Richard Coker

Liposomal doxorubicin (doxil): an effective new treatment for Kaposi's sarcoma in AIDS

The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposis sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposis sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV associated tuberculosis.

People who are infected with HIV are at an increased risk of contracting tuberculosis. The WHO estimates that just over 20 million people are currently infected with HIV and of these 6 million are co-infected with Mycobacterium tuberculosis . Worldwide there has been a resurgence of tuberculosis, mainly in developing countries but also in the United States and Europe. Between 1987 and 1993 tuberculosis rates increased by 35.5% in London (with the increase most notable in inner London) compared with 15% in England and Wales as a whole.1 2 However, it is unclear to what extent the prevalence of HIV associated tuberculosis has increased in the capital, largely because notification of tuberculosis in the HIV infected population is unreliable and probably underestimates the problem.3 Nosocomial spread has occurred in …

Public health, civil liberties, and tuberculosis

Drug resistant tuberculosis is a global health threat. Perhaps because of the size and urgency of the threat and the fact that vulnerable populations are most affected by the disease, some control programmes include coercion. The responses to this threat reflect how society views those on the margins, who are vulnerable—perhaps homeless, stateless, or psychologically disturbed. When treatment compliance is required for public health reasons (to prevent the development of drug resistant strains) how society encourages compliance reflects as much on society itself as it does on the irresponsible, poorly compliant individual. A tension has always existed between the protection of individual civil liberties and the protection of public health. In the liberal era of the 1960s and 1970s somewhat draconian approaches to the mentally ill, for example, were questioned. Legislation was amended to put individual patients at the centre, to emphasise their rights, and to provide them with greater legal protection. Detention of the mentally ill became dependent on a determination of the threat they posed to themselves or others. Historically a similar …

Lessons from New York's tuberculosis epidemic. Tuberculosis is a political as much as a medical problem-and so are the solutions.

In the late 1980s New York city witnessed a dramatic epidemic of tuberculosis. By 1990, with 3% of the US population, the city had 15% of the countrys cases. From 1984 to 1991 incidence increased from 23 to 50/100 000, and in some poor areas rates were much higher. In central Harlem, for example, incidence rose from 90 to 220/100 000. Among black men aged 35-44 the incidence in 1991 was 469/100 000, almost 45 times the national average.1 Now, however, the number of cases and the incidence have both declined dramatically. How has this been achieved and what are the lessons for other places facing a tuberculosis epidemic? Two aspects of the New York epidemic suggested that it was home grown rather than associated with immigration.2 Firstly, childhood tuberculosis rates (suggesting recent acquisition) were rising, particularly among black Americans. Between 1987 and 1990 cases in children under 15 rose by 97%, from 74 cases to 146; 92% of these cases occurred in children aged 4 …

Tuberculosis, non-compliance and detention for the public health

Coercion, the act of compelling someone to do something by the use of power, intimidation, or threats, has been deemed a necessary weapon in the public health armamentarium since before public health fell under the remit of physicians and out of the grip of “sanitarians” and civil engineers. This article examines the ethics of detention in the pursuit of public health and uses a contemporary example, detention of poorly compliant individuals with tuberculosis, to highlight the moral dilemmas posed, and examine whether recently proposed approaches are just. In particular I focus upon the public health response to non-infectious individuals who fail to comply with treatment (and who, therefore, may be at risk of relapsing and becoming infectious). Our response to them helps clarify contemporary attitudes to recalcitrant, often marginalised, individuals who pose an uncertain threat. Globally tuberculosis control is failing. The World Health Organisation (WHO) recently called this public health threat a global emergency.1 Transmission occurs through often casual contact from individuals who have pulmonary disease. Although there is much that is uncertain regarding the infectiousness of this ancient disease, we do know that those who are smear-positive, that is who have organisms of Mycobacterium tuberculosis visible in stained respiratory secretions, are considerably more infectious than those who do not.2, 3 Compliance with effective treatment rapidly (within a couple of weeks) makes previously infectious patients non-infectious. Standard treatment for fully drug-sensitive tuberculosis usually lasts for six months. Erratic adherence to chemotherapy, however, may result in relapse and the development of drug-resistant disease which is considerably more difficult to treat. In the 1980s and early 1990s New York City witnessed an epidemic of tuberculosis and, of particular concern, a marked increase in drug-resistant and multidrug-resistant strains. In the early 1990s the threat of a virtually untreatable, casually communicable, …

Schistosomiasis: an unusual cause of pruritus vulvae

Presentation pruritus vulvae with nodular lesions.

Evolution of pulmonary HIV-1 infection in a patient with Pneumocystis carinii pneumonia

Introduction Changes in the biological characteristics of HIV-l from peripheral blood leucocytes (PBL) have been well documented. It has been suggested that changes with time in the biological features of HIV are signs of increased virulence. Attempts have been made to link replication potential and the cytopathic syncytiainducing properties of HIV isolates with the clinical status and severity of HIV infection in the host. Despite the fact that HIV has been isolated from the lung, little is known about the properties of these isolates in contrast to isolates derived from PBL. We report the changing nature of HIV infection in the lung in a patient following the successful treatment of Pneumocystis carinii pneumonia (PCP). Pulmonary HIV infection, but not HIV isolated from PBL, evolved to become syncytium-inducing within 3 months. This may have important implications regarding the pathogenesis of HIV disease.

Prophylaxis of Pneumocystis carinii pneumonia in patients with HIV infection

Pneumocystis carinii pneumonia (PCP) is a frequent complication of immunosuppression secondary to infection by the human immunodeficiency virus (HIV). The use of primary and secondary prophylaxis for many of the opportunist infections associated with acquired immunodeficiency syndrome (AIDS) have reduced their incidence and prophylaxis for PCP is no exception. There are, however, still problems associated with the different regimens currently widely used. The efficacy, toxicity and cost of prophylaxis agents are considered.