Altered distributions in circulating follicular helper and follicular regulatory T cells accountable for imbalanced cytokine production in multiple sclerosis.

Follicular T helper (Tfh) and regulatory (Tfr) cells are distinct subsets of CD4+ T lymphocytes, regulating humoral immune responses in the germinal center. It is widely accepted that dysregulated Tfh and Tfr cells are associated with autoimmunity. In this study, we evaluated the frequencies of circulating chemokine receptor (CXCR)5+ programmed cell death 1 (PD-1+ ) Tfh (cTfh) and CXCR5+ PD-1+ forkhead box protein 3 (FoxP3+ ) CD25+ Tfr (cTfr) cells, and their corresponding cytokines from the peripheral blood mononuclear cells of 28 patients with relapsing-remitting multiple sclerosis (MS) and 16 age- and sex-matched healthy controls (HC). Subsets of cTfh cells by Th1- and Th17-related surface markers (CXCR3 and CCR6) were also evaluated. We found that the frequency of cTfh cells was significantly higher in MS patients compared to that of HC. Conversely, the frequency of cTfr cells was lower in MS patients than that of HC. Interleukin (IL)-21-producing cTfh cells were significantly increased in MS patients, while IL-10-secreting cTfr cells were lower in MS patients compared to levels in HC. Among cTfh cells, cTfh17.1 cells were the major subtypes that were significantly increased in MS patients compared to HC, with the frequency of IL-21-secreting cells being the highest. These results suggest that an imbalanced distribution of cTfh and cTfr exist in MS patients, which contributes to the reciprocally altered IL-21 and IL-10 production.

Rehabilitation Approach of a Patient with Myositis Ossificans: Non-surgical Management, Hazard of being Unguided Over Exercised.

Myositis ossificans (MO) is a condition where calcification occurs in the soft tissue as well as around the bone following fracture, vigorous exercise or trauma. Although it is a radiological diagnosis, it often leads physician to an incorrect or missed diagnosis as recurrent fracture. Frequently, it follows haemorrhage into the muscle in the tissue space. We report a 45 years old house-wife presented with the complaints of weakness of right side of body and pain with restricted range of motion (ROM) in right lower limb. She was a diagnosed case of recurrent stroke with rheumatic valvular heart disease. After discharge, vigorous physical exercise was done at home by local physiotherapist without appropriate guidance from physiatrist. Gradually pain was so severe that she didn't allow moving her right lower limb. Over the course of time, she became incapacite and bed bound. She denied any positive family history. With the hip and lower limb problems she consulted with orthopedic surgeon and was referred to Physical Medicine and Rehabilitation department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh for further management & rehabilitation. This case is presented to focus on hazard of being unguided, over-exercised and non-surgical management approach of this rare condition.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial.

BACKGROUND: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. METHODS: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. RESULTS: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). CONCLUSION: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.

In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.

Huge bilateral polycystic kidneys with suspicion of malignancy, recurrent bleeding in cysts, and acute abdomen.

UNLABELLED: We present a case of huge bilateral polycystic kidneys, with suspicion of malignancy and repeated admissions with acute abdomen, secondary to bleeding in cysts, and anaemia, requiring affected side nephrectomy. KEY MESSAGE: Autosomal dominant polycystic kidney disease (ADPKD) mostly ends up with end stage renal disease (ESRD), requiring haemodialysis, with increased risk of malignancy and enlargement of kidneys with its associated complications, mostly dealt with conservatively, except malignancy, which requires nephrectomy.

Anaphylaxis to patent blue V: a case series and proposed diagnostic protocol.

Patent blue V is widely used in the identification of sentinel lymph nodes in patients with breast cancer and other malignancies. Individual case reports of allergy to patent blue V have been described in the medical literature since the 1960s. However, there is little data on clinical features and little experience of which allergy tests are appropriate or useful. We gathered all cases of patent blue V allergy that had been seen and diagnosed in the Department of Allergy, Addenbrooke's Hospital over a 3-year period. We collected clinical details of each case including skin test results. For comparison we recruited 12 healthy control subjects who then underwent skin testing to patent blue V. Six cases of patent blue V allergy were identified, all occurring during sentinel lymph node identification for breast carcinoma. All 6 had positive skin prick tests to neat patent blue V (25 mg/ml). Skin prick testing with a 1 : 10 dilution (2.5 mg/ml) produced positive results in 3 of 4 patients tested, and intradermal testing at a 1 : 100 dilution was (0.25 mg/ml) was positive in all patients tested. Of 12 control subjects, 11 had negative skin prick tests to both neat and 1 : 10 patent blue V with one subject showing a positive reaction to the higher concentration only. On the basis of our experience of patent blue V allergy, we propose a diagnostic protocol that can be safely and reliably utilised in centres equipped for allergy testing.

Cervical cancer in Bangladesh: community perceptions of cervical cancer and cervical cancer screening.

We investigated the awareness of, and the attitude towards screening for, cervical cancer in Bangladesh. We performed a qualitative study using focus group discussions (FGD). The framework approach to qualitative analysis was used. The study was performed in the catchment areas of Addin Hospital, Jessore, Southern Bangladesh (peri-urban) and LAMB hospital, Parbatipur, North West Bangladesh (rural). A total of 220 men, women and adolescents participated in 28 FGDs. Awareness of cervical cancer was widespread. Knowledge about causes was often inadequate. The perceived consequences of cervical cancer were numerous and awareness of the need for cervical cancer treatment was present. Barriers to accessing care include: low priority for seeking help for symptoms, limited availability of health services and cost. Most women were unaware of the possibility of screening via speculum examination, which was considered acceptable to women (and men), as long as the examination was done by a female healthcare provider in an environment with sufficient privacy. In conclusion, adequate gynaecological services are not available or accessible for most women in rural and peri-urban Bangladesh. However, awareness of cervical cancer is widespread. Screening for cervical cancer in these communities is acceptable if done by a female healthcare provider under conditions with sufficient privacy.

Capsaicin cough sensitivity in bronchiectasis.

BACKGROUND: Bronchiectasis is a suppurative airway disease characterised by persistent cough and sputum production associated with bronchial dilatation. A study was undertaken to determine whether cough sensitivity is increased in bronchiectatic patients. METHODS: Twenty two patients with bronchiectasis and 20 healthy non-smoking controls matched for age and sex were recruited into the study. Quality of life (Leicester Cough Questionnaire score), total cough symptom score, and extent of bronchiectasis on HRCT scans were recorded. Cough sensitivity was assessed using incremental inhalation of capsaicin concentrations; the concentration at which 5 or more coughs occurred (C5) was recorded. RESULTS: Patients with bronchiectasis had increased sensitivity to capsaicin compared with controls (mean (SE) log10 C5 1.22 (0.20) v 1.89 (0.21); p<0.03). Capsaicin sensitivity correlated positively with the Leicester Cough Questionnaire score (r = 0.64; p = 0.005) and inversely with the total cough symptom score (r = -0.58; p = 0.004), but not with the extent of the disease. It also correlated with forced expiratory volume in 1 second (FEV1) in litres (r = 0.58; p = 0.005) but not with FEV1 % predicted. Capsaicin sensitivity was not related to the presence of infected sputum or to corticosteroid or bronchodilator use. CONCLUSIONS: : Patients with bronchiectasis have a sensitive cough reflex which reflects the severity of cough symptoms. A measure of cough severity could be part of health assessment for patients with bronchiectasis.

Occult alveolar haemorrhage in pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension that affects predominantly post-capillary pulmonary vessels. A major concern with PVOD is the poor response to available therapies and the risk of pulmonary oedema with continuous intravenous epoprostenol. The present authors hypothesised that alveolar haemorrhage may be a characteristic feature of pulmonary veno-occlusive disease, as compared with other forms of pulmonary arterial hypertension that predominantly involve pre-capillary pulmonary arteries. This paper reports a series of 19 patients with either PVOD (n = 8) or idiopathic pulmonary arterial hypertension (IPAH; n = 11) who underwent bronchoalveolar lavage. Cytological analyses were performed and differential counts were made on Perls-stained preparations. The Golde score was used to assess alveolar haemorrhage. As compared with IPAH, PVOD was characterised by a higher percentage of haemosiderin-laden macrophages (40+/-37 versus 3+/-6%), resulting in elevated Golde scores (81+/-88 versus 4+/-10). It was concluded that occult alveolar haemorrhage is a common feature of pulmonary veno-occlusive disease. Detecting occult alveolar haemorrhage may be of interest in the diagnostic approach of pulmonary veno-occlusive disease.

Treatment of lentigo maligna with topical imiquimod.

A published case report and anecdotal experience suggested that topical imiquimod is an effective treatment for stage 0 melanoma (lentigo maligna). To gauge the efficacy of this therapy, we undertook a trial of topical imiquimod in 30 subjects with histologically confirmed lentigo maligna. Thirty subjects with lentigo maligna were recruited for an open-labelled efficacy trial with daily topical application of imiquimod 5% cream for 3 months. Study subjects were enrolled from the Dermatology service of the University of Oklahoma, the Oklahoma City Veteran's Administration Hospital Dermatology service and from referrals for the study from other practitioners. In order to determine an initial response rate, a four-quadrant biopsy was carried out on all patients 1 month after cessation of treatment, targeting the most clinically and dermatoscopically suspicious areas. Of 28 evaluable subjects who have completed the 3-month treatment phase, 26 (93%) were complete responders and two were treatment failures at the time of the 4-quadrant biopsy. Over 80% of the 28 subjects that completed treatment have been followed for more than 1 year with no relapses. The results of this study demonstrate that topical imiquimod produces a high complete response rate in lentigo maligna when applied daily for 3 months.

Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide-induced biochemical toxicity.

Walnut (Juglans regia L.) is extensively used in traditional systems of medicine for treatment of various ailments. It is described as an anticancer, tonic, blood purifier and detoxifier agent. The present study was undertaken to investigate modulatory effects of walnut extract on the toxicity of an anticancer drug, cyclophosphamide (CP) with special reference to protection against disruption of drug metabolizing and antioxidant enzymes. Plant extract+CP group animals showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione S-transferase (GST), glutathione peroxidase (GP) and catalase (CAT) in both liver and kidneys. But plant extract restored the activity of superoxide dismutase (SOD) and the level of reduced glutathione (GSH) in the kidneys only when compared with CP-treated animals. Plant extract treatment alone caused significant reduction in the content of CYP in the kidneys mainly. The extract showed a significant increase in the level of GSH and in the activities of GP in both the tissues and CAT in liver only, whereas no significant change was observed in the activities of GST and SOD. CP treatment resulted in a significant (P < 0.01) increase in the lipid peroxidation (LPO) in the liver and kidneys compared with controls, while the extract+CP treated group showed a significant decrease in the LPO in liver and kidneys when compared with the CP-treated group. The study shows that the use of J. regia extract might be helpful in abrogation of CP toxicity during the chemotherapy.

Delineation of the minimal catalytic domain of human Galbeta1-3GalNAc alpha2,3-sialyltransferase (hST3Gal I).

The CMP-Neu5Ac:Galbeta1-3GalNAc alpha2,3-sialyltransferase (ST3Gal I, EC 2.4.99.4) is a Golgi membrane-bound type II glycoprotein that catalyses the transfer of sialic acid residues to Galbeta1-3GalNAc disaccharide structures found on O-glycans and glycolipids. In order to gain further insight into the structure/function of this sialyltransferase, we studied protein expression, N-glycan processing and enzymatic activity upon transient expression in the COS-7 cell line of various constructs deleted in the N-terminal portion of the protein sequence. The expressed soluble polypeptides were detected within the cell and in the cell culture media using a specific hST3Gal I monoclonal antibody. The soluble forms of the protein consisting of amino acids 26-340 (hST3-Delta25) and 57-340 (hST3-Delta56) were efficiently secreted and active. In contrast, further deletion of the N-terminal region leading to hST3-Delta76 and hST3-Delta105 gave also rise to various polypeptides that were not active within the transfected cells and not secreted in the cell culture media. The kinetic parameters of the active secreted forms were determined and shown to be in close agreement with those of the recombinant enzyme already described (H. Kitagawa, J.C. Paulson, J. Biol. Chem. 269 (1994)). In addition, the present study demonstrates that the recombinant hST3Gal I polypeptides transiently expressed in COS-7 cells are glycosylated with complex and high mannose type glycans on each of the five potential N-glycosylation sites.

Effect of endosulfan on antioxidants of freshwater fish Channa punctatus Bloch: 1. Protection against lipid peroxidation in liver by copper preexposure.

Effect of a single exposure of endosulfan (5 ppb) on catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and reduced glutathione (GSH) of liver, kidney, and gill of a freshwater fish (Channa punctatus Bloch) were evaluated after 24 h of treatment. Endosulfan exposure resulted in a significant induction (p < 0.05-0.001) of GPx, GST activity, and GSH levels in all the organs. However, CAT activity was found to be significantly decreased (p < 0.01-0.001). Lipid peroxidation (LPO) values were also determined in liver, kidney, and gill and a significant increase in LPO values (p < 0.05-0.01) was observed in all the organs. We also investigated whether preexposure to low concentration of copper (10 ppb) for 4 weeks has any protective effect against endosulfan-induced oxidative damage. In copper-acclimatized endosulfan-exposed fish, a significant decrease in GPx (p < 0.001), GST (p < 0.05), GSH (p < 0.001) levels, and LPO (p < 0.01) was observed in the liver, whereas CAT activity was increased significantly (p < 0.001). However, kidney and gill did not show any significant alterations in antioxidant levels. The results of this study demonstrate that endosulfan induces peroxidative damage in liver, kidney, and gill in response to which levels of antioxidant were modulated. However, when fish preacclimatized to copper were exposed to endosulfan, protection against oxidative damage was observed only in the liver. It is proposed that measurement of antioxidants in fish tissues may prove to be useful in biomonitoring of exposure to aquatic pollutants.

Regulation of cAMP by light and dopamine receptors is dysfunctional in photoreceptors of dystrophic retinal degeneration slow(rds) mice.

cAMP levels in dark and light were studied in dystrophic retinal degeneration slow(rds) mice, which carry a mutation in the rds/peripherin gene. cAMP levels were measured in vivo, in freshly isolated retinas, and in vitro in the presence of glutamate, which confines light modulation to photoreceptors. Experiments were conducted on young animals, when significant numbers of viable photoreceptor cells are present. In vivo levels of cAMP are higher in illuminated rds/rds retinas than levels measured in normal BALB/c retinas. Light-evoked down-regulation of cAMP levels was observed in vitro in normal photoreceptors. These measurements were made in the presence of the cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine; therefore, they reflect an inhibition of cAMP formation. In contrast, light had no effect on cAMP formation in photoreceptors of mutant mice, measured under identical conditions. Thus, elevated levels of cAMP in rds/rds retinas in vivo result from abnormalities in cAMP synthesis in the mutant photoreceptor cells. In addition to regulation by light, cAMP formation in photoreceptor cells is regulated by dopamine, acting through dopamine D4 receptors. A dopamine D2/D4 receptor agonist, quinpirole, reduced cAMP levels in dark-adapted normal retinas in vitro, but not in rds/rds retinas. Our data indicate that alterations in a signal transduction pathway that leads to inhibition of adenylyl cyclase might underlie the abnormalities in cAMP levels in mutant rds/rds retinas. Heterozygous rds/+ photoreceptors demonstrated a normal pattern of light-evoked and quinpirole-mediated down-regulation of cAMP. Thus, partial expression of the normal phenotype is sufficient to render normal characteristics of cAMP regulation to the photoreceptors of the heterozygous mouse. The data obtained in the present study might be relevant to the understanding of photoreceptor pathology of patients with peripherin/rds mutations.

Protective effect of Cassia occidentalis L. on cyclophosphamide-induced suppression of humoral immunity in mice.

Cassia occidentalis L. (Kasaundi) is a widely used medicinal plant. Earlier, we have shown that it possesses antimutagenic activity against benzo[a]pyrene (BaP) and cyclophosphamide (CP)-induced mutagenicity in mice. In this study, we investigated if this plant could also provide protection against CP-induced immunosuppression in animal models. Swiss albino male mice were treated per os with the aqueous extract of C. occidentalis (100 mg/kg, body weight (b.w.)) for 14 days. Cyclophosphamide was given intraperitoneally in a single dose of 50 mg/kg b.w. Body weight, relative organ weight, lymphoid organ cellularity, hemagglutination titre (HT), plaque forming cell (PFC) assay and quantitative hemolysis of SRBC (QHS) were studied in these animals. CP, as expected, showed suppressive effects on lymphoid organ weight and cellularity and other parameters of humoral immunity. Plant extract treatment itself produced no toxicity. The administration of plant extract to CP-exposed animals resulted in improved humoral responses. C. occidentalis treatment significantly (P<0.01) enhanced PFC response in CP-treated animals. In QHS assay, also C. occidentalis showed protection in CP-treated animals. Bone marrow cell counts, which were reduced in CP-treated animals, were reversed significantly (p<0.01) to normal levels in CP+ plant extract group animals. In our earlier study, we found that C. occidentalis modulated hepatic drug metabolizing enzymes. It is suggested that by a similar mechanism, it may be influencing the hematotoxic and immunotoxic responses of cyclophosphamide.

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice.

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs in spite of its toxic side effects including immunotoxicity, hematotoxicity, mutagenicity and a host of others. The present study was undertaken to assess the protective effects of total aqueous extract of a medicinal plant, Indian gooseberry (Emblica officinalis Gaertn.) in mice treated with CP. These protective effects were studied on immunological parameters and kidney and liver antioxidants. Plant extract treatment at a dose of 100 mg/kg body weight per os (p.o.) for 10 days resulted in the modulation of these parameters in normal as well as CP (50 mg/kg)-treated animals. Plant extract in particular was very effective in reducing CP-induced suppression of humoral immunity. Plant extract treatment in normal animals modulated certain antioxidants of kidney and liver. In CP-exposed animals, plant pretreatment provided protection to antioxidants of kidney. Not only were the reduced glutathione levels significantly (p<0.001) increased but plant extract treatment resulted in restoration of antioxidant enzymes in CP-treated animals. It is suggested that E. officinalis or its medicinal preparations may prove to be useful as a component of combination therapy in cancer patients under CP treatment regimen.

Genitourinary tuberculosis: a profile of 55 in-patients.

OBJECTIVE: To outline the pattern and trends in major cases of genito-urinary tuberculosis (GUTB) which require hospital treatment. METHOD: We retrospectively reviewed 55 patients with proven GUTB who were treated as in-patients in a major referral hospital in Pakistan. RESULTS: The male/female ratio was 3:1. Prevailing symptoms were lower urinary tract symptoms, flank pain, gross hematuria and fever. A urine culture was positive for tuberculosis (TB) in 57%, bladder biopsies in 54%. For renal TB, intravenous urogram (IVU) and ultrasound were suggestive in about 50% of cases. Ultrasound was very helpful in the diagnosis of testicular TB. Patients underwent surgery in 36% of cases. In contrast to the general trend reported worldwide, surgery was mainly ablative rather than re-constructive. Patient compliance in clinical follow-up and drug therapy was poor. CONCLUSION: Surgery for GUTB in Pakistan is still mainly ablative, probably due to a high number of complicated and progressed cases. To date, therapy of GUTB is mainly based on anti-tuberculosis chemotherapy (ATT). However, huge efforts will be required to improve patient compliance without which every therapeutic approach will remain futile.

Serotonin N-acetyltransferase mRNA levels in photoreceptor-enriched chicken retinal cell cultures: elevation by cyclic AMP.

Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EC 2.3.1.87) is a key regulatory enzyme in the biosynthesis of melatonin. Previous studies have shown that the activity of this enzyme in the chicken retina is regulated by a cyclic AMP-dependent mechanism. In the present report, we investigated whether cyclic AMP can regulate the levels of AA-NAT mRNA in photoreceptor-enriched chick retinal cell cultures. AA-NAT mRNA levels were elevated by acute treatment with cyclic AMP protagonists, including forskolin; this response was blocked by H-89, a selective inhibitor of cyclic AMP-dependent protein kinase. Forskolin did not alter the rate of disappearance of AA-NAT mRNA in actinomycin D-treated cells, suggesting that cyclic AMP enhances transcription of the AA-NAT gene. Forskolin-induced elevation of AA-NAT mRNA levels was enhanced by cycloheximide, which decreased the degradation of the transcript in cells treated with actinomycin D. These studies indicate that the abundance of AA-NAT mRNA is regulated in part through a cyclic AMP-dependent mechanism.

Arsenic levels in drinking water and the prevalence of skin lesions in West Bengal, India.

BACKGROUND: A cross-sectional survey was conducted between April 1995 and March 1996 to investigate arsenic-associated skin lesions of keratosis and hyperpigmentation in West Bengal, India, and to determine their relationship to arsenic water levels. METHODS: In all, 7683 participants were examined and interviewed, and the arsenic levels in their drinking water measured. RESULTS: Although water concentrations ranged up to 3400 microg/l of arsenic, over 80% of participants were consuming water containing <500 microg/l. The age-adjusted prevalence of keratosis was strongly related to water arsenic levels, rising from zero in the lowest exposure level (<50 microg/l) to 8.3 per 100 for females drinking water containing >800 microg/l, and increasing from 0.2 per 100 in the lowest exposure category to 10.7 per 100 for males in the highest exposure level (> or =800 microg/l). However, 12 cases with keratosis (2 females and 10 males) were drinking water containing <100 microg/l of arsenic. Findings were similar for hyperpigmentation, with strong dose-response relationships. Among those with hyperpigmentation, 29 cases were exposed to drinking water containing <100 microg/l. Calculation by dose per body weight showed that men had roughly two to three times the prevalence of both keratosis and hyperpigmentation compared to women apparently ingesting the same dose of arsenic from drinking water. Subjects who were below 80% of the standard body weight for their age and sex had a 1.6 fold increase in the prevalence of keratoses, suggesting that malnutrition may play a small role in increasing susceptibility. CONCLUSION: The surprising finding of cases who had arsenic-associated skin lesions with apparently low exposure to arsenic in drinking water needs to be confirmed in studies with more detailed exposure assessment. Further research is also needed concerning susceptibility factors which might be present in the exposed population.