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Biomedical subjects

A Jain

Publications and source records attributed to A Jain.

At least 19 recordsLinked to original sources
PubMed1999

General practitioners' experiences of patients' complaints: qualitative study.

OBJECTIVE: To examine how general practitioners experience patients' complaints. SETTING: General practices in Lambeth, Southwark, and Lewisham health authority. PARTICIPANTS: Representative sample of 30 general practitioners who had had complaints made against them under either the old or new complaints system. DESIGN: Qualitative study with detailed interviews. RESULTS: Participants described their experiences of patients' complaints in three stages: initial impact, conflict, and resolution. The first stage described being out of control, feelings of shock and panic, and a sense of indignation towards patients generally. The second stage described the many conflicts generated by the complaint: emotional conflicts such as feelings of anger, depression, and even suicide, conflicts around aspects of professional identity including doubts about clinical competence, conflicts with family and colleagues, and conflicts arising from the management of the complaint. The third stage described a sense of resolution. For many this meant practising defensively, for others it meant planning to leave general practice, and for a minority no resolution was achieved. Not all participants, however, reported such a negative experience. Some described how they had become immune to complaints, and a small minority described the complaint as a learning experience. CONCLUSION: The initial impact stage and conflict stage may be necessary aspects of the experience that general practitioners endure when they have a complaint made against them. Support structures should, however, be in place to help general practitioners through these stages.

Attitude of Health Personnel↗
PubMed1999

Immunosuppressive therapy.

Although several new immunosuppressive medications have been developed in the past decade, many possible avenues are yet to be explored. Although the newer agents have not reflected any clear benefit in patient or graft survival over CsA or tacrolimus, they have been useful in reducing the incidence and severity of rejection, reducing the concomitant use of steroids, and decreasing the doses of CsA or tacrolimus to minimize their toxicity profile. The appearance of these new agents has given more options to clinicians, who can select the one with the least toxicity and most efficacy for individual patients. In the future, combinations of these agents, in conjunction with a strategy to induce tolerance of the donor organ without drug toxicity, will be the goal.

Antibodies, Monoclonal↗
PubMed1999

Liver transplantation for metabolic liver diseases.

Liver transplantation has revolutionized the outcome of metabolic liver diseases that are caused by defects in hepatocytes (e.g., Wilson's disease) or by excessive deposition of substrates secondary to their increased absorption (e.g., hemochromatosis). Early diagnosis and referral are the keys to successful outcome. The timing of liver transplantation for patients on medical therapy depends on a lack of biochemical and clinical evidence of improvement. Overall outcome following liver transplantation depends on the severity of multisystem involvement and preoperative decompensation.

Hemochromatosis↗
PubMed1999

A prospective study on conversion from sandimmune to neoral in stable adult liver transplant recipients.

Neoral is a microemulsion formulation of cyclosporin (CyA), which has more consistent and better pharmacokinetics parameters with improved bioavailability compared to conversional formulation of Sandimmune. Sixty-four stable adults (age >18 years), who had received liver transplants (LTx) and were on Sandimmune-based immunosuppression, were converted to Neoral on milligram for milligram basis. Mean age was 52.5 +/- 13.5 years and male/female distribution was 22/42. Mean interval from LTx to conversion was 109.2 +/- 136 months. In 13 patients (20%) the dose of Neoral was reduced because of an increase in serum creatinine (N = 9), hyperkalemia (N = 1), headache (N = 1), peripheral parasthesia (N = 1), and a general sense of discomfort (N = 1). Interestingly, in two patients a decrease in the trough concentration was observed with the increase in liver enzymes. Both patients responded to an increase in Neoral dose. The present study suggests while the majority of the stable liver transplant patients (77%) can be safely converted to Neoral from Sandimmune on a milligram to milligram basis, they need to be carefully monitored for renal function, liver function, and trough concentration of CyA.

Adult↗
PubMed1999

Pentazocine induced widespread cutaneous and myo-fibrosis.

We report a case of extensive subcutaneous and muscle fibrosis in a 26-year-old Indian woman caused by repeated intramuscular pentazocine injections over five years to highlight the extent and sequelae of this avoidable condition.

Abdominal Pain↗
PubMed1999

Ultrasound study of heel to calcaneum depth in neonates.

AIM: To investigate whether it would be safe to extend the currently recommended area of sampling to the whole heel in neonates. METHODS: Eighty newborn infants were studied, weight range 0.56 to 4.34 kg, gestation 24 to 42 weeks. Ultrasound scanning was used to measure the shortest distance between the skin and the perichondrium of the calcaneum. RESULTS: The shortest depth of perichondrium was in the centre of the heel and ranged from 3 to 8 mm. In 78 of the 80 infants the distance was 4 mm or more. There was a small but significant positive correlation with weight. CONCLUSIONS: Standard automated lancets for preterm use that puncture to a depth of 2.4 mm may be safely used anywhere over the plantar surface of the heel. The posterior aspect of the heel should be avoided. Reducing the density of heel pricks should reduce the associated pain.

Blood Specimen Collection↗
PubMed1999

Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome.

X-linked hyper-IgM syndrome (XHIM) results from mutations in the gene encoding for CD40 ligand (CD154). Patients with the syndrome suffer from infections with opportunistic pathogens such as Cryptosporidium and Pneumocystis carinii. In this study, we demonstrate that activated T cells from patients with XHIM produce markedly reduced levels of IFN-gamma, fail to induce antigen-presenting cells to synthesize IL-12, and induce greatly reduced levels of TNF-alpha. In addition, we show that the patients' circulating T lymphocytes of both the CD4(+) and CD8(+) subsets contain a markedly reduced antigen-primed population, as determined by CD45RO expression. Finally, we demonstrate that the defects in antigen priming are likely due to the lack of CD154 expression and insufficient costimulation of T cells by CD80/CD86 interactions. Taken together, this study offers a basis for the increased susceptibility of patients with XHIM to certain opportunistic infections.

Adolescent↗
PubMed1998

Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) after pediatric liver transplantation has been associated with high mortality rates. METHODS: The present study examined 282 consecutive pediatric liver transplant recipients from October 1989 to June 1996 who received primary tacrolimus immunosuppression. The aim was to determine the incidence of PTLD, management strategies, and patient outcome. RESULTS: The incidence of PTLD was 13% (361282) with a mean age of 5.5+/-0.7 years (range 0.6 to 15) at diagnosis. The average time from transplantation to PTLD was 10.1+/-2.1 months. Initial treatment of PTLD consisted of reduction (3 patients) or discontinuation (33 patients) of tacrolimus and initiation of antiviral therapy (intravenous ganciclovir, 14 patients; intravenous acyclovir, 22 patients; or both, 5 patients). Alpha-interferon was used in four patients (two successfully). One patient also received gamma-interferon, chemotherapy, and radiation for a central nervous system lesion. Chemotherapy was also used in one patient with Burkitt's, whereas one patient with a pulmonary lesion received additional radiation therapy. Three patients received supportive surgery for gastrointestinal involvement, and one patient had a splenectomy for hemolysis. Overall mortality was 22% (8/36) with 5 (14%) PTLD-related deaths (disseminated disease, 4 patients; bowel perforation, 1 patient). Of 31 survivors, 23 had acute rejection at a median time of 24 days after PTLD, with 2 patients developing chronic rejection. One patient required retransplantation. Present immunosuppression consists of tacrolimus monotherapy in 14 patients, tacrolimus/prednisone in 8 patients, and none in 6 patients. CONCLUSION: In summary, PTLD can be successfully treated with reduction of immunosuppression and administration of antiviral agents in most patients. The management of rejection after PTLD requires reassessment of disease status and judicious reintroduction of immunosuppression therapy.

Adolescent↗
PubMed1998

Stent supported angioplasty in Takayasu arteritis.

Eleven patients with Takayasu Arteritis (TA) underwent angioplasty and stent placement in aorta, renal, carotid, subclavian and coronary arteries. Five wall stents were deployed in aorta in four patients. Indications for angioplasty and stent placement in aorta included hypertension in four patients and claudication and erectile impotence in one patient each. Post-procedure the peak systolic pressure gradient across the stenotic segment in the aorta disappeared. Six patients underwent angioplasty and stent placement in carotid arteries. Indications were syncope in 6 patients, loss of vision, stroke, transient ischaemic attack and seizures in one patients each. There was a marked improvement in symptoms in the patients following the procedure. For chronic total occlusion of subclavian arteries, two stents were deployed in two patients. Following the stent placement pulses in upper limb reappeared. Stents were also deployed to treat near total occlusion of right coronary artery and flow limited dissection of renal artery in one patient each. Complications of the procedure included pain in the back, mild hypertension, transient bradycardia and conduction block in one patient each. In conclusion, the stenotic and obliterative vascular lesions in TA can be managed successfully with angioplasty and stent placement. A long term follow up is required to determine the re-stenosis rate.

Adolescent↗
PubMed1998

Outcome of liver transplantation in critically ill patients with alcoholic cirrhosis: survival according to medical variables and sobriety.

BACKGROUND: At our center from August 1989 to December 1992, 834 adults underwent orthotopic liver transplantation (OLT) using tacrolimus as the primary immunosuppressive agent. A total of 183 adults (22%) had alcohol-related liver disease. Patients with alcoholic cirrhosis had a better though not statistically significant 5-year survival rate compared with all other patients. We were interested in specific predictors of survival, particularly for alcoholic cirrhotics who were gravely ill at the point of transplantation. METHODS: For the 78 patients with alcohol-related liver disease who were United Network for Organ Sharing status IIA (critically ill) at the point of transplantation, variables of length of sobriety, alcohol rehabilitation, and medical variables (ventilator support, dialysis, vasopressor support, degree of encephalopathy, and infection) were assessed for contribution to survival. RESULTS: Although there was a trend toward poorer survival in patients with the shortest length of sobriety (< or =1 month), pre-OLT length of sobriety or alcohol rehabilitation did not predict survival. However, these patients tended to be in multiorgan failure and encephalopathic. Nevertheless, pre-OLT dialysis requirement was the only variable that predicted poorer survival (P < 0.002). This study was not designed to evaluate recidivism. However, we know that 24% of these patients have used alcohol at some point after OLT. CONCLUSIONS: Short pre-OLT length of sobriety may not predict which patients are likely to resume alcohol consumption after OLT, but it may identify patients in whom there will exist a variety of poor outcome variables. In our study, in these patients, post-OLT survival was associated with medical rather than alcohol history variables.

Adult↗
PubMed1998

Generating controlled reducing environments in aerobic recombinant Escherichia coli fermentations: effects on cell growth, oxygen uptake, heat shock protein expression, and in vivo CAT activity.

The independent control of culture redox potential (CRP) by the regulated addition of a reducing agent, dithiothreitol (DTT) was demonstrated in aerated recombinant Escherichia coli fermentations. Moderate levels of DTT addition resulted in minimal changes to specific oxygen uptake, growth rate, and dissolved oxygen. Excessive levels of DTT addition were toxic to the cells resulting in cessation of growth. Chloramphenicol acetyltransferase (CAT) activity (nmoles/microgram total protein min.) decreased in batch fermentation experiments with respect to increasing levels of DTT addition. To further investigate the mechanisms affecting CAT activity, experiments were performed to assay heat shock protein expression and specific CAT activity (nmoles/microgram CAT min.). Expression of such molecular chaperones as GroEL and DnaK were found to increase after addition of DTT. Additionally, sigma factor 32 (sigma32) and several proteases were seen to increase dramatically during addition of DTT. Specific CAT activity (nmoles/microgram CAT min. ) varied greatly as DTT was added, however, a minimum in activity was found at the highest level of DTT addition in E. coli strains RR1 [pBR329] and JM105 [pROEX-CAT]. In conjunction, cellular stress was found to reach a maximum at the same levels of DTT. Although DTT addition has the potential for directly affecting intracellular protein folding, the effects felt from the increased stress within the cell are likely the dominant effector. That the effects of DTT were measured within the cytoplasm of the cell suggests that the periplasmic redox potential was also altered. The changes in specific CAT activity, molecular chaperones, and other heat shock proteins, in the presence of minimal growth rate and oxygen uptake alterations, suggest that the ex vivo control of redox potential provides a new process for affecting the yield and conformation of heterologous proteins in aerated E. coli fermentations.

Aerobiosis↗
PubMed1998

Transdermal nitroglycerin patch therapy improves left ventricular function and prevents remodeling after acute myocardial infarction: results of a multicenter prospective randomized, double-blind, placebo-controlled trial.

BACKGROUND: Nitrates are widely used in the treatment of angina in patients with acute myocardial infarction (AMI). Short-term administration prevents left ventricular (LV) dilation and infarct expansion. However, little information is available regarding their long-term effects on LV remodeling in patients surviving Q-wave AMI. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial designed to investigate the long-term (6-month) efficacy of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291 survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide angiography (RNA) followed by randomization to placebo or active NTG patches delivering 0.4-, 0.8-, or 1.6-mg/h. RNA was repeated at 6 months and 6.5 days after withdrawal of double-blind medication. The primary study end point was the change in end-systolic volume index (ESVI). Both ESVI and end-diastolic volume index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and -11.6 mL/m2, respectively, P<.03). This beneficial effect was observed primarily in patients with a baseline LV ejection fraction < or =40% (deltaESVI, -31 mL/m2; deltaEDVI, -33 mL/m2; both P<.05) and only at the 0.4-mg/h dose. After NTG patch withdrawal, ESVI significantly increased but did not reach pretreatment values. CONCLUSIONS: Transdermal NTG patches prevent LV dilation in patients surviving AMI. The beneficial effects are limited to patients with depressed LV function and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to maintain efficacy. Whether these remodeling effects confer a clinical or survival advantage will need to be addressed in an adequately powered cardiac event trial.

Administration, Cutaneous↗
PubMed1998

Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon.

Interferon alfa-2b (IFN-alpha) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-alpha often leads to allograft rejection. The aim of the present study was to determine if IFN-alpha therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients with HBV (n = 32), HCV (n = 58), or Non A Non B Non C (n = 15) viral infections were treated with a 6-month course of IFN-alpha, 5 million U subcutaneously three times a week, which began 2 to 97 months after transplantation. The mean hepatitis activity index (HAI) at the beginning of the therapy was 10.1 +/- 3.0. The baseline immunosuppression was achieved by tacrolimus in 77 patients and by cyclosporine A (CyA) in 28 patients. Contemporaneous controls consisted of 132 OLT patients (100 who received tacrolimus and 32 who received CyA) who did not receive IFN-alpha. A retrospective analysis was performed on this group of patients. The incidence of rejection and the baseline immunosuppression were compared. All biopsies were reviewed without knowledge of clinical data and scored for HAI and for rejection activity index (RAI). The biochemical response to IFN-alpha was also examined. The mean baseline maintenance dose of prednisone was greater by 2 mg daily in patients who received IFN-alpha with tacrolimus compared with control patients who did not receive IFN-alpha with tacrolimus (IFN-alpha 5. 3 +/- 5.2 mg daily v controls 3.3 +/- 4.9 mg daily; P </= .05). Similarly, the mean maintenance dose of prednisone was greater by 2.5 mg daily in patients who received IFN-alpha compared with controls who received CyA-based immunosuppression (IFN-alpha 9.8 +/- 3.1 mg daily v controls 7.3 +/- 3.3 mg daily; P = .01). Acute rejection episodes were detected in 10.5% (n = 11) of IFN-alpha-treated patients compared with 8.8% of controls for the similar time period from OLT and period of exposure to risk of rejection. Mean RAI was 2.0 +/- 2.4 for the IFN-alpha-treated group and 2.1 +/- 1.7 for controls. Rejection episodes with IFN-alpha treatment were mild and responded to steroid therapy. In OLT recipients, the risk of acute rejection was not increased by the introduction of IFN-alpha. However, in this study, patients were exposed to greater levels of immunosuppression.

Biopsy↗
PubMed1998

Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation.

OBJECTIVE: To examine the phenotypic expression of CYP2E1 in liver transplant patients, as measured by the in vivo probe chlorzoxazone, and to evaluate CYP2E1 activity over time after transplantation. METHODS: Thirty-three stable liver transplant patients were given 250 mg chlorzoxazone within 1 year after transplantation as part of a multiprobe CYP cocktail; urine and blood were collected for 8 hours. Chlorzoxazone and 6-hydroxychlorzoxazone concentrations were determined by HPLC. Twenty-eight healthy control subjects, eight patients with moderate to severe liver disease, and four patients who had not received liver transplants were also studied for comparison. The chlorzoxazone metabolic ratio, calculated as the plasma concentration of 6-hydroxychlorzoxazone/chlorzoxazone at 4 hours after chlorzoxazone administration, was used as the phenotypic index. In a subgroup of patients and control subjects, additional blood samples were obtained to allow for the calculation of chlorzoxazone pharmacokinetic parameters by noncompartmental methods. RESULTS: The chlorzoxazone metabolic ratio for the liver transplant patients in the first month after transplantation (mean +/- SD, 6.4 +/- 5.1) was significantly higher than that after 1 month after surgery (2.1 +/- 2.0), when the chlorzoxazone metabolic ratio was not different from control subjects (0.8 +/- 0.5). The chlorzoxazone metabolic ratios in the patients who had not received liver transplants (1.1 +/- 0.7) were equivalent to those of healthy control subjects. The maximum observed 6-hydroxychlorzoxazone plasma concentration was 3046 +/- 1848 ng/ml in seven liver transplant patients in the first month after surgery compared with 1618 +/- 320 ng/ml in 16 healthy control subjects (p < 0.05). The maximum observed concentration of chlorzoxazone, the chlorzoxazone apparent oral clearance, and the formation clearance of 6-hydroxychlorzoxazone were also significantly different between the groups. CONCLUSIONS: We conclude that significant induction of CYP2E1, as indicated by the chlorzoxazone metabolic ratio, occurs in the first month after surgery in liver transplant patients and that drugs that are substrates for CYP2E1 may require dosage alteration during that period. Contrary to expectations, drug metabolism is not uniformly depressed after liver transplantation.

Adult↗