Vitamin a cost-effectiveness model

To assist in the selection of a preferable vitamin A deficiency control policy, a model has been developed to organize information on program costs and program-related effects. The model was designed to compare three approaches: (1) diet modification; (2) fortification of processed foods; and (3) periodic large doses. Health effects projected are rates of specific eye pathologies associated with vitamin A deficiency (xerophthalmia), and mortalities within age cohorts. Effectiveness is calculated as a function of coverage, biological efficacy, and incidence of vitamin A deficiency. The model was applied to data from the Province of West Java in Indonesia. The results of this application suggest that funding level considerations are an important factor in selecting a preferred control strategy. In addition to determining the relative resource requirements of alternative interventions aimed at reducing the morbidity and mortality effects of vitamin A deficiencies, the model, using marginal cost and marginal effectiveness information, can serve as a guide to the most efficient allocation of resources for each type of intervention.     

竹红菌甲素敏化S-180肿瘤细胞膜的光氧化反应及机理探讨

本文研究了竹红菌甲素(简称甲素)对S-180肿瘤细胞膜的作用。结果表明,甲素结合光照可引起S-180肿瘤细胞膜蛋白质交联、脂质过氧化产物MDA含量增加。但在SDS-PAGE分析中观察到的高分子蛋白质交联带并非由MDA所引起。甲素同样可引起小牛胸腺组蛋白光氧化、发生分子交联,并可敏化色氨酸、酪氨酸和组氨酸的无氧化。     

Suppression of B cell differentiation by ligation of membrane-bound IgM

Using B cells from the transgenic mouse line B6-Sp6 and control littermates, stimulated by lipopolysaccharide (LPS) under novel culture conditions that provide for the response of all B cells, we show here that specific ligation of the surface IgM molecules always results in inhibition of terminal differentiation and immunoglobulin secretion by activated cells, regardless of the ligand. Thus, monoclonal antibodies to (a) the CH region of Ig (anti-μ. and anti-allotype), (b) the Cx region, (c) the V region (anti-idiotype) of surface IgM, as well as (d) multivalent antigen (2,4,6-trinitrophenyl-bovine serum albumin), all show similar effects and dose-response curves. IgD-negative transgenic B cells are equally sensitive to IgM ligation-dependent inhibition, as control (IgD-positive) B cells. The allotype specificity of this inhibition, assessed by using anti-u, allotype reagents to inhibit and assay the responses, suggests that B cells expressing transgenic or endogenous IgM in transgenic B6-Sp6 mice are largely independent populations. These observations establish that anti-IgM antibodies in conjunction with appropriate LPS stimulation, provide a universal model system for functional characterization of B cell responses.     

环孢霉素A滴眼治疗角膜移植排斥反应

应用0.5％环孢霉素A(cyclosporin A,CsA)滴眼治疗穿透性角膜移植术后发生免疫排斥患者16例(16只眼),治愈9只眼,好转6只眼,无效1只眼。随访5～24个月,其中2只眼因停药复发,1只眼于拆线后复发,继续用药或增加给药次数后治愈。研究表明0.5％CsA滴眼剂治疗术前移植床条件较好,角膜移植术后发生免疫排斥的病例可得到良好疗效;而对术前移植床条件较差,角膜移植术后发生免疫排斥的病例有一定的疗效。作者对眼局部应用CsA治疗角膜移植排斥的疗效和作用机理进行了讨论。     

Determination of functional kidney volume by single-photon emission computed tomography in patients with insulin-dependent diabetes mellitus.

Functional parenchymal kidney volume was determined by single-photon emission computed tomography (SPECT) for 99mTc-dimercaptosuccinic acid (DMSA) using a rotating gamma camera in phantom experiments and in patients with insulin-dependent diabetes mellitus (IDDM). The results from the patient examinations were corrected according to the phantom studies and were thereafter set in relation to renal haemodynamics, blood pressure, and urinary albumin excretion. Functional parenchymal kidney volume was significantly greater in diabetic patients compared to that of 11 healthy controls (P < 0.003). Urinary albumin excretion was increased and glomerular filtration rate (GFR) per renal parenchymal volume significantly less in patients with a duration of diabetic disease of more than 15 years compared to patients with shorter duration of disease (P < 0.03 and P < 0.05 respectively). Diabetic patients with a GFR of more than 120 ml/min had greater renal parenchymal volume than patients with lower GFR (P < 0.02). Patients with increased GFR, renal plasma flow (RPF), renal blood flow, or filtration fraction had significantly greater functional parenchymal volume than the healthy subjects (P < 0.01 for all comparisons). We conclude that by application of SPECT for DMSA we were able to show that IDDM patients have greater renal parenchymal volumes than healthy subjects. GFR/kidney volume was increased in IDDM patients with a duration of disease of < 15 years compared to patients with long-standing diabetes. The SPECT technique seems suitable for prospective long-term follow-up studies of functional kidney volume in IDDM patients.     

Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Chronic anemia as a complication of parvovirus B19 infection in a pediatric kidney transplant patient

. This is a report of unexplained anemia that persisted for 4 months in an adolescent renal transplant patient receiving immunosuppression that included prednisone, tacrolimus, and mycophenolate mofetil. This patient required monthly blood transfusions for fatigue, palpitations, and hematocrit levels between 15% and 17%. In addition, his posttransplant course was notable for the development of insulin-dependent diabetes mellitus. While receiving low-dose prednisone, he was switched from tacrolimus to cyclosporin and tapered off insulin injections over the next 2 months. At 4.5 months post-transplantation, further diagnostic evaluation was suggestive of parvovirus B19 infection as the cause for our patient’s chronic anemia. After testing negative for serum-specific parvovirus B19 IgM and IgG antibodies, parvovirus B19 infection was detected in blood by the polymerase chain reaction. Treatment with intravenous immunoglobulin (1 g/kg per day × 2 days) resulted in normalization of both his reticulocyte count and hematocrit within 6 weeks. At 4 months after receiving the immunoglobulin infusion, he has maintained a normal hematocrit level and stable renal function without requiring further blood transfusions. Received August 23, 1996; received in revised form and accepted November 20, 1996     

N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis.

The objectives of this study was to assess the overall effect of N-acetylcysteine (NAC) in preventing radiocontrast-induced nephropathy (RCIN) using all available data in the literature. RCIN is associated with increased morbidity and mortality. Existing randomized trials of NAC are small and show inconsistent results. Prior meta-analyses do not include data from the most current studies. We used standard search protocols to identify all published articles and abstracts of prospective trials using NAC with fluid hydration compared to hydration alone in patients with chronic renal insufficiency undergoing contrast procedures. A rise in serum creatinine by 0.5 mg/dl or 25% above baseline at 48-72 hr after contrast exposure was used as the primary outcome. We identified 14 trials of NAC with 1,584 patients published as full-text articles. Using a random-effects model, the use of oral NAC resulted in a significant reduction in the risk for developing RCIN (RR = 0.57; 95% CI = 0.37-0.84; P = 0.01). This finding did not significantly change in a fixed-effect model (RR = 0.55; 95% CI = 0.42-0.73) or when the data were reanalyzed using only randomized trials in all forms (i.e., articles and abstracts; RR = 0.67; 95% CI = 0.47-0.95). We identified only one important difference between the positive and the negative studies: the cumulative exposure to contrast media (174 vs. 152 ml). Metaregression did not show a significant relationship between contrast volume and the RR of developing RCIN (P > 0.10). In the trials showing benefit for NAC, the treated patients' postprocedure creatinine unexpectedly decreased by 0.21 mg/dl (95% CI = 0.33-0.08). Prophylaxis with NAC significantly reduces the risk for RCIN. The reasons for improvement in serum creatinine in patients treated with NAC are unclear, but may include improved renal blood flow due to NAC and/or vigorous hydration.