Regulation of neutrophil migration and superoxide production by recombinant tumor necrosis factors-alpha and -beta: comparison to recombinant interferon-gamma and interleukin-1 alpha

We compared the ability of recombinant human tumor necrosis factor- alpha (rHuTNF-alpha) and tumor necrosis factor-beta (rHuTNF-beta) to stimulate polymorphonuclear neutrophil (PMN) migration and superoxide production. Significant PMN migration occurred across polycarbonate filters after stimulation with rHuTNF-alpha at concentrations ranging from 10(-7) to 10(-10) mol/L and at 10(-7) to 10(-8) mol/L for rHuTNF- beta and N-formylmethionyl-leucyl phenylalanine (FMLP), whereas recombinant human interferon-gamma was only minimally active at 10(-7) mol/L and recombinant human interleukin-1 alpha was inactive at the doses tested. In addition, antibodies to rHuTNF-alpha completely inhibited rHuTNF-alpha but not rHuTNF-beta or FMLP-induced PMN migration. Combinations of rHuTNF-alpha and rHuTNF-beta (at similar molar concentrations) stimulated PMN migration levels comparable to that obtained with rHuTNF-alpha alone. Checkerboard analyses performed by placing different concentrations of rHuTNF-alpha and rHuTNF-beta above and below polycarbonate filters of microchemotaxis chambers demonstrated that rHuTNF-alpha and rHuTNF-beta stimulated both chemotactic and chemokinetic responses by PMN. Additional studies demonstrated that 1 X 10(-8) mol/L rHuTNF-alpha and 3 X 10(-9) mol/L rHuTNF-beta (which represents 10(4) U/mL of each cytokine) were similar in their ability to induce superoxide production by PMNs; however, at ten- to 100-fold lower molar concentrations (10(3) and 10(2) units), rHuTNF-alpha was significantly more active than rHuTNF-beta. At the doses tested, both cytokines were less active than phorbol myristate acetate at stimulating O2- release. The results demonstrate that rHuTNF- alpha and rHuTNF-beta differ quantitatively but not qualitatively in their effects on PMN functions in vitro and suggest that rHuTNF-beta may be less toxic than rHuTNF-alpha in vivo.     

Bile duct obstruction: radiologic evaluation of level, cause, and tumor resectability

In a prospective study of 65 patients with bile duct obstruction, various radiologic modalities were compared for their capability to demonstrate the level and cause of obstruction and to indicate accurately tumor resectability. Ultrasound (US) was performed in 65 patients, computed tomography (CT) in 51, direct cholangiography (DC) in 57, and angiography in 35. The level of obstruction was correctly indicated by US in 95% of patients and by CT in 90%, and the cause was correctly indicated by US in 88%, by CT in 63%, and by DC in 89%. In predicting tumor resectability, US was correct in 71% of patients, compared with 42% for CT, 58% for DC, and 25% for angiography. US therefore appears to be the single most useful modality in the evaluation bile duct obstruction.     

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

Facteurs associés aux perdus de vue des patients sous traitement antirétroviral dans un centre de traitement ambulatoire du VIH à Conakry,Guinée

Background

Late or inadequate therapeutic management increases the risk of mortality associated with HIV/AIDS. The aim of this study was to analyze the proportion and factors associated with loss of follow-up in HIV patients who receiving antiretroviral therapy at Conakry.

Intestinal permeability in kwashiorkor

Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation.     

Outcome predictors in the management of spinal cord ependymoma

The aim of this study was to determine predictors of functional outcome and survival in a retrospective cohort of spinal cord ependymomas treated at a single institution. Twenty-six patients who underwent treatment of spinal cord ependymoma at a single institution were retrospectively analysed. The clinicopathological features were reviewed and correlated with functional outcome (measured using the Frankel grade), recurrence (clinical or radiological), progression-free survival (PFS) and overall survival (OS). Seventy-nine percent of patients with complete excision had maintained or improved functional outcome, compared to 75% in the incomplete resection plus radiotherapy group. Patients with a good pre-operative Frankel grade tended to maintain their functional status, though this did not reach statistical significance (Fisher’s Exact test, P = 0.090). Univariate analysis revealed that longer symptom duration prior to treatment was associated with poorer functional outcome (P = 0.006). Extent of resection and the use of adjuvant radiotherapy did not influence PFS or OS; however, early diagnosis and treatment are paramount in the management of spinal ependymoma if a good functional outcome is to be achieved.