-455G/A polymorphism and preprocedural plasma levels of fibrinogen show no association with the risk of clinical restenosis in patients with coronary stent placement

The effect of preprocedural fibrinogen levels on in-stent restenosis is largely unknown. The -455G/A polymorphism of the fibrinogen beta-gene is associated with baseline plasma level or acute phase increase of fibrinogen. Therefore, we hypothesized that there is a relationship between this polymorphism and preprocedural fibrinogen level and clinical restenosis at follow-up among patients with coronary stent placement. The GENetic DEterminants of Restenosis (GENDER) project is a multicenter follow-up study that enrolled 3,146 consecutive patients after successful percutaneous coronary intervention. A coronary stent was placed in 2,309 patients. Of these, 2,257 (97.7%) patients were successfully genotyped for the -455G/A polymorphism. Plasma fibrinogen levels were measured at baseline in a subpopulation of 623 stented patients with the von Clauss method and patients were grouped into tertiles according to fibrinogen levels. Primary endpoint was target vessel revascularization (TVR); secondary combined endpoint was defined as death presumably from cardiac causes, MI not attributable to another coronary artery than the target vessel, and TVR. No association was observed between the -455G/A polymorphism and TVR or combined endpoint (p=0.99, p=0.97, respectively). Multivariate regression analysis revealed that the risk of TVR and combined endpoint was not higher for patients in the highest tertile for fibrinogen versus the lowest tertile (RR=0.60, 95% CI: 0.26-1.37 for TVR, RR=0.64, 95% CI: 0.29-1.44 for combined endpoint). In conclusion, the presence of -455G/A polymorphism in the fibrinogen beta-gene and preprocedural fibrinogen level is not associated with an increased risk of TVR or combined endpoint in a patient population with coronary stent placement. Therefore, these parameters are not worthwhile for stratifying patients at risk for restenosis pre-stenting.     

Long-term diagnostic stability and outcome in recent first-episode cohort studies of schizophrenia

Knowing the long-term outcomes of schizophrenia and stability of a schizophrenia diagnosis are important from a clinical standpoint as well as essential to future research on diagnostic classifications and outcome. As in prior research on schizophrenia, prospectively designed long-term studies over the past 30 years find that the predominant course of illness includes chronically poor functioning, with little evidence of long-term improvement. Mortality due to suicide is significant at about 10% over 10-year periods of follow-up. Within studies, outcome domains are interrelated, and the relatively consistent predictors of poorer outcome include family history of schizophrenia, insidious onset, poor premorbid functioning, severity of negative symptoms, and severity and duration of untreated psychosis. Residing in a developed rather than a developing country is also associated with a poorer long-term course. The diagnostic stability of schizophrenia is less well studied. The positive predictive value exceeds 90%, and preliminary findings from the 10-year follow-up of the Suffolk County Mental Health Project cohort have found that the agreement across time increased from k = .52 (baseline to 10 years) to k = .76 (6 or 24 months to 10 years). After discussing several limitations of the existing body of research, we suggest that future studies incorporate more "modifiable" risk factors into the assessment battery that could potentially be used as building blocks in experimental intervention designs.     

Long-haul air travel before major surgery: a prescription for thromboembolism?

OBJECTIVE: To investigate the Incidence of postoperative venous thromboembolism (VTE) in patients who had flown long distances before major surgery. PATIENTS AND METHODS: Using the Mayo Clinic computerized patient database, we Identified patients who had flown more than 5000 km before major surgery (travelers) and had experienced an episode of clinically significant VTE within 28 days after surgery. Individual medical records were reviewed for the diagnosis of VTE, pertinent risk factors, and outcome. We compared the Incidence of VTE in travelers to the incidence of VTE in patients from North America (nontravelers) undergoing similar surgical procedures. RESULTS: Eleven patients met our criteria for long-haul air travel and clinically significant VTE within 28 days after surgery. Compared with nontravelers undergoing similar surgical procedures, long-haul travelers had a higher Incidence of VTE (4.9% vs 0.15%; P < .001). Compared with nontravelers who developed VTE, travelers were younger (P = .006), developed VTE earlier in the postoperative course (P = .01), had higher American Society of Anesthesiologists physical status classification (P = .02), and had higher prevalence of smoking (P = .007). Of the 11 travelers with VTE, 10 were of Middle Eastern origin. CONCLUSION: Prolonged air travel before major surgery significantly increases the risk of perioperative VTE. Such patients should receive more Intensive VTE prophylactic measures during the flight and throughout the perioperative period.     

Metabolic syndrome and risk of restenosis in patients undergoing percutaneous coronary intervention

OBJECTIVE: Patients with metabolic syndrome have increased risk of cardiovascular events. The number of patients with metabolic syndrome is rapidly increasing, and these patients often need revascularization. However, only limited data are available on the effect of metabolic syndrome on restenosis in patients undergoing percutaneous coronary intervention (PCI). RESEARCH DESIGN AND METHODS: To assess the role of metabolic syndrome in the development of restenosis, we performed an analysis in a population of patients from the GENetic DEterminants of Restenosis (GENDER) study. The GENDER project, a multicenter prospective study, included consecutive patients after successful PCI and was designed to study the predictive value of various genetic and other risk factors for subsequent clinical restenosis, defined as target vessel revascularization (TVR) or combined end point of death, myocardial infarction, and TVR. This subpopulation of GENDER consisted of 901 patients, 448 of whom (49.7%) had metabolic syndrome. RESULTS: On multivariable Cox regression analysis, controlling for age, sex, previous myocardial infarction, stent length, current smoking, and statin therapy, there was no association between increased risk of TVR (hazard ratio 1.03 [95% CI 0.68-1.57]) or the combined end point (1.05 [0.71-1.55]) and the presence of metabolic syndrome. CONCLUSIONS: This study demonstrates that metabolic syndrome is not associated with TVR or the combined end point after PCI. Furthermore, accumulating characteristics of metabolic syndrome were neither associated with increased risk of TVR nor with the combined end point. Therefore, PCI has equal beneficial results in patients with or without metabolic syndrome. This is important information in light of the pandemic proportion of metabolic syndrome that the medical community will face.     

Prospective evaluation of lactose malabsorption by lactose hydrogen breath test in individuals infected with Entamoeba histolytica and passing cysts

The aim of the present prospective study was to detect lactose malabsorption in subjects in northern India infected with Entamoeba histolytica and passing cysts. The study group included forty-one patients with E. histolytica cysts in at least one of three consecutive faecal samples. Lactose malabsorption was detected by a lactose H2 breath test. The results were compared with those of forty controls subjects. Thirty-two of forty-one (78.0 %) subjects passing E. histolytica cysts had lactose malabsorption compared with seventeen of forty (42.5 %) control subjects (P<0.01). In conclusion, the present study shows that lactose malabsorption is significantly more common in individuals infected with E. histolytica and passing cysts compared with control subjects.     

Effects of creatine and cyclocreatine supplementation on kainate induced injury in pre-pubescent rats

Purpose: To investigate if energy precursor supplementation is neuroprotective in two neuroexcitotoxicity models; the kainate and the kainate followed by chronic phenobarbital models.

Methods: Rats in experiment 1 received 1% creatine or cyclocreatine chow from age (P) 21-65 days, underwent kainate induced status epilepticus on P35 and were compared, as adults, to kainate alone rats and to normal controls. Rats in experiment 2 received 1% creatine chow (P21-P85), underwent kainate status epilepticus on P35, received daily phenobarbital (or saline) injections (P36-P85) and were compared, as adults, to kainate, kainate-phenobarbital and to normal control rats that received regular chow.

Results: In experiment 1, the cyclocreatine-kainate group had increased emotionality and visuospatial learning deficits on the handling and watermaze tests as compared to all other groups. Creatine supplementation did not have any effects. In experiment 2, creatine supplementation did not prevent spontaneous recurrent seizures, aggressivity on the handling test or hippocampal histologic injury.

Conclusion: Energy precursor supplementation in the doses used did not have neuroprotective effects in the kainate or kainate-phenobarbital models in pre-pubescent rats.     

Whole-blood cultures from renal-transplant patients stimulated ex vivo show that the effects of cyclosporine on lymphocyte proliferation are related to P-glycoprotein expression

BACKGROUND: Cyclosporine (CsA) is a substrate for the MDR-1 gene product P-glycoprotein (P-gp). CsA efficacy may be modulated by lymphocyte P-gp expression levels. In this study, CsA inhibition of lymphocyte proliferation in whole-blood cultures ex vivo has been related to (1) lymphocyte P-gp expression and (2) the C3435T polymorphism in the MDR-1 gene, which has been reported to alter P-gp function. METHODS: In 30 renal-transplant recipients taking CsA monotherapy, P-gp expression was measured by flow cytometry. Whole-blood samples were stimulated with purified protein derivative (PPD) and phytohemagglutinin (PHA). CsA resistance ex vivo was defined as less than 10% reduction in proliferation with either PPD or PHA at 2 hours compared with 0 hours. RESULTS: CsA resistance was associated with greater P-gp expression using either PPD (median expression, resistant 1.89 vs. sensitive 0.96, P =0.02) or PHA (1.66 vs. 0.96, respectively, P =0.02). Whole-blood CsA levels in resistant and sensitive patients were similar. The C3435T polymorphism did not affect inhibition of proliferation by CsA (P >0.05 for all between genotype group comparisons). CONCLUSIONS: Our results indicate that lymphocyte P-gp expression determines the degree of inhibition of proliferation by CsA ex vivo; whether this also affects CsA effectiveness in vivo and therefore graft survival requires further study.     

Metastatic melanoma of mesentery

A case of malignant melanoma metastatic to small bowel mesentery in an old female is reported. Her primary malignant melanoma of nasal mucosa was already treated. She presented with intestinal obstruction, underwent surgical excision of the tumour and was tumour-free postoperatively.