Inflammatory cytokine gene expression in the urinary sediment of patients with lupus nephritis

OBJECTIVE: Lupus nephritis is characterized by intrarenal inflammation and lymphocyte activation. In the present study, the expression of cytokine genes in the urinary sediment of patients with systemic lupus erythematosus (SLE) was examined. METHODS: We studied 3 SLE patient groups (25 with active lupus nephritis [active group], 25 with inactive SLE and previous renal involvement [remission group], 20 with inactive SLE and no history of renal involvement [nonrenal SLE group]) and 2 control groups (10 patients with noninflammatory renal diseases [non-SLE group] and 10 healthy volunteers [healthy group]). Cytokine gene expression in the urinary sediment was studied by real-time quantitative polymerase chain reaction. RESULTS: Expression of interferon-gamma (IFNgamma) in urinary sediment was significantly higher in the active group than in all other groups (P < 0.001 by Kruskal-Wallis test). Among the SLE patient groups, there was a close correlation between IFNgamma expression and the overall SLE Disease Activity Index (SLEDAI) score (Spearman's r = 0.590, P < 0.001) and the SLEDAI renal score (r = 0.642, P < 0.001). Urinary expression of interleukin-2 (IL-2) in the active group was significantly higher than that in the healthy group (P = 0.046) but not in the remission or nonrenal SLE groups. There was no difference in the levels of IL-4 expression among the SLE groups. CONCLUSION: We found a predominance of Th1 cytokine in the urinary sediment of patients with active lupus nephritis. Measurement of cytokine gene expression in urinary sediment may be a useful noninvasive tool for assessing the severity of renal involvement in SLE.     

ABO blood groups,grass pea preparation,and neurolathyrism in Ethiopia

An exploratory study was conducted in the rural Estie district of Ethiopia in 1997 to identify the role of ABO blood group, rhesus factor, and type of grass pea (Lathyrus sativus) diet in the susceptibility to neurolathyrism. Five-hundred study subjects (250 cases and 250 controls) were examined and interviewed, and had their ABO and rhesus blood groups determined. The majority (86%) of the cases were males. Blood group O was the most common in the patients and controls followed by groups A, B, and AB. The vast majority of the study subjects were rhesus-positive. The gravy (Shiro) grass pea preparation was consumed by 91.6% of the study population, boiled (Nifiro) by 86%, and roasted (Kollo) by 56.4%. Almost half (48%) of the cases had consumed grass pea for > 4 months compared to 8% of controls (P < 0.001). There was a significant association between the risk for neurolathyrism and the consumption of boiled (adjusted odds ratio [AOR] = 98.4) and roasted (AOR = 55.62) forms of grass pea. There was no risk of paralysis associated with consumption of the gravy form of grass pea (AOR = 0.40, 95% confidence interval 0.1-2.0). Blood group O remained significantly associated with the disease after adjusting for age, type of grass pea preparation consumed, and duration of consumption (AOR = 2.90).     

Comparison of the effects of EM-652 (SCH57068), tamoxifen, toremifene, droloxifene, idoxifene, GW-5638 and raloxifene on the growth of human ZR-75-1 breast tumors in nude mice

EM-652 exerts pure antiestrogenic activity in the mammary gland and endometrium, while tamoxifen, the antiestrogen most widely used for the treatment of breast cancer, exerts mixed antiestrogenic-estrogenic activity in these tissues. Our objective was to compare the agonistic and antagonistic effects of EM-652 with tamoxifen and 5 other antiestrogens on the growth of ZR-75-1 human breast xenografts in ovariectomized nude mice. During the 23 weeks of treatment at a daily oral dose of 50 microg, EM-652 was the only compound that decreased tumor size relative to pretreatment values, whereas the 6 other antiestrogens only decreased to various extents the progression rate stimulated by estrone. Under estrone stimulation, all groups of animals had more than 60% of their tumors in the progression category except for the EM-652-treated group, where only 7% of the tumors progressed. In the absence of estrone stimulation, progression was seen in 60%, 33%, 21% and 12% of tumors in the tamoxifen-, idoxifene-, toremifene- and raloxifene-treated groups, respectively, while only 4% of tumors progressed in the EM-652-treated group. The agonistic and antagonistic actions of each antiestrogen were also measured on endometrial epithelial cell thickness. Our present findings indicate that EM-652, in addition to being the most potent antiestrogen on human breast tumor growth, has no agonistic effect in breast and endometrial tissues. Since previous data have shown benefits of EM-652 on bone density and lipid profile, this compound could be an ideal candidate for chemoprevention of breast and uterine cancers, while protecting against osteoporosis and cardiovascular disease.     

Pattern and associated factors of the neurolathyrism epidemic in Ethiopia

OBJECTIVES: To describe the neurolathyrism epidemic in Ethiopia and to identify associated household factors. METHODS: We interviewed 589 randomly selected heads of household in Debre Sina district of Ethiopia, the area afflicted by the recent neurolathyrism epidemic. Disease information was obtained for 2987 family members. RESULTS: Neurolathyrism patients were detected in 56 (9.5%) households (prevalence rate 2.38%). The mean number of affected family members per household was 1.27 (SD 0.65, range 1-3). Most (77.5%) patients developed the disability during the epidemic (1995-1999). The median age at onset of paralysis was 11 years with a range of 41 (range 3-44). Younger people were more affected during the epidemic than during the non-epidemic period (P=0.01). The presence of a neurolathyrism patient in the family was associated with illiteracy [adjusted OR (95% CI)=2.23 (1.07-5.10)] of the head of household, with owning a grass pea farm [adjusted OR (95% CI)=2.01 (1.04-3.88)] and with the exclusive cooking of grass pea foods using handmade traditional clay pots [adjusted OR (95% CI=2.06 (1.08-3.90)]. CONCLUSION: Males aged 10-14 years were most affected by neurolathyrism. Increased household risk was associated with illiteracy of the head of the household and exclusive cooking of grass pea foods with handmade traditional clay pots.     

Recurrent Legg-Calvé-Perthes disease revisited: fake or reality?

The objective of this study was to assess the course, the epidemiologic features and the prognosis of recurrent Legg-Calvé-Perthes disease. We reviewed seven reported cases and one personal case of recurrent Perthes' disease. In all cases, complete recovery from the previous episode was documented, and a thorough diagnostic work-up to rule out other diseases was undertaken. There were five boys. Age at onset ranged from 2 to 6 years. Five patients had bilateral involvement. Recurrence took place 1-5 years after complete healing of the initial one. Clinical and radiological pictures were similar to those found in primary Perthes' disease of the adolescent and consisted in a greater epiphyseal involvement. Recurrent Perthes' disease is very rare. We did not identify any risk factors for recurrence. A worse outcome is more closely related to an older age of the patient at recurrence than to recurrence itself.     

The selective estrogen receptor modulator acolbifene reduces cholesterolemia independently of its anorectic action in control and cholesterol-fed rats

The cancer-preventing selective estrogen receptor modulator (SERM) acolbifene (ACOL) exerts a potent and pure antiestrogenic action in the mammary gland and uterus, yet it displays beneficial, estrogen-like actions on energy and lipid metabolism in rodents. The compound reduces food intake and strongly decreases cholesterolemia in rats fed a cholesterol-free diet. This study was designed to establish whether the anorectic effect of ACOL is involved in its cholesterol-lowering action, and whether the compound retains its ability to lower cholesterol concentrations in rats with diet-induced hypercholesterolemia. Female rats were fed a purified diet devoid of cholesterol (reference diet) or containing 2% cholesterol (C-diet); they were either not treated or treated daily with ACOL or not treated and pair-fed to the ACOL-treated rats. The C-diet did not affect food intake or weight and fat gains. ACOL reduced food intake (16%) and weight gain (45%, mainly fat) similarly in both dietary cohorts. ACOL, but not pair feeding, reduced cholesterolemia by 33% in rats fed the reference diet. As expected, the C-diet raised serum total cholesterol almost 3-fold and this increase was largely prevented by ACOL but not by pair feeding. Cholesterol was reduced by ACOL, mainly in the HDL fraction, in rats fed the reference diet, but only in the non-HDL fraction in those fed the C-diet. In livers of rats fed the reference diet, ACOL, but not pair feeding, increased protein abundance of the scavenger receptor, class B, type 1, and the LDL receptor, thought to be involved in ACOL-mediated cholesterol lowering. These findings demonstrate that the potent hypocholesterolemic action of ACOL is independent of the concomitant reduction in food intake and fat accretion, and that such action occurs in rats with overt diet-induced hypercholesterolemia.     

Screening decreases prostate cancer mortality: 11-year follow-up of the 1988 Quebec prospective randomized controlled trial

PURPOSE: This clinical trial is aimed at evaluating the impact of prostate cancer screening on cancer-specific mortality. SUBJECTS AND METHODS: Forty-six thousand four hundred and eighty-six (46,486) men aged 45-80 years registered in the electoral roll of the Quebec city area were randomized in 1988 between screening and no screening. Screening included measurement of serum prostatic specific antigen (PSA) using 3.0 ng/ml as upper limit of normal and digital rectal examination (DRE) at first visit. At follow-up visits, serum PSA only was used. RESULTS: Seventy-four (74) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following randomization. Median follow-up of screened men was 7.93 years. A Cox proportional hazards model of the age at death from prostate cancer shows a 62% reduction (P < 0.002, Fisher's exact test) of cause-specific mortality in the screened men (P = 0.005). These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America.     

Association of glomerulopathy with the 5'-end polymorphism of the aldose reductase gene and renal insufficiency in type 2 diabetic patients

The expression of nephropathy in type 2 diabetes has several levels of abnormalities. To define the primary abnormalities of diabetic nephropathy, we conducted an autopsy study of 186 consecutive patients with type 2 diabetes to determine correlations among the aldose reductase gene, renal histopathologies, extracellular matrix, glomerular function, and clinical characteristics. Compared with cases of near-normal renal structure (n = 51) and atypical diabetic glomerulopathy (n = 75), patients with classic diabetic glomerulopathy (n = 60) had advanced glomerular disease, as reflected by elevated plasma creatinine levels (133.2 +/- 59.8 vs. 166.0 +/- 65.7 vs. 243.8 +/- 82.6 micromol/l; P < 0.001), glomerular matrix fractions (20.8 +/- 6.7 vs. 33.5 +/- 16.8 vs. 39.2 +/- 14.3%; P < 0.001), and risk of renal failure (odds ratio [OR] 1 vs. 3.5 vs. 21.4; P < 0.001). Compared with noncarriers of the aldose reductase z-2 allele (n = 92) and z-2 heterozygotes (n = 77), z-2 homozygotes (n = 17) had elevated plasma creatinine (164.1 +/- 73.7 vs. 190.6 +/- 60.9 vs. 241.1 +/- 86.2 micromol/l; P < 0.001) and an increased risk of classic diabetic glomerulopathy (OR 1 vs. 0.9 vs. 3.3; P = 0.026). Overexpression of transforming growth factor-beta1, mesangial cell transdifferentiation by expression of alpha-smooth muscle actin, and aberrant deposition of collagen type IV, fibronectin, and laminin were found in classic diabetic glomerulopathy. These data suggest genetic, biochemical, pathophysiological, and clinical correlations among the aldose reductase gene, extracellular matrix, classic diabetic glomerulopathy, and renal insufficiency. Gene mutation, cellular transdifferentiation, growth factor upregulation, extracellular matrix expansion, and glomerular filtration impairment are the primary abnormalities in type 2 diabetic patients with nephropathy.