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Biomedical subjects

S B Lucas

Publications and source records attributed to S B Lucas.

At least 109 records · Page 6Linked to original sources

Is HIV infection a risk factor for leprosy?

A case control study was undertaken during 1988 and 1989 within the framework of the LEPRA Evaluation Project (LEP)/Karonga Prevention Trail (KPT) in Karonga District, northern Malawi, to investigate whether HIV infection is a risk factor for clinical leprosy. Cases were newly ascertained, biopsy-confirmed, incident leprosy patients older than 14 years of age. Controls were selected from the computer data base on over 170,000 people who form the basis of LEP/KPT. They were matched for sex, age, and area of residence. HIV seropositivity rates were 1.8% (2/112) for incident leprosy cases and 2.4% (24/1011) for controls. The Mantel Haenszel odds ratio is 0.6 (95% confidence interval 0.1-3.3). Thus, no evidence for an association between HIV infection and leprosy incidence has been observed in this population. In a parallel investigation, an odds ratio of 7.4% (95% confidence interval 3.3-16.7) was found for 102 microscopy- and/or culture-confirmed, incident pulmonary tuberculosis cases in the same population during 1989, a result similar to those obtained elsewhere in Africa. Among leprosy relapses, 16.7% (2/12) were HIV positive.

Adult↗

Comparative pharmacokinetics of escalating doses of doxorubicin in patients with metastatic breast cancer.

Recombinant human granulocyte colony-stimulating factor (G-CSF) has been shown to reduce neutropenia following cytotoxic therapy, thereby enabling dose escalation to improve the response rate. It is important to know whether drug kinetics change as doses are increased. Doxorubicin was selected because of its broad spectrum of activity and its known efficacy in metastatic breast cancer. Doses of 75, 100, 125 and 150 mg/m2 were given to 11 patients with metastatic breast cancer by infusion over 30 min. Serum concentrations of parent drug and metabolites were determined during the first 48 h following the infusion by high-performance liquid chromatography (HPLC). The serum concentration vs time curve decayed as a triple exponential function in four patients and as a double exponential function in seven. A four-compartment model, one central and three peripheral, would predict concentrations to within 1 SE of the observed values. Doxorubicinol was the principal metabolite, and doxorubicinone and 7-deoxydoxorubicinone were clearly identified. There was a linear increase in the AUC infinity with dose. In addition, a small and transient increase in circulating levels of doxorubicinol and other important metabolites was observed 6 h following the administration of doxorubicin, which suggests the existence of an enterohepatic, or other, re-circulation mechanism. We conclude that in the dose range selected the kinetics of doxorubicin are linear and that the increase in toxicities seen with the higher doses of doxorubicin, following the second and third fortnightly administration, may be due to intracellular drug accumulation in tissues.

Adult↗

Missing infections in AIDS.

In north America and Europe, the opportunistic infections from which patients with acquired immune deficiency syndrome (AIDS) frequently suffer are Pneumocystis carinii pneumonia and Mycobacterium avium-intracellulare: in central Africa these infections are uncommon or non-existent. Serious infections with Entamoeba histolytica and Strongyloides stercoralis would be expected to occur in AIDS patients: they do not. Falciparum malaria might be expected to interact with HIV infection: it does not. The epidemiology and pathophysiology of these infections are discussed with respect to HIV co-infection.

Acquired Immunodeficiency Syndrome↗

Pneumocystis carinii pneumonia in patients with AIDS in Central Africa.

Over a period of 11 months, 37 patients infected with the Human Immunodeficiency Virus (HIV) presenting with symptoms of bronchopulmonary disease were investigated. Patients presented with cough, weight loss, fever and dyspnoea. Investigations included fibreoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. In eight patients (22%) Pneumocystis carinii was found. Pulmonary infiltrates were found on chest radiographs of six patients, while in the remaining two patients chest radiographs showed clear lung fields. P. carinii was found in two patients with pulmonary Kaposi's sarcoma. Infection with P. carinii often occurred with other pathogens: Streptococcus pneumoniae was found in four patients, Staphylococcus aureus in two and tuberculosis in two. P. carinii pneumonia does occur in patients with HIV infection in Africa and the diagnosis is relatively simple to make provided that transbronchial biopsy and bronchoalveolar lavage are carried out through a fibreoptic bronchoscope and specimens examined after appropriate staining. However, the prevalence of P. carinii in patients with HIV infection in Africa appears to be lower than that found in patients with HIV infection in Europe and North America.

Acquired Immunodeficiency Syndrome↗

Serum type III procollagen peptide, dynamic liver function tests and hepatic fibrosis in psoriatic patients receiving methotrexate.

The serum level of the aminoterminal peptide of type III procollagen (P3NP) was measured in 51 psoriatic patients on long-term, once weekly, low-dose methotrexate and in a control group of patients with extensive psoriasis who had never had systemic treatment. Serum P3NP levels were normal in all control patients, but were elevated in the majority of methotrexate-treated patients, even those with normal or non-specific liver histology. Although the highest P3NP values were found in the groups of patients with fibrosis and cirrhosis, isolated P3NP measurements did not discriminate between individuals with and without significant liver pathology. Neither standard nor dynamic liver function tests were able to identify patients with significant liver damage and in most cases results were in the normal range.

Adult↗

Endemic and atypical Kaposi's sarcoma in Africa--histopathological aspects.

Atypical HIV-associated and endemic Kaposi's sarcoma (KS) differ in their clinical presentation and behaviour. To assess the possible histological differences, a detailed review of 32 cases of atypical KS and 170 cases of endemic KS from sub-Saharan Africa was undertaken. Both forms of KS had similar histological appearances, and evolved through a chronological sequence of patch, plaque and nodule. There was an increase in the proportion of early patch and plaque lesions in cutaneous and mucosal atypical KS (54%) compared with endemic KS (23%). However, nodular lesions were still seen in atypical KS, and formed 56% of the total cases. In addition, atypical KS tended to have more small blood vessels and a lesser degree of inflammatory infiltrate. However, within each of the three stages of the disease, it was not possible to distinguish between the HIV- and non-HIV-related forms.

Adolescent↗

HIV-related enteropathy in Zambia: a clinical, microbiological, and histological study.

To investigate the etiology of chronic diarrhea associated with human immunodeficiency virus (HIV) infection in Lusaka, we studied 63 HIV-positive patients and 36 seronegative controls clinically and endoscopically. Stools were studied for morphology and for opportunist infections. Fifty-five percent of patients seropositive for HIV who presented with a history of chronic diarrhea had parasites; the most common were Cryptosporidium (32%), Isospora belli (16%), and Strongyloides stercoralis (6%). As indicated by villous blunting and inflammation on duodenal histology, those with diarrhea and parasites showed the most severe damage. We could not implicate mycobacteria or bacterial overgrowth as causes for the enteropathy associated with HIV.

Chronic Disease↗

Positive Mitsuda lepromin reactions in long-term treated lepromatous leprosy.

Twenty-four lepromatous (LL) patients, treated for 22 to 40 years with chemotherapy, including sulphones and with multidrug therapy, were tested with standard Wade-Mitsuda lepromin. Thirteen gave weak positive (3-4 mm) Mitsuda reactions, confirmed histologically in the ten whose reactions were biopsied. Six of the eleven negative reactors were partly accounted for by a history of relapse, and two others had probably taken dapsone irregularly. Eleven control LL patients, treated for less than 20 years, were uniformly lepromin negative. Spontaneous lepromin conversion appears to occur around 24 years after commencing successful chemotherapy. The late Mitsuda conversions are attributed to delayed clearance of the reservoir of bacterial antigen, but a poor correlation between Mitsuda and Fernandez positivity is not explained.

Humans↗

Schistosoma bovis as an immunological analogue of S. haematobium.

The host-parasite relationships of Schistosoma bovis and S. haematobium have been compared in normal and T-cell-deprived mice, and have been found to contrast with that of S. mansoni. Deprived mice infected with either of the former two schistosome species survived as long as, or longer than, comparably infected immunologically intact controls, and hepatocytes of infected deprived mice were not damaged in the absence of granuloma formation. S. mansoni-infected deprived mice, however, die earlier than intact controls, and suffer extensive hepatocellular abnormalities. A high degree of cross-reactivity between S. bovis, S. haematobium and S. mansoni antibodies and antigens was noted in immunoprecipitation but a greater degree of homology between S. haematobium and S. bovis egg antigens was demonstrated by enzyme immunoassay (ELISA). S. haematobium and S. bovis thus resemble each other more closely than either resembles S. mansoni, and in view of the apparent antigenic similarities between S. haematobium and S. bovis and the relatively greater ease with which the S. bovis life-cycle can be maintained in the laboratory, the animal parasite may be useful in providing material for further immunological studies of the human infection.

Animals↗

T-cell recognition of the 18-kilodalton antigen of Mycobacterium leprae.

The 18-kilodalton (kDa) antigen of Mycobacterium leprae was expressed as a fusion protein with a 2-kDa leader peptide and used in proliferation assays with peripheral blood cells. Fifty percent of untreated tuberculoid leprosy patients and 93% of long-term leprosy contacts responded to the recombinant protein in lymphocyte transformation tests. Comparison of the stimulation indices in the two groups showed that the contacts responded more strongly than the tuberculoid leprosy patients. Seventy percent of Mycobacterium bovis BCG-vaccinated European donors responded, although with low stimulation indices. The isolation of 18-kDa antigen-responsive T-cell lines from a BCG-vaccinated British donor confirmed that the 18-kDa antigen contains at least one cross-reactive epitope. These results indicate that the 18-kDa protein is an important antigen in the immune response to leprosy.

Amino Acid Sequence↗

The occurrence of depression following mania. A method of predicting vulnerable cases.

In a retrospective analysis of 100 cases of mania (1981-1985), the incidence of subsequent depression was found to be 30%. Its occurrence was significantly associated with three factors: cyclothymic pre-morbid personality, family history of affective disorder, and past history of depression. By discriminant analysis, outcome could be predicted successfully in 81% of cases.

Adult↗