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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 55 records · Page 3Linked to original sources
PubMed2004

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats.

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg(-1) I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7-8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg(-1) urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 +/- 16.9 mg dl(-1), n = 6, prior to insulin and 42.0 +/- 8.4 mg dl(-1), n = 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg(-1), I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 +/- 14.0 mg dl(-1), n = 10, prior to insulin and 386.6 +/- 43.6 mg dl(-1), n = 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation.

Anesthesia↗
PubMed2004

Mechanisms of signal transduction mediated by oxidized lipids: the role of the electrophile-responsive proteome.

Cellular redox signalling is mediated by the post-translational modification of proteins by reactive oxygen/nitrogen species or the products derived from their reactions. In the case of oxidized lipids, several receptor-dependent and -independent mechanisms are now emerging. At low concentrations, adaptation to oxidative stress in the vasculature appears to be mediated by induction of antioxidant defences, including the synthesis of the intracellular antioxidant glutathione. At high concentrations apoptosis occurs through mechanisms that have yet to be defined in detail. Recent studies have revealed a mechanism through which electrophilic lipids, formed as the reaction products of oxidation, orchestrate these adaptive responses in the vasculature. Using a proteomics approach, we have identified a subset of proteins in cells that we term the electrophile-responsive proteome. Electrophilic modification of thiol groups in these proteins can initiate cell signalling events through the transcriptional activation of genes regulated by consensus sequences for the antioxidant response element found in their promoter regions. The insights gained from our understanding of the biology of these mechanisms will be discussed in the context of cardiovascular disease.

Animals↗
PubMed2004

Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment.

The class Zygomycetes is divided into two orders, Mucorales and Entomophthorales. These two orders produce dramatically different infections. Genera from the order Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella and Saksenaea) cause an angioinvasive infection called mucormycosis. Mucormycosis presents with rhino-orbito-cerebral, pulmonary, disseminated, cutaneous, or gastrointestinal involvement. Immunocompromising states such as haematological malignancy, bone marrow or peripheral blood stem cell transplantation, neutropenia, solid organ transplantation, diabetes mellitus with or without ketoacidosis, corticosteroids, and deferoxamine therapy for iron overload predispose patients to infection. Mucormycosis in immunocompetent hosts is rare, and is often related to trauma. Mortality rates can approach 100% depending on the patient's underlying disease and form of mucormycosis. Early diagnosis, along with treatment of the underlying medical condition, surgery, and an amphotericin B product are needed for a successful outcome. Genera from the order Entomophthorales produce a chronic subcutaneous infection called entomophthoramycosis in immunocompetent patients. This infection occurs in tropical and subtropical climates. The genus Basidiobolus typically produces a chronic subcutaneous infection of the thigh, buttock, and/or trunk. Rarely, it has been reported to involve the gastrointestinal tract. The genus Conidiobolus causes a chronic infection of the nasal submucosa and subcutaneous tissue of the nose and face. This paper will review the clinical manifestations, diagnosis and treatment of mucormycosis and entomophthoramycosis.

Humans↗
PubMed2004

Cost effective use of satellite packs in neonates: importance of birth weight.

BACKGROUND: Blood banks split an adult packed red cell bag (usually 250 ml) into 30 ml bags, making a total of eight neonatal "satellite" packs per donor. These packs are then "allocated"/"committed" to be used to serially transfuse a newborn. AIM: To study transfusion requirements of premature infants in relation to their birth weight and thereby attempt to rationalise the method of dispensing satellite blood packs. METHOD: Data on the distribution of neonatal transfusions with respect to weight were obtained retrospectively from unit A (51 infants, 168 transfusions) and unit B (46 infants, 151 transfusions). These data were used to model the effect of different policies on donor exposure and number of unused packs. RESULTS: Infants weighing less than 1000 g at birth have significantly higher transfusion requirements than those weighing 1000 g or more (p = 0.001 (unit A), p = 0.004 (unit B)). Our model predicted a significant reduction in donor exposure if eight packs/infant were allocated to those weighing < 1000 g, and a significant cut in the number of unused packs if four satellite packs/infant were allocated to those weighing > or = 1000 g. CONCLUSIONS: It would be safer and cost effective to allocate eight packs/infant to those with birth weights < 1000 g and four packs/infant to those with birth weights > or = 1000 g.

Birth Weight↗
PubMed2004

Some observations on the spectrum of dementia.

A study was designed to generate epidemiological and clinical data on dementia, in a teaching hospital in India. It was conducted on 124 (94 male and 30 female) elderly patients (aged more than 60 years) presenting with clinical syndrome of dementia (DSM-3). Their age range was 64-78 (mean 65.7 4.1) years. Detailed clinical, biochemical, radiological and electrophysiological evaluation was done to establish etiology. Patients with psychiatric ailments, cranial trauma and tumors were excluded. The study period was 4.2 years. Multi-infarct dementia (MID) was observed to be commonest cause of dementia and was present in 59 (47.6%) cases. There were 10 (8%) patients each of tuberculosis (TB) and neurocysticercosis (NCC). Alcohol-related dementia was present in 13 (10.5%), while malnutrition (Vitamin B12 deficiency) was present in 9 (7.2%). Alzheimer's Disease (AD) was present (NINCDS-ADRDA criteria) in 6 patients (4.8%). There were 3 (2.4%) cases 1 each of Huntington's disease, Parkinson's and Normal Pressure Hydrocephalus and 2 each of diabetes, hypothyroidism, hyperthyroidism and Creutzfeldt' Jakob Disease. We conclude that AD, which is irreversible and common in the west, is relatively uncommon in India as compared to MID, infections and malnutrition, which are potentially treatable.

Aged↗
PubMed2004

Kluver-Bucy syndrome -- an experience with six cases.

The Kluver-Bucy syndrome (KBS) is a neurobehavioral syndrome and can be seen in association with a variety of neurological disorders. Case records of 6 patients with KBS seen during a period of 5 years in a university hospital were reviewed. During the study period 6 patients with KBS, aged between 4 and 14 years, were seen. Hyperorality, hypersexuality, and abnormal behavior were the most common manifestations. Of the 6 patients, 5 had recurrent unprovoked seizures. The associated neurological disorders included anoxia-ischemic encephalopthy (2), herpes simplex encephalitis (1), neurocysticercosis (NCC) (1), traumatic brain injury with gliosis (1 case) and tuberculous meningitis (1 case). Prognosis was poor in all the patients except in the patient with NCC.

Adolescent↗
PubMed2004

Clinical spectrum, pitfalls in diagnosis and therapeutic implications in herpes simplex encephalitis.

OBJECTIVES: High index of suspicion is mandatory for early diagnosis of Herpes Simplex Encephalitis (HSE), since acyclovir therapy can prevent its mortality and limit morbidity. We report our observations on clinical spectrum, pitfalls in diagnosis and therapeutic aspects in patients of HSE. METHODS: There were 34 patients of HSE (26 males and eight females) in age range 6 -72 (mean 23.8 +/- 8.9) years. Diagnosis was confirmed by cranial MRI, EEG and PCR in CSF. Acyclovir was given to 24 patients. Carbamazepine and sodium valproate were the antiepileptic drugs used. RESULTS: Most of the patients were referred either as Japanese encephalitis, cerebral malaria or tubercular meningitis. High fever, seizures, behavioral abnormality and encephalopathy were present in all, either at onset or later. EEG, CSF abnormality and cranial MRI were abnormal in all 34 patients. PCR for Herpes Simplex virus was positive in 65 % cases CT was performed in 10 cases but abnormality was detected only in four. We observed features of Kluver Bucy syndrome in three patients, suffering from HSE. Following complete acyclovir therapy in 24 patients, 12 recovered completely and four partially. There was no improvement in four patients including two patients who had features of Kluver Bucy Syndrome, while four expired. Among the seven patients who refused therapy of acyclovir, five expired, while two remained in unaltered status. Treatment could not be completed in three patients as they expired during therapy. CONCLUSION: HSE is commonly misdiagnosed. Important factors influencing mortality and morbidity of HSE were; early acyclovir therapy, age, immune status of patient, duration of illness, and consciousness level before initiation of therapy. We conclude that acyclovir should be given to all patients as soon as suspected, while confirmatory investigations are in progress.

Acyclovir↗
PubMed2003

Optical control of the rotational angular momentum of a molecular Rydberg wave packet.

An intuitive scheme for controlling the rotational quantum state of a Rydberg molecule is demonstrated experimentally. We determine the accumulated phase difference between the various components of a molecular electron wave packet, and then employ a sequence of phase-locked optical pulses to selectively enhance or depopulate specific rotational states. The angular momentum composition of the resulting wave packet, and the efficiency of the control scheme, is determined by calculating the multipulse response of the time-dependent Rydberg populations.

Feedback↗
PubMed2003

A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer.

A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy. The QW portion (n=102) was an open-label, sequential, dose-escalation design; cohorts received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25, or 4.5 micro g kg(-1) week(-1) for 12 weeks. The 12-week placebo-controlled, double-blind Q3W (6.75 micro g kg(-1)) and Q4W (6.75 or 10.0 micro g kg(-1)) schedules (n=86), which enrolled different patients, took place after the QW schedule and were followed by a 12-week, open-label phase. Patients were evaluated for change in haemoglobin end points and red blood cell transfusions, serum darbepoetin alpha concentration, and safety. Selected domains of health-related quality of life (HRQOL) were measured. With QW dosing, at least 70% of each cohort had a haemoglobin increase from baseline of > or =2 g dl(-1) or a concentration > or =12 g dl(-1) (haematopoietic response). In the 4.5 micro g kg(-1) QW cohort, all patients achieved a haematopoietic response (100%; 95% confidence interval (CI)=100, 100). In the Q3W and Q4W schedules, all cohorts had at least 60% of patients who achieved a haematopoietic response. Darbepoetin alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W. Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike.

Aged↗
PubMed2003

Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects.

AIMS/HYPOTHESIS: Maternal diabetes increases oxidative stress in embryos. Maternal diabetes also inhibits expression of embryonic genes, most notably, Pax-3, which is required for neural tube closure. Here we tested the hypothesis that oxidative stress inhibits expression of Pax-3, thereby providing a molecular basis for neural tube defects induced by diabetic pregnancy. METHODS: Maternal diabetes-induced oxidative stress was blocked with alpha-tocopherol (vitamin E), and oxidative stress was induced with the complex III electron transport inhibitor, antimycin A, using pregnant diabetic or non-diabetic mice, primary cultures of neurulating mouse embryo tissues, or differentiating P19 embryonal carcinoma cells. Pax-3 expression was assayed by quantitative RT-PCR, and neural tube defects were scored by visual inspection. Oxidation-induced DNA fragmentation in P19 cells was assayed by electrophoretic analysis. RESULTS: Maternal diabetes inhibited Pax-3 expression and increased neural tube defects, and alpha-tocopherol blocked these effects. In addition, induction of oxidative stress with antimycin A inhibited Pax-3 expression and increased neural tube defects. In cultured embryo tissues, high glucose-inhibited Pax-3 expression, and this effect was blocked by alpha-tocopherol and GSH-ethyl ester, and Pax-3 expression was inhibited by culture with antimycin A. In differentiating P19 cells, antimycin A inhibited Pax-3 induction but did not induce DNA strand breaks. CONCLUSION/INTERPRETATION: Oxidative stress inhibits expression of Pax-3, a gene that is essential for neural tube closure. Impaired expression of essential developmental control genes could be the central mechanism by which neural tube defects occur during diabetic pregnancy, as well as other sources of oxidative stress.

Animals↗
PubMed2003

Mitoxantrone-cyclophosphamide-rituximab: an effective and safe combination for indolent NHL.

Treatment for extensive indolent lymphoma should combine optimization of efficacy without excessive toxicity. Rituxan may be an ideal agent for combinations with chemotherapy because of its non-cross-resistant toxicity profile and the potential for synergism. We present the results of 32 patients with indolent B-cell NHL who received a novel three-drug combination designed with the intent of preservation of both efficacy and quality of life. Patient characteristics were as follows, median age, 58 years (36-75 years); histology, follicular 16, SLL/CLL five, lymphoplasmacytic six, marginal cell five; relapsed or refractory, 10; untreated, 22. Patients first received cyclophosphamide 800 mg/m(2) and mitoxantrone 8 mg/m(2), iv on the same day, every 3 weeks for two cycles. Subsequently, patients received rituximab followed by mitoxantrone 8 mg/m(2) every 2 weeks for four cycles. The regimen, and particularly rituximab, was extremely well tolerated. Grade I/II, infusion-related toxicity was noted in 10%. Six patients achieved a PR and 23 a CR for an overall response of 90% (95% CI: 79-100%). The actuarial median TTP for all patients was 30 months. Molecular remissions were noted in 8/14 patients tested in CR. We conclude that the cyclophosphamide-mitoxantrone-rituxan (CyMiR) regimen is effective and extremely well tolerated. Furthermore, rituximab infusion-related morbidity is nearly completely eliminated.

Adult↗
PubMed2003

Systemic neutrophil activation in acute preschool viral wheeze.

BACKGROUND: In preschool children, attacks of wheeze are usually triggered by viral colds. The inflammatory substrate in preschool viral wheeze (PVW) is unclear, but epidemiological data suggest that most PVW is not caused by allergic inflammation. We therefore speculated that the neutrophils are an important effector cell. Systemic neutrophil activation is the first stage for the development of pulmonary neutrophilia. Markers of neutrophil activation are shedding of the adhesion molecule L-selectin from the cell surface, upregulation of Mac-1 expression, and an increase in serum soluble L-selectin. AIMS: To obtain evidence for systemic neutrophil activation during PVW. METHODS: Preschool children (1-5 years) admitted to hospital with acute PVW (n = 20) and normal controls (n = 18) were studied. Adhesion molecule expression on CD16 positive neutrophils was determined in both groups and expressed as molecules of equivalent fluorochrome (MEF). Serum soluble L-selectin was analysed by ELISA. RESULTS: Compared with controls, children with PVW had reduced neutrophil L-selectin expression (median MEF (IQR): 69 (11 to 96) units versus 136 (109 to 163) units, p < 0.001) and higher serum soluble L-selectin (2.8 (2.3 to 3.1) versus 2.4 (2.2 to 2.6) micro g/ml, p = 0.04). There was no significant difference in neutrophil Mac-1 expression. CONCLUSION: Systemic neutrophil activation is associated with acute PVW.

Acute Disease↗
PubMed2003

Intravenous sodium valproate in status epilepticus.

A study was conducted to observe the effect of intravenous sodium valproate in status epilepticus. Eleven patients with status epilepticus, who were resistant to conventional drugs, underwent treatment with intravenous sodium valproate. The seizures were controlled in 10 patients within 24-48 hrs of starting treatment. No complications were observed during therapy. We conclude that intravenous sodium valproate can be recommended for Myoclonic status epilepticus and non-convulsive status epileticus.

Adolescent↗
PubMed2002

Prevalence of cataract in the Speedwell Cardiovascular Study: a cross-sectional survey of men aged 65-83.

AIMS: To ascertain the prevalence of cataract in a representative group of men who have been followed since 1979 for cardiovascular disease. METHODS: Of 2348 men aged 45-63 recruited in 1979 to the Speedwell Cardiovascular Study, 1420 were alive and willing to take part in further studies in 1997. They were sent a questionnaire about their eye health and invited to an ophthalmological examination at Bristol Eye Hospital. Cataract was graded using the Lens Opacities Classification System III (LOCS III) method. RESULTS: Of the 1420 men, 26 died before they could be examined. Out of the remaining 1394 men, 949 presented for examination and full information was available for 936. Some information about eye health was obtainable for 394 men and 51 were not contactable. The prevalence of cataract increased with age and 36 men (3.8%) had had previous cataract surgery in either or both eyes. Of the remaining 903 men with no previous history of cataract surgery, cortical cataract was present in the right eye of 75 men (8.3%), nuclear (opalescence) in 128 (14.2%) and posterior subcapsular in 15 (1.7%). Five men (0.6%) had visual acuity of 6/60 or worse attributable to cataract in the right eye and 232 (25%) had visual acuity in one or both eyes of 6/24 or less at least partially attributable to cataract. There was no association between social class and the presence of cataract. CONCLUSIONS: The prevalence of cataract in a representative cohort of men followed since 1979 for cardiovascular disease was comparable to that previously reported in the UK and is consistent with studies from around the world. It appears that substantial amounts of visual loss, attributable to cataract, are present in men. Further studies establishing the reasons for this should be undertaken.

Age Factors↗
PubMed2002

Human glioma PKC-iota and PKC-betaII phosphorylate cyclin-dependent kinase activating kinase during the cell cycle.

Cell cycle phase transition is regulated in part by the trimeric enzyme, cyclin-dependent kinase activating kinase (CAK) which phosphorylates and activates cyclin-dependent kinases (cdks). Protein kinase C (PKC) inhibitors prevent cell cycle phase transition, suggesting a fundamental role for PKCs in cell cycle regulation. We report that in glioma cells, CAK (cdk7) is constitutively associated with PKC-iota. In vitro phosphorylation, co-immunoprecipitation, and analysis of phosphorylated proteins by autoradiography indicate that CAK (cdk7) is a substrate for PKC-iota and PKC-betaII hyperphosphorylation. These results establish a role for PKC-iota and PKC-betaII in the activation of CAK during the glioma cell cycle.

Cell Cycle↗