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IgA nephropathy. Correlation of clinical and histologic features.

The clinical and histologic features of 81 patients with IgA nephropathy were analyzed. Azotemia was present in 32 per cent of the patients, proteinuria was present in 88 per cent, and gross or microscopic hematuria was present in all of the patients tested. The median age of histologic diagnosis was 27 years. The median age at onset of clinical signs was 20 years. There was no increased incidence in any HLA-A or -B antigen within the patient population over our control population. All patients had glomerular mesangial IgA deposition (by definition) greater than or equal to IgG or IgM. Histologic changes were quantitated and ranged from normal to necrotizing and/or crescentic glomerulonephritis. Many patients (48 per cent) had mild or moderate generalized glomerlular hypercellularity. Nonparametric statistical analysis showed strong correlations among patient age at histologic diagnosis, creatinine, proteinuria, global glomerular sclerosis, and interstital fibrosis. Our analysis suggests that IgA nephropathy is an indolent disease generally beginning in childhood. It is a cause of renal insufficiency in a significant number of patients. Interpretation of this series and other reported studies suggests that most cases of IgA nephropathy in the United States are best considered idiopathic but that hereditary and secondary forms may exist.

Adolescent↗

[Value of the analysis of lipoproteins after myocardial infarction].

Lipid and apoprotein constituents of plasma lipoproteins were determined in survivors of myocardial infarction in relation to a control population. Compared to controls, the patients had significantly higher concentrations of total triglycerides, VLDL + LDL - cholesterol and apo-B, but lower concentrations of HLD-cholesterol, HDL2-cholesterol, HDL3-cholesterol, apo A-I and A-II. Survivors with normal lipaemia also had perturbations in HDL and subfractions (HDL2 and HDL3). In addition, the patients exhibited a significant decrease in HDL-cholesterol to VLDL + LDL-cholesterol ratio and in apo A-I to apo-B ratio. These results demonstrate the importance of determining all lipoproteins in future biological studies to evaluate more precisely the relationship between these compounds and atherosclerosis.

Adult↗

[Risk factors in bladder cancer. A case-control study in the department of Hérault, France].

The excess of morbidity and mortality for cancers of the bladder in the french department of Hérault (South of France, on the side of the Mediterranean Sea) justified the implementation of a new epidemiologic study. A case-control study was designed, including 219 cases, 196 hospital-controls and 794 population controls. The collected information concerned profession, habits, behaviour (smoking, alcohol and coffee drinking), places of living, since childhood. The study confirms the role of tobacco, with a highly significant dose-effect, for total consumption, daily dose, and duration of consumption (p < 10(-4)). The classical risk of coffee is confirmed, but it seems not to be due to quantity of caffeine, but to the mouldered form of coffee. As far as alcohol is concerned, the sole risk is due to anisis beverages. When one considers the role of either tobacco, or coffee, or alcohol, the risk is strongly increased (p < 0.02) when exposure begins very early in life (childhood or teen age). But the effect does not depend on the beginning-of-exposure age, when the latter is posterior to teen age (p > 0.95). One may indeed think that the carcinogenic action of these factors concerns mainly the induction phase of the disease. Finally, when place of birth and place of living were considered, a North to South increasing effect was strongly suggested by the study.

Case-Control Studies↗

Enriched natural killing and antibody-dependent cellular cytotoxicity in lymphocyte populations adherent to tumor cell monolayers.

We have previously shown that human peripheral blood lymphocytes that do not adhere to natural killer (NK)-sensitive target cell monolayers are at least partially depleted of NK activity. To demonstrate directly that NK effector cells adhere to the monolayers, we have now recovered the adherent populations by treatment with ethylenediaminetetraacetic acid. When tested immediately after isolation, these adherent populations show NK activity that is intermediate between that of the nonadherent and control cells. When antibody-dependent cellular cytotoxicity is tested concomitantly, the adherent fractions are consistently found to be enriched relative to control, unfractionated lymphocytes. In further studies, control populations and fractions nonadherent and adherent to HSB monolayers are incubated overnight at 37 degrees C and then tested for NK activity. We find that the adherent fractions are selectively enhanced in activity, causing the NK activity of the adherent fractions to exceed that of control populations. The possible involvement of interferon in the augmentation of NK activity is considered.

Adult↗

Median sensory distal amplitude and latency: comparisons between nonexposed managerial/professional employees and industrial workers.

To test for associations between occupation and median nerve dysfunction, measures of median motor and median and ulnar sensory amplitude and distal latency were compared among three populations: control subjects without occupational exposure to highly forceful or repetitive hand exertions (N = 105), industrial workers with hand/wrist symptoms (N = 103), and asymptomatic industrial workers (N = 137). Mean sensory amplitudes were significantly smaller (p < 0.05) and motor and sensory distal latencies were significantly longer (p < 0.001) in the industrial "asymptomatic hand" population compared to the control population. Prolongation of median relative to ulnar latency was significantly longer in the asymptomatic industrial population (p < 0.05). Results were most plausibly explained by differences in checklist identified ergonomic stressors. Median sensory amplitudes were significantly smaller (p < 0.01) and latencies longer (p < 0.05) for industrial workers with exposure to high grip forces compared to those without. Exposure misclassification may have reduced power to detect statistically significant differences between exposed and nonexposed population groups.

Adult↗

Chromium status of tannery workers in relation to metabolic disorders.

Chromium (Cr), being an excellent tanning agent, is widely used in the leather industry. In the process of leather production, tannery workers are exposed to either inorganic Cr(III) compounds or Cr bound to proteins (leather dust). The total Cr content in tannery air (1-54 microg m(-3)) is rather high in comparison to ambient air (4-6 ng m(-3)) but the amount of Cr in inhalable particles (<10 microm) is two to three orders of magnitude less (20-60 ng m(-3)). The total daily intake of Cr was estimated by the analysis of diet (24.3 +/- 4.0 microg Cr day(-1)), drinking water (0.3 +/- 0.1 microg Cr dm(-3)) and ambient air. The contribution of the latter was dominant for tannery workers and almost negligible (8%) for the unexposed population. Chromium is an essential nutrient required for sugar and fat metabolism. The normal dietary intake of Cr for the occupationally unexposed population is found to be suboptimal (<30 microg Cr day(-1)) whereas tannery workers receive on average 150-325 microg of supplemental Cr day(-1). Assessment of the Cr status of both populations was made on the basis of the Cr contents of their scalp hair, pre-shift urine and thermally induced sweat. The median Cr contents in these tissues and fluids were significantly higher (P<0.01) in tannery workers (hair: 4 microg Cr g (-1), urine: Cr/creatinine 1.7 microg Cr g(-1), sweat: 25 microg Cr dm(-3)) in comparison with the control group (hair: 0.16 microg Cr g(-1), urine: Cr/creatinine 0.13 microg Cr g (-1), sweat: 0.7 microg Cr dm(-3)). Tannery workers absorbed up to 13 times more Cr in comparison to controls, the amount varying considerably depending on the workplace and duration of exposure. The main route of Cr absorption appears to be through the gastrointestinal tract, where medium to large particles play a dominant role. The absorption of Cr from leather dust may be more efficient in comparison to inorganic Cr(III) compounds. Under normal circumstances sweat Cr losses represent at least 20% of urinary Cr excretion. The incidence of glucose intolerance and disturbed lipid metabolism was compared between the unexposed (control) population (n=150) and a population of tannery workers (n=138) from the same residential area. The percentage of glucose-intolerant subjects was significantly (P<0.01) lower in the older subgroup (age>48 years), who were even more obese, but not in the whole tannery population in comparison to controls. In the group of subjects displaying glucose intolerance, those from the control population showed a significantly higher body mass index (BMI) of 32.3 and a considerably larger proportion of females (86%) in comparison to subjects from the tannery population (28.2 and 60%, respectively). There was no significant difference in total serum cholesterol levels between the groups. Results of other lipid variables, such as high-density lipid (HDL) cholesterol, low-density lipid (LDL) cholesterol and triglycerides, are controversial: namely, the HDL/LDL ratio was higher for the controls, who showed in contrast significantly higher serum triglyceride levels in comparison to the older subgroup of tannery workers. The possible effects of other parameters on serum HDL-cholesterol level are outlined but the influence of Cr on lipid metabolism in tannery workers remains unclear.

Adult↗

Total body and regional bone mineral content in hemodialysis patients.

Bone mineral content (BMC) in the total body and lumbar spine was evaluated in 126 hemodialysis patients (60 males, 66 females) by dual photon absorptiometry with the Norland DBD 2600. Measurements of: 1) total body BMC divided by lean body mass (BMCTB/LBM), 2) bone mineral density (BMD) of total body, 3) BMD of four regional sections (head, trunk, pelvis, and legs), and 4) BMD of lumbar spine, generally showed a significant decrease in the hemodialysis patients compared to the reference population. However, arm BMD did not show a significant difference between patients and control populations. The z-score of BMCTB/LBM declined significantly throughout the duration of hemodialysis, although that of the lumbar spine BMD did not. It should be noted that the degree of decrease in BMC was more prominent in the total body measurement than in the lumbar spine measurement. There was preferential osteopenia of the total body in the hemodialysis patients. Although the lumbar spine BMD showed a lower value than the control population, the lumbar spine is not the recommended region to monitor the BMD change in hemodialysis patients.

Absorptiometry, Photon↗

Association of HLA-DR4 with ocular cicatricial pemphigoid.

HLA typing for A, B, and C locus antigens was performed on 70 patients with ocular cicatricial pemphigoid (OCP) and on 1849 controls. Additionally, typing for DR and DQ antigens and for the complement proteins (C2, factor B, C4A, and C4B) was performed on 63 patients and on the same control population. A significantly higher incidence of the following antigens was found in the OCP patients when compared to the control population: DR4 (43% in patients compared to 18% in controls, p = 0.0001); DR5 (41% compared to 16%, p = 0.0001); DQw3 (57% compared to 31%, p = 0.0010); A2 (60% compared to 28%, p = 0.0001); B8 (24% compared to 13%, p = 0.0086); B35 (19% compared to 9%, p = 0.0097); and B49 (7% compared to 2%, p = 0.0052). The complement types SC01, SC30, SC32, SC41, and SC42 were also significantly increased in patients compared to controls. No significant differences were found based on ethnic background, involvement of multiple mucous membranes, history of glaucoma, or deposition of specific immunoreactants in conjunctival biopsy samples. These findings may provide further insights into the pathogenesis of OCP and may help to localize a susceptibility gene for this autoimmune disease.

Complement Fixation Tests↗

Follow-up of 2000 second-trimester amniocenteses.

The authors analyzed the outcome of 2000 consecutive second-trimester amniocenteses. Seventy-three percent were performed for maternal age of 34 years or more. The risk of spontaneous abortion before 28 weeks' gestation was 1.3% and for stillbirth or neonatal death, 1.4%. Total fetal loss was 2.7%, compared with 2.2% in a control population. Congenital malformations were found in 1.6% of the study group and in 1.9% of controls; no increase in skeletal problems was observed. Prematurity, defined as a birth weight of less than 2500 g, was noted in 3.6%, compared with 3.7% and 3.9% in 2 control populations. Respiratory difficulties persisting for more than 24 hours were observed in 0.8% of patients, compared with 0.7% of controls. Analyses of the outcome of amniocenteses performed at a single large center do not show an increase in perinatal complications or malformations.

Abortion, Spontaneous↗

Central venous catheters and upper-extremity deep-vein thrombosis complicating immune heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a transient antibody-mediated hypercoagulability state strongly associated with lower-limb deep-vein thrombosis (DVT). Whether HIT is additionally associated with upper-limb DVT--either with or without central venous catheter (CVC) use--is unknown. We therefore studied 260 patients with antibody-positive HIT to determine the influence of CVC use on frequency and localization of upper-extremity DVT in comparison with 2 non-HIT control populations (postoperative orthopedic surgery and intensive-care unit patients). Compared with the control populations, both upper- and lower-extremity DVTs were found to be associated with HIT. Upper-extremity DVTs occurred more frequently in HIT patients with a CVC (14 of 145 [9.7%]) versus none of 115 (0%) patients without a CVC (P =.000 35). All upper-extremity DVTs occurred at the CVC site (right, 12; left, 2; kappa = 1.0; P =.011). We conclude that a localizing vascular injury (CVC use) and a systemic hypercoagulability disorder (HIT) interact to explain upper-extremity DVT complicating HIT.

Arm↗

Bone metabolism in type 2 diabetes mellitus.

Several conditions have been described to cause osteoporosis, including diabetes mellitus. While the relationship between type 1 diabetes and osteopenia is well documented in the literature, data on the presence of this complication in type 2 diabetes have not been well established. We studied a population composed of 66 post-menopausal women with type 2 diabetes and a control population. We examined bone mineral density with the dual-energy X-ray absorptiometry (DXA) technique at the lumbar and femoral levels and, in a subgroup of patients, we also measured the levels of markers of bone remodelling. We found significantly higher levels of bone mineral density at the femoral (but not lumbar) level in the diabetic subjects compared with the control population in all the examined subregions, except Ward's triangle. Moreover, we found higher levels of some markers of bone resorption (urinary calcium and hydroxyproline, telopeptide) in the patients with diabetes, while urinary crosslinks were higher in the controls. On the basis of these results, we suggest that osteoporosis cannot be considered a complication of type 2 diabetes and that, from a metabolic point of view, bone resorption is greater in diabetic patients than in normal subjects, as suggested by the high levels of most of the markers of osteoclastic activity.

Absorptiometry, Photon↗

A major locus for hereditary prostate cancer in Finland: localization by linkage disequilibrium of a haplotype in the HPCX region.

BACKGROUND: Prostate cancer (PRCA) is the most common cancer in males in the western world. In Finland PRCA has an age-adjusted incidence of 81.5 per 100,000. We previously reported that in Finland, the late-onset cases in families with "no-male-to-male" (NMM) transmission of PRCA accounted for most of the linkage to the HPCX region (Xq27-28). The aim of the present study was to test for linkage disequilibrium (LD) and haplotype-sharing around marker DXS1205 between cases from hereditary prostate cancer (HPC) families and population controls. The initial allelic association was performed between 108 PRCA cases and 257 population controls genotyped for 23 markers in the Xq26-28 region. This resulted in a highly significant nominal one-sided Fisher's exact P-value of 0.0003 for allele ''180'' of marker DXS1205. Subsequently, a similar level of significance was observed for the same allele for marker DXS1205 (P=0.0002) when comparing 60 NMM cases and 257 controls. These results were still significant after Bonferroni correction for multiple testing. Fine mapping efforts included the genotyping of four additional markers D3S2390, bG82i1.9, bG82i1.1, bG82i1.0 and four single nucleotide polymorphisms (SNPs) to augment the original markers around DXS1205. RESULTS: Our major finding is that markers extending from ''D3S2390'' to ''bG82i1.0'' flank the critical locus, about 150 kb. Levin and Bertell's LD measure (delta), a guide to localization of a possible variant, was 0.42 and 0.41 for alleles of markers bG82i1.9 and DXS1205, respectively. CONCLUSIONS: In this study, the most significant haplotype comprised the three tightly linked, contiguous markers: ''cen-bG82i1.9-SNP-Hap B-bG82i1.1-tel'' [''197-2-234''] among several possible haplotypes (nominal Fisher's one-sided P=0.003). The two transcription units mapping within this interval are the LDOC1 and SPANXC genes. Positional cloning of the HPCX gene(s) is being facilitated by this exploration of the Xq26-28 region. This study represents the first report identifying a haplotype in the Xq27-28 region for an association between HPCX and X-linked prostate cancer with no-male-to-male transmission in the Finnish population.

Chromosome Mapping↗

Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study.

OBJECTIVE: To evaluate the role of hormone replacement therapy (HRT) as a risk factor for the development of epithelial ovarian cancer. METHODS: A case-control study was performed that used 491 patients with epithelial ovarian cancer frequency matched for age at diagnosis (+/-5 years) with a control population of 741 patients with malignancies of nonestrogen-dependent tissues. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, and education. RESULTS: One hundred of 491 patients (20.4%) in the study population had ever used HRT, and 160 of 741 patients (21.6%) in the control population had ever used HRT (OR 0.85; 95% confidence interval [CI] 0.62, 1.2). A significant association between HRT and specific histologic subtypes of epithelial ovarian cancer was not demonstrable for serous cystadenocarcinoma (OR 1.2, 95% CI 0.8, 1.7), Clear cell carcinoma (OR 1.1, 95% CI 0.4, 3.4), or endometrioid carcinoma (OR 0.4; 95% CI 0.2, 1.2). A significant association between duration of use of HRT and the risk of developing epithelial ovarian cancer was not demonstrable for under 5 years (OR 0.8; 95% CI 0.5, 1.2), 5-9 years (OR 0.6; 95% CI 0.3, 1.1), or 10 or more years (OR 0.6; 95% CI 0.3, 1.4). CONCLUSION: A significant association between the use of HRT and the risk of developing epithelial ovarian cancer, even with prolonged exposure, is not demonstrable.

Case-Control Studies↗

Genetic variation of human mononuclear leukocyte lysosomal acid lipase activity. Relationship to atherosclerosis.

Lysosomal acid lipase activity was measured in mononuclear leukocytes of patients selected on the basis of premature cardiovascular disease, with or without hyperlipidemia. Enzyme activity was significantly lower in the patient population (4.8 +/- 1.3 nmol/min/mg protein, n = 190 males) than in an age-matched control population (5.4 +/- 1.3 nmol/min/mg protein, n = 124 males). There was no effect of hypercholesterolemia or hypertriglyceridemia on the enzyme activity. In the group of patients with normal plasma lipids (n = 77), 18% had mononuclear leukocyte acid lipase activity which fell below the control population 5th percentile, and in the range of enzyme activity observed in cells from obligate heterozygotes for inherited acid lipase deficiency (Wolman disease and cholesteryl ester storage disease). Studies of acid lipase activity in families of our patients provided evidence that an autosomal mutation is associated with (or responsible for) this reduced enzymatic activity and may represent an independent risk factor for the premature development of atherosclerosis.

Adult↗

Associations between cigarette smoking and each of 21 types of cancer: a multi-site case-control study.

BACKGROUND: Although the effects of cigarette smoking on cancer risk have been well documented, there remain several outstanding issues to be clarified, including the determination of which types of cancer are associated with smoking and estimation of the magnitude of the effect of smoking on different types of cancer. A further issue is whether the effects seen elsewhere can be demonstrated in Canada, where tobacco products differ somewhat from those in other countries. METHODS: A case-control study was undertaken in Montreal to investigate the associations between a large number of environmental and occupational exposures on the one hand, and several types of cancer on the other. Between 1979 and 1985, interviews were carried out with incident male cases of 21 types of cancer, including 15 anatomical sites and six histological subtypes. The interview was designed to obtain detailed information on smoking histories, job histories, and other potential confounders. Altogether, 3730 cancer patients and 533 population controls were interviewed. For each type of cancer analysed, two control groups were used: population controls and cancer controls (selected from among other cancer patients). The purpose of the present analysis is to estimate the relative risk of each of 21 types of cancer in relation to smoking and to estimate the percentage of cancer cases attributable to cigarette smoking. RESULTS: Separate analyses conducted with the two control groups produced similar results. Of the many sites of cancer examined, the following were not associated with cigarette smoking: colon, rectum, liver, prostate, kidney and skin (melanoma). Within the lymphoreticular system, there was no excess risk of Hodgkin's lymphoma, although the results for non-Hodgkin's lymphoma were weakly suggestive of an association with smoking. The following sites were clearly associated with smoking: lung (odds ratio [OR] = 12.1), bladder (OR = 2.4), oesophagus (OR = 2.4), stomach (OR = 1.7), and pancreas (OR = 1.6). Population attributable risk percentages due to smoking were 90% for lung, 53% for bladder, 54% for oesophagus, 35% for stomach, and 33% for pancreas. CONCLUSIONS: Of the 21 types of cancer examined, the following were associated with smoking among men in Montreal: lung (including all major histological subtypes), bladder (and its main histological subtypes), oesophagus, stomach and pancreas. Smoking likely accounts for a large proportion of cancers occurring at these sites.

Adult↗

A community-based study on the effect of hexachlorocyclo-hexane (HCH) exposure in spraymen and general population.

The study was carried out in Allahabad district, (Uttar Pradesh) with 260 spraymen as test subjects and 50 persons as controls from a sprayed and unsprayed village respectively. Majority of the spraymen (44%) had worked for 3-4 years (seasons) and 31% had worked in the programme for 5-10 years. The spraymen were relatively healthy with no complaints in 77% whereas the figures were 76% for the Community living in the sprayed village, and 50% for the Community in the unsprayed village. A comparison of the biochemical parameters revealed lowered Cholesterol more than 150 mg % in 38% of the spraymen and 58% had altered A:G ratio. Other biochemical estimations were not significantly different from the control population. The mean residue of Alpha, Beta and Gamma Isomers and the total Alpha, Beta and Gamma isomers were 0.0317, 0.2254, 0.0288 and 0.2859 mg/1 respectively; the corresponding mean values in the control population were 0.0211, 0.1112, 0.0197 and 0.1520 mg/1 respectively. The values in spraymen were twice those of the general population. A significant association (p < .05) was observed between their length of exposure and the levels of Cholesterol and HCH isomers in blood of spraymen. No significant morbidity was evident in spraymen due to HCH exposure.

Case-Control Studies↗

Seroepidemiology of Toxoplasma gondii infection in psychiatric inpatients in a northern Mexican city.

BACKGROUND: Patients with psychiatric disorders were found to show a high seroprevalence of Toxoplasma gondii infection. There is scarce information about the epidemiology of T. gondii infection in psychiatric patients in Mexico. Therefore, we sought to determine the prevalence of T. gondii infection and associated socio-demographic, clinical and behavioural characteristics in a population of psychiatric patients in Durango City, Mexico. Seroprevalence in patients was compared with that obtained in a control population. METHODS: One hundred and thirty seven inpatients of a public psychiatric hospital and 180 controls were examined for the presence of IgG and IgM antibodies against T. gondii by enzyme-linked immunoassay (Diagnostic Automation Inc., Calabasas, CA, USA). The control population consisted of blood donors of a public blood bank and elderly persons attending a senior center in the same city. Age in controls (42 years +/- 20.2) was comparable with that of the psychiatric patients (43.7 years +/-13.8) (p = 0.42). Socio-demographic, clinical and behavioral characteristics from the patients were also obtained. RESULTS: Anti-T. gondii IgG antibodies indicating latent infection with T. gondii was found in 25 (18.2%) of 137 psychiatric inpatients and 16 (8.9%) of 180 controls (p = 0.02). Ten (26.3%) of 38 schizophrenic patients had latent infection and this prevalence was also significantly higher than that observed in controls (p = 0.005). Prevalence of anti-T. gondii IgM antibodies was comparable among patients and controls (4.4% vs 2.2%, respectively, p = 0.22). Multivariate analysis showed that T. gondii infection in inpatients was positively associated with sexual promiscuity (adjusted OR = 15.8; 95% CI: 3.8-64.8), unwashed raw fruit consumption (adjusted OR = 5.19; 95% CI: 2.3-11.3), and a history of surgery (adjusted OR = 6.5; 95% CI: 2.6-16), and negatively associated with lamb meat consumption (adjusted OR = 0.26; 95% CI: 0.10-0.63). CONCLUSION: In the present study, psychiatric inpatients in Durango, Mexico, in general and schizophrenia inpatients in particular had a significantly higher prevalence of T. gondii infection than the control group. Results suggest that unwashed raw fruit consumption might be the most important route of T. gondii transmission in our psychiatric inpatients while lamb meat consumption the less important. Additional studies will have to elucidate the causative relation between infection with T. gondii and psychiatric disorders.

Adolescent↗