Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration

Oxysterols are biologically active molecules generated during oxidation of LDL. Several of these oxysterols were found in macrophage-derived foam cells from human atherosclerotic tissue (eg, 7-hydroxycholesterol, 7-ketocholesterol, 5-epoxycholesterol, and 25-hydroxycholesterol). A specific stimulation of interleukin-8 (IL-8) production by oxidized LDL (oxLDL) has been shown by other investigators. In foam cells from human atherosclerotic tissue, we found high levels of IL-8 (183.1 pg/10(6) cells) compared with monocytes (23.2 pg/10(6) cells) or monocyte-derived macrophages in culture (1.5 pg/10(6) cells). When monocytes and monocyte-derived macrophages, in vitro, were exposed to a series of different oxysterols, we found that all oxysterols tested had a tendency to stimulate IL-8 production but that 25-hydroxycholesterol was the most potent one. This stimulation of IL-8 production was time and dose dependent and could be blocked by cycloheximide. These results indicate that oxysterols in oxLDL may have a regulatory effect on IL-8 production. IL-8, a potent chemoattractant, may play a role in the recruitment of T lymphocytes and smooth muscle cells into the subendothelial space and may contribute to the formation of atherosclerotic lesions.     

Cantrell''s pentalogy: a case report

Nine chemotherapy-naive women with recurrent (2 patients) or high risk factors (bilateral or extraovarian spread, poorly-differentiated tumor, age > or = 40 years at diagnosis, residual disease after surgery) granulosa-cell tumors were treated with cisplatin, cyclophosphamide with or without doxorubicin (PAC, PC) or cisplatin, etoposide and bleamycin (PVP-16B). Toxicity was acceptable and the most frequently encountered adverse reactions were WHO grade 3 gastrointestinal toxicity in 77% of patients, and grade 3 myelosuppression in 22% of cases. Clinical complete response was achieved in the 2 patients with recurrent disease. Five patients underwent second look surgery which documented: complete response in 3 patients, partial response in 1 patient and progressive disease in 1 case. Median survival was 85 months (range 14-103). Cisplatin-based cytotoxic regimens may be of benefit in the treatment of recurrent or high risk granulosa-cell tumors.     

Strong hydrogen bonding interactions involving a buried glutamic acid in the transmembrane sequence of the neu/erbB-2 receptor

The receptor tyrosine kinase encoded by the neu/erbB-2 proto-oncogene is constitutively activated by a single valine to glutamic acid substitution at position 664 in the predicted membrane-spanning sequence of the receptor. We have explored the structural changes involved in receptor activation with polarized FTIR and magic angle spinning NMR spectroscopy. The hydrophobic transmembrane sequence folds into a well-defined alpha-helical structure spanning the membrane bilayer. Measurements of the pKa and 13C chemical shift anisotropy of Glu 664 reveal that the side chain carboxyl group is protonated and strongly hydrogen bonded. These studies provide direct evidence for glutamate hydrogen-bonding interactions in the mechanism of receptor dimerization and activation.     

Effect of valve holder flexibility on cavitation initiation with mechanical heart valve prostheses: an in vitro study

The records of 98 patients with 160 hypoplastic thumbs seen between 1923 and 1993 were reviewed to determine the salient characteristics of this population. Physical findings, photographs, and x-ray films were studied. Sixty-three percent of patients were male, and 63% had bilateral thumb hypoplasia, 59% had radial dysplasia, and 86% had other anomalies. An associated syndrome, most commonly the vertebral, anal, tracheosophageal, renal, and radial limb anomalies association or Holt-Oram syndrome, was present in 44%. Patients with spine, genitourinary, or gastrointestinal anomalies were most likely to have the vertebral, anal, tracheosophageal, renal, and radial limb anomalies association, those with cardiac anomalies were most likely to have Holt-Oram syndrome, and those with lower extremity anomalies were most likely to have a different syndrome. One hundred thirty-nine thumbs were classifiable, using a modification of Blauth's classification; 19% were types 1 and 2, 23% were type 3, and 58% were types 4 and 5. One hundred seven operations were performed on 63 upper limbs, including 24 thumb reconstructions and 35 pollicizations. These patients must be carefully examined for bilaterality, other anomalies, and syndromes. Classification using a modification of Blauth's criteria is useful and helps the surgeon determine a treatment plan.     

Temporal patterns of clonality and parasitism in a population of freshwater bryozoans

Clonal reproduction is commonly incorporated into the life cycles of many metazoans. However, whether and how such highly clonal animals persist in the face of natural enemies remains poorly understood. Here we report the first temporal genetic study of a clonal population, the freshwater bryozoan Cristatella mucedo, and the associated prevalence of a myxozoan parasite. High levels of both clonality and parasitism persisted over a 3 year period. Random amplified polymorphic DNA markers revealed four distinct clones of C. mucedo. The two most common clones varied in abundance with the significantly more common clone in the first year becoming the significantly less common by the third year. There was no evidence that the most common clone was disproportionately infected. These results are discussed in relation to predictions of the Red Queen and the metapopulation dynamics of clonal organisms.     

Multiple-outcome meta-analysis of clinical trials

When several clinical trials report multiple outcomes, meta-analyses ordinarily analyse each outcome separately. Instead, by applying generalized-least-squares (GLS) regression, Raudenbush et al. showed how to analyse the multiple outcomes jointly in a single model. A variant of their GLS approach, discussed here, can incorporate correlations among the outcomes within treatment groups and thus provide more accurate estimates. Also, it facilitates adjustment for covariates. In our approach, each study need not report all outcomes nor evaluate all treatments. For example, a meta-analysis may evaluate two or more treatments (one 'treatment' may be a control) and include all randomized controlled trials that report on any subset (of one or more) of the treatments of interest. The analysis omits other treatments that these trials evaluated but that are not of interest to the meta-analyst. In the proposed fixed-effects GLS regression model, study-level and treatment-arm-level covariates may be predictors of one or more of the outcomes. An analysis of rheumatoid arthritis data from trials of second-line drug treatments (used after initial standard therapies prove unsatisfactory for a patient) motivates and applies the method. Data from 44 randomized controlled trials were used to evaluate the effectiveness of injectable gold and auranofin on the three outcomes tender joint count, grip strength, and erythrocyte sedimentation rate. The covariates in the regression model were quality and duration of trial and baseline measures of the patients' disease severity and disease activity in each trial. The meta-analysis found that gold was significantly more effective than auranofin on all three treatment outcomes. For all estimated coefficients, the multiple-outcomes model produced moderate changes in their values and slightly smaller standard errors, to the three separate outcome models.