Biomedical subjects

Rakesh Shukla

Publications and source records attributed to Rakesh Shukla.

29 records · Page 2Linked to original sources

PubMed2004

Stroke in a biracial population: the excess burden of stroke among blacks.

BACKGROUND AND PURPOSE: Excess mortality resulting from stroke is an important reason why blacks have higher age-adjusted mortality rates than whites. This observation has 2 possible explanations: Strokes occur more commonly among blacks or blacks have higher mortality rates after stroke. Our population-based epidemiological study is set in the Greater Cincinnati/Northern Kentucky region of 1.31 million people, which is representative of the US white and black populations with regard to many demographic and socioeconomic characteristics. METHODS: Hospitalized cases were ascertained by International Classification of Diseases (ninth revision) discharge codes, prospective screening of emergency department admission logs, and review of coroner's cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses, followed by physician review. Race-specific incidence and case fatality rates were calculated. RESULTS: We identified 3136 strokes during the study period (January 1, 1993, to June 30, 1994). Stroke incidence rates were higher for blacks at every age, with the greatest risk (2- to 5-fold) seen in young and middle-aged blacks (<65 years of age). Case fatality rates did not differ significantly in blacks compared with whites. Applying the resulting age- and race-specific rates to the US population in 2002, we estimate that 705,000 to 740,000 strokes have occurred in the United States, with a minimum of 616,000 cerebral infarctions, 67,000 intracerebral hemorrhages, and 22,000 subarachnoid hemorrhages. CONCLUSIONS: Excess stroke-related mortality in blacks is due to higher stroke incidence rates, particularly in the young and middle-aged. This excess burden of stroke incidence among blacks represents one of the most serious public health problems facing the United States.

Adult↗

PubMed2004

Increase of metabolic activity and disruption of normal contractile protein distribution by bilirubin oxidation products in vascular smooth-muscle cells.

OBJECT: Cerebral vasospasm is a common cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). Previous research has shown that bilirubin oxidation products (BOXes) are present in the cerebral spinal fluid in patients with SAH-induced cerebral vasospasm and can contribute to vasoconstriction and vasospasm in vitro and in vivo. The events leading to cerebral vasospasm are not understood; however, one component of the occlusion may be due to vascular remodeling. In this study the authors have investigated the actions of BOXes, okadaic acid ([OA], a phosphatase inhibitor), and phorbol-12 myristate-13 acetate ([PMA], a protein kinase activator) on vascular smooth-muscle cell (VSMC) morphology and metabolism. METHODS: Immunohistochemical analysis was performed to assess VSMC morphology and alpha-smooth-muscle actin (alphaSMA) distribution following the application of BOXes, OA, or PMA. Changes in the level of lactate dehydrogenase (LDH) release and oxidative metabolism were also measured. The BOXes, OA, or PMA caused VSMCs to change their shape and exhibit altered alphaSMA distribution. These treatments increased LDH release (p < 0.05), which is an index of increased cell stress. Oxidative metabolism significantly increased at low and high doses of BOXes, that is, 143 +/- 8.5% and 180 +/- 11.8%, respectively (p < 0.0001). Both PMA and OA also caused a significant increase in metabolism. CONCLUSIONS: The authors concluded that BOXes, OA, and PMA alter VSMC morphology and metabolic activity, events that have been observed during vascular remodeling. Although the mechanism remains unclear, the results indicate that BOXes may play a role in the vascular remodeling that occurs following aneurysmal SAH.

Animals↗

PubMed2004

Bilirubin as a cerebrospinal fluid marker of sentinel subarachnoid hemorrhage: a preliminary report in pigs.

OBJECT: A model of subarachnoid hemorrhage (SAH) in pigs was developed to investigate bilirubin concentration in cerebrospinal fluid (CSF) as a potential marker of sentinel SAH. METHODS: Seven male Yorkshire pigs received a 250-microl injection of either whole autologous arterial blood (four animals) or isotonic saline (three animals) into the cisternae magna in an effort to produce volumetrically a model of sentinel SAH and a control injection model, respectively. Cerebrospinal fluid volumes of 100 microl were then collected from both the lumbar cistern and cisternae magna at 1 to 2-hour intervals for a total of 24 hours postinjection. The CSF was then tested for bilirubin. Mean concentrations of bilirubin (+/- standard deviation [SD]) obtained from the lumbar cistern 24 hours following the injection of blood or saline were 4.38 +/- 1.04 microM in the SAH animals and 1.02 +/- 0.05 microM in the controls. At 24 hours postinjection, mean concentrations (+/- SD) of cisternae magna bilirubin were 7.29 +/- 1.33 microM and 1.33 +/- 0.14 microM in the SAH animals and controls, respectively. In the SAH group, both the lumbar cistern and cisternae magna bilirubin concentrations differed significantly from baseline values 12 hours following SAH. CONCLUSIONS: Elevated concentrations of CSF bilirubin can be detected following a low-volume SAH, and the production of bilirubin occurred over a predictable time course. Twelve hours after hemorrhage, an elevated CSF bilirubin concentration was an indicator of hemolysis occurring in the subarachnoid spaces. The presence of bilirubin in CSF is a potential marker for differentiating SAHs from traumatic lumbar punctures in humans.

Animals↗

PubMed2003

Short course of prednisolone in Indian patients with solitary cysticercus granuloma and new-onset seizures.

PURPOSE: To evaluate the role of a short course of oral corticosteroids in Indian patients with solitary cysticercus granuloma with seizures. METHODS: In this open-label, randomized, prospective follow-up study, 97 patients with new-onset seizures and a single enhancing computed tomography (CT)-detected lesion of cysticercosis were randomly divided in two groups to receive either antiepileptic monotherapy alone (n = 48) or antiepileptic monotherapy with prednisolone (n = 49). The patients in the latter group received prednisolone, 1 mg/kg/day for 10 days, followed by tapering over next 4 days. The patients were followed up for 6 months. Repeated CT scans were performed after 1 and 6 months. RESULTS: The majority of patients were young. Simple partial seizure, with or without secondary generalization, was the commonest seizure type encountered. Follow-up CT scans at 1 and 6 months demonstrated a significantly better response for prednisolone as far as complete resolution of CT lesion was concerned. Kaplan-Meier analysis suggested significantly less probability of seizure recurrence for prednisolone-treated patients. At 6 months, Kaplan-Meier estimated risk of seizure after first seizure was 2% in prednisolone-treated patients in comparison to 13% for those who were not given prednisolone. CONCLUSIONS: Short-term prednisolone therapy helps in rapid resolution of solitary cysticercus granuloma in Indian patients with new-onset seizures. Resolution of lesions is associated with improved seizure-related prognosis.

Adolescent↗

PubMed2003

Modulation of inflammatory mediators by ibuprofen and curcumin treatment during chronic inflammation in rat.

Inflammation is a protective tissue response occurring in three distinct phases, acute, subacute and a chronic proliferative phase. We undertook the present study to understand the overall immune response of the body during adjuvant induced chronic inflammation in rat and the effect of ibuprofen and curcumin on this response. Inflammatory mediators were estimated on day 21 and day 35 after adjuvant injection. The level of C-reactive protein increased to 200% on day 21 and then reduced to 50% on day 35 compared to control. Curcumin and ibuprofen further reduced the increased levels at both the time intervals. Haptoglobin level decreased to 42% on day 21 but increased to 5 times of control on day 35. Curcumin and ibuprofen reduced the increased levels at day 35. No significant change was observed in Prostaglandin-E2 and Leukotriene-B4 levels and in Lymphocyte proliferation. The level of Tumor Necrosis Factor-alpha increased by three folds on day 21, but came down to 88% on day 35. Ibuprofen treatment decreased the raised level on day 21 and increased the reduced level on day 35. Interleukin-1beta increased to 2 folds on day 21 and 10 folds on day 35 which were significantly brought down by curcumin and ibuprofen. Nitric oxide level was reduced at both the time intervals, which were increased by drug treatment.

Animals↗

PubMed2002

Urinary reproductive hormone level differences between African American and Caucasian women of reproductive age.

OBJECTIVE: To compare urinary levels of reproductive hormones in African American and Caucasian women. DESIGN: Cross-sectional study. SETTING: Ten United States Air Force (USAF) bases. PATIENT(S): African American (n = 33) and Caucasian (n = 65) women of reproductive age from a larger study of USAF women (n = 170). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary endocrine end points: follicular luteinizing hormone (LH), preovulatory LH, level of LH surge peak, early follicular follicle stimulating hormone (FSH), follicular LH:FSH ratio, midluteal FSH, FSH rise before menses, early follicular estrone 3-glucuronide (E(1)3G), midfollicular E(1)3G, periovulatory E(1)3G peak, midluteal E(1)3G, early follicular pregnanediol 3-glucuronide (Pd3G), follicular Pd3G, rate of periovulatory Pd3G increase, E(1)3G:Pd3G on the day of luteal transition, slope of E(1)3G:Pd3G, and midluteal Pd3G. RESULT(S): Relative to Caucasians, African American women had significantly lower follicular phase LH:FSH ratios (mean +/- SD: 0.7 +/- 0.4 vs. 1.0 +/- 0.6), lower follicular phase Pd3G levels (1.0 +/- 0.5 vs. 1.2 +/- 0.8 microg/mg creatinine), and lower rates of periovulatory Pd3G increase (0.5 +/- 0.7 vs. 1.0 +/- 1.2 microg/mg creatinine). CONCLUSION(S): Findings of this analysis should be considered preliminary evidence of racial differences in hormone levels. Future studies are needed to determine whether these differences have clinical significance.

Adult↗

PubMed2002

Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study.

BACKGROUND: Herbal products are widely used by consumers as alternatives to prescription drugs in treating symptoms of allergic rhinitis. However, there have been few placebo-controlled clinical trials that have examined the efficacy or safety of these products. Although grapeseed extract (GSE) is an herbal that is marketed for treating allergic rhinitis, its efficacy is unproven. OBJECTIVE: The aim of this study was to compare the efficacy and safety of GSE with placebo in the treatment of seasonal allergic rhinitis (SAR). METHODS: This was a randomized, double-blind, placebo-controlled study of GSE 100 mg, twice daily, versus placebo. Patients with SAR and skin prick test sensitivity to ragweed were randomized to 8 weeks of active treatment or placebo which was begun before the ragweed pollen season. Outcomes included: daily symptom diary scores recorded by patients, rhinitis quality of life scores at baseline and after 4 and 8 weeks of treatment; and requirements for rescue chlorpheniramine. Safety was monitored with routine laboratory studies. RESULTS: Over 8 weeks of treatment, no significant differences were observed between active and placebo groups in rhinitis quality of life assessments, symptom diary scores, or requirements for rescue antihistamine. No significant laboratory abnormalities were detected. CONCLUSIONS: This study did not show trends supporting the efficacy of GSE in the treatment of SAR.

Adolescent↗

PubMed2002

Subarachnoid hemorrhage: a preventable disease with a heritable component.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysm affects approximately 16 000 Americans annually, and almost 40% of affected patients die within 30 days despite the best current therapy. Prevention of SAH is therefore of paramount importance. We present a preliminary analysis of risk factors for SAH from our population-based, case-control study. METHODS: Cases were prospectively collected and matched 2:1 by age, race, and gender to controls using random digit dialing. Personal risk factor history, family history, neuroimaging data, and genetic samples were obtained. Univariate and bivariate analyses were performed and population-attributable risks estimated. Multivariable analysis was performed using conditional logistic regression. RESULTS: Between June 1997 and February 2000, 107 cases and 197 controls were enrolled. In bivariate analyses, a large proportion of population-attributable risk for SAH could be explained by modifiable risk factors: smoking, hypertension, and heavy alcohol use. In multivariable analysis, current cigarette smoking, history of hypertension, frequent alcohol use, lower body mass index, and a family history of a relative with SAH or intracranial aneurysm were found to be significant, independent risk factors for SAH. CONCLUSION: Our data confirm previous reports that SAH clusters within some families independent of environmental risk factors, suggesting that SAH has a significant genetic component. Yet, even among families at increased risk of SAH, smoking cessation, treatment of hypertension, and reduced alcohol intake may substantially decrease SAH risk. The independent associations with heavy alcohol use and low body mass index with SAH may be confounded by smoking and require further study.

Alcoholism↗

PubMed2002

Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has a 30-day mortality rate of 40% to 50% and lacks a proven treatment. We report a preplanned, midpoint analysis of the first population-based, case-control study that examines both genetic and environmental risk factors of ICH. METHODS: We prospectively identified cases of hemorrhagic stroke at all 16 hospitals in the Greater Cincinnati/Northern Kentucky region. All cases underwent medical record and neuroimaging review. Cases enrolled in the direct interview and genetic sampling arm of the study were matched to population-based control subjects by age, race, and sex. Multivariable logistic regression was performed to identify significant independent risk factors. RESULTS: We enrolled 188 cases of ICH (67 lobar, 121 nonlobar) and 366 control subjects in the direct interview arm of the study. Significant independent risk factors for lobar ICH included the presence of an apolipoprotein E2 or E4 allele, frequent alcohol use, prior stroke, and first-degree relative with ICH. Significant independent risk factors for nonlobar ICH were hypertension, prior stroke, and first-degree relative with ICH. An increasing level of education was associated with a decreased risk of nonlobar ICH. The attributable risk of apolipoprotein E2 or E4 for lobar ICH was 29%, and the attributable risk of hypertension for nonlobar ICH was 54%. CONCLUSIONS: There is significant epidemiological evidence that the pathophysiology of ICH varies by location. We estimate that a third of all cases of lobar ICH are attributable to possession of an apolipoprotein E4 or E2 allele and that half of all cases of nonlobar ICH are attributable to hypertension.

Age Distribution↗

PubMed2002

Evidence of reproductive endocrine effects in women with occupational fuel and solvent exposures.

Hydrocarbons (HCs) found in fuels and solvents are ubiquitous in the environment, yet we know little about their effects on the endocrine system. The objective of this study was to assess the potential reproductive endocrine effects of low-dose HCs encountered by female U.S. Air Force personnel with fuel (primarily JP-8 jet fuel) and solvent exposures (n = 63). We estimated the internal dose of HCs in fuels and solvents by measuring their levels in exhaled breath, including the sum of aliphatic HCs (C6H14-C16H34) and the sum of aromatic HCs (benzene, ethylbenzene, toluene, and m,p,o-xylenes). Adverse outcome measures included urinary endocrine markers that have been associated with nonconceptive (vs. conceptive) menstrual cycles in ovulatory women: lower preovulatory luteinizing hormone (LH) and mid-luteal phase pregnanediol 3-glucuronide (Pd3G) and estrone 3-glucuronide, and higher follicle phase Pd3G. We also obtained reproductive and exposure information from baseline questionnaires and daily diaries. Toluene was the most frequently found analyte in the breath, with values up to 52.0 ppb, and benzene breath levels were up to 97.5 ppb. Regression analysis revealed that preovulatory LH levels were significantly lower (p = 0.007) among women whose total aliphatic HC levels were above the median. The relationship between elevated aliphatic HC exposure and lowered preovulatory LH levels in the present study suggests that compounds in fuels and some solvents may act as reproductive endocrine disruptors. Confirmation of these findings is needed, not only to determine if fuel and solvent exposure may impact other LH-dependent physiologic functions but also to examine effects of fuels and solvents on conception.

Adult↗

PubMedDate not supplied

Use of monofilament in the detection of foot lesions in older adults.

The purpose of this study was to compare Semmes-Weinstein monofilament testing between elderly and young patients in both a diabetic and nondiabetic population. Monofilament mapping (10 g) was performed on 115 patients: 74 who were greater than 60 years of age (47 with diabetes) and 41 who were younger than 60 years (20 with diabetes). Sensations were assessed at 15 predefined pressure/risk points. Sensations were found to have perfect correlation between the same point on the left and right foot (r = 1.0) for each of the 15 points. The data for the 15 points were divided in 2 subsets: one for 8 points similar to a validated method and another with 7 new points on the dorsum and ankle area. Scores on both subsets differed significantly by age group (P < .0001) and diabetes status (P < .001), with older patients and patients with diabetes having higher scores. Analysis of covariance was used to estimate 15-point scores for the 4 combinations of age group and diabetes status, adjusting for foot ulceration, callus, deformity, and ischemia. In older patients without diabetes, each subset score was used to detect future neuropathy if 4 or more points were insensitive. The detections agreed in 37 of 47 cases. In all 10 cases of disagreement, the 7-point subset detected no neuropathy, suggesting that inclusion of the additional points could improve diagnostic specificity. The significant differences noted between young and old patients suggest the importance of aging-related changes, and raise questions about current scoring methods for detection of neuropathy in older adults with diabetes.

Adult↗