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Biomedical subjects

K Bhagat

Publications and source records attributed to K Bhagat.

At least 19 recordsLinked to original sources
PubMed2005

Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience.

BACKGROUND: One of the most active chemotherapy combinations in advanced or recurrent cervical cancer is cisplatin-paclitaxel. However, this palliative regimen is associated with significant toxicity. Carboplatin-paclitaxel is thus an attractive option. METHODS: Patients with advanced or recurrent carcinoma of the cervix treated with carboplatin-paclitaxel from April 2000 were included in the study. Starting doses of carboplatin-paclitaxel were: AUC 5-6 and 155-175 mg/m(2), respectively, repeated every 28 days. RESULTS: Twenty-five women treated with this combination were identified. Twenty-three women (92%) had prior treatment with pelvic radiotherapy and 14 (56%) had had concurrent radio-sensitizing cisplatin. There was a 20% PR and a 20% CR rate (10/25). The median progression-free survival for the entire group was 3 months. Responders had a median PFS of 16 months. Fourteen patients (56%) had died of disease progression. The median overall survival (OS) was 21 months. Common toxicities included: grade 1 or 2 anemia, 68%; grade 3 or 4 anemia, 32%; grade 3 or 4 neutropenia, 32%; and grade 1 or 2 peripheral neuropathy, 24%. ECOG PS did not change significantly while on treatment. Eighty-four percent of treatments were delivered on time, and 96% at full dose. CONCLUSIONS: Carboplatin-paclitaxel is an active combination in advanced and recurrent cervical cancer. In this predominantly pre-irradiated group, the combination was deliverable, well tolerated, and the most commonly observed toxicity was anemia.

Adult↗
PubMed2001

General practitioners and clinical guidelines.

OBJECTIVE: To assess the attitudes of general practitioners in Harare, Zimbabwe, towards the use of clinical practice guidelines (CPG's). DESIGN: Cross sectional survey. SETTING: General practitioners in private practice within the urban Harare (Zimbabwe) environs. SUBJECTS: Two hundred and thirty two general practitioners in Harare, Zimbabwe. MAIN OUTCOME MEASURES: The response to a questionnaire enlisting attitudes to CPGs. RESULTS: Questionnaires were sent to 232 general practitioners. Of these, 137 (59.1%) returned a completed questionnaire. Among the respondents, 95.6% felt that general practitioners should be involved in the development of guidelines, 72.6% had read at least one guideline, 65.9% were prepared to use guidelines in their practice, 61.6% thought that guidelines would improve their treatment ability, and 59.7% thought that guidelines would improve their knowledge of disease. 76.5% felt that the government should not legislate, 66.2% felt that guidelines reduce practitioners' flexibility and 57.9% felt that guidelines would not improve their diagnostic ability. CONCLUSION: The respondents were, in general, favourably disposed towards CPGs. Most had already read some guidelines, and about two thirds were prepared to use them. Almost all respondents felt that general practitioners should be involved in the development of guidelines for use in general practice. These general practitioners felt that guidelines were likely to help them treat patients than to make a diagnosis. Despite these favourable attitudes, many practitioners felt that guidelines would limit their personal flexibility in caring for patients. Organisations developing or implementing CPGs in general practice should address these concerns.

Adult↗
PubMed2001

Compliance with medication in patients with heart failure in Zimbabwe.

OBJECTIVES: To determine the extent of adherence to prescribed medication in patients with chronic heart failure and to determine to what extent patients recall information given regarding their medication. DESIGN: Compliance and knowledge of prescribed medication was studied in 22 heart failure patients [mean age 45 +/- 4 (range 40-67); 14 (64%) male], using in-depth interviews performed 30 days after having been prescribed medication. All patients received standardised verbal and written information regarding their medication. SETTING: Patients attending four general practices in the private sector (in Harare, Zimbabwe) for at least six months prior to enrolling were in included in the study. RESULTS: Only 12 (55%) patients could correctly name what medication had been prescribed, 11 (50%) were unable to state the prescribed doses and 14 (64%) could not account for when the medication was to be taken, that is to say, at what time of day and when in relation to meals the medication was to be taken. In the overall assessment six (27%) patients were found non-compliant and 16 (73%) patients were considered as possibly being compliant with their prescribed medication. CONCLUSIONS: Non-compliance was common in heart failure patients, as were shortcomings in patients' knowledge regarding prescribed medication, despite efforts to give adequate information. There exists a need for alternative strategies to improve compliance in these patients.

Adult↗
PubMed2001

Effects of non-steroidal anti-inflammatory drugs on hypertension control using angiotensin converting enzyme inhibitors and thiazide diuretics.

OBJECTIVES: To determine the impact of three non-steroidal anti-inflammatory drugs on the efficacy of two anti-hypertensive drugs. DESIGN: Fifteen women with arthritis and hypertension who were receiving lisinopril and HCT, and administered sequentially in random order ibuprofen, sulindac, and diclofenac for one month each, with an intervening two-week washout period between each treatment period. During the washout period, subjects received paracetamol. SETTING: Hypertension Clinic, Medical Centre, Harare, Zimbabwe. SUBJECTS: Fifteen female hypertensive women with documented arthritis. MAIN OUTCOME MEASURES: Blood pressure at the end of two weeks of paracetamol was compared with blood pressure after one month of treatment with each of the NSAID. RESULTS: Mean blood pressure was unchanged before and after all NSAIDs: 108 +/- 7 versus 107 +/- 9 for diclofenac, 108 +/- 9 versus 108 +/- 9 for sulindac, and 108 +/- 8 versus 107 +/- 9 for ibuprofen. The 24 hour urinary sodium excretion was not significantly different. CONCLUSION: The three NSAIDs investigated did not neutralise the antihypertensive effect of the combination of lisinopril and HCT, and hence the blood pressure lowering action of the combination may not be prostaglandin dependent.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Acute systemic inflammation impairs endothelium-dependent dilatation in humans.

BACKGROUND: We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation. METHODS AND RESULTS: Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal. CONCLUSIONS: S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.

Acetylcholine↗
PubMed2000

Neuropathic pain--from mice to men.

The past decade has seen great progress in understanding the syndrome of neuropathic pain, its causes and in finding new drugs that promise great benefit. For example, an early outcome of the research has been the observation that the new drugs do not blunt normal pain sensation--a pattern beginning to find explanation through the realisation that neural pain circuits rewire themselves, both anatomically and biochemically, after nerve injury. In this article, we discuss a case of a known diabetic patient with intractable pain and the course of management provided by the use of novel tools and devices coming to the fore in this rapidly expanding specialty.

Adult↗
PubMed2000

Trends in cancer pain management.

BACKGROUND: Pain is a prevalent symptom in cancer patients, affecting up to 50% of patients undergoing active cancer treatment and up to 90% of those with advanced disease. Although adequate relief can be achieved in the majority of cancer patients, pain is often treated inadequately in traditional settings and sometimes even under the management of more specialised units. In this review the authors use their experience and that of others to review the evaluation and diagnosis of pain syndromes and the principles of management. This is in keeping with increasing recognition by bodies such as the World Health Organisation and other governmental agencies who have recognised the importance of pain management as part of routine cancer care. Conducting a comprehensive assessment, competently providing analgesic drugs, and communicating with the patient and family allow effective management of pain in the cancer patient.

Acute Disease↗
PubMed2000

Use of a simple pain model to evaluate analgesic activity of ibuprofen versus paracetamol.

OBJECTIVE: To evaluate the analgesic activity of ibuprofen against paracetamol using a simple pain model. DESIGN: A double-blind study. SETTING: Twenty general practitioners in Harare, Zimbabwe. PATIENTS: Adults with acute sore throat of a maximum of two days' duration. INTERVENTIONS: One hundred and thirteen patients with acute pain associated with tonsillo-pharyngitis randomly received either 400 mg ibuprofen or 1000 mg paracetamol. The study design included repeated administration up to 48 hours to assess tolerability. MAIN OUTCOME MEASURES: At hourly intervals for six hours after the first dose of treatment, the patients evaluated pain intensity on swallowing, difficulty in swallowing and global pain relief according to visual analogue scales. RESULTS: Ibuprofen 400 mg was significantly more effective than paracetamol 1000 mg in all three ratings, at all time-points for pain intensity and difficulty in swallowing, and from two hours onwards for pain relief. There were no serious adverse effects and no statistically significant difference in the incidence of adverse effects in the two treatment groups. CONCLUSIONS: Sore throat pain provided a sensitive model to assess the analgesic efficacy of class I analgesics and discriminated between the analgesic efficacy of ibuprofen and paracetamol.

Acetaminophen↗
PubMed2000

Ethics and HIV research in Zimbabwe.

A plethora of articles are now being published in both local and international journals on research activities conducted on the human immunodeficiency virus (HIV) in Zimbabwe. Some of the bioethical issues they raise, however, are neither unique to HIV nor unique to developing countries. In this article we discuss several of these issues, including the failure to provide interventions of known efficacy, ethical relevance of study design, informed consent, and exploitation. A challenge raised by much of the research in HIV/AIDS is whether, or under what conditions, it is ethical in research to fail to provide an intervention of known efficacy. The further we diverge from this situation, in which an effective, easy to implement intervention is available, to situations that resemble the controversial international clinical trials to prevent perinatal transmission of HIV the less clear the ethical mandate becomes. In relation to clinical trials the debate has focused on whether the standard of care in the United States--an expensive and complex regimen of Zidovudine--must be provided to all HIV infected pregnant women who join a research study in developing countries. Different scientists and scholars in bioethics have drawn the line differently in terms of what interventions routinely available in the developed world must be provided to research participants in developing countries. At an extreme, no one suggests that the most expensive and complex of Western tertiary care, for example, renal dialysis or coronary bypass, must be provided in research conducted in Zimbabwe. Indeed, public debates about the HIV perinatal transmission trials have not even focused on whether the women in the trials should be provided with HIV combination therapy as they would be in the West or whether they should even have the Zidovudine continued post partum.

Ethics, Medical↗
PubMed2000

Investigation of ascites--are we doing enough?

A case of ascites with peritonitis is described. Delayed diagnosis might have contributed to the death of our patient. The current tools used in investigating ascites with peritonitis and a review of the existing guidelines for a workup of these patients are discussed. The use of the laparoscopic technique is recommended.

Aged↗
PubMed2000

Pharmacological management of benign prostatic hyperplasia.

In men with mild to moderate BPH, pharmacotherapy is a safe and effective alternative to surgery. The primary care physician should be able to manage the treatment without referral to a urologist, provided he has undertaken appropriate steps to assure himself, and the patient, that there is no evidence of cancer of the prostate.

5-alpha Reductase Inhibitors↗
PubMed2000

White coat hypertension in Zimbabwean African women.

BACKGROUND: The prevalence of white coat hypertension in the Zimbabwean African female population has not been well defined. OBJECTIVE: To determine the prevalence of white coat hypertension and to compare the cardiovascular risk profiles of those with white coat hypertension to those with sustained hypertension. DESIGN: A cross-sectional study. SETTING: Out patient department of Parirenyatwa Medical School Teaching Hospital, Harare, Zimbabwe. SUBJECTS: Females with an average blood pressure of 140-160/90-105 mmHg. INTERVENTIONS: Females with an average blood pressure of 140-160/90-105 mmHg wore 24 hour ambulatory blood pressure monitors (ABPM). Subjects with >20 mmHg systolic or >10 mmHg diastolic difference between the average out-patient blood pressure and the average awake blood pressure from the ABPM were labelled as white coat hypertensives. RESULTS: The prevalence of white coat hypertension was 38% and the average number of risk factors per patient for the white coat group was 2.9. This result was similar to that for the sustained hypertensive group which had an average of 3.1 risk factors per patient. CONCLUSION: White coat hypertension may be a common finding in black hypertensive Zimbabwean females who have out patient blood pressure measurements of 140-160/90-105 mmHg. The cardiovascular risk profile of these white coat hypertensives was found to be very similar to that of sustained hypertensives.

Adolescent↗
PubMed2000

HIV and vasculitis: case report.

Manifestation of vasculitis and HIV is now being increasingly being observed. However, clinicians need to be conscious of the possible direct association of this virus with vascular disease. It would appear that the nervous and musculoskeletal systems are most commonly affected. No systematic data exist on the benefit of pharmacological agents currently used and there is an axiomatic need to study these agents in terms of the risk/benefit.

Adult↗
PubMed1999

Cytokine-induced venodilatation in humans in vivo: eNOS masquerading as iNOS.

OBJECTIVE: Venodilatation is a feature of endotoxaemia and sepsis. We have tested directly the hypothesis that three cytokines (IL-1 beta, TNF alpha and IL-6) generated during endotoxaemia affect venous tone in humans in vivo by increasing NO generation and explored whether the NO comes from the iNOS or eNOS isoform. DESIGN AND INTERVENTION: Cytokines were given into a superficial vein in very low doses sufficient only to produce changes in the study vessel. The effects of cytokines on the response to noradrenaline were examined. RESULTS: IL-1 beta increased basal NO-induced dilatation in the study vein, and this was sufficient to attenuate the constrictor response to exogenous noradrenaline or sympathetic stimulation. The effects were maximal at 6 h and both NG-monomethyl-L-arginine and aminoguanidine caused significant reversal of the IL-1 beta effects. However, no induction of iNOS mRNA was detected in the tissue samples. Instead, mRNA encoding eNOS and GTP cyclohydrolase-1 was detected in all vessels. CONCLUSION: The simplest explanation of these results is that IL-1 beta induces expression of GTP cyclohydrolase-1 which leads to increased generation of BH4 and activation of eNOS. This study identifies IL-1 beta as a key cytokine causing physiologically significant venodilatation in humans by increasing NO generation and suggests that this can occur even in the absence of iNOS expression.

Adult↗
PubMed1999

Effects of cytokines on nitric oxide pathways in human vasculature.

Proinflammatory cytokines exert a number of important effects on vascular reactivity. At one end of the spectrum, certain cytokines may induce vascular paresis leading to profound vasodilatation and hyporesponsiveness to constrictor stimuli. This may be relevant to the pathogenesis of septic shock and other types of inflammatory vasodilatation. At the other end of the spectrum, inflammatory cytokines can impair endothelium-dependent dilatation and the endothelium may lose its ability to respond to circulating hormones or autacoids. This effect may case a predisposition to vessel spasm, thrombosis or atherogenesis. Studies in human vessels suggest that interleukin-1 is particularly important as a mediator of inflammatory dilatation; the underlying mechanisms include induction of the inducible isoform of nitric oxide synthase in vascular smooth muscle, or over-production of nitric oxide from the endothelial isoform of nitric oxide synthase. Induction of the enzyme GTP cyclohydrolase 1 and consequent production of tetrahydrobiopterin contributes to the increase in the activity of endothelial nitric oxide synthase. In contrast, tumour necrosis factor-alpha considerably impairs endothelium-dependent relaxation. The mechanisms of these effects are not yet fully understood, but tumour necrosis factor can induce endothelial dysfunction in human endothelial cells in culture, and human blood vessels in vitro and in vivo. The implications of these observations for cardiovascular disease are discussed.

Animals↗