Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial

OBJECTIVE: To compare differences in hospital mortality and resource use in adult severe sepsis subjects randomized to receive drotrecogin alfa (activated) (DrotAA) or placebo in the PROWESS trial. DESIGN: Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial. SETTING: One hundred sixty-four tertiary care institutions in 11 countries. PARTICIPANTS: The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1,220 were alive at 28 days (the end of the original PROWESS follow-up). INTERVENTIONS: DrotAA (n = 850), 24 microg/kg/hr for 96 hrs, or placebo (n = 840). MEASUREMENTS AND MAIN RESULTS: New follow-up data through hospital discharge were merged with existing 28-day follow-up data. Hospital mortality was calculated for designated subgroups. Intensive care unit and hospital length of stay and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) scores were calculated overall and in designated subgroups. Hospital discharge location was recorded. The 95% confidence interval of most subgroups contained the relative risk estimate for overall 28-day and hospital mortality. Median hospital length of stay and intensive care unit length of stay were similar in both treatment groups: 16 vs. 17 days (p = .22) and 9 vs. 9 days (p = .7) for placebo vs. DrotAA. No significant difference in TISS-28 scores was observed between treatment groups overall or in subgroups of disease severity. In subjects for whom discharge destination was reported, 42.8% of placebo subjects and 46.8% of DrotAA subjects (two thirds of survivors in each group) were discharged directly to home. CONCLUSIONS: Reduction in hospital mortality with DrotAA in most of the subgroups of PROWESS is consistent with the reduction in 28-day and hospital mortality observed in the overall PROWESS population. Additional survivors created with DrotAA treatment did not increase per-patient resource use or intensive care unit or hospital length of stay.     

Repeated episodes of endosulfan poisoning

INTRODUCTION: A number of families in a rural area of Jabalpur District (Madhya Pradesh), India, were affected by repeated episodes of convulsive illness over a period of three weeks. The aim of this investigation was to determine the cause of the illness. METHODS: The investigation included a house-to-house survey, interviews of affected families, discussions with treating physicians, and examination of hospital records. Endosulfan poisoning was suspected as many villagers were using empty pesticide containers for food storage. To confirm this, our team collected blood and food samples, which were transported to the laboratory and analyzed with GC-ECD. RESULTS: Thirty-six persons of all age groups had illness of varying severity over a period of three weeks. In the first week, due to superstitions and lack of treatment, three children died. In the second week, symptomatic treatment of affected persons in a district hospital led to recovery but recurrence of convulsive episodes occurred after the return home. In the third week, 10 people were again hospitalized in a teaching hospital. Investigations carried out in this hospital ruled out infective etiology but no facilities were available for chemical analysis. All persons responded to symptomatic treatment. The blood and food samples analyzed by our team showed presence of endosulfan, which was confirmed by GCMS. One of the food items (Laddu) prepared from wheat flour was found to contain 676 ppm of alpha-endosulfan. CONCLUSIONS: Contamination of wheat grains or flour with endosulfan and its consumption over a period of time was the most likely cause of repeated episodes of convulsions, but the exact reason for this contamination could not be determined. This report highlights the unsafe disposal of pesticide containers by illiterate farm workers, superstitions leading to delay in treatment, and susceptibility of children to endosulfan.     

Immunomodulation of human natural killer cell cytotoxic function by organochlorine pesticides

Organochlorine pesticides are used worldwide. To our knowledge there have been no studies dealing with the effects of these agents under in vitro conditions on human natural killer (NK) cell cytotoxic function. NK cells play a central role in immune defense against tumor development and viral infections. Thus, any agent that interferes with the ability of NK cells to lyse their targets could increase the risk of tumor incidence and/or viral infections. In this study, we examined the effects of organochlorine pesticides and some of their breakdown products on the ability of human NK cells to lyse tumor cells. A total of 11 compounds were tested. The compounds were tested in both purified NK cells as well as a cell preparation that contained other mononuclear cells (predominantly T cells) and NK lymphocytes (referred to as T/NK cells). Lymphocytes were exposed to the compounds for periods of time ranging from 1 hour to 6 days. Exposure of highly purified NK cells to 5 microM alpha-chlordane, gamma-chlordane, 4,4'-DDT, heptachlor, oxychlordane, or pentachlorophenol (PCP) inhibited their ability to destroy K562 tumor-cells by 88+/-5, 92+/-8, 61+/-13%, 64+/-10%, 69+/-11%, 76+/-12%, respectively, after a 24 h exposure. The loss of cytotoxic function seen with alpha-and gamma-chlordane remained essentially constant out to 6 days, while that seen with 4,4'-DDT, oxychordane and PCP increased with longer exposures (6 d). PCP was the most effective of the compounds tested at decreasing NK function. Of the compounds that caused decreased lytic function when tested in purified NK cells, only PCP and oxychordane decreased the lytic function of the T/NK cell preparation after any exposure. The results provide evidence of relative toxic potential for the 11 compounds and their immunomodulatory effects on other mononuclear cells (such as T-cells, B-cells, and monocytes) as well as NK lymphocyte function.     

Non-obese (body mass index < 25 kg/m2) Asian Indians with normal waist circumference have high cardiovascular risk

OBJECTIVE: Although the prevalence of obesity is not high in Asian Indians, increased prevalence rates of metabolic perturbations and cardiovascular risk factors have been reported. In this study, we evaluated body mass index (BMI), anthropometric measurements, and body fat profiles of obese and non-obese subjects and correlated those values with cardiovascular risk factors. METHODS: This cross-sectional study involved 639 subjects (170 men and 469 women) from low socioeconomic stratum residing in urban slums of New Delhi. Non-obese subjects were categorized into quartiles of percentage of body fat (%BF) and waist circumference (WC). Using logistic regression analysis, the odds ratios (ORs) and 95% confidence intervals (CIs) for the occurrence of cardiovascular risk factors (diabetes mellitus [DM], hypertension, hypercholesterolemia, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, and high levels of low-density lipoprotein cholesterol) were computed with first quartile in the non-obese group as the reference category for the following five categories: %BF and WC quartiles in the non-obese group and obese group (BMI > or = 25 kg/m(2)). RESULTS: In the non-obese group, approximately 66% of men and 88% of women had at least one risk factor. In non-obese women, significantly high ORs and 95% CIs were found for hypertension (3.2, 1.4-7.2), DM (2.8, 1.2-6.3), and hypertriglyceridemia (3.9, 1.9-8.3) in the upper quartiles of %BF, and significantly high OR (95% CIs) was observed for hypertriglyceridemia (3.9, 1.4-10.8) in non-obese men. Among non-obese men, significantly high OR (95% CIs) was found for hypertriglyceridemia (3.2, 1.0-10.3); among non-obese women, significantly high ORs (95% CIs) were observed for hypertension (2.5, 1.1-5.8) and hypertriglyceridemia (2.5, 1.2-5.2) in the normal range of WC (70-80 cm). CONCLUSION: The study showed that Asian Indians have excess cardiovascular risk at BMI and WC values considered "normal." These data suggested that definitions of "normal" ranges of BMI and WC need to be revised for Asian Indians.     

Chronic lower limb ulcer? No--chloroma!

Extra medullary deposits are often associated with myeloproliferative disorders, especially with myeloid neoplasia. These are called granulocytic sarcoma, aleukemic leukemia cutis, myeloblastoma, chloroleukemia, extra-medullary myeloid tumor, and chloroma. They commonly present in the bone, periosteum, soft tissue, lymph nodes, and the skin but can occur anywhere. The authors present their experience with a patient with no history of neoplasm presented with a nonhealing ulcer of the lower limb that was a chloroma associated with chronic myeloid leukemia.     

Time-dependent actions of D2 family agonist quinpirole on spontaneous behavior in the rat: dissociation between sniffing and locomotion

RATIONALE: Dopamine agonists elevate locomotion, sniffing, grooming, and a number of other behaviors. However, the D2 family (D2/D3/D4) agonist quinpirole, across a wide dose range, produces a period of locomotor inhibition that precedes the drug's locomotor excitatory effects. OBJECTIVES: The present study asked whether the suppressive actions of quinpirole also extend to other aspects of spontaneous behavior, such as sniffing, rearing and grooming, or whether this suppression of locomotion occurs while the frequency of other behaviors is increased or unaffected. METHODS: Locomotion, sniffing, rearing and grooming were observed over a 150-min test session in rats treated with 0, 0.1, 0.5, 1.0, or 10.0 mg/kg quinpirole. RESULTS: At 0.1 mg/kg, quinpirole suppressed locomotion. Higher doses (0.5-10.0 mg/kg) produced locomotor suppression followed by locomotor excitation. During the period of locomotor suppression, quinpirole also reduced the frequency of rearing and grooming. However, animals under high doses (1 and 10 mg/kg) of quinpirole showed elevated sniffing during the period of locomotor, rear and groom suppression. CONCLUSIONS: These results demonstrate that the well-documented locomotor suppression that precedes quinpirole's excitatory locomotor actions occurs in the midst of active sniffing. These results suggest that the suppressive effects of quinpirole on locomotion do not reflect a state of general behavioral suppression.     

Genotyping of Hepatitis C virus (HCV) in infected patients from South India

Hepatitis C virus shows substantial nucleotide sequence diversity distributed throughout the viral genome. In the present study genotyping for Hepatitis C virus (HCV) infected patients was based on RFLP analysis of 5' UTR and using type specific primers of NS5B regions. It was observed that 60% of the patients (30 patients with chronic hepatitis) were infected with variants of genotype 1 and 40% of the patients (4 chronic hepatitis patients, 12 patients with chronic renal failure and 4 cirrhosis) were infected with variants of type 3 of HCV. None of the cirrhotic patients and patients with chronic renal failure, in the present study, were infected with type 1 of HCV. While PCR-RFLP, typing was rapid in conjunction with the primers used for RT-PCR, NS5 typing was helpful in determining the subtype. There was good correlation between the two typing methods and this method can be used as a cost-effective method for studying large number of samples. The study shows that predominant genotypes of HCV in South India include type 1 and 3. Type 3 seems to be transmitted nosocomially as suggested by the results in patients with chronic renal failure, as these patients are exposed to multiple medical interventions.