A Case of Cervical Carcinoid and Review of the Literature.

Uterine cervix carcinoids are distinct neuroendocrine cervical tumors, representing a comparatively small percentage of them. These well-differentiated neoplasms are far less prevalent than small- and large-cell carcinomas, characterized by a more favorable biological course. We report a case of a 43-year-old woman with a nonmetastatic cervical carcinoid, managed with radical hysterectomy. She still remains free of disease. Scant reports in the literature prohibit any reliable prediction of cervical carcinoid prognosis. Thus, prompt identification of the disease and subsequent therapeutic intervention could alter the final outcome.

Microvessel Density as a Surrogate Prognostic Marker in Patients with Multiple Myeloma: A Meta-Analysis.

BACKGROUND/AIMS: Bone marrow (BM) angiogenesis is considered a hallmark of multiple myeloma (MM) development and progression, and can be quantified with the use of microvessel density (MVD). The purpose of this study is to provide a review and a meta-analysis of the current literature regarding the prognostic value of MVD in the overall survival (OS) of MM patients. METHODS: MEDLINE was screened for studies evaluating the OS of MM patients with regard to their MVD count in BM trephine. The pooled hazard ratio (HR) and its associated 95% confidence interval (CI) among MM patients with a high and low MVD count was the primary end point. Secondary outcomes included odds ratios (OR) for 12-, 36-, and 60-month survival. RESULTS: Ten eligible trials were identified for the analysis of the primary end point and 9 for the secondary end points. Pooled HR for OS was 1.85 (95% CI: 1.25-2.73, p = 0.002). The pooled OR of survival were 1.59 (95% CI: 1.02-2.46, p = 0.04) at 12 months, 2.90 (95% CI: 1.68-5.03, p = 0.0001) at 36 months, and 3.42 (95% CI: 2.41-4.85, p < 0.00001) at 60 months, in favor of the low MVD group. CONCLUSION: This meta-analysis provides persuasive evidence that MVD has significant impact on the clinical outcome of MM patients.

TNFα induces expression of HIF-1α mRNA and protein but inhibits hypoxic stimulation of HIF-1 transcriptional activity in airway smooth muscle cells.

Airway smooth muscle cells (ASMCs) participate in tissue remodeling characteristic of airway inflammatory diseases like asthma. Inflammation and hypoxia pathways are often interconnected and the regulatory subunit of the hypoxia inducible factor, HIF-1α, has been recently shown to be induced by cytokines. Here we investigate the effect of individual or combined treatment of ASMCs with the inflammatory mediator TNFα and/or hypoxia on the expression of HIF-1α, HIF-1 targets and inflammation markers. TNFα enhances HIF-1α protein and mRNA levels, under both normoxia and hypoxia. TNFα-mediated induction of HIF-1α gene transcription is repressed by inhibition of the NF-κB pathway. Despite the up-regulation of HIF-1α protein, the transcription of HIF-1 target genes remains low in the presence of TNFα at normoxia and is even reduced at hypoxia. We show that the reduction in HIF-1 transcriptional activity by TNFα is due to inhibition of the interaction of HIF-1α with ARNT and subsequent blocking of its binding to HREs. Comparison between hypoxia and TNFα for their effects on the expression of inflammatory markers shows significant differences: hypoxia up-regulates the expression of IL-6, but not RANTES or ICAM, and reduces the induction of VCAM by TNFα. Finally, ex vivo treatment of rabbit trachea strips with TNFα increases HIF-1α protein levels, but reduces the expression of HIF-1 targets under hypoxia. Overall, TNFα induces HIF-1α mRNA synthesis via an NF-κB dependent pathway but inhibits binding of HIF-1α to ARNT and DNA, while hypoxia and TNFα have distinct effects on ASMC inflammatory gene expression.

Effect of transosseous application of low-intensity ultrasound at the tendon graft-bone interface healing: gene expression and histological analysis in rabbits.

The present study investigates the effect of transosseous low-intensity pulsed ultrasound (LiUS) on the healing at tendon graft-bone interface, in molecular and histological level. The anterior cruciate ligament (ACL) in both knees of 52 New Zealand White rabbits was excised and replaced with the long digital extensor. A custom-made ultrasound transducer was implanted onto the medial tibial condyle, adjacent to the surface of the bone tunnel at both knees of the rabbits. The LiUS-treated right knees received 200-mus bursts of 1 MHz sine waves at a pulse repetition rate of 1 kHz and with 30 mW/cm(2) spatial-average temporal-average intensity for 20 min daily (study group), while the left knee received no LiUS (control group). Thirty-six rabbits were used to perform semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis from both study and control groups for transforming growth factor-beta1 (TGF-beta1), biglycan and collagen I. RT-PCR products showed statistically significant upregulation of biglycan and collagen I gene expression in the study group, while TGF-beta1 gene expression exhibited a bimodal profile. Histological examination performed in 16 rabbits from both groups supported the findings of the molecular analysis, indicating a faster healing rate and a more efficient ligamentization process after ultrasound treatment. These findings suggest that transosseous application of LiUS enhances the healing rate of the tendon graft-bone interface, possibly by affecting the expression levels of genes significant for the tendon to bone healing process.

Retractile mesenteritis presenting with malabsorption syndrome. Successful treatment with oral pentoxifylline.

Retractile mesenteritis is a rare benign inflammatory disease of the mesentery. Computed tomographic findings usually suggest the diagnosis, which is confirmed by surgical biopsies. Conservative treatment is empirical, based on corticosteroids, colchicine, immunosuppressive agents and progesterone. Surgical resection is sometimes attempted for definitive therapy, although the surgical approach is often limited. This report describes a 62-year old man with histologically proven retractile mesenteritis presenting with malabsorbtion syndrome, who presented pulmonary tuberculosis after initial therapy with corticosteroids. He was subsequently treated with oral pentoxifylline (800 mg/day), with substantial clinical and radiological improvement.

Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1{alpha} and airway responsiveness to ACh.

Airway smooth muscle (ASM) cells are characterized by phenotypic plasticity and can switch between differentiated and proliferative phenotypes. In rabbit tracheal ASM cells that had been differentiated in vitro by serum starvation, readdition of FBS caused initiation of proliferation and induction of nuclear and transcriptionally active hypoxia-inducible factor (HIF)-1alpha. In addition, FBS stimulated the induction of HIF-1alpha by the hypoxia mimetic cobalt. Treatment with actinomycin D, cycloheximide, the phosphatidylinositol 3-kinase inhibitors LY-294002 and wortmannin or the reactive oxygen species scavenger diphenyleneiodonium inhibited the FBS-dependent induction of HIF-1alpha. These data indicate that, in differentiated ASM cells, FBS upregulates HIF-1alpha by a transcription-, translation-, phosphatidylinositol 3-kinase-, and reactive oxygen species-dependent mechanism. Interestingly, addition of FBS and cobalt also induced HIF-1alpha in organ cultures of rabbit trachea strips and synergistically increased their contractile response to ACh, suggesting that HIF-1alpha might be implicated in airway hypercontractility.