Antegrade puncture of the femoral artery: morphologic study

To determine the optimal site for antegrade puncture of the femoral artery, the authors evaluated three cadaver specimens and computed tomographic (CT) scans of 50 patients. The relationships among the common femoral artery, the femoral artery bifurcation, the center of the femoral head, and the inguinal ligament were evaluated. CT showed that the center of the femoral head was always located caudal to the level of the inguinal ligament but cranial to the bifurcation of the common femoral artery. Therefore, the femoral head seems to provide a reliable landmark for entering the common femoral artery.     

Sustained protective effects of 7-monohydroxyethylrutoside in an in vivo model of cardiac ischemia-reperfusion

Earlier studies have shown that 7-monohydroxyethylrutoside (monoHER), an antioxidant flavonoid, protects against doxorubicin-induced cardiotoxicity. In this study, we investigated potential sustained cardioprotective effects of monoHER in a model of ischemia-reperfusion (I/R) in mice. Ischemia was induced for 30 min by ligating the left anterior descending coronary artery. Afterwards, the ligature was removed and reperfusion was allowed for 6 or 24 h or 2 weeks. MonoHER (500 mg/kg) was given intraperitoneally (i.p.) one hour before ischemia. Treatment with monoHER significantly attenuated myocardial neutrophil influx both at 6 and 24 h after reperfusion by 77% and 76%, respectively. Infarct size was also significantly reduced, 24 h and 2 weeks after reperfusion by 58% and 49%, respectively. Whereas ischemia-reperfusion had no influence on basal levels of cardiac contractility (+dp/dt), responses to dobutamine were blunted 24 h and 2 weeks after reperfusion. In mice treated with monoHER, cardiac contractility response was significantly restored. These results indicate that monoHER exerts a sustained cardioprotective effect on ischemia-reperfusion injury and prevents deterioration of cardiac contractility.     

ACUTE MYOCARDIAL INFARCTION: A RARE COMPLICATION OF THE THROMBOTIC TENDENCY IN NEPHROTIC SYNDROME

SUMMARY The association of nephrotic syndrome with a hypercoagulable state and vascular thrombosis is well recognised. We present a case of acute anterior myocardial infarction in a young man with nephrotic syndrome secondary to minimal change glomerulonephritis, in which subsequent coronary angiography showed no evidence of atherosclerotic coronary artery disease and thrombotic occlusion of an otherwise normal left anterior descending coronary artery was the likely cause of presentation.     

Diffuse postoperative peritonitis -value of diagnostic parameters and impact of early indication for relaparotomy

Objective

Current criteria for performing relaparotomy for suspected peritonitis are non explicit and based on non-quantitative, subjective arguments or hospital practice. The aim of this study was to determine the value of routinely used clinical and diagnostic parameters in early detection of postoperative, diffuse peritonitis (PP). Furthermore, the prognosis and outcome after early indication for relaparotomy in patients with PP compared to community-aquired peritonitis (CAP) was evaluated.

Methods

Between 1999 and 2008, a total of 251 patients with diffuse secondary peritonitis either postoperative (PP) or community acquired (CAP) were analyzed retrospectively. PP (n = 114) and CAP (n = 137) were compared regarding physical examination, MPI-Score, APACHE II-Score, evidence of organ failure, laboratory parameters, diagnostic instruments and clinical course. The treatment regimen comprised surgical source control (with/without programmed lavage), abdominal closure and relaparotomy on demand, broad spectrum antibiotic therapy and intensive care support.

Results

The APACHE II-Score (20 CAP vs. 22 PP, p = 0.012), MPI-Score (27 CAP vs. 30 PP, p = 0.001) and the number of lavages differed significantly. Positive phyiscal testing and signs of sepsis [abdominal pain (81.6% PP vs. CAP 97.1%, p = 0.03), rebound tenderness (21.9% vs. 35.8%, p = 0.02), fever (35.1% vs. 51.8%, p = 0.03)] occurred significantly less often in the PP patients than in the CAP group. Conventional radiography (66.2%) and ultrasonography (44.3%) had a lower diagnostic sensitivity than did abdominal CT-scan (97.2%). Mortality was higher in the PP group but did not differ significantly between the two groups (47.4% PP vs. 35.8% CAP, p = 0.06).

Conclusion

The value of physical tests and laboratory parameters in diagnosing abdominal sepsis is limited. CT-scanning revealed the highest diagnostic accuracy. A treatment regimen of early relaprotomy appears to be the most reasonable strategy for as early discovery of postoperative peritonitis as possible.     

The trend in mental health-related mortality rates in Australia 1916-2004: implications for policy

Background

This study determines the trend in mental health-related mortality (defined here as the aggregation of suicide and deaths coded as "mental/behavioural disorders"), and its relative numerical importance, and to argue that this has importance to policy-makers. Its results will have policy relevance because policy-makers have been predominantly concerned with cost-containment, but a re-appraisal of this issue is occurring, and the trade-off between health expenditures and valuable gains in longevity is being emphasised now. This study examines longevity gains from mental health-related interventions, or their absence, at the population level. The study sums mortality data for suicide and mental/behavioural disorders across the relevant ICD codes through time in Australia for the period 1916-2004. There are two measures applied to the mortality rates: the conventional age-standardised headcount; and the age-standardised Potential Years of Life Lost (PYLL), a measure of premature mortality. Mortality rates formed from these data are analysed via comparisons with mortality rates for All Causes, and with circulatory diseases, cancer and motor vehicle accidents, measured by both methods.

Results

This study finds the temporal trend in mental health-related mortality rates (which reflects the longevity of people with mental illness) has worsened through time. There are no gains. This trend contrasts with the (known) gains in longevity from All Causes, and the gains from decreases achieved in previously rising mortality rates from circulatory diseases and motor vehicle accidents. Also, PYLL calculation shows mental health-related mortality is a proportionately greater cause of death compared with applying headcount metrics.

Conclusions

There are several factors that could reverse this trend. First, improved access to interventions or therapies for mental disorders could decrease the mortality analysed here. Second, it is important also that new efficacious therapies for various mental disorders be developed. Furthermore, it is also important that suicide prevention strategies be implemented, particularly for at-risk groups. To bring the mental health sector into parity with many other parts of the health system will require knowledge of the causative factors that underlie mental disorders, which can, in turn, lead to efficacious therapies. As in any case of a knowledge deficit, what is needed are resources to address that knowledge gap. Conceiving the problem in this way, ie as a knowledge gap, indicates the crucial role of research and development activity. This term implies a concern, not simply with basic research, but also with applied research. It is commonplace in other sectors of the economy to emphasise the trichotomy of invention, innovation and diffusion of new products and processes. This three-fold conception is also relevant to addressing the knowledge gap in the mental health sector.

     

Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by human cytochrome P4501A1, P4501A2 and P4501B1

While the metabolic activation of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) by N-hydroxylation has been well documented, the relative roles of the human cytochrome P450 (CYP) enzymes that catalyze this reaction have not been established. Previous studies indicated that the mutagenic activation product, 2-hydroxyamino-PhIP (N2-OH- PhIP), is produced primarily by CYP1A2, and to a lesser extent by CYP1A1. We recently reported that human CYP1B1 also produces N2-OH-PhIP (Carcinogenesis, 18, 1793-1798, 1997). In the present study, we examined PhIP metabolism by microsomes containing recombinant human CYP1A1, 1A2 or 1B1 expressed in Sf9 insect cells and compared the kinetic values for PhIP metabolite formation. PhIP metabolites were analyzed by high pressure liquid chromatography with fluorescence and absorbance detection. Vmax values for N2-OH-PhIP formation were 90, 16 and 0.2 nmol/min/nmol P450, and the apparent Km values were 79, 5.1 and 4.5 microM for human CYP1A2, 1A1 and 1B1, respectively. The non- mutagenic metabolite, 4'-hydroxy-PhIP, was also formed by all three CYP enzymes with Vmax values of 1.5, 7.8 and 0.3 nmol/ min/nmol P450 and apparent Km values of 43, 8.2 and 2.2 microM for human CYP1A2, 1A1 and 1B1, respectively. Although the Vmax for N2-OH-PhIP production was highest for CYP1A2, the catalytic efficiency (Vmax/Km) of CYP1A1 was greater than that of CYP1A2. These results suggest that, for humans, extrahepatic CYP1A1 may be more important than previously thought for the metabolic activation of the dietary carcinogen PhIP.      

Nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia: association with high-risk clinical features

To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more "lymphomatous" disease characteristics (including presence of a mediastinal mass in 15%. T- cell phenotype in 26%, splenomegaly greater than 8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P = .01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P = .06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21-22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.