Search PubMed⌕ Search

Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 199 records · Page 11Linked to original sources

Observation of a new nonfluorescent malondialdehyde-acetaldehyde-protein adduct by 13C NMR spectroscopy.

It has been shown that malondialdehyde (MDA) and acetaldehyde react with proteins via the epsilon-amino group of a lysine residue to yield hybrid MDA-acetaldehyde (MAA)-protein adducts. The structure of one MAA adduct has been confirmed to be 4-methyl-1, 4-dihydropyridine-3,5-dicarbaldehyde (3). In this study, 13C NMR spectroscopy was used to identify the structure of a second MAA adduct as 2-formyl-3-(alkylamino)butanal (4). Isotopically labeled [1-13C]acetaldehyde was reacted with MDA and the protein, bovine serum albumin, under a variety of conditions, and the reactions were monitored at various time intervals by 13C NMR. In each experiment, new signals grew in at 50 and 22 ppm. By comparison to model compounds, the signals at 50 ppm correspond to a 2-formyl-3-(alkylamino)butanal adduct and the signals at 22 ppm correspond to the known 1,4-dihydropyridine-3,5-dicarbaldehyde adduct. Similar results were found when the BSA was replaced with polylysine. Overall, it appears that MAA-protein adducts are composed of two major products, 3 and 4.

Acetaldehyde↗

Intrathymic inoculation of donor antigen: an ineffective strategy for prolonging xenograft survival.

The aim of this study was to determine whether intrathymic inoculation of the recipient with donor antigen and short-term depletion of peripheral lymphocytes would lead to donor-specific unresponsiveness to rat pancreatic islet xenografts. The results were compared directly with an allograft model to determine whether there were substantial differences in the mechanisms of graft prolongation between allografts and xenografts using an identical conditioning regimen. Streptozotocin-induced diabetic C57B6 mice were injected with up to 0.3 ml of rat anti-mouse lymphocyte serum (ALS) 1 day before intrathymic injection of donor splenocytes. DA rat islet xenografts or Balb/c mouse islet allografts were transplanted 3 days later. ALS depleted CD3+ and CD4+ peripheral blood T lymphocytes to less than 5% of values in control mice by 24 h. Median islet xenograft survival (MGS) was 9 days in untreated mice, 28 days in mice receiving 0.2 ml of ALS and 32 days in mice receiving 0.3 ml of ALS alone. Intrathymic injection of 5 x 10(6) DA splenocytes plus 0.2 ml of ALS did not improve islet xenograft survival beyond 28 days. Increasing the intrathymic inoculum to 10(7) DA splenocytes with or without a higher dose of ALS (0.3 ml) did not increase MGS beyond 26 days, although 2 out of 18 animals survived beyond 100 days. These long-term surviving mice rejected a second DA rat islet graft in less than 22 days, indicating that tolerance was not achieved. To confirm the efficacy of this treatment regimen in allotransplantation, diabetic C57B6 mice received 10(7) Balb/c splenocytes intrathymically and 0.3 ml of ALS. A Balb/c islet allograft was performed 3 days later. Allograft survival was similar to that of rat islet xenografts with 40%, (4 out of 10) of grafts surviving beyond 100 days. In contrast to the xenograft recipients, a second Balb/c islet allograft survived indefinitely, indicating that tolerance was achieved. Histology of the long-surviving allografts showed intact islets with a sparse cellular infiltrate, whereas the long-surviving xenografts (> 100 days) showed a large cellular infiltrate and significant islet destruction. To investigate further the role of the thymus, adult thymectomized C57B6 mice were treated with 0.3 ml of ALS and received a DA rat islet xenograft. The median graft survival was 52 days and no graft survived beyond 80 days, suggesting that peripheral xenoreactive T cells remained after ALS treatment and greater T-cell depletion was necessary to obtain permanent engraftment. These results show that peripheral xenoreactive T cells which remain after profound T-cell depletion are capable of rejecting an islet xenograft despite intrathymic inoculation of donor antigen. The T-cell-mediated xenograft response appears to be stronger and more difficult to suppress than the allograft response using this strategy.

Animals↗

Randomized clinical trial of early laparoscopy in the management of acute non-specific abdominal pain.

BACKGROUND: Abdominal pain of uncertain aetiology (non-specific abdominal pain; NSAP) is the commonest reason for emergency surgical admission. The aim of this study was to examine the role of early laparoscopy in the management of NSAP. METHODS: Some 120 patients, admitted between November 1995 and October 1998 with acute abdominal pain of uncertain aetiology, were randomized into two groups: group 1 had laparoscopy during the first 18 h of admission and group 2 had close observation, conventional investigation and surgical intervention if signs of peritonism developed. Outcome measures were diagnosis, operative procedures, duration of hospital stay, readmission rate, morbidity and death, patient satisfaction and total number of investigations performed. RESULTS: Median hospital stay was 2 (range 1-13) days in both groups (P = 0.87). A diagnosis was established in 48 (81 per cent) of 59 patients in group 1 compared with 22 (36 per cent) of 61 in group 2 (P < 0.0001). The morbidity rate was 14 (24 per cent) of 59 in group 1 and 19 (31 per cent) of 61 in group 2 (P = 0.3629). The readmission rate at a median follow-up of 21 (range 1-35) months was 17 (29 per cent) of 59 in group 1 compared with 20 (33 per cent) of 61 in group 2 (P = 0. 6375). Well-being scores improved from 134 on admission to 149 of 177 6 weeks later in group 1 (P = 0.007) and from 132 to 143 of 177 in group 2 (P = 0.089). CONCLUSION: Early laparoscopy provided a higher diagnostic accuracy and improved quality of life in patients with NSAP.

Abdominal Pain↗

Crusted scabies in two immunocompromised children: successful treatment with oral ivermectin.

Two immunodeficient children, aged 4 and 12 years, with crusted scabies were successfully treated with a single oral dose of ivermectin (200 micrograms/kg). One child had been diagnosed in infancy with an undefined congenital T cell immunodeficiency and the other with chronic mucocutaneous candidiasis. Both had failed to respond to conventional topical therapy. In view of the excellent therapeutic response and absence of side-effects, ivermectin should be considered in the treatment of recalcitrant crusted scabies in children.

Administration, Oral↗

Topical treatment of interdigital tinea pedis: terbinafine compared with clotrimazole.

A multicentre, prospective, randomized, double-blind, parallel group study was undertaken to compare the efficacy and tolerability of topical terbinafine with topical clotrimazole in the treatment of interdigital tinea pedis. Patients were randomized to receive either terbinafine 1% cream twice daily for 1 week, followed by a similar placebo cream for 5 weeks, or clotrimazole 1% cream twice daily for 4 weeks. Outcome measures were: (i) mycological cure (negative culture); (ii) effective treatment (negative culture plus a symptom score of 2 or less out of a maximum score of 18); and (iii) complete cure (negative culture and a symptom score of 0); measured at 1, 4, 8 and 12 weeks after the commencement of the study. One hundred and four of the 217 patients randomized had a culture-confirmed dermatophyte infection at baseline. In these patients, 84.6% in the terbinafine group were culture negative after 1 week, compared with only 55.8% in the clotrimazole group. Both agents were well tolerated. The study showed that terbinafine achieves mycological cure more rapidly than clotrimazole. This may result in improved compliance and better control over transmission of infection.

Administration, Cutaneous↗

Completeness and efficiency of prostate tissue removal: loop resection compared with a new operative technique of transurethral electrovaporization.

OBJECTIVE: To compare the completeness and efficiency of the removal of prostatic adenomatous tissue between transurethral resection (TURP) and a new operative technique of electrovaporization (TUEVAP) using a modified roller electrode. PATIENTS AND METHODS: In a prospective double-blind study, patients with moderate to severe lower urinary tract symptoms and objective evidence of obstruction, were randomized to undergo either TURP (using a standard cutting-wire loop) or TUEVAP (performed with a new operative technique and the spiked-bar electrode). The prostate volume measured using transrectal ultrasonography (TRUS-PV) was used to assess the completeness of tissue clearance after treatment. Results were compared using group median values. For the TURP group, the TRUS-PV estimate of tissue removed was divided by the dry resected weight to derive a correction factor for any discrepancy between the values. This factor was applied to the TRUS-PV reduction in the TUEVAP group (where there was no tissue to be weighed) to estimate the actual tissue removal in this group. The efficiency of tissue removal for each treatment modality was derived by dividing the amount of tissue removed by the operative duration. RESULTS: There was no difference in the reduction in TRUS-PV at 3 months (23.9 cm3 vs 21.45 cm3, P<0.9), or in the operative duration (45 min vs 52.5 min, P<0.2), between TURP and TUEVAP, respectively. The TRUS-PV of tissue removed exceeded the actual dry resected weight after TURP (15 g) by a factor of 1.59. After applying this factor to the TRUS-PV reduction for the TUEVAP group, the calculated dry weight of tissue removed for this group was 13.49 g (P<0.55); the difference in tissue removal rate by TRUS criteria was 0.48 cm3/min vs 0.37 cm3/min (P<0.15). CONCLUSIONS: These data suggest an equivalent completeness of removal of adenomatous prostate tissue between TURP and TUEVAP. The efficiency of tissue removal for TUEVAP was slightly less than that of regular loop resection, but this difference was not statistically significant. These results are specific to the combination of electrode, electrosurgical unit and operative technique used in this study, and may differ if any of these variables are altered.

Aged↗

Evidence for cytokine mediation of disease expression in adults experimentally infected with influenza A virus.

The roles of interleukin (IL)-6 and IL-8 in mediating the symptoms and signs of influenza A infection were examined. Adults were intranasally inoculated with a rimantadine-sensitive strain of influenza A HlNl virus and treated with rimantadine or placebo. Viral shedding, secretion weights, symptom scores, and concentrations of IL-6 and IL-8 in nasal lavage fluids were compared between treatment groups. Viral shedding was associated with increases in local and systemic symptoms, in expelled secretion weights, and in levels of IL-6 and IL-8. Compared with placebo, rimantadine treatment reduced viral shedding, systemic symptoms, and levels of IL-8. Days of viral shedding and IL-6 but not IL-8 concentrations were significantly correlated with the other measures of symptoms and signs. These data support a causal relationship between viral replication, cytokine production, and symptom expression, and they suggest that IL-6 may have a role in mediating symptom and sign expression during influenza A infection.

Adolescent↗

Molecular fingerprinting reveals non-overlapping T cell oligoclonality between an inflamed site and peripheral blood.

We have demonstrated a stable expansion of CD8+ T cells in the peripheral blood of a child with chronic arthritis. The expanded TCRBV family (TCRBV14) was enriched for CD57hiCD28- T cells. Sequencing of the TCRBV14 amplification products showed a TCR sequence which contributed 32% of the total TCR in the CD8+TCRBV14 population. Using the modified heteroduplex technique, the CD8+TCRBV14 cells showed a clonal pattern and these bands were restricted to the CD28- population. This method also detected multiple other clones within the CD8+ population but few in the CD4+ cells. The dominant TCRBV14+ clone was not detectable in synovial fluid T cells from two inflamed joints by CDR3 length analysis or heteroduplex probing, suggesting that this long-lived clone is excluded from inflammatory sites. Synovial fluid T cells showed an unexpected discordance of the CD28 and CD57 phenotype compared to peripheral blood mononuclear cells. T cells from both inflamed joints both showed marked oligoclonality in all TCR families and had almost identical heteroduplex patterns. Taken together these data suggest that some clones are actively excluded from inflamed sites in juvenile chronic arthritis, yet the pattern of restricted T cell expansion is shared between sites of inflammation.

Arthritis, Juvenile↗

Costs and disability among stroke patients.

BACKGROUND: The high costs of health and social care support for stroke survivors, and the development of new service arrangements, have concentrated growing attention on economic issues. However, there are few data on costs and their association with levels of disability. METHODS: Secondary analyses of data from the OPCS (Office of Population Censuses and Surveys) Surveys of Disability conducted in the mid-1980s were used to examine service utilization and costs for more than 1000 people who have had a stroke. Costs were estimated for all health and social care services. Regression analyses examined the cost-disability association in the context of other covariates for people living in private households. RESULTS: Disability problems were common among stroke survivors, particularly in relation to locomotion, self-care and holding. Among people living alone, the major contributors to costs were in-patient care (Pound Sterling 27 per week) and home help (Pound Sterling 30 per week). Among people living with others, in-patient hospital care was also a major cost (Pound Sterling 28 per week). Other services costing more than Pound Sterling 5 per week were general practitioner consultations, hospital out-patient care and day centre attendances. Resource use patterns varied considerably. Costs were associated with severity of disability, time since stroke and whether the person was living alone. Looking at the overall balance of care, a greater proportion of stroke survivors with severe disability were resident in communal establishments. CONCLUSION: The analyses provide a baseline from which more recent local studies and evaluations can be compared. Key issues for economic studies of stroke are the inclusion of a broad range of services, a reasonable duration of follow-up and consideration of the impact of the substitution of informal for formal services.

Adult↗

Technical solution for an interactive functional MR imaging examination: application to a physiologic interview and the study of cerebral physiology.

Studies with functional magnetic resonance (MR) imaging produce large unprocessed raw data sets in minutes. The analysis usually requires transferring of the data to an off-line workstation, and this process frequently occurs after the subject has left the MR unit. The authors describe a hardware configuration and processing software that captures whole-brain raw data files as they are being produced from the MR unit. It then performs the reconstruction, registration, and statistical analysis, and displays the results in seconds after completion of the MR image acquisition.

Brain↗

Differential expression of VEGF mRNA splice variants in newborn and adult hyperoxic lung injury.

Lung development and repair of hyperoxic injury require closely regulated growth and regeneration of alveolar capillaries. Vascular endothelial growth factor (VEGF), a mitogen for endothelial cells, is expressed by alveolar epithelial cells. Alternative splicing of VEGF mRNA results in isoforms of varying mitogenicity and solubility. We examined changes in the proportions of the VEGF splice variant mRNAs in rabbit lung development and in control, oxygen-injured, and recovering newborn and adult rabbit lungs. The proportion of the 189-amino acid VEGF mRNA, which codes for an isoform that binds to the extracellular matrix, increased fivefold during development (from 8% of total VEGF message at 22 days gestation to 40% in 10-day newborn lungs; P < 0.001). During neonatal oxygen injury, its expression declined from 38 to 8% of VEGF message (P < 0.002) and returned to the control value in recovery. A similar pattern was observed in adults. VEGF protein in lung lavage fluid increased slightly during hyperoxia, declined to barely detectable levels at the 50% lethal dose time point, and increased 10-fold (newborn) or up to 40-fold (adult) in recovering animals. We conclude that alternative splicing may have important roles in the regulation of VEGF activity in developing and injured lungs.

Aging↗

Effect of oral glutamine on whole body carbohydrate storage during recovery from exhaustive exercise.

The purpose of this study was to determine the efficacy of glutamine in promoting whole body carbohydrate storage and muscle glycogen resynthesis during recovery from exhaustive exercise. Postabsorptive subjects completed a glycogen-depleting exercise protocol, then consumed 330 ml of one of three drinks, 18.5% (wt/vol) glucose polymer solution, 8 g glutamine in 330 ml glucose polymer solution, or 8 g glutamine in 330 ml placebo, and also received a primed constant infusion of [1-13C]glucose for 2 h. Plasma glutamine concentration was increased after consumption of the glutamine drinks (0.7-1.1 mM, P < 0.05). In the second hour of recovery, whole body nonoxidative glucose disposal was increased by 25% after consumption of glutamine in addition to the glucose polymer (4.48 +/- 0.61 vs. 3.59 +/- 0.18 mmol/kg, P < 0.05). Oral glutamine alone promoted storage of muscle glycogen to an extent similar to oral glucose polymer. Ingestion of glutamine and glucose polymer together promoted the storage of carbohydrate outside of skeletal muscle, the most feasible site being the liver.

Adult↗

Antithrombotic efficacy of a novel murine antihuman factor IX antibody in rats.

A murine antihuman factor IX monoclonal antibody (BC2) has been generated and evaluated for its capacity to prolong the activated partial thromboplastin time (aPTT) in vitro and ex vivo and to prevent arterial thrombosis in a rat model in vivo. BC2 extended aPTT to a maximum of 60 to 80 seconds at 100 to 1000 nmol/L in vitro (rat and human plasma, respectively) and ex vivo (rat) after dosing of rats up to 6 mg/kg in vivo. BC2, administered as bolus (1 to 6 mg/kg) followed by infusion (0.3 to 2 mg x kg(-1) x h(-1)), dose-dependently prevented thrombosis of an injured rat carotid artery (FeCl(3)-patch model), increased time to artery occlusion, and reduced incidence of vessel occlusion. BC2 efficacy in preventing arterial thrombosis exceeded that of heparin (bolus 15 to 120 U/kg followed by infusion 0.5 to 4.0 U x kg(-1) x min(-1)), whereas the latter rendered the blood incoagulable (aPTT>1000 seconds). BC2 demonstrated complete antithrombotic efficacy also as a single bolus given either as prevessel or postvessel injury as evidenced by reduction of thrombus mass (from 4.18+/-0.49 to 1.80 +/-0.3 mg, P<0.001), increasing vessel patency time (from 14.9+/-0.9 minutes to 58.3+/-1.7 minutes, P<0.001) and decreasing incidence of vessel occlusion from 100% to 0% in vehicle- versus BC2-treated rats, respectively. BC2 (3 mg/kg, IV) administered in a single bolus resulted in 50% reduction in thrombus mass (P<0.01), extended vessel patency time (P<0.001), extended aPTT only 4-fold, and had no effect on blood loss via a tail surgical wound; heparin, at doses that reduced thrombus mass to a similar extent, extended aPTT beyond 1000 seconds (over 500-fold) and increased blood loss from 1.8+/-0.7 to 3.3 +/-0.6 mL (P<0.001). These data suggest that BC2 may provide enhanced therapeutic efficacy in humans at lesser interference with blood hemostasis than heparin.

Anesthesia↗