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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 91 records · Page 5Linked to original sources
PubMed2000

Mitochondrial superoxide production in kainate-induced hippocampal damage.

The objective of this study was to determine the role of mitochondrial superoxide radical-mediated oxidative damage in seizure-induced neuronal death. Using aconitase inactivation as an index of superoxide production, we found that systemic administration of kainate in rats increased mitochondrial superoxide production in the hippocampus at times preceding neuronal death. 8-Hydroxy-2-deoxyguanosine, an oxidative lesion of DNA, was also increased in the rat hippocampus following kainate administration. Manganese(III) tetrakis(4-benzoic acid)porphyrin, a catalytic antioxidant, inhibited kainate-induced mitochondrial superoxide production, 8-hydroxy-2-deoxyguanosine formation and neuronal loss in the rat hippocampus. Kainate-induced increases of mitochondrial superoxide production and hippocampal neuronal loss were attenuated in transgenic mice overexpressing mitochondrial superoxide dismutase-2. We propose that these results demonstrate a role for mitochondrial superoxide production in hippocampal pathology produced by kainate seizures.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Factors affecting the ability of dental cements to alter the pH of lactic acid solutions.

Two related studies have been carried out to determine the effect of (a) powder:liquid ratio and (b) relative amounts of cement on the extent of buffering of a lactic acid storage solution using zinc polycarboxylate and glass-ionomer cements (both water-activated). The effect of varying the powder:liquid ratio was found to be slight and not statistically significant. On the other hand, increasing the numbers of specimens in a given volume of storage solution was found to have a significant influence on the final pH (at the 0.0005 level of significance). The fact that powder:liquid ratio did not affect the final pH led to the conclusion that attack occurs mainly at the matrix of these cements, confirming previous findings about the acid erosion process. The finding that increasing the relative amount of cement to acid storage solution strongly influenced pH suggested that, under clinical conditions, buffering would be important. When five specimens were used, the final pH corresponded to that of arrested caries, from which it was concluded that these cements have the ability to be cariostatic in vivo.

Acrylic Resins↗
PubMed2000

High seroprevalence of antibodies to varicella zoster virus in adult women in a tropical climate.

OBJECTIVES: To determine whether the seroprevalence of antibodies to varicella zoster virus (VZV) in adults is similar to that reported in tropical populations elsewhere. METHODS: We measured the seroprevalence of VZV IgG antibodies, using an enzyme immunoassay (EIA) in women attending an antenatal clinic in an urban centre in tropical Australia. RESULTS: The overall seroprevalence of VZV antibodies in 298 women was 92% (95% CI 88-95), with no difference between women who spent their childhoods in the tropics and colleagues. None of the overseas-born women was seronegative. CONCLUSION: The seroprevalence of VZV antibodies in this tropical population in Australia is as high as that reported from temperate regions, suggesting that social and cultural factors and population mobility are more important determinants of age distribution of VZV immunity than tropical climate.

Adolescent↗
PubMed2000

A protocol of early spiral computed tomography for the detection of stones in patients with renal colic has reduced the time to diagnosis and overall management costs.

BACKGROUND: The recent use of spiral computed tomography (CT) without contrast for the diagnosis of acute flank pain has been shown to be highly sensitive and specific for the detection of urolithiasis. This method has not, however, been evaluated for its contribution to savings in management costs. The present study aims to evaluate the cost savings gained by instituting a protocol of early spiral CT to investigate these patients. METHODS: The records of 200 patients presenting to the Accident and Emergency Department (A&E) with acute flank pain during two periods were retrospectively reviewed. The first period was before the spiral CT protocol was instituted and the second was after. Cost analyses between the two periods were performed. RESULTS: After the spiral CT protocol, 72 versus 31 patients had a definitive diagnosis prior to discharge from hospital. The time taken to diagnosis was also significantly shorter after the protocol implementation (6.3 vs. 16.8 h). This resulted in a shorter time spent in the A&E, and hence bed cost savings. Radiological costs were reduced by 22%, but the major cost saving was made by a reduction in time spent in A&E (44%). CONCLUSIONS: The implementation of a protocol of early spiral CT for patients with suspected renal colic has led to earlier definitive diagnosis and shorter hospital stays. This is associated with a significant reduction in costs associated with managing this condition.

Adult↗
PubMed2000

High creatinine excretion ratio predicts a good outcome in peritoneal dialysis patients.

The creatinine excretion (CrEx) ratio was first described as a method for detecting noncompliance in peritoneal dialysis (PD) patients. However, a high CrEx ratio is not specific for noncompliance and may also be found in compliant patients with a relatively greater lean body mass (LBM). A cohort of 44 PD patients was followed up for a mean of 13 +/- 8 months after measurement of baseline CrEx ratio to investigate whether greater values were predictive of good or poor clinical outcomes. During this follow-up, 11 patients died, 12 patients transferred to hemodialysis, 4 patients underwent transplantation, 1 patient recovered renal function, and 16 patients continued on PD. The mean CrEx ratio in all patients was 1.14 +/- 0.32. It did not differ between men and women (1.15 versus 1.13, respectively; P = 0.76) but showed a trend toward being less in patients with diabetes (1.03 versus 1.19; P = 0. 19). The mean weekly Kt/V, weekly creatinine clearance, normalized protein equivalent of nitrogen appearance, and serum albumin values were 2.18 +/- 0.57, 73.57 +/- 33.75 L/1.73 m(2), 0.80 +/- 0.22 g/kg/d, and 3.22 +/- 0.59 g/dL, respectively. Technique failure (P < 0.001) and death (P < 0.05) were significantly more common in patients with a CrEx ratio less than 1 compared with those with a CrEx ratio greater than 1. On Cox regression analysis, the CrEx ratio was the only significant predictor of technique failure and was also an independent predictor of death. High CrEx ratio is a predictor of good, rather than poor, outcome in PD patients, perhaps because it is primarily an index of nutrition. This further weakens the argument that it is a reliable or useful marker of noncompliance.

Biomarkers↗
PubMed2000

Use of shunts with eversion carotid endarterectomy.

PURPOSE: The purpose of this study was to examine the utility of carotid shunting in the context of eversion endarterectomy. A comparison of patients who underwent carotid endarterectomy by eversion with and without shunts was performed. METHODS: Over a 5-year period, 2724 eversion carotid endarterectomies were performed. In most of these operations patients were under cervical block anesthesia. A shunt was used in 112 eversion endarterectomies (4.1%). Cervical block anesthesia was used in 103 patients (92.0%), general anesthesia was used in 5 patients (4.5%), and 4 patients (3.6%) were converted from cervical block to general anesthesia intraoperatively. The indications for shunting were neurologic deterioration in 99 patients (88.4%) who were under cervical block anesthesia, procedures performed in neurologically unstable or otherwise compromised patients who were under general anesthesia, and the operator's discretion in the remaining eight patients. RESULTS: There was a combined stroke/death rate of 2.7% in the shunt group. These three cases included one death from myocardial infarction and one delayed death due to intracerebral hemorrhage after discharge. Shunt insertion was unrelated to the negative outcome in these two cases. One perioperative major stroke in the shunt group was identified. Follow-up averaged 12.3 months (range, 1-53 months). CONCLUSION: Carotid shunts can be used effectively in the context of eversion endarterectomy. Shunt insertion is not associated with an increased stroke/death rate in these patients.

Aged↗
PubMed2000

Interaction of platelet activating factor, reactive oxygen species generated by xanthine oxidase, and leukocytes in the generation of hepatic injury after shock/resuscitation.

OBJECTIVE: To evaluate the putative relation of platelet activating factor (PAF), xanthine oxidase, reactive oxidants, and leukocytes in the pathogenesis of hepatic injury after shock/resuscitation (S/R) in vivo. BACKGROUND: Reactive oxygen metabolites generated by xanthine oxidase at reperfusion have been found to trigger postischemic injury in many organs, including the liver. However, the precise linear sequence of the mechanism of consequent hepatic injury after S/R remains to be characterized. METHODS: Unheparinized male rats were bled to a mean blood pressure of 45 +/- 3 mmHg. After 2 hours of shock, they were resuscitated by reinfusion of shed blood (anticoagulated with citrate-phosphate-dextrose) and crystalloid and observed for the next 6 or 24 hours. RESULTS: S/R caused the oxidation of hepatic glutathione and generated centrolobular leukocyte accumulation at 6 hours, followed by predominantly centrolobular hepatocellular injury at 24 hours. Each of these components was attenuated by PAF inhibition with WEB 2170, xanthine oxidase inhibition with allopurinol, antioxidant treatment with N-acetylcysteine, or severe leukopenia induced by vinblastine. In each case, the degree of leukocyte accumulation at 6 hours correlated with the hepatocellular injury seen at 24 hours. However, xanthine oxidase inhibition with allopurinol failed to attenuate further the small level of residual hepatocellular injury seen in leukopenic rats. CONCLUSION: These findings suggest that reactive oxidants generated by xanthine oxidase at reperfusion, stimulated by PAF, mediate hepatocellular injury by triggering leukocyte accumulation, primarily within the centrolobular sinusoids.

Animals↗
PubMed2000

Diagnosing spinal osteomyelitis: a comparison of bone and Ga-67 scintigraphy and magnetic resonance imaging.

PURPOSE: The objective of this investigation was to compare the accuracies of bone and Ga-67 scintigraphy and magnetic resonance imaging (MRI) for diagnosing spinal osteomyelitis and to determine the optimal radionuclide approach to this disorder. METHODS: Twenty-two patients, with 24 sites of possible spinal osteomyelitis, who underwent three-phase bone scintigraphy with SPECT, Ga-67 scintigraphy with SPECT, and MRI with and without contrast were included in this retrospective review. Bone scans were interpreted as three-phase studies, delayed planar images alone, delayed planar plus SPECT, and SPECT alone (to identify uptake patterns). Sequential bone/ Ga-67 images were interpreted as planar and as SPECT studies. Planar and SPECT Ga-67 images were also interpreted alone. Precontrast MRI studies were used to identify osteomyelitis, whereas postcontrast images were used to identify soft tissue infection. RESULTS: Eleven sites of spinal osteomyelitis were identified. Tracer uptake in two contiguous vertebrae, as noted on SPECT, was the most accurate bone scan criterion for detecting spinal osteomyelitis (71 %). SPECT bone/Ga-67 was significantly more accurate (92%) than both planar bone/Ga-67 (75%) and bone SPECT (P = 0.15 and P = 0.2, respectively). SPECT Ga-67 was as accurate as SPECT bone/Ga-67 and as sensitive as MRI (91 %); the radionuclide study was slightly but not significantly more specific (92% vs. 77%) than MRI. Of 11 sites of extraosseous infection, 10 were identified on MRI, 9 on SPECT Ga-67, 7 on planar Ga-67, and none on bone scintigraphy. CONCLUSIONS: Spinal osteomyelitis and accompanying soft tissue infection can be diagnosed accurately with a single radionuclide procedure: SPECT Ga-67. This procedure can be used as a reliable alternative when MRI cannot be performed and as an adjunct in patients in whom the diagnosis is uncertain.

Adult↗
PubMed2000

Preliminary X-ray analysis of a new crystal form of the Escherichia coli KDO8P synthase.

3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase catalyzes the biosynthesis of an essential component of the lipopolysaccharide of all Gram-negative bacteria. The structure and mechanism of KDO8P synthase are being actively studied as this enzyme represents an important target for antibiotic therapy. The structure of the Escherichia coli KDO8P synthase in cubic crystals (space group I23) has recently been determined and the enzyme shown to be a tetramer of identical subunits. However, this information is challenged by biochemical studies, which suggest that the enzyme behaves in solution as a homotrimer. Here, the preparation and preliminary X-ray analysis of monoclinic crystals of KDO8P synthase are reported. The crystals belong to space group P2(1), with unit-cell parameters a approximately 50, b approximately 140, c approximately 74 A, beta approximately 105 degrees. The structure of KDO8P synthase in the monoclinic crystal form was determined by molecular replacement, using as a search model one of the subunits of the enzyme in the cubic crystals. A tetramer of KDO8P synthase with 222 local symmetry is also present in the asymmetric unit of the P2(1) crystals, with a solvent content of 43%. The observation that the same quaternary structure of KDO8P synthase is observed in two different crystal forms belonging to distinct crystal systems (monoclinic and cubic) suggests that a tetramer is the native form of the enzyme.

Aldehyde-Lyases↗
PubMed2000

The role of brain computed tomography in evaluating children with new onset of seizures in the emergency department.

BACKGROUND: The purpose of neuroimaging of a patient with new onset of seizures is to demonstrate cause and explore the prognosis. It was recently recommended that emergency brain computed tomography (CT) be performed only in adult seizure patients with an increased likelihood of life-threatening lesions, i.e., those with new focal deficits, persistent altered mental status, fever, recent trauma, persistent headaches, history of cancer, history of anticoagulation, or suspicion of acquired immunodeficiency syndrome. The objective of this study was to determine the diagnostic utility of emergency brain CT in children who present to the emergency department with new onset of seizures. METHODS: A 1-year retrospective chart review of all children who presented to the emergency department of the Schneider Children's Hospital with a new onset of seizures and who underwent CT of the brain, excluding children with simple febrile seizures. RESULTS: Sixty-six patients, 34 boys and 32 girls with a mean age of 4.9 years, qualified for inclusion in the study. Fifty-two patients (78.8%) had normal CT results and 14 patients (21.2%) had abnormal CT results. Seizure cause was considered cryptogenic in 33 patients, of whom 2 (6%) had abnormal CT results; neither patient required intervention. Seizure cause was considered symptomatic in 20 patients, of whom 12 (60%) had abnormal CT results (p < 0.0001). In two patients with abnormal CT scans (both acute symptomatic), the imaging findings were of immediate therapeutic significance and were predictable from the clinical history and the physical examination. None of the 13 patients with complex febrile seizure cause had an abnormal CT scan. Patients with partial convulsive seizures were more likely to have abnormal CT scans than patients with generalized convulsive seizures, but the difference was not statistically significant. CONCLUSIONS: The routine practice in many pediatric emergency departments of obtaining brain CT scans for all patients with new onset of nonfebrile seizures is unjustified. History and physical examination are sufficient to identify those patients for whom such studies are likely to be appropriate. Emergent CT is not indicated for patients with no known seizure risk factors, normal neurological examinations, no acute symptomatic cause other than fever, and reliable neurological follow-up. For these patients, referral to a pediatric neurologist for further workup, including electroencephalography and the more diagnostically valuable magnetic resonance imaging, would be more appropriate.

Adolescent↗
PubMed2000

Xanthine oxidase contributes to host defense against Burkholderia cepacia in the p47(phox-/-) mouse model of chronic granulomatous disease.

Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide and downstream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme known to produce superoxide in many tissues. Using the p47(phox-/-) mouse model of CGD, we evaluated the residual antibacterial activity of XO. Clearance of Burkholderia cepacia, a major pathogen in CGD, was reduced in p47(phox-/-) mice compared to that in wild-type mice and was further inhibited in p47(phox-/-) mice by pretreatment with the specific XO inhibitor allopurinol. Hepatic B. cepacia burden was similar in the two genotypes, but allopurinol significantly reduced net hepatic killing and killing efficiency only in p47(phox-/-) mice. Clearance and killing of intravenous Escherichia coli was intact in p47(phox-/-) mice and was unaffected by pretreatment with allopurinol. In CGD, XO may contribute to host defense against a subset of reactive oxidant-sensitive pathogens.

Allopurinol↗
PubMed2000

Histoplasmosis of the small bowel in patients with AIDS.

Two cases of jejunal strictures caused by Histoplasma capsulatum in AIDS patients are presented. Both patients were intravenous drug abusers. One patient, who was being treated for Pneumocystis carnii pneumonia, presented with jejunal perforation and the other presented with lower gastrointestinal bleeding and intestinal obstruction. On exploration, both patients were found to have jejunal strictures; one had intestinal perforation, and the other had intestinal obstruction with ulcers and strictures resulting in gastrointestinal bleeding. In areas where it is endemic, histoplasmosis is rarely disseminated. Dissemination is most commonly seen in immunosuppressed patients. Dissemination and extrapulmonary histoplasmosis is now included in the case definition of AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2000

Molecular determinants for the distinct pH sensitivity of Kir1.1 and Kir4.1 channels.

Kir1.1 (ROMK1) is inhibited by hypercapnia and intracellular acidosis with midpoint pH for channel inhibition (pK(a)) of approximately 6.7. Another close relative, Kir4.1 (BIR10), is also pH sensitive with much lower pH sensitivity (pK(a) approximately 6. 0), although it shares a high sequence homology with Kir1.1. To find the molecular determinants for the distinct pH sensitivity, we studied the structure-functional relationship using site-directed mutagenesis. An NH(2)-terminal residue (Lys-53) was found to be responsible for the low pH sensitivity in Kir4.1. Mutation of this lysine to valine (K53V), a residue seen at the same position in Kir1. 1, markedly increased channel sensitivity to CO(2)/pH. Reverse mutation on Kir1.1 (V66K) decreased the CO(2)/pH sensitivities. Interestingly, mutation of these residues to glutamate greatly enhanced the pH sensitivity in both channels. Other contributors to the distinct pH sensitivity were histidine residues in the COOH terminus, whose numbers are fewer in Kir4.1 than Kir1.1. Mutation of two of these histidine residues in Kir1.1 (H342Q/H354N) reduced CO(2)/pH sensitivities, whereas the creation of two histidines (S328H/G340H) in Kir4.1 increased the CO(2)/pH sensitivities. Combined mutations of the lysine and histidine residues in Kir4.1 (K53V/S328H/G340H) gave rise to a channel that had CO(2)/pH sensitivities almost identical to those of the wild-type Kir1.1. Thus the residues demonstrated in our current studies are likely the molecular basis for the distinct pH sensitivity between Kir1.1 and Kir4.1.

Amino Acid Sequence↗
PubMed2000

Hypoxic pulmonary vasoconstriction is modified by P-450 metabolites.

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A (CYP4A) metabolite of arachidonic acid (AA) in human and rabbit lung microsomes and is a dilator of isolated human pulmonary arteries (PA). However, little is known regarding the contribution of P-450 metabolites to pulmonary vascular tone. We examined 1) the effect of two mechanistically distinct omega- and omega1-hydroxylase inhibitors on perfusion pressures in isolated rabbit lungs ventilated with normoxic or hypoxic gases, 2) changes in rabbit PA ring tone elicited by 20-HETE or omega- and omega1-hydroxylase inhibitors, and 3) expression of CYP4A protein in lung tissue. A modest increase in perfusion pressure (55 +/- 11% above normoxic conditions) was observed in isolated perfused lungs during ventilation with hypoxic gas (FI(O(2)) = 0.05). Inhibitors of 20-HETE synthesis, 17-oxydecanoic acid (17-ODYA) or N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), increased baseline perfusion pressure above that of vehicle and amplified hypoxia-induced increases in perfusion pressures by 92 +/- 11% and 105 +/- 11% over baseline pressures, respectively. 20-HETE relaxed phenylephrine (PE)-constricted PA rings. Treatment with 17-ODYA enhanced PE-induced contraction of PA rings, consistent with inhibition of a product that promotes arterial relaxation, whereas 6-(20-propargyloxyphenyl)hexanoic acid (PPOH), an epoxygenase inhibitor, blunted contraction to PE. Conversion of AA into 20-HETE was blocked by 17-ODYA, DDMS, and hypoxia. CYP4A immunospecific protein confirms expression of CYP4A in male rabbit lung tissue. Our data suggest that endogenously produced 20-HETE could modify rabbit pulmonary vascular tone, particularly under hypoxic conditions.

Amides↗