Search PubMed⌕ Search

Biomedical subjects

A Agrawal

Publications and source records attributed to A Agrawal.

At least 37 records · Page 2Linked to original sources
PubMed2005

Illicit drug use and abuse/dependence: modeling of two-stage variables using the CCC approach.

Drug use and abuse/dependence are stages of a complex drug habit. Most genetically informative models that are fit to twin data examine drug use and abuse/dependence independent of each other. This poses an interesting question: for a multistage process, how can we partition the factors influencing each stage specifically from the factors that are common to both stages? We used a causal-common-contingent (CCC) model to partition the common and specific influences on drug use and abuse/dependence. Data on use and abuse/dependence of cannabis, cocaine, sedatives, stimulants and any illicit drug was obtained from male and female twin pairs. CCC models were tested individually for each sex and in a sex-equal model. Our results suggest that there is evidence for additive genetic, shared environmental and unique environmental influences that are common to illicit drug use and abuse/dependence. Furthermore, we found substantial evidence for factors that were specific to abuse/dependence. Finally, sexes could be equated for all illicit drugs. The findings of this study emphasize the need for models that can partition the sources of individual differences into common and stage-specific influences.

Adult↗
PubMed2005

Performance decrements resulting from illness in the workplace: the effect of headaches.

OBJECTIVES: Studies on the impact of illness on work productivity are important to rationally allocate healthcare resources and to design programs to mitigate these effects. This investigation was conducted to develop and apply daily measures of illness episodes, and to collect subjective and objective data on work performance impacts. Medical bill reviewers completed daily responses to a questionnaire about headache manifestations, severity, and speed of work using interactive voice response (IVR). Of 134 eligible enrolled subjects, 117 (86%) provided at least 30 daily reports over 3 months. Their responses were matched to difficulty-adjusted objective measures: daily output, time on the system, and productivity. Respondents were clinically classified as migraineurs (n = 56), other headache disorders (n = 47), or having no headache disorder (n = 14). Each headache episode was classified as a migraine or nonmigraine headache based on reported manifestations. RESULTS: The three groups were similar in a variety of demographic factors, and mean subject-specific measures of speed, output, and productivity. In a multivariate model using general estimating equations, only episode severity (not type of headache or person-specific diagnosis) was found to be associated with a significant decrement in speed or productivity. The self-reported decrement in speed (approximately 20%) was much greater than the actual measured effect on productivity (approximately 8%). Intensive daily diary collection by IVR on symptoms and work performance is feasible. However, analysis of detailed daily objective productivity data can be complex, with significant unmeasured sources of variance. Severity may be a more important determinant of headache effect on work performance than specific diagnosis. Future studies on illness episodes and work performance should measure informal accommodations that may enable employees to compensate for episodic illnesses.

Adult↗
PubMed2005

Disposable balloon-based oesophageal motility catheters: comparison with solid-state transducers.

BACKGROUND: Current oesophageal manometry systems use either water-perfused or solid-state pressure transducers. Recently developed single-use disposable catheters use small balloons prefilled with air that transmit the pressure of oesophageal contractions to external transducers. AIM: To compare data obtained from single-use disposable balloon catheters to data from solid-state systems. METHODS: Healthy volunteers, patients with ineffective oesophageal motility and nutcracker oesophagus were studied to include a broad range of pressures. A single-use disposable Clinical Innovations (CI) catheter was placed adjacent to a solid-state Konigsberg Instruments (KI) catheter with pressure transducers at 5, 10, 15 and 20 cm above the lower oesophageal sphincter (LOS). Subjects received liquid and viscous swallows at 30-s intervals. Healthy volunteers received additional sets of swallows while having only one catheter in the oesophagus. RESULTS: When both catheters were present in the oesophagus, no differences were noted between mean pressure measurements in the distal oesophagus and there was good correlation between pressures recorded in response to individual swallows. When present alone in the oesophagus the CI catheter recorded lower mean pressures compared with the KI catheter. Overall there was good agreement in classifying swallows as normal, ineffective and simultaneous. CONCLUSION: Single-use oesophageal manometry catheters are promising alternatives to solid-state manometry systems in measuring intra-oesophageal pressures.

Adult↗
PubMed2005

Identification of hiatal hernia by esophageal manometry: is it reliable?

Hiatal hernias are frequently diagnosed during upper endoscopy or barium radiography. They can also be identified based on the typical 'double high pressure zone' or 'double hump' during stationary manometric pull-through. This paper aims to compare manometric and endoscopic identification of hiatal hernias. We retrospectively reviewed records of patients who had an esophageal manometry performed in our laboratory between July 2002 and July 2003. We identified 153 patients (104 females, mean age 56 years) who had both an esophageal manometry and upper endoscopy. The manometric studies were reviewed looking for the characteristic double high-pressure zone characteristic of hiatal hernia. The endoscopic reports were reviewed for the independent identification of an hiatal hernia. Information on race, gender, presence of hiatal hernias, esophagitis, and symptoms during esophagogastroduodenoscopy (EGD) exams was recorded from the reports of patients who had both EGD and manometric studies at our institution. Of the 153 patients with both endoscopy and manometry, 11 (7%) had an hiatal hernia identified by manometry compared to 51 (33%) by endoscopy. Ten (91%) of the manometrically identified hiatal hernias were also seen on endoscopy. Compared to endoscopy (gold standard), esophageal manometry had a sensitivity of 20% and a specificity of 99% for detecting hiatal hernias. Manometric identification of an hiatal hernia is an infrequent finding with low sensitivity but high specificity compared to endoscopy.

Adolescent↗
PubMed2005

Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy.

While night-time symptoms of gastroesophageal reflux disease (GERD) are common, considerable controversy exists regarding the use of histamine-2 receptor antagonists (H2Ras) for night-time reflux control. Some studies have suggested possible tolerance to H2RA while others have suggested that long-term efficacy of gastric acid control can be maintained with night-time H2RA use. The aim of this study was to identify if GERD patients have sustained symptom improvement with long-term use of night-time H2RA. Records of 56 consecutive GERD patients on twice daily proton pump inhibitor (PPI) and night-time H2RA therapy were reviewed. During a phone interview patients were asked a 5-item questionnaire, which included overall assessment of symptoms, night-time symptoms, sleep disturbance, duration and frequency of therapy. Of the 56 patients, 39 (31 women, mean age 56) completed the questionnaire (15 were not reached and 2 did not recall enough information). All respondents had taken night-time H2RA for at least 1 month (28/39 patients with > 6 months duration) with 33/39 patients taking H2RAs every night. The addition of H2RA led to an improvement in overall symptoms in 28/39 (72%) patients, improvement in night-time reflux symptoms in 25/34 (74%) patients and improvement of GERD-associated sleep disturbance in 18/27 (67%) patients. Five (13%) patients had stopped the H2RA on their own, stating that its efficacy waned after 1 month. Our results suggest that the majority of patients report persistent improvement in GERD symptoms from night-time H2RA use and that possible clinically important tolerance to H2RAs occurs in a small number of patients. Further prospective, placebo-controlled studies may help confirm that there is a role for night-time H2RAs in GERD symptom control.

Drug Administration Schedule↗
PubMed2005

Fundoplication eliminates chronic cough due to non-acid reflux identified by impedance pH monitoring.

The symptoms of extra-oesophageal gastro-oesophageal reflux disease (GORD) (such as chronic cough and hoarseness) are traditionally more difficult to treat than typical GORD symptoms (heartburn and regurgitation). Patients with extra-oesophageal manifestations may require longer and higher doses of acid suppressive therapy. In patients not responding to acid suppressive therapy the physician faces a dilemma as to whether the symptoms are due to ongoing acid reflux, non-acid reflux, or not associated with reflux. We report the case of a 45 year old woman with a history of a chronic cough referred for fundoplication after documenting her symptoms were associated with non-acid reflux using multichannel intraluminal impedance and pH (MII-pH).

Chronic Disease↗
PubMed2005

Overview of tyrosine kinase inhibitors in clinical breast cancer.

Studies of cell models and profiling of clinical breast cancer material to reveal the mechanisms of resistance to anti-oestrogen therapy, and to tamoxifen in particular, have reported that this phenomenon can be associated with increased expression and signalling through erbB Type 1 growth factor receptors, notably the epidermal growth factor receptor (EGFR) and HER2. Further molecular studies have revealed an intricate interlinking between such growth factor receptor pathways and oestrogen receptor (ER) signalling. Inhibition of receptor tyrosine kinase activity involved in the EGFR signalling cascade forms the basis for the use of EGFR specific tyrosine kinase inhibitors exemplified by gefitinib (ZD1839, Iressa) and erlotinib (OSI-774, Tarceva). Such agents have proved promising in pre-clinical studies and are currently in clinical trials in breast cancer, where gefitinib has been studied more extensively to date. Here, we present an overview of the current development of gefitinib in clinical breast cancer. This includes results from our clinical breast cancer trial 1839IL/0057 that demonstrate the efficacy of gefitinib within ER-positive, tamoxifen-resistant patients with locally advanced/metastatic disease, where parallel decreases in EGFR signal transduction and the Ki67 (MIB1) proliferation marker can be detected as predicted from model system studies. We also consider trials examining combination treatment with gefitinib and anti-hormonal strategies that will begin to address the clinically important question of whether gefitinib can delay/prevent onset of anti-hormone resistance.

Antineoplastic Agents↗
PubMed2004

Anthrax lethal toxin: a weapon of multisystem destruction.

Lethal toxin (LT) is a major virulence factor secreted by anthrax bacteria. It is composed of two proteins, PA (protective antigen) and LF (lethal factor). PA transports the LF inside the cell, where LF, a zinc-dependent metalloprotease cleaves the mitogen activated protein kinase kinase (MAPKK) enzymes of the mitogen activated protein kinase (MAPK) signaling pathway, thereby impairing their function. This disruption of the MAPK pathway, which serves essential functions such as proliferation, survival and inflammation in all cell types, results in multisystem dysfunction in the host. The inactivation of the MAPK pathway in both macrophages and dendritic cells leads to inhibition of proinflammatory cytokine secretion, downregulation of costimulatory molecules such as CD80 and CD86, and ineffective T cell priming. The net result is an impaired innate and adaptive immune response. Endothelial cells of the vascular system undergo apoptosis upon LT exposure, also likely due to inactivation of the MAPK pathway. The activity of various hormone receptors such as glucocorticoids, progesterone and estrogen is also blocked, due to inhibition of p38 MAPK phosphorylation, thus affecting the body's response to stress. The present review summarizes the various disarming effects of Bacillus anthracis through the use of a single weapon, the lethal toxin.

Animals↗
PubMed2004

Azathioprine-induced pure red cell aplasia: case report and review.

The major adverse effect of azathioprine is its myelotoxicity, with leukocytes being affected more commonly than the other bone marrow elements. Although megaloblastic change is frequent, reportedly seen in 16% to 82% of bone marrow aspirates, long-term use of azathioprine rarely causes severe anemia. We report a case of refractory pure red cell aplasia resulting from long-term use of azathioprine in a renal transplant recipient and examine the possible underlying mechanisms. There was no response to dose reduction or to erythropoietin administration. However, there was immediate recovery after complete drug withdrawal. A review of the literature revealed that only ten cases of azathioprine-induced red cell aplasia have so far been described, all in transplant recipients.

Azathioprine↗
PubMed2004

Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.

AIMS: To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). METHODS: Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. RESULTS: Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). CONCLUSIONS: Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.

Adult↗
PubMed2004

Vasculitis syndrome: an approach.

Vasculitides are clinical syndromes characterized by vessel wall inflammation and resultant organ damage. Pathogenesis involves autoimmune reactions from type I to type IV. Vasculitis may be primary or secondary to infective and connective tissue disorders. The extent of damage may involve multiple organ systems or may remain limited to skin only. As the vasculitic syndromes display a multitude of variable presentations, there can be no uniform laid out guidelines or evaluation scale for the diagnosis of these conditions. High degree of suspicion, a detailed history regarding onset of disease and course of illness, meticulous physical examination, and appropriate laboratory tests to determine organ systems involved and the extent of involvement, lead to the diagnosis of specific syndrome. Anti-neutrophil cytoplasmic antibodies (ANCA), urinalysis, organ-specific biopsy and arteriography are the main diagnostic modalities for the diagnosis of vasculitis.

Angiography↗
PubMed2003

Horseshoe kidney transplantation.

Even though the number of patients awaiting renal transplant is rapidly increasing, the donor pool remains relatively stable. In an attempt to increase this pool, marginal kidneys and kidneys with congenital anatomical variations are being used. Horseshoe kidneys, being the most common renal fusion anomaly, can provide a useful solution to the ever-increasing gap between demand and supply. These kidneys have been successfully transplanted en bloc into a single recipient or, alternatively they have been divided and transplanted into 2 recipients. We report a case of the successful transplantation of an en bloc horseshoe kidney into a single recipient. To the best of our knowledge this is the first of its kind in the U.K. The relevant literature is also reviewed with the aim of raising awareness about the necessity and promising outcomes of such transplants.

Adult↗
PubMed2003

Oesophageal stricturing secondary to adult Stevens-Johnson syndrome: similarities in presentation and management to corrosive injury.

Clinical decisions often have to be made in the absence of evidence. In some cases, it is appropriate to use evidence from similar but more common conditions for which studies have resulted in evidence-based practice. This report describes a case of oesophageal stricture following Stevens-Johnson syndrome illustrating this concept, although it is likely that there are many other conditions in which the same principle will stand the clinician in good stead. Dilatation led to long-standing relief of dysphagia in our case.

Barium Sulfate↗
PubMed2003

Role of Ca2+ in radiation-induced damage in murine splenocytes.

PURPOSE: To address the links between calcium, peroxidation, cell damage and death and the response of the enzymes involved in free radical metabolism, in splenocytes of mice irradiated with gamma-rays. MATERIALS AND METHODS: Splenocytes of Swiss albino mice were irradiated with various doses (0-7 Gy) of gamma-rays (60Co) at a dose-rate of 0.0575 Gy s(-1). Membrane peroxidation and fluidity were determined by the thiobarbituric acid-reactive substances (TBARS) method, and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), respectively. Apoptosis was analysed by nucleosomal ladder formation and activity of NF-kappaB by electrophoretic mobility shift assay (EMSA). The specific activities of the antioxidant enzymes, lactate dehydrogenase (LDH), levels of nitric oxide (NO*) and glutathione were determined spectrophotometrically. Modulatory effects of Ca2+ were examined at 3 Gy using different concentrations (1, 3 and 5 mM) in the presence or absence of the ionophore A23187. RESULTS: Irradiation of splenocytes resulted in enhanced peroxidative damage. membrane fluidity, apoptosis and DNA binding activity of NF-kappaB. The specific activities of LDH and antioxidant enzymes superoxide dismutase (SOD), DT-diaphorase (DTD), glutathione S-transferase (GST) and levels of glutathione (GSH) and NO* were increased with radiation dose up to 4Gy. Ca2+ augmented the radiation-induced responses. The presence of ionophore A23187 potentiated the modulatory effects of Ca2+. CONCLUSIONS: These findings show that Ca2+ augments radiation damage and is more effective intracellularly. Ca2+, peroxidation, cellular damage and apoptosis are possibly interlinked through signals, as is evident from the increased activity of NF-kappaB and generation of NO*. The enhanced antioxidant status suggests an attempt made by the irradiated cells to maintain their normal functions.

Animals↗