Post-load insulin resistance does not predict virological response to treatment of chronic hepatitis C patients without the metabolic syndrome

Background and aimThe role of insulin resistance in predicting virological response to therapy of chronic hepatitis C is debated. We assessed the association between basal (defined as homeostasis model assessment of insulin resistance (HOMA-IR) > 2) and post-load insulin resistance (as oral glucose insulin sensitivity index < 9.8 mg/kg/min) with the rapid and sustained virological responses in chronic hepatitis C.MethodsObservational prospective study of 124 treatment-naïve patients with chronic hepatitis C not fulfilling the metabolic syndrome criteria, adherent to a standard treatment with pegylated interferon alpha plus ribavirin.ResultsInsulin resistance was detected in 50% (by HOMA-IR) and 29% (by oral glucose insulin sensitivity index) of patients. Independent predictors of rapid virologic response were hepatitis C virus (HCV) genotype 2 (odds ratio 5.66; 95% confidence interval 1.88–17.01), HCV genotype 3 (odds ratio 5.23; 95% confidence interval 1.84–14.84) and lower basal ferritin levels (odds ratio 0.99; 95% confidence interval 0.993–0.998). Independent predictors of sustained virologic response were HCV genotype 2 (odds ratio 19.54; 95% confidence interval 2.29–166.41) and HCV genotype 3 (odds ratio 3.24; 95% confidence interval 1.10–9.58). Rapid virologic response was by itself predictive of sustained virologic response (odds ratio 40.90; 95% confidence interval 5.37–311.53).ConclusionsInsulin resistance, measured by both static and dynamic methods, does not predict rapid or sustained virologic response in chronic hepatitis C patients without the metabolic syndrome.     

Gender differences in benign renal masses

Purpose

To examine gender-specific differences in benign renal tumors.

Methods

This retrospective study included 135 adult Caucasian patients with 143 benign renal tumors, which were treated surgically at a single institution. Demographics, comorbidity, histology, renal function, and management were compared by gender. A systematic review and meta-analysis of the literature were performed.

Results

A total of 73 women were compared with 62 men. The female-to-male ratio was significantly higher in patients with benign renal tumors than in those with renal cell carcinoma (1.18:1 vs. 0.57:1, p < 0.001). Only 17 % of benign renal tumors were correctly classified by preoperative computed tomography. The most frequently observed histological types were oncocytoma (44 %) and angiomyolipoma (37 %). Angiomyolipoma occurred more than twice as often in women than in men (72 vs. 28 %), while oncocytoma was more frequently found in men (59 vs. 41 %, p = 0.001). Men with benign renal tumors were older (p = 0.002) and had higher body mass indices (p = 0.019), higher comorbidity indices (p < 0.001), lower ECOG performance status (p < 0.001), and smaller tumors (p = 0.045). No differences were seen in pack years, mode of diagnosis, bilaterality, renal function, use of laparoscopic surgery, and the rate of radical nephrectomy. In the meta-analysis of 9,665 renal tumors, women had a 2.55-fold increased chance of benign pathology and a greater chance of angiomyolipoma (OR 4.66) than men.

Conclusions

This study demonstrated several gender-specific differences in benign renal tumors, especially in the histological types. Despite this, clinical–pathological features and management of benign renal tumors in men and women appear more alike than different.     

Hilar interneuron vulnerability distinguishes aged rats with memory impairment

Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.     

Neurogenesis in temporal lobe epilepsy: Relationship between histological findings and changes in dentate gyrus proliferative properties

Objective

The relationship between hippocampal histopathological abnormalities, epileptogenesis and neurogenesis remains rather unclear.

Methods

Tissue samples including the subgranular zone of dentate gyrus (DG) were freshly collected for tissue culture for neurospheres generation in 16 patients who underwent surgery for drug-resistant temporal lobe epilepsy. Remaining tissues were histologically examined to assess the presence of mesial temporal sclerosis (MTS) and focal cortical dysplasia.

Results

MTS was detected in 8 cases. Neurospheres were formed in 10/16 cases. Only three out of these 10 cases exhibited MTS; on the contrary 5/6 cases lacking neurosphere proliferation presented MTS. There was a significant correlation between presence of MTS and absence of proliferation (p = 0.0389). We also observed a correlation between history of febrile seizures (FS) and presence of MTS (p = 0.0004) and among the 6 cases lacking neurosphere proliferation, 4 cases (66.6%) had experienced prolonged FS. Among “proliferating” cases the percentage of granular cells pathology (GCP) was lower (20% vs 50%) compared to “non proliferating” cases.

Conclusion

A decreased potential to generate neurosphere from the SGZ is related to MTS and to alterations of dentate gyrus granule cells, especially in MTS type 1b and GCP type 1. These histological findings may have different prognostic implications, regarding seizure and neuropsychological outcome, compared to patients with other epileptogenic lesions (such as FCD, glioneuronal tumours, vascular lesions).