Identification Of Two New Pmp22 Mouse Mutants Using Large-Scale Mutagenesis And A Novel Rapid Mapping Strategy

In some alcohol-related pathologies of chronic alcoholism women are more vulnerable than men. A consecutive sample of 62 chronic alcoholics was studied, 18 females and 44 males, aged between 28 and 69 years to assess the incidence and distribution of peripheral neuropathy with regard to gender. All patients underwent clinical and neurological observations, laboratory tests, and electroneurography. Total lifetime dose of ethanol (TLDE) and other risk factors for neuropathy (disease duration, age, nutritional status) were calculated and correlated to sural nerve sensory-evoked potential (SEP) amplitude. In 42 patients (67.7%), we observed the presence of clinical and/or infraclinical neuropathy, mostly axonal, in 29 males (65.9%) and 13 females (72.2%). In women, compared to men, TLDE and disease duration were significantly inversely correlated to sural nerve SEP amplitude, i.e in women, SEP amplitude is significantly reduced in relation to TLDE and disease duration increase. These data indicate a higher sensitivity of females towards the toxic effects of ethanol, other than malnutrition, on peripheral nerve fibres.     

Do women carry higher operative risk compared to men while undergoing coronary artery bypass grafting?

Background This study was aimed to determine influence of gender on result of coronary artery bypass grafting. It is a retrospective analysis. Methods Ninety six patients, 48 men and 48 women of similar body surface area operated between 1991 to 1997 were compared. Associated comorbid conditions were identical in both the groups, except that none of the women smoked. Results One patient (2.08%) died in each group. (p=NS). Although left anterior descending artery was smaller in diameter in women as compared to men, it did not express higher operative risk in women. No statistically significant difference was observed in perioperative and post operative morbidity including hospital stay. Conclusion This study does not support the view that women carry higher surgical risk in comparison to men of similar body surface area. Paper presented in the Annual Conference of Indian Association of Cardiovascular and Thoracic Surgeons at Mumbai, India on 8th March, 2000.     

Preimplantation diagnosis of non-deletion Duchenne muscular dystrophy (DMD) by linkage polymerase chain reaction analysis

The use of preimplantation diagnosis for sex determination and detection of exon deletion means that unaffected babies can be born to parents suffering from Duchenne muscular dystrophy (DMD). However, those who do not have exon deletion should also be considered for further investigation. A new method, known as linkage analysis, has been developed to diagnose the presence of non-deletion DMD in preimplantation embryos. Linkage analysis uses informative intragenic and flanking markers to track the chromosome bearing the mutated gene. The present study reports the analysis of two polymorphic sites, in blastomeres biopsied from embryos from a female carrier of DMD. A single male embryo was obtained who had inherited alternate maternal alleles to the woman's affected surviving son, and this embryo was transferred.      

Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth

We evaluated the safety of ciprofloxacin administered in a dose of 15–25 mg/kg for 9–16 days, in a case series of 58 children who were between 8 months and 13 years of age. No arthropathy was observed during therapy and follow–up. Blinded evaluation of 22 pairs of nuclear magnetic resonance scans obtained before and between day 10 and 15 of therapy did not reveal any cartilage damage. After the first dose of ciprofloxacin (10 mg/kg), serum fluoride levels increased at 12 h in 15 of 19 (79%) patients; 24–h urinary fluoride excretion was higher on day 7 compared with basal values in 16 of 18 (88.9%) patients. Height z scores of 53 patients at a mean of 22.5 months of follow–up were not significantly different from basal scores ( p = 0.12). In conclusion, ciprofloxacin may be recommended for use in children for short duration when effective alternative antibacterials are unavailable. However, there is a need for further studies to evaluate the tissue accumulation of fluoride and its potential to cause toxic effects.     

Population based standards for pulmonary function in non-smoking adults in Singapore

Abstract Ethnic differences in lung function are well recognized, hence the use of normative data should therefore be based on reference equations that are derived specifically for different ethnic groups. We have collected data ( n =406) for population-based reference values of lung function from randomly selected samples of healthy non-smoking adults of both gender (aged 20–79 years) for each of the three major ethnic groups (Chinese, Malay and Indians) in Singapore. Lung function forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), FEV₁/FVC, diffusion capacity (transfer factor) for carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV), RV/TLC and functional residual capacity (FRC) was measured using standardization procedures and acceptability criteria recommended by the American Thoracic Society. Lung function values were predicted from age, height, weight, body mass index (BMI) and transformed variables of these anthropometric measures, using multiple regression techniques. Ethnic differences were demonstrated, with Chinese having the largest lung volumes and flow rates, and Indians the smallest. These prediction equations provide improved and additional (TLC, RV, RV/TLC, FRC) population-based reference values for assessment of pulmonary health and disease in Singapore     

Clinical isolates of Staphylococcus aureus have osteolytic surface proteins and a proportion of the population have antibodies that block this activity: is this of prognostic significance?

Staphylococcus aureus is directly implicated in the bone destruction associated with infected orthopaedic implants and bacterial arthritis. The Oxford (laboratory) strain of this organism has surface-associated proteins (SAPs) which have potent osteolytic activity. In this study, we have examined the osteolytic activity of SAPs from clinical isolates and also investigated the role of the humoral immune response to such proteins. Nine patients with infected orthopaedic prostheses or infective arthritis, and six volunteers not suffering from overt S. aureus infection, were examined. The sera from 5/9 patients and 4/6 volunteers were able to neutralize the osteolytic activity of the SAPs. The SAPs were extracted from four clinical isolates and were found to have osteolytic activity, but with a wide range of efficacies and potencies. All four patients from whom the clinical isolates were obtained had serum IgG antibodies to the surface proteins from their autologous isolates as determined by ELISA. In conclusion, clinical isolates of S. aureus contain osteolytic SAPs which may be responsible for bone destruction. Apparently disease-free individuals and patients have antibodies able to block this activity. However, since the capacity of patients' sera to neutralize the activity of the SAPs derived from their own S. aureus isolate was not investigated, it is unclear whether these findings are of prognostic value.      

Allogeneic bone marrow transplantation in acute nonlymphocytic leukemia: a pilot study

The objective of the current study, initiated in 1976, was to improve upon the high relapse rate and subsequent mortality in children and young adults with acute nonlymphocytic leukemia (ANLL). Seventeen patients, ages 6--28, with ANLL in first bone marrow remission, received cyclophosphamide and total body irradiation using a radiation scheme of 750 rad (7.5 Gy) total dose, delivered at a dose rate of 26 rad (26 cGy) per minute. Allogeneic marrow from HLA-matched sibling donors was followed by prophylactic therapy or graft-versus-host disease (GVHD). Median follow-up of the entire group is 20+ mo; survivors have been followed for a minimum of 14+ mo. Interstitial pneumonitis was observed in 6% of patients, and GVHD was observed in 29%. Seventy percent of patients are alive and in complete continuous remission. Two patients have relapsed (at 7 and 24 mo). Actuarial relapse-free survival is 76% at 1 yr and 64% at 5 yr. Quality of life in this disease-free survivors is excellent; all patients are free of active GVHD, receive no maintenance chemotherapy, and have high Karnofsky performances scores. High dose rate total body irradiation plus cyclophosphamide followed by allogeneic BMT may provide an opportunity for long-term complication-free survival in a substantial proportion of children and young adults with ANLL.     

In vivo administration of recombinant human granulocyte/macrophage colony-stimulating factor in acute lymphoblastic leukemia patients receiving purged autografts [see comments]

Based on the recent reports that recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) accelerates the rate of engraftment in a variety of autologous bone marrow transplantation settings, we have investigated its effects on hematopoietic recovery of patients with acute lymphoblastic leukemia (ALL) undergoing autologous bone marrow transplantation. Our studies, which involved 25 autologous ALL recipients who received rhGM-CSF and 27 controls similar for disease status (remission or relapse) and disease type (B- or T-lineage) differed from previous studies in one important aspect: the bone marrows were purged with 4- hydroperoxcyclophosphamide (4HC) and anti-T or anti-B-cell lineage- specific antibodies before transplantation. Such treatments frequently lead to a reduction in the CFU-GM content of the transplanted marrow. Eighteen of 25 patients completed the entire course of rhGM-CSF. Of the 16 patients who received greater than or equal to 64 micrograms/M2/d for at least eight days, there were five patients who had an apparent rhGM-CSF response and 11 patients who did not respond. Of the parameters analyzed, only the number of CFU-GM progenitor cells infused per kilogram was significantly associated with an rhGM-CSF response. All patients receiving greater than or equal to 1.2 x 10(4) CFU-GM progenitors per kilogram achieved an absolute neutrophil count (ANC) greater than or equal to 1,000/microL by day 21 and had a greater than 50% decrement in ANC within 48 to 72 hours of discontinuing rhGM-CSF, as contrasted to none of the patients receiving less than or equal to 7.2 x 10(3) CFU-GM progenitors per kilogram.(ABSTRACT TRUNCATED AT 250 WORDS)