High rates of discitis following surgery for prolapsed intervertebral discs at a hospital in Pakistan

OBJECTIVES: To confirm the presence of an outbreak of postoperative infections following laminectomy and to determine the infection rate after interventions were instituted. DESIGN: Retrospective cohort study. Medical records were reviewed, personnel interviewed, and premises examined. SETTING: Surgical unit of hospital A in Pakistan. SUBJECTS: Patients who had surgical laminectomy between January 1993 and July 1994. INTERVENTION: Instructive program for nursing and medical staff in December 1993. RESULTS: From January to December 1993, 6 (15%) of 41 laminectomy patients developed postoperative discitis. The risk of discitis varied significantly by surgeon (P = .016); patients who had one particular surgeon, surgeon A, were nine times more likely to develop postoperative infections than patients who did not have surgeon A. Patients were not consistently cleaned or shaved before coming to the operating room, and personnel moved back and forth between the operation theater and other parts of the hospital without changing their gowns or slippers. After the instructional intervention, between January and July 1994, 2 (6%) of 31 laminectomy patients developed postoperative discitis, a rate not significantly lower than in the preceding 12 months (P = .45). Overall, from January 1993 through July 1994, female patients were more likely to develop discitis than males (31% vs 7%; relative risk, 4.4; 95% confidence interval, 1.3-15.6; P < .032). CONCLUSION: Endemic conditions require that laminectomy at hospital A be limited to those situations where the benefits of the surgery exceed the considerable risk of postoperative discitis.     

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.     

Effect of plasma TNF-alpha on filgrastim-stimulated hematopoiesis in mice and humans

Marshall syndrome is a rare, autosomal dominant skeletal dysplasia that is phenotypically similar to the more common disorder Stickler syndrome. For a large kindred with Marshall syndrome, we demonstrate a splice-donor-site mutation in the COL11A1 gene that cosegregates with the phenotype. The G+1-->A transition causes in-frame skipping of a 54-bp exon and deletes amino acids 726-743 from the major triple-helical domain of the alpha1(XI) collagen polypeptide. The data support the hypothesis that the alpha1(XI) collagen polypeptide has an important role in skeletal morphogenesis that extends beyond its contribution to structural integrity of the cartilage extracellular matrix. Our results also demonstrate allelism of Marshall syndrome with the subset of Stickler syndrome families associated with COL11A1 mutations.     

Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1

The sphingolipid metabolite sphingosine-1-phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)-coupled orphan receptor EDG-1, originally cloned as Endothelial Differentiation Gene-1. EDG-1 bound SPP with high affinity (dissociation constant = 8.1 nM) and high specificity. Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.     

Segregation analysis of breast cancer in a population-based sample of postmenopausal probands: The Iowa Women's Health Study

Inheritance of a major susceptibility gene for breast cancer has been primarily investigated in families with early-onset disease. However, familial clustering of late-onset breast cancer is well documented, and genetic factors may also be relevant. In the Iowa Women's Health Study, we evaluated evidence for a major gene after allowing for measured environmental risk factors. Two hundred sixty-five incident breast cancer probands were identified from a prospective cohort study of 41,837 women aged 55 to 69 years at baseline in 1986. A pedigree development form was mailed to the probands to ascertain all first-degree female relatives. A questionnaire and body measurement protocol were mailed to identified living relatives or surrogates. Segregation analyses were conducted on a total of 1,145 women in 251 families using regressive models as implemented in S.A.G.E. Mendelian codominant inheritance of an allele that produced an earlier-age-at-onset provided the best fit to the data. Incorporation of measured environmental risk factors as covariates yielded no significant improvements in the likelihoods. Approximately 50% of this population could be expected to carry a late-onset breast cancer susceptibility gene, and 23% of the population is susceptible because of the environment in which they live. Homozygous gene carriers are predicted to have a mean age-at-onset of 48 years, over 20 years earlier than heterozygotes; few cases would be expected among non-gene carriers. In conclusion, the transmission pattern of late-onset breast cancer may be determined by a common susceptibility gene.     

Regulation of beta-adrenoceptors in the guinea-pig sinoatrial node

This study examined the changes of beta-adrenoceptors in the guinea-pig sinoatrial nodal region following 7 day (-)-isoprenaline (400 micrograms/kg/h s.c.) infusion and the relationship between beta-adrenoceptor desensitization and receptor down-regulation. Changes in beta 1- and beta 2-adrenoceptor density were measured using quantitative autoradiography and function in organ bath studies. (-)-Isoprenaline treatment produced a marked decrease in total (from 57.5 to 33.9 fmol/mg protein), beta 1- (from 49.4 to 32.8 fmol/mg protein), and beta 2-adrenoceptor density (from 8.1 to 1.05 fmol/mg protein) in the sinoatrial node. In adjacent right atrium, treatment produced no change in total (39.5 and 36.7 fmol/mg protein) or beta 1-adrenoceptors (35.9 and 36.4 fmol/mg protein) but did decrease beta 2-adrenoceptors (from 3.7 to 0.3 fmol/mg protein). Chronotropic effects were measured in spontaneously beating right atrium. Procaterol, a selective beta 2-adrenoceptor agonist, caused a biphasic chronotropic response in control right atria, the first part of which was abolished in the tissue from treated animals. The maximum increase in right atrial rate to RO363, a beta 1-adrenoceptor selective partial agonist, was reduced from 114 bpm in control to 43 bpm in treated animals. In electrically driven right atrium with the sinoatrial node removed procaterol failed to produce a positive inotropic response via beta 2-adrenoceptors, but the maximum response to RO363 was reduced from 0.75 g in the control tissue to 0.12 g in the treated tissue. This study showed that changes in beta 2-adrenoceptor density following 7 day (-)-isoprenaline infusion are compatible with reduced functional responsiveness in the SA node. The reduction of beta 1-adrenoceptor number in the SA node was also compatible with the reduced chronotropic response in this tissue. However the lack of effect on beta 1-adrenoceptor density in the right atrium was not consistent with the decrease in beta 1-adrenoceptor mediated inotropic response in this tissue. This suggests that beta-adrenoceptor desensitization is not always associated with receptor down-regulation but depends also on the changes in the cell signalling system beyond the level of the receptor which differ according to the cardiac location.