Insulin resistance in chronic hepatitis B and C.

AIM: To determine whether insulin resistance occurs in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC) and its relationship with the presence of liver fibrosis and steatosis. METHODS: Untreated patients with CHC (n=60) or CHB (n=40), similar in age, gender, body mass index and waist-hip ratio, were studied. Relationship between anthropometric, biochemical (fasting serum insulin, C-peptide, ferritin, iron, TNF-alpha, cholesterol, triglyceride, bilirubin, hemoglobin and platelet concentrations) and liver biopsy (43 CHC and 20 CHB patients) findings was investigated by insulin resistance determined via the homeostasis model assessment (HOMA-IR). RESULTS: The mean fasting serum insulin was 14.9 (11.9) mU/mL in CHC and 21.4 (17.4) in the CHB group (normal range 0.7-9; p=0.049) and mean HOMA-IR was 3.1 (2.6) in CHC versus 4.7 (4.1) in the CHB group (normal range 0.12-4.61; p=0.036). HOMA-IR was significantly associated with fibrosis stage in the CHC group (p=0.015), but not in the CHB group. CONCLUSION: Hyperinsulinemia occurs in chronic viral hepatitis B and hepatitis C; insulin resistance is associated with stage of fibrosis in hepatitis C.     

The incidence of hip fracture in Malaysians above 50 years of age: variation in different ethnic groups

Aims: Hip fracture is frequently studied to reflect osteoporosis related fractures. The aim of this study was to look at ethnic differences in the incidence of hip fractures between the three races in Malaysia. Methods: This was a retrospective study performed for the years 1996 and 1997. Data from hospitals treating hip fractures in elderly patients were collected throughout the whole country. Result: The overall incidence of hip fractures was 90 per 100 000 individuals. Sixty‐three percent of patients presenting with hip fractures were Chinese. This was followed by Malays at 20% and Indians, 13%. Race‐specific incidence data showed that the fracture rates are highest among the Chinese (160 per 100 000) followed by Indians (150 per 100 000) and Malays (30 per 100 000). Females were twice as commonly affected compared to males. Race and sex‐specific incidence data showed that the incidence was highest among Chinese females (220 per 100 000), followed by Indian females (200 per 100 000). The age‐specific incidence was 500 per 100 000 for patients above 75 years, compared to 10 per 100 000 in those between 50 and 54 years. Conclusion: Hip fractures are common in Malaysia. There are differences in hip fracture incidence depending upon ethnicity.     

Fibroblasts from naked mole-rats are resistant to multiple forms of cell injury, but sensitive to peroxide, ultraviolet light, and endoplasmic reticulum stress

Fibroblasts from long-lived mutant mice are resistant to many forms of lethal injury as well as to the metabolic effects of rotenone and low-glucose medium. Here we evaluated fibroblasts from young adult naked mole-rats (NMR; Heterocephalus glaber), a rodent species in which maximal longevity exceeds 28 years. Compared to mouse cells, NMR cells were resistant to cadmium, methyl methanesulfonate, paraquat, heat, and low-glucose medium, consistent with the idea that cellular resistance to stress may contribute to disease resistance and longevity. Surprisingly, NMR cells were more sensitive than mouse cells to H(2)O(2), ultraviolet (UV) light, and rotenone. NMR cells, like cells from Snell dwarf mice, were more sensitive to tunicamycin and thapsigargin, which interfere with the function of the endoplasmic reticulum (ER stress). The sensitivity of both Snell dwarf and NMR cells to ER stress suggests that alterations in the unfolded protein response might modulate cell survival and aging rate.     

Pulse transmission coefficient: a nonhyperemic index for physiologic assessment of procedural success following percutaneous coronary interventions.

Intracoronary pressure measurements and the determination of fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) predict adverse events. Coronary lesions may impair the transmission of pressure waves across a stenosis, potentially acting as a high-frequency filter. The pulse transmission coefficient (PTC) is a nonhyperemic parameter that calculates the transmission of high-frequency components of the pressure signal through a stenosis. It was shown recently that PTC is highly correlated with FFR. This study was designed to examine the change of PTC as compared to FFR following PCI. Pressure signals were obtained by pressure guidewire in 27 lesions pre- and post-PCI and were analyzed with an algorithm that identifies the high-frequency component in the pressure signal. The PTC was calculated at baseline as the ratio between distal and proximal high-frequency components of the pressure waveform across the lesion. FFR measurements were assessed with intracoronary adenosine. There was a significant increase in PTC following PCI (0.15 +/- 0.17 at baseline vs. 0.84 +/- 0.11 post-PCI; P < 0.001). Comparable changes were observed for FFR (0.58 +/- 0.12 at baseline vs. 0.91 +/- 0.05 post-PCI; P < 0.001). PTC is a nonhyperemic parameter for physiologic assessment of coronary artery stenoses. Similar to FFR, PTC is significantly increased following PCI. Thus, it may serve as an adjunct index for the functional assessment of procedural success following PCI.     

Immune and functional role of nitric oxide in a mouse model of respiratory syncytial virus infection

BACKGROUND: Respiratory syncytial virus (RSV) infection of respiratory epithelial cell cultures increases expression of inducible nitric oxide synthase (iNOS). The present study was designed to evaluate both the effect of RSV infection on expression of iNOS and the role of NO in the host responses to RSV infection in vivo. METHODS: RSV infection was performed by nasal inoculation of BALB/c mice (6-8 weeks old). Total cell and differential counts were measured in bronchoalveolar lavage (BAL) fluid. Lung nitrates were measured in BAL fluid by use of the Greiss reaction, and cytokines were measured by enzyme-linked immunosorbent assay. Lung hyperresponsiveness to methacholine was measured by use of a Buxco unrestrained whole-body plethysmograph. RESULTS: RSV infection increased levels of lung nitrites, levels of iNOS protein and activity, and levels of iNOS mRNA. RSV infection resulted in recruitment of neutrophils and lymphocytes into the lungs, enhanced levels of interferon (IFN)-gamma, and increased airway hyperresponsiveness (AHR). Treatment with iNOS inhibitors (2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine and N-nitro-L-arginine methyl ester) increased RSV titers in the lungs yet reduced lung inflammation and RSV-induced AHR. Inhibition of iNOS activity with either agent did not significantly alter levels of IFN-gamma or interleukin-4 in the lungs. CONCLUSIONS: The results of the present study suggest that RSV-induced production of NO participates in complex host responses and may mediate important aspects of the clinical disease.     

Breast cancer classification and prognosis based on gene expression profiles from a population-based study

Comprehensive gene expression patterns generated from cDNA microarrays were correlated with detailed clinico-pathological characteristics and clinical outcome in an unselected group of 99 node-negative and node-positive breast cancer patients. Gene expression patterns were found to be strongly associated with estrogen receptor (ER) status and moderately associated with grade, but not associated with menopausal status, nodal status, or tumor size. Hierarchical cluster analysis segregated the tumors into two main groups based on their ER status, which correlated well with basal and luminal characteristics. Cox proportional hazards regression analysis identified 16 genes that were significantly associated with relapse-free survival at a stringent significance level of 0.001 to account for multiple comparisons. Of 231 genes previously reported by others [van't Veer, L. J., et al. (2002) Nature 415, 530-536] as being associated with survival, 93 probe elements overlapped with the set of 7,650 probe elements represented on the arrays used in this study. Hierarchical cluster analysis based on the set of 93 probe elements segregated our population into two distinct subgroups with different relapse-free survival (P < 0.03). The number of these 93 probe elements showing significant univariate association with relapse-free survival (P < 0.05) in the present study was 14, representing 11 unique genes. Genes involved in cell cycle, DNA replication, and chromosomal stability were consistently elevated in the various poor prognostic groups. In addition, glutathione S-transferase M3 emerged as an important survival marker in both studies. When taken together with other array studies, our results highlight the consistent biological and clinical associations with gene expression profiles.     

Large‐cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with fludarabine–rituximab‐containing regimens: natural history‐ or therapy‐related complication?

Novel therapeutic regimens containing purine analogs and monoclonal antibodies have led to significant improvement in the course of indolent lymphoproliferative diseases (LPD). Complete clinical and even molecular remissions have been achieved in an increasing proportion of patients. In parallel to their tumor cytotoxic effect, these agents are inevitably associated with prolonged immunosuppression inherent to their mechanism of antilymphocytic activity. Until now, attention has been paid mainly to opportunistic infection occurring as a result of the above drug-induced immunosuppression and less to other possible complications, such as malignancy or tumor progression in the immunocompromised host. Here we briefly report nine patients with previously treated indolent LPD in whom the onset of large-cell transformation occurred during or shortly after the initiation of regimens containing these agents before transformation occurred. One patient had received rituximab alone, three fludarabine-containing regimens and five received sequential regimens containing both agents. This