between moxalactam and cefazolin. An additional 50 patients who were either allergic to penicillin or refused participation in this study were simultaneously observed to establish a base line level of infection on our service during this time period. Dosage for both antibiotic groups was 1 gram given intravenously or intramuscularly on call to the operating room followed by two 1 gram doses at six and 12 hours after the first dose. Standard febrile morbidity was 36, 30 and 42 per cent for moxalactam, cefazolin and control groups, respectively. Postoperative surgical infection requiring antibiotic treatment occurred in 8, 6 and 4 per cent, respectively; urinary tract infection or symptomatic findings, or both, requiring treatment occurred in 8, 10 and 10 per cent, respectively. No pelvic abscesses occurred in this series. In every statistical evaluation of postoperative morbidity, there were no differences noted among the three groups. Our results suggest no benefit from the use of prophylactic antibiotics in abdominal hysterectomy in terms of standard febrile or infectious morbidity or urinary tract pathologic findings. In addition, there was no difference between the two antibiotic groups.     

Diabetes mellitus in the family: perceptions of offspring's risk.

AIMS: The study aimed to explore the beliefs and concerns of people with Type 2 diabetes mellitus (DM) about their children's risk of developing the disease and the possibilities for prevention. METHODS: Questionnaires were posted to all patients with Type 2 DM in four randomly selected general practices in South London. Two hundred and thirteen (73%) responded. The main outcome measures were: estimated risk of Type 2 DM in their offspring; worry about diabetes in their offspring; knowledge about the possibilities for prevention of Type 2 DM and its complications. RESULTS: Of the 159 respondents with children, at least 35% and perhaps as many as 64% underestimated the risk of their offspring developing Type 2 DM; 44% thought it possible to reduce the risk of Type 2 DM and its complications; 28% thought altering diet and 6% taking exercise might be useful preventive strategies; 49% worried about their children developing diabetes. CONCLUSIONS: Although risk of Type 2 DM was underestimated for their children and little was known about prevention, about half of the respondents worried about their children developing diabetes. Education and counselling about risk and prevention are needed. This is important in view of growing interest in and opportunities for both the primary and secondary prevention of Type 2 DM.     

The in vivo contribution of motor neuron TrkB receptors to mutant SOD1 motor neuron disease

Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) are widely expressed in the vertebrate nervous system and play a central role in mature neuronal function. In vitro BDNF/TrkB signaling promotes neuronal survival and can help neurons resist toxic insults. Paradoxically, BDNF/TrkB signaling has also been shown, under certain in vitro circumstances, to render neurons vulnerable to insults. We show here that in vivo conditional deletion of TrkB from mature motor neurons attenuates mutant superoxide dismutase 1 (SOD1) toxicity. Mutant SOD1 mice lacking motor neuron TrkB live a month longer than controls and retain motor function for a longer period, particularly in the early phase of the disease. These effects are subserved by slowed motor neuron loss, persistence of neuromuscular junction integrity and reduced astrocytic and microglial reactivity within the spinal cord. These results suggest that manipulation of BDNF/TrkB signaling might have therapeutic efficacy in motor neuron diseases.     

Pre-symptomatic detection of chronic motor deficits and genotype prediction in congenic B6.SOD1 ALS mouse model

Amyotrophic lateral sclerosis (ALS) is an incurable progressive paralytic motor neuron disease with limited therapeutic options. Since their creation by Gurney et al. (1994) [Science 264:1772–1775], transgenic superoxide dismutase-1 with glycine to alanine switch at codon 93 (SOD1^G93A) mice have become the benchmark pre-clinical model for screening ALS therapies. Surprisingly, despite physiological, anatomical, ultrastructural and biochemical evidence of early motor system dysfunction, it has proven difficult to detect motor performance deficits in pre-symptomatic SOD1^G93A mice. As an alternative to conventional forced motor tests, we investigated the progression of motor performance deficits in freely behaving pre-symptomatic congenic B6.SOD1^G93A mice. We found that motor performance deficits began several weeks prior to the onset of overt clinical symptoms (postnatal day 45). More importantly, once motor performance deficits manifested, they persisted in parallel with disease progression. In addition, two physical measures of muscle girth revealed progressive hindlimb muscle atrophy that predicted genotype in individual pre-symptomatic mice with 80% accuracy. Together, these data suggest that muscle girth is a reliable and indirect measure of hindlimb muscle denervation and an early, objective marker for disease onset in congenic B6.SOD1^G93A ALS mice. Moreover, we present regression equations based on hindlimb muscle girth for predicting genotype in future studies using B6.SOD1^G93A mice. These findings support new objective criteria for clinical disease onset and provide objective measures that require little expertise. These studies demonstrate a cost-effective approach for more thorough evaluation of neuroprotective strategies that seek to disrupt disease mechanisms early in the disease process. To our knowledge, these findings are the first to report early chronic motor performance and physical deficits that are coincident with the earliest known motor dysfunction in any ALS mouse model.     

Quality of life in young fibromyalgia patients and effect of depression

Aim: The purpose of this study was to compare the depression and quality of life (QOL) scores of fibromyalgia (FM) patients and control subjects. We also aimed to detect relationships between different QOL scales, depression and clinical symptoms. Method: Ninety‐eight fibromyalgia patients and 48 healthy volunteers were included in the study. Depression was evaluated by a psychiatrist according to the Hamilton Depression Rating Scale and Diagnostic and Statistical Manual for Mental Disorders Edition 4 (DSM‐IV) criteria. QOL of the FM patients was assessed according to the Nottingham Health Profile (NHP), Health Assessment Questionnaire (HAQ), and Fibromyalgia Impact Questionnaire (FIQ). Results: We found significantly higher scores of depression, NHP, FIQ and HAQ in FM patients compared with controls (P < 0.000). Pain, tender point count (TPC), pain intensity, skinfold tenderness, FIQ, HAQ, and NHP scores were higher in patients with depression than in those without depression. Depression scores correlated with FIQ (r = 0.39, P < 0.01), HAQ (r = 0.35, P < 0.01), NHP (r = 0.55, P < 0.01) scores, TPC (r = 0.34, P < 0.01) and duration of disease (r = 0.21, P < 0.05). Fibromyalgia Impact Questionnaire scores correlated with HAQ scores (r = 0.45, P < 0.01), NHP scores (r = 0.49, P < 0.01) and TPC (r = 0.21, P < 0.05). HAQ scores correlated with NHP scores (r = 0.40, P < 0.01) and TPC (r = 0.29, P < 0.05). Nottingham Health Profile scores correlated with TPC (r = 0.43, P < 0.01) and duration of disease (r = 0.22, P < 0.05). Conclusion: We found higher scores of TPC, pain intensity, skinfold tenderness, NHP, FIQ, and HAQ in depressive FM patients as compared with non‐depressive FM patients. Our study indicates that there is an important relationship between pain, depression and QOL scales in young FM patients. Therefore; these patients should be managed using a multidisciplinary approach including psychiatric support.