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Biomedical subjects

J M Grange

Publications and source records attributed to J M Grange.

At least 19 recordsLinked to original sources
PubMed2000

Advances in the management of tuberculosis: clinical trials and beyond.

Modern short-course treatment for tuberculosis is highly effective and cost-effective, yet the disease remains a leading cause of suffering and death. The problem has been exacerbated in recent years by the human immunodeficiency virus (HIV) pandemic and the increasing prevalence of multidrug-resistant tuberculosis. Improvements in diagnosis, vaccination, chemoprophylaxis, and therapy are thus urgently needed. Molecular techniques are facilitating the development of rapid and sensitive diagnostic tests and the rational approach to the production of new vaccines. New forms of treatment are being investigated and there is also considerable emphasis on optimizing the deployment of the available treatment regimens. This has resulted in the World Health Organization's five-point directly observed therapy, short course (DOTS) strategy and proposed modifications (DOTS-plus) for the management of multidrug-resistant (MDR) tuberculosis. Despite these advances, it is becoming abundantly clear that the failure to control tuberculosis is a direct consequence of the gross inequities in the distribution of wealth and health care provision worldwide, which do not allow for putting advances in the management of tuberculosis into practice. The control of tuberculosis will therefore require attention to justice and human rights as well as greatly increased technical and financial support from the developed nations.

Antitubercular Agents↗
PubMed2000

Impact of HIV infection on tuberculosis.

Tuberculosis is increasing in prevalence in many countries and is now the leading infectious cause of death world wide, being responsible for three million deaths annually. Infection with HIV, likewise increasing in prevalence, has emerged as the most important predisposing factor for developing overt tuberculosis in people co-infected with Mycobacterium tuberculosis. Owing to the widespread geographical overlap of these two infections, it is estimated that in 1999, HIV related tuberculosis will reach one million cases and will cause 30% of the expected 2.5 million AIDS related deaths. Tuberculosis in HIV infected individuals may have unusual clinical features and can cause diagnostic difficulties. Despite the effectiveness of modern short course treatment, the mortality of HIV related tuberculosis during and after treatment remains high, and this may be due to other HIV related infections. The "cursed duet" of infection with both HIV and M tuberculosis is generating a threat to human health of unparalleled proportions which, if not taken seriously by health workers and decision makers, could become totally unmanageable.

AIDS-Related Opportunistic Infections↗
PubMed1999

Possible improved survival of patients with stage IV AJCC melanoma receiving SRL 172 immunotherapy: correlation with induction of increased levels of intracellular interleukin-2 in peripheral blood lymphocytes.

PURPOSE: This phase I-II study was designed to assess safety and clinical efficacy of SRL 172 vaccine in patients with advanced stage IV (AJCC) malignant melanoma. Induction of intracellular cytokines (IL-2 and INF-gamma) in peripheral blood lymphocytes (PBLCs) from these patients was assayed and correlated to clinical outcome. PATIENTS AND METHODS: SRL 172 was administered intradermally to 24 patients with stage IV malignant melanoma, initially at 15-day intervals for three vaccinations and then at monthly intervals. Lymphocyte activation for cytokines in PBLCs was assayed prior to each vaccine administration using a FACS-based intracellular cytokine assay. Survival was compared to historical controls. RESULTS: The vaccination schedule resulted in sustained intracellular IL-2 induction in PBLCs in 9 of 23 patients (39%) who received at least three doses. Cytokine induction became apparent within the first three administrations of vaccine and was maximal at 8-12 weeks. Induction of intracellular IL-2 production (group 1) was associated with improved survival (P < 0.036). The median survival of the nine patients demonstrating IL-2 induction was 59 (95% confidence interval (95% CI): 47-71) weeks compared to 31 (95% CI: 18-44) weeks for the non-inducers. Induction of INF-gamma (group 2) was found in 10 patients and 6 patients had IL-2 and INF-gamma induction (group 3). There was no survival advantage for these patient groups. Although no objective responses were documented the group as a whole had a median survival of 44 (95% CI: 31-59) weeks which is better than that of historical controls. SRL 172 was safe and well tolerated. CONCLUSION: SRL 172 is effective in inducing intracellular IL-2 responses in PBLCs of a significant number of patients with stage IV (AJCC) melanoma. This is correlated with improved survival. The survival analysis is sufficiently encouraging to suggest that further prospective trials are justified. The methodology we present in this study may help in developing surrogate markers that will allow rational immunotherapeutic strategies to be designed for cancer patients.

Cancer Vaccines↗
PubMed1999

DOTS with a SMILE.

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Antitubercular Agents↗
PubMed1999

A study of maternal mortality at the University Teaching Hospital, Lusaka, Zambia: the emergence of tuberculosis as a major non-obstetric cause of maternal death.

SETTING: The Department of Obstetrics and Gynaecology, University Teaching Hospital, Lusaka, Zambia. OBJECTIVES: To ascertain 1) the non-obstetric causes of maternal mortality, 2) the importance of tuberculosis as a cause of maternal deaths, and 3) the trends in the aetiology of non-obstetric causes of maternal deaths during the past decade in the light of the human immunodeficiency virus epidemic. DESIGN: A 2-year retrospective study of the aetiology of all maternal deaths occurring at the University Teaching Hospital (UTH), Lusaka, Zambia between 1 January 1996 and 31 December 1997. Comparison of these data with available data published between 1974 and 1989. RESULTS: There were 251 maternal deaths recorded during the study period. Of these, 106 (42%) were due to direct (obstetric) causes and 145 (58%) were due to indirect (non-obstetric) causes. Malaria (30%), tuberculosis (25%) and unspecified chronic respiratory tract infections (22%) accounted for 77% of non-obstetric causes of maternal deaths and 44% of all causes of maternal deaths. The diagnosis of AIDS was closely linked with that of tuberculosis (92% of cases), and unspecified chronic respiratory illnesses (97%), but not with malaria (37%). The maternal mortality ratio for UTH was calculated at 921 per 100,000 live births, a significant increase from the 118 noted in 1982 and 667 in 1989. CONCLUSIONS: Despite improved obstetric services, the maternal mortality ratios at UTH, Lusaka, have increased eight-fold over the past two decades. This dramatic increase is mainly due to non-obstetric causes of death. Malaria and AIDS-associated tuberculosis and unspecified 'chronic respiratory illnesses' are now major causes of maternal death in Zambia. Greater emphasis is urgently required on early detection, accurate diagnosis, treatment and prevention of malaria and tuberculosis in pregnancy. Further definition of chronic 'unspecified' respiratory illnesses is also required.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Jabberwocky.

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Humans↗
PubMed1999

Tuberculosis acquired in laboratories and necropsy rooms.

The resurgence of tuberculosis, and the increasing number of cases that are HIV-related and/or multidrug resistant, has renewed interest in the occupational hazards posed by tuberculosis to staff in laboratories and necropsy rooms. A search undertaken using Medline and Pre-Medline identified few comprehensive reviews: the last was published in 1982. Staff may acquire pulmonary infection by inhalation of aerosols and skin lesions through cuts and abrasions. Particular hazards for laboratory staff include specimen containers contaminated on the outside, unfixed sputum smears, and the generation of aerosols during examination procedures. Examination of patients with tuberculosis not diagnosed during life constitutes a particular risk to necropsy room staff. Staff of laboratories and necropsy rooms are estimated to be between 100 and 200 times more likely than the general public to develop tuberculosis. Training in good laboratory practice is the most important aspect of staff protection, especially in resource-poor countries where well-maintained safety cabinets are rarely available. This article summarises requirements and recommendations for safe handling of tuberculous material and the available guidelines for work in developed and resource-poor countries.

Autopsy↗
PubMed1998

Complications of bacille Calmette-Guérin (BCG) vaccination and immunotherapy and their management.

Complications of bacille Calmette-Guérin (BCG) vaccination are uncommon. Fewer than one in 1000 people vaccinated develop significant local reactions, and serious disseminated disease develops in fewer than one in a million. Localised complications--which include hypersensitivity reactions, abscesses at the injection site, and localised lymphadenopathy--are usually self limiting. They usually result from faulty technique, including the accidental intracutaneous injection of the stronger percutaneous vaccine, or poor selection of subjects for vaccination. Abscesses at the injection site usually respond to drainage and chemotherapy with isoniazid or erythromycin. Lymphadenopathy responds poorly to antimicrobial treatment and surgery may be needed for suppurating or discharging lesions to hasten recovery and give a good cosmetic result. Disseminated disease usually occurs in people with impaired immunity, in whom it is often fatal. BCG should never be given to people who are known to be infected with HIV, but the risk of complications in children born to HIV infected mothers is low. Disseminated disease can also result from intravesical instillation of BCG to treat bladder cancer, but this responds to antituberculosis chemotherapy.

Abscess↗