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3201. HIV infection and neoplasia.
HIV infection predisposes to several neoplastic conditions, especially non-Hodgkin lymphoma (NHL) and Kaposi's sarcoma (KS), and also intraepithelial cervical neoplasia (CIN) and anal neoplasia (AIN) (but not cervical or anal invasive cancer) and possibly seminoma. For neoplasias associated with oncogenic human viruses (ie, some NHL, CIN, AIN, and probably KS) the role of HIV is most probably linked to its immunosuppressive effect and interference with immune-mediated tumour surveillance. HIV-1, through its regulatory protein tat, might also have a direct promoting effect on KS lesions but it is not essential for their development. The increased frequency of Burkitt's lymphoma and Epstein-Barr-virus-negative large-cell lymphoma in AIDS patients, but not in immunosuppressed transplant patients, and the increased rate of testicular tumours in HIV-infected individuals remain unexplained and may indicate either a direct role for HIV or other cofactors.
3202. AIDS and the eyes.
The eye is affected in 50-75% of adult AIDS patients. This rate of ocular involvement is much higher than that in symptom-free HIV-seropositive patients, and seems to increase in incidence with severity of disease. These observations indicate that regular screening of HIV-positive patients is warranted to allow early identification of potential vision and life threatening disease.
3204. Neurological complications of HIV infection.
Neurological complications of HIV infection cause considerable morbidity and are often associated with high mortality. These complications include not only the more common opportunistic diseases affecting the brain (cerebral toxoplasmosis, primary central nervous system lymphoma, progressive multifocal leucoencephalopathy, and cryptococcal meningitis) but also the AIDS dementia complex, with its characteristic cognitive and motor dysfunction, which is caused by HIV itself. Additionally, the peripheral nervous system is the target of several disorders, including a common painful neuropathy. Because these and other, less common, central and peripheral nervous system complications of HIV can often be specifically treated or effectively palliated, their accurate and timely diagnosis is important.
3206. Systematic review of randomised trials of interventions to assist patients to follow prescriptions for medications.
Low adherence of patients to prescribed, self-administered medical interventions is ubiquitous. Low adherence limits the benefits of current medical care. Efforts to assist patients to follow treatments might improve the efficiency of care and substantially enhance benefits. Our objective was to summarise the results of randomised controlled trials (RCTs) of interventions to help patients follow prescriptions for medications.
3207. Gastrointestinal manifestations of HIV infection.
The harrowing picture of emaciated terminally ill AIDS patients is a reminder of our lack of understanding of immunological mechanisms that normally control opportunistic infections. Many gastrointestinal pathogens in patients with AIDS are resistant to treatment and lead inexorably to weight loss and death. Although knowledge of the pathogenesis and clinical significance of weight loss has improved considerably, this has not yet led to a sustained effort to improve nutritional status during early stages of disease.
3208. Benefits from specialised cancer care.
The Expert Advisory Group's recommendations to establish cancer centres, cancer units, and a network involving primary care for the treatment of cancer patients in the UK is based on the view that specialisation in cancer care will improve outcomes. Evidence to support the various aspects of specialisation (eg, training, caseload, and the formation of multidisciplinary teams) is strongest for breast cancer, ovarian cancer, and some haematological malignant diseases. There is evidence to support the view that some specialised care can be successfully delivered by a network of district hospitals and main general or teaching hospitals and does not always require referral to cancer centres.
3209. HIV-associated respiratory diseases.
The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours; over two-thirds of patients have at least one respiratory episode during the course of their disease. Despite the availability of effective prophylaxis, infection with the fungus Pneumocystis carinii remains a common cause of respiratory disease. Bacterial infections, which occur more frequently in HIV-infected persons than in the general population, and tuberculosis are increasing causes of morbidity and mortality. Kaposi's sarcoma, the commonest HIV-associated malignancy, may affect the lungs in addition to the skin. Pulmonary involvement by non-Hodgkin lymphoma is common in those with disseminated disease.
3211. Changing the natural history of HIV disease.
Our understanding of the pathogenesis of AIDS has advanced considerably since the disease was first reported 15 years ago. We now know that the primary damage inflicted by HIV-1 is mainly brought about by active virus replication. With the advent of sensitive tools for monitoring HIV replication in vivo, an individual's risk of disease progression can be assessed early in the course of the infection and the efficacy of antiviral therapies can now be determined accurately and expeditiously. When used appropriately, potent combinations of antiviral drugs seem to be able to circumvent the inherent tendency of HIV-1 to generate drug-resistant viruses, the main reason for failure of all antiviral therapies, and are significantly more effective than earlier approaches. For the first time, rational approaches to contain and perhaps eliminate HIV-1 infection can be pursued.
3212. Difficulties and strategies of HIV diagnosis.
HIV infection is commonly diagnosed by detection of antibodies (anti-HIV) by ELISA or agglutination. Reactive results are confirmed by western blot (immunoblot) or further specific tests such as competitive ELISA, which, when evaluated quantitatively, allow the differentiation of HIV types and partially subtypes. Detection of infection of newborn babies, characterisation of individual strains for subtyping and forensic identification, and therapeutic monitoring are the domain of nucleic-acid-based assays. Nucleic-acid-based assays narrow the serological diagnostic window period in early HIV infection and, when quantified, give some indication of clinical status.
3213. Global burden of the HIV pandemic.
Within the global pandemic of HIV infection there are many different epidemics, each with its own dynamics and each influenced by many factors including time of introduction of the virus, population density, and cultural and social issues. Effective management strategies depend on knowledge of all these factors. By the year 2000, WHO projections are that 26 million persons will be infected with HIV, more than 90% of whom will be in developing countries. To control AIDS, countries must not only promote changes in individual behaviour but also address social issues such as unemployment, rapid urbanisation, migration, and the status of women.
3215. Are both genetic and reproductive associations with rheumatoid arthritis linked to prolactin?
The risk of rheumatoid arthritis (RA) seems to be associated with reduced fecundity and with breastfeeding; these apparently contradictory risk factors can be explained by their association with high prolactin concentrations. The only consistent genetic association with RA is for genes encoded in the HLA complex, particularly HLA DR4. We have identified some data indicating that the effects of breastfeeding and nulliparity are modified by HLA DR4 status, suggesting an interaction between genetic and reproductive risk factors in the aetiology of RA. The prolactin gene is in close proximity to the HLA region on the short arm of chromosome six. We therefore propose the hypothesis that the associations between DR4 and reproductive risk factors in RA are due to linkage disequilibrium between DR4 and an abnormally regulated prolactin gene polymorphism.
3216. HIV as the cause of AIDS.
The two known types of HIV are members of a family of primate lentiviruses. HIV, like other retroviruses, contains a virus capsid, which consists of the major capsid protein, the nucleocapsid protein, the diploid single-stranded RNA genome, and the viral enzymes protease, reverse transcriptase, and integrase. HIV isolates show extensive genetic variability, resulting from the relatively low fidelity of reverse transcriptase in conjunction with the extremely high turnover of virions in vivo. These features of HIVs may have strong implications for vaccine development. Simian immunodeficiency viruses from naturally infected animals differ from HIV in one fundamental respect: they do not cause disease in their natural hosts. Study of these viruses may therefore lead to information about the interaction between lentiviruses and host immune response that could be exploited to combat AIDS.
3217. Current situation and control strategies for resurgence of diphtheria in newly independent states of the former Soviet Union.
Since 1990, an epidemic of diphtheria has spread throughout the newly independent states of the former Soviet Union, and by 1995 a total of 47 808 cases were reported. During the early stages of the epidemic, adequate control measures were not taken and vaccine was in short supply; possible contributing factors to the spread of the epidemic are the presence of highly susceptible child and adult populations, socioeconomic instability, population movement, and a deteriorating health infrastructure. Although WHO views the epidemic as an International public-health emergency and, together with UNICEF and the International Red Cross, has formulated a strategy to combat the epidemic, the necessary funds have not been made fully available. Current vaccination recommendations also need to be reviewed to ensure that population immunity will be adequate to prevent any resurgence of diphtheria in Europe and North America.
3218. Abortion and fertility regulation.
To achieve their desired fertility, women use a combination of contraception and abortion, and some societies also place constraints on marriage and sexual activity. The degree to which these means are adopted varies considerably, but for the foreseeable future abortion will remain an important element of fertility regulation. Globally, complications of unsafe abortion affect hundreds of thousands of women each year, and account for as many as 100,000 deaths annually (about two in ten maternal deaths), mainly in poor countries, where abortion typically remains illegal. Access to safe abortion is both essential and technically feasible and should be provided in combination with good quality family planning services.
3219. Syringomyelia as a cause of body hypertrophy.
Among 26 patients with communicating syringomyelia who came to our out-patient clinic from April, 1989, to March, 1995, three (11.5%) had hypertrophy in limbs, hands, or feet. One had crossed hypertrophy. We considered the possibility that syringomyelia caused body hypertrophy.
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