Evaluation of advanced D-dimer assay for the exclusion of venous thromboembolism

The performances for thromboembolic disease exclusion of a new microlatex-enhanced D-dimer immunoassay have been evaluated. Advanced D-dimer (Dade-Behring, Marburg, Germany) was tested with two automated analyzers, namely BCS and CA-1500. Precision studies yielded coefficients of variation (within-run and run-to-run) of 3% and 6.3% at D-dimer levels near the cut-off value, for BCS and CA-1500 respectively. Frozen samples from 294 consecutive symptomatic outpatients suspected of either deep venous thrombosis (140) or pulmonary embolism (154) from a previous management study were tested with both analyzers, as well as with the VIDAS New assay (BioMerieux, Marcy-l'Etoile, France). For BCS, sensitivity and specificity were 96.6% (95% CI, 90.5, 99.3) and 42% (35.1, 49.0) respectively at a cut-off value of 1.35 microg/ml. For CA-1500, the corresponding figures were 95.5% (88.9, 98.8) and 47.8% (40.8, 54.9) at a cutt-off value of 1.1 microg/ml. This assay appears promising and should be validated in clinical practise to assess its place in the work-up schemes of thromboembolism.     

Use of out-of-hospital variables to predict severity of injury in pediatric patients involved in motor vehicle crashes

STUDY OBJECTIVE: We sought to create a clinical decision rule, on the basis of variables available to out-of-hospital personnel, that could be used to accurately predict severe injury in pediatric patients involved in motor vehicle crashes as occupants. METHODS: We analyzed the National Automotive Sampling System database, a national probability sample, using pediatric patients up to 15 years old (occupants only) involved in motor vehicle crashes from January 1993 to December 1999. The National Automotive Sampling System database includes patients from regions throughout the country, weighted to represent a nationwide sample. Twelve out-of-hospital variables were used in classification and regression tree analysis to create a decision rule separating children with severe injuries (Injury Severity Score [ISS] > or =16) from those with minor injuries (ISS < 16). Misclassification costs and complexity parameters were selected to yield a decision tree with appropriate sensitivity and specificity for the identification of severely injured patients, while also being simple and practical for out-of-hospital use. Probability weights were used throughout the analysis to account for the sampling design and sampling weights. RESULTS: Using a sample size of 8,392 children, we constructed a decision rule using 3 out-of-hospital variables (Glasgow Coma Scale score, passenger space intrusion > or =6 in [> or =15 cm], and restraint use) to predict those patients with an ISS of 16 or more. Internal cross-validation was used to determine the sensitivity and specificity, yielding values of 92% and 73%, respectively, for the prediction of patients with an ISS of 16 or more. CONCLUSION: Out-of-hospital variables available to field personnel could be used to effectively triage pediatric motor vehicle crash patients using the decision rule developed here. Prospective trials would be needed to test this decision rule in actual use.     

Clonal chromosomal defects in the molecular pathogenesis of refractory hyperparathyroidism of uremia

Indirect X chromosome-inactivation analyses have demonstrated that most parathyroid glands from patients with uremic refractory secondary/tertiary hyperparathyroidism are monoclonal neoplasms. However, little is known regarding the specific acquired genetic abnormalities that must underlie such clonal expansion or the molecular pathogenetic features of this disorder, compared with primary parathyroid adenomas. To address these issues in a uniquely powerful manner, both comparative genomic hybridization (CGH) and genome-wide molecular allelotyping were performed with a large group of uremia-associated parathyroid tumors. As indicated by CGH, one or more chromosomal changes were present in 24% of the tumors, which is markedly different from the value for common sporadic adenomas (72%). Two recurrent abnormalities that had not been previously described for sporadic parathyroid adenomas were noted with CGH, i.e., gains on chromosomes 7 (9%) and 12 (11%). Losses on chromosome 11 occurred in only one of the 46 uremia-associated tumors (2%); the tumor also contained a somatic mutation of the remaining MEN1 allele (221del18). A total of 13% of tumors demonstrated recurrent allelic loss on 18q, with 18q21.1-q21.2 being defined as the putative tumor suppressor-containing region. In conclusion, the powerful combination of genome-wide molecular allelotyping and CGH has identified recurrent clonal DNA abnormalities that suggest the existence and locations of genes important in uremic hyperparathyroidism. In addition, genome-wide patterns of somatic DNA alterations, including disparate roles for MEN1 gene inactivation, indicate that markedly different molecular pathogenetic processes exist for clonal outgrowth in severe uremic hyperparathyroidism versus common parathyroid adenomas.     

Induction of interleukin-6 by hepatitis C virus core protein in hepatitis C-associated mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma.

PURPOSE: Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non-Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA. RESULTS: HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14(+) cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P < 0.05). CONCLUSIONS: Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C-associated MC and B-NHL.     

Functional results after laparoscopic rectopexy for rectal prolapse

We investigated the functional results after laparoscopic rectopexy for rectal prolapse in 29 patients at least 12 months postoperatively. Twenty patients were evaluated completely pre- and postoperatively (median 22 months postoperatively, range 12 to 54 months). Six patients were interviewed by telephone, two patients were lost to follow-up, and one patient died of causes unrelated to rectal prolapse. Patients underwent a proctologic examination, anoscopy, rigid sigmoidoscopy, fluoroscopic defecography, and anorectal manometry pre- and postoperatively, and an additional standardized interview postoperatively. Anorectal manometry showed a significant increase in maximum anal resting and squeeze pressures postoperatively (resting pressure 72 ±8 vs. 95 ±13 mm Hg, pre- vs. postoperatively; P = 0.046; squeeze pressure 105 ±17 vs. 142 ±19 mm Hg, pre- vs. postoperatively; P = 0.035), and continence improved postoperatively (Wexner incontinence score 6.0 ±1.0 vs. 3.9 ± 0.8 pre- vs. postoperatively, P = 0.02). Twenty (77%) of 26 patients were satisfied with the operative result, but functional morbidity was observed in four patients, with two patients complaining of severe evacuation problems. Rectal prolapse recurred in one patient 42 months postoperatively (recurrence rate 1 [3.8%] of 26 patients). Functional results were very similar to those obtained after open rectopexy, with symptoms of prolapse and incontinence improved in the great majority of patients. Presented at the Fortieth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Fla., May 16–19, 1999.     

Effect of repetitive prenatal corticosteroid medication on intrauterine growth and growth in early childhood

OBJECTIVE: The evaluation of the effects of repeated antenatal corticosteriod (CS) medication on birth size and size at the age of 4 years. METHODS: 82 children exposed to CS initially between 26 and 28 weeks of gestation were matched with 82 controls of the same gestational age and sex. RESULTS: No differences were observed between the CS and control groups with regard to weight, head circumference, and length at birth and at the age of 4 years. CONCLUSIONS: Our study failed to demonstrate that repetitive antenatal medication with CS in order to induce lung maturation has a negative impact on intrauterine growth and growth in early childhood.     

The proteasome inhibitor MG132 induces apoptosis in human pancreatic cancer cells

The ubiquitin-proteasome system plays a critical role in the regulation of programmed cell death. Proteasome inhibitors induce apoptosis in various cancer cells and have antitumor effects in murine tumor models. In the present study, we investigated whether the cell-permeable proteasome inhibitor MG132 (carbobenzoxyl-L-leucyl-L-leucyl-L-leucinal) reduced the growth of a human pancreatic cancer cell line through induction of apoptosis in vitro. The effects of MG132 (0.125-1.000 microM) on the growth of the human pancreatic cancer cell line BxPC-3 were analyzed by cell count and MTT assay. Apoptosis was determined by FACS analysis after annexin V and propidium iodide staining and the enrichment of intracellular nucleosomes. The proteasome inhibitor MG132 decreased cell growth of the human pancreatic cancer cell line BxPC-3 in a dose- and time-dependent manner. This effect was at least in part mediated by the induction of apoptosis. A combination therapy with standard cytotoxic agents and proteasome inhibitors could potentially be a novel therapeutic strategy in treatment of pancreatic cancer.     

Airways and respiratory function in obese patients. Anaesthetic and intensive care aspects and recommendations

In obese patients, perioperative pulmonary complications have an increased frequency and are associated with higher morbidity and mortality compared with non-obese patients. The management of surgical procedures in these patients is a challenge for the anaesthetist. Knowledge of pathophysiological and pharmacological aspects of the obese patients' condition is essential for their care during preoperative assessment, intra-operative management and, if necessary, postoperative intensive care. Special information on airway and lung protection as well as cases involving laparoscopic surgery, obstetric and paediatric anaesthesia in obese patients are also discussed.     

Priming effects in the fusiform gyrus: changes in neural activity beyond the second presentation

Repetition priming typically leads to a decrease in the activation of sensory cortical areas upon a second exposure to the same visual stimulus. This effect is thought to reflect more efficient or fluent re-processing of previously seen stimuli so that less neural activity is required. Fluent re-processing has been hypothesized to be a potential link from repetition priming to neural changes associated with visual expertise. To examine this potential connection, the neural correlates of priming were examined across eight stimulus repetitions using functional magnetic resonance imaging. Sizeable regions of bilateral ventral occipito-temporal cortex (including the fusiform gyrus) exhibited reduced responses to the second presentation of a stimulus. Most of these areas displayed no further reduction in response to subsequent repetitions of the same stimuli. Because expertise accrues over many exposures, these areas, while clearly involved in priming, do not exhibit an activity pattern consistent with the development of expertise. In contrast, an area in the right posterior fusiform gyrus exhibited reductions in evoked response that grew in magnitude for stimulus repetitions from the second to the eighth presentations. This region exhibits a pattern of activity consistent with a gradual and cumulative enhancement of the fluency effect across trials, suggesting that it may mediate the link between priming and the development of visual expertise.