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Biomedical subjects

S Lucas

Publications and source records attributed to S Lucas.

At least 109 records · Page 6Linked to original sources
PubMed1991

Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis.

The effects of the human immunodeficiency virus (HIV) on tuberculosis management was investigated in 227 patients initially treated with a regimen containing streptomycin, isoniazid, and thiacetazone (STH). 93 of these 227 were HIV-seropositive. 60 patients, of whom 18 were HIV-seropositive, received a regimen consisting of streptomycin, isoniazid, rifampicin, and pyrazinamide (SHRZ) in the initial phase, and thiacetazone and isoniazid (TH) in the continuation phase. Cutaneous hypersensitivity reactions occurred in 22 of 111 (20%) HIV-seropositive patients, and in 2 of 176 (1%) HIV-seronegative patients (RR = 18, 95% CI 4.4-76, p less than 10(-7]. During the first 8 weeks of treatment 18 reactions occurred among the 93 HIV-seropositive patients on STH, whereas no reaction occurred in 17 HIV-seropositive patients during the initial phase of SHRZ/TH (p = 0.04). None of the 18 HIV-seropositive patients with cutaneous reactions who were subsequently challenged with isoniazid reacted, nor did any of the 10 tested with streptomycin, but 6 of the 7 challenged with thiacetazone reacted. 3 patients (all HIV-positive and with toxic epidermal necrolysis) died as a result of the cutaneous reaction. These results have major implications for tuberculosis control programmes in Africa.

Adult↗
PubMed1991

Crisnatol mesylate: phase I dose escalation by extending infusion duration.

Crisnatol mesylate is a rationally designed cytotoxic arylmethylamino-propanediol with broad spectrum cytotoxic activity. A phase I study with an unconventional escalation scheme was developed using a constant drug infusion rate (mg/m2/hr) and prolonging the infusion duration from 6 to 96 hours. Sixty-five patients received crisnatol at doses from 18 mg/m2 in 6 hrs to 3400 mg/m2 in 72 hours. The dose-limiting toxicity in two of five patients at 2700 mg/m2 and two of three patients at 3400 mg/m2 was neurologic and consisted of a syndrome of confusion, agitation, and disorientation. Phlebitis mandated the use of a central line. The mean terminal phase half-life (T1/2 beta) was 3.3 hours with a total body clearance (CL) of 22.8 L/hr/m2 and a volume of distribution (Vdss) of 53 L/m2. The median steady-state peak plasma concentration (Css) at 2700 mg/m2/72 hours was 2.7 micrograms/ml and at 3400 mg/m2/72 hours was 3.8 micrograms/ml. No responses were seen. The maximum tolerated dose (MTD) on this schedule is 2700 mg/m2/72 hours in patients with no liver disease and good performance status.

Adolescent↗
PubMed1991

pH dependence of hydrochloric acid diffusion through gastric mucus: correlation with diffusion through a water layer using a membrane-mounted glass pH electrode.

Solute diffusion coefficients (D) can indicate a dependence upon actual solute concentrations. Here a single compartment has been utilized, in which effective HCl diffusion to a membrane-mounted glass pH electrode can be measured across the pH spectrum. The study has investigated HCl diffusion through both mucus and water layers as a function of HCl concentration. The observed dynamic responses of a liquid-film and mucus-coated electrodes over a range of HCl concentrations suggest that the speed at which equilibrium is attained is pH dependent; equilibrium was reached rapidly under more acidic and alkaline conditions. Estimated values of DHCl also indicate a strong pH dependence for both liquid film and mucus. In both instances, a greater than 10-fold reduction in DHCl at pH 7.5 as compared with that at pH 3.5 has been demonstrated. Furthermore, estimated values of DHCl are approximately 4-fold smaller through the mucus gel, as compared with a water layer. The findings indicate that the most powerful influence on diffusional resistance is pH itself, whereby a marked drop in H+ diffusion is likely to occur towards neutral pH irrespective of the composition of the gel barrier. Possible implications of the findings are discussed in relation to mucosal protection from acid.

Animals↗
PubMed1991

Altered small-intestinal permeability associated with diarrhoea in human-immunodeficiency-virus-infected Caucasian and African subjects.

1. Small-intestine integrity in Caucasian and African patients infected with human immunodeficiency virus was determined by measuring the permeation across the mucosa of two sugars, lactulose and mannitol. 2. The sugars were assayed by h.p.l.c. and pulsed amperometric detection in 6 h urine samples. Stool microscopy for enteropathogens was performed in all patients. 3. The ratio of lactulose to mannitol recovered in urine was increased in Caucasian and African patients with advanced human immunodeficiency virus infection. Asymptomatic human-immunodeficiency-virus-infected subjects had a normal lactulose/mannitol ratio. African patients with diarrhoea showed a twofold reduction in mannitol excretion. Such a change in mannitol absorption was not detected in Caucasian patients and occurred regardless of the presence of enteropathogens. 4. Altered small-intestinal permeability is associated with symptomatic diarrhoea in human immunodeficiency virus infection in both Caucasian and African patients.

Adult↗
PubMed1991

Sex differences in gallstone pancreatitis.

From a computerized database comprising 28 pertinent items in each of a consecutive series of 664 patients with cholelithiasis, differences were studied between men and women. In 52 patients there was a documented attack of acute pancreatitis (7.8%). Twenty-five of 174 men had pancreatitis, compared with 27 of 490 women (p less than 0.0001). Men developed gallstones later in life than women, but suffered gallstone pancreatitis earlier in life and in the course of their gallstone-related disease. A history of flatulent dyspepsia, chronic cholecystitis, and biliary colic was less common in men than in women with pancreatitis (p less than 0.0001). Men with pancreatitis had fewer stones in their gallbladders than did women (p = 0.0002). The cystic duct and the common bile duct in the pancreatitic patient were more likely to be dilated (p less than 0.0001). In the nonpancreatic group, these ducts were larger in men. Pancreatic duct reflux on operative cholangiography was more common both in patients with pancreatitis 62% cf 14% (p less than 0.0001), and in men (p less than 0.001). Predisposition to pancreatitis relates to duct size rather than stone size per se. Men are more susceptible to gallstone migration at an early stage of their disease. In addition they have a larger diameter duct system and possibly a different anatomic disposition of the sphincter of Oddi, which predisposes them to a higher incidence of pancreatitis than women. The data suggest that it is cystic duct size that is critical in the pathogenesis of gallstone pancreatitis.

Acute Disease↗
PubMed1990

Heterogeneity of protein kinase C expression and regulation in T lymphocytes.

The purpose of the present study was to examine protein kinase C (PKC) isotype expression in T lymphoblasts derived from peripheral blood and the T leukaemic cell Jurkat. Using antisera reactive with PKC alpha, beta 1, and beta 2 and gamma, it was observed that T cells expressed two PKC isotypes, PKC alpha and beta 1. No PKC gamma was detected in T lymphocytes. In lymphoblasts, high levels of PKC beta compared to PKC alpha were found whereas Jurkat cells expressed high levels of alpha compared to PKC beta. Differences in the calcium sensitivity of phorbol ester-induced phosphorylation were observed in Jurkat and T lymphoblasts which correlated with the relative levels of PKC alpha and beta isotypes expressed by the cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

The involvement of the cerebral cortex in human immunodeficiency virus encephalopathy: a morphological and immunohistochemical study.

The encephalopathy resulting from direct infection of the brain by human immunodeficiency virus (HIV), which correlates clinically with the AIDS dementia complex, has been reported as being localized to the white matter where it induces myelin loss, gliosis and perivascular infiltration by mononuclear macrophages and multinucleated giant cells. Damage to the cortical grey matter in HIV encephalopathy was investigated in nine randomly selected HIV-positive cases with or without clinical or morphological evidence of encephalopathy and in five age-matched controls, using routine histology and immunohistochemical methods [glial fibrillary acidic protein (GFAP), microglia and HIV antibodies]. Increased numbers of GFAP-expressing astrocytes and Ricinus communis agglutinin 1-120-expressing microglial cells were found in all the HIV-positive cases (including asymptomatic) and their severity could be correlated with the severity of the encephalopathy in the white matter; the increase in number of cells expressing GFAP was diffuse and the intensity of the staining higher than that of microglial cells. The subpial region was the most severely involved. It is suggested that involvement of the cortical grey matter is more common in HIV infection than previously suspected and that clinical evidence of a dementing process in AIDS is not necessarily due only to white matter lesions.

AIDS Dementia Complex↗
PubMed1990

Mycobacterium vaccae in immunoprophylaxis and immunotherapy of leprosy and tuberculosis.

Both leprosy and tuberculosis present continuing problems in their control, especially in the developing world, despite the availability of drugs effective in producing a bacteriological cure. Improved immunoprophylaxis, and an effective immunotherapy to be used with chemotherapy are urgently required. Intradermal injection of a suspension of killed Mycobacterium vaccae promotes cell-mediated responses to antigens common to all mycobacteria, and switches off the tissue-necrotizing aspects of the Koch phenomenon. These properties led to the use of the suspensions as an improved vaccine, either alone or in combination with BCG. The same properties led to the employment of the suspension in immunotherapy as an adjunct to chemotherapy in the treatment of both leprosy and tuberculosis. The evidence leading to these conclusions is reviewed and discussed.

Animals↗
PubMed1990

Why do patients with ulcerative colitis relapse?

To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis.

Adolescent↗
PubMed1990

Malignant tumors in children of northeastern Zaire. A comparison of distribution patterns.

In an effort to better understand the epidemiology of cancer in Zaire, a retrospective review of biopsy-proven malignant tumors was undertaken. Of 188 biopsies taken from children aged 0-15 years over a 4.5 year period, 73 (39%) revealed malignancy. Fifty-six percent of patients with malignant tumors were boys. Lymphoma was the most common tumor (28 patients, 15 with Burkitt's Lymphoma). Sarcoma (15 patients), carcinoma (8 patients), Wilms' Tumor (6 patients), and retinoblastoma (5 patients) were also seen. Lymphomas were most heavily represented in the first 5 years of life, while sarcoma and carcinoma accounted for most of the malignancies in children after 10 years of age. Lymphomas and sarcomas are relatively more common in Zaire than in North America and Europe, while leukemia and central nervous system tumors are notably less common in Zaire. In view of current limitations on health care in rural Zaire, cancer care should be directed toward early diagnosis, quick referral for appropriate surgical care, and use of the limited arsenal of chemotherapy.

Adolescent↗
PubMed1990

[Duodenal leiomyoblastoma. Apropos of a new case and review of the literature].

The authors report a new case of duodenal leiomyoblastoma. Since local anatomical factors were favorable, the tumor was removed by resecting the entire second portion of duodenum with reanastomosis of the remaining ends. This case can be added to the very small number of cases reported in the literature regarding leiomyoblastoma at this site in the gastrointestinal tract. Since diagnostic is difficult, and often made per-operatively following and acute complication, a precise topographical study of the region needs to be performed. It is only by this means that a completely safe operative procedure may be chosen and performed. From an anatomo-pathological viewpoint, several criteria exist to distinguish the potentially benign from the potentially malignant form. However, this remains to be confirmed given the controversial aspects of the subject. Study has mainly involved gastric localisations where a greater number of lesions have been found. At present, only time will show whether these tumors are benign or malignant.

Cholangiography↗
PubMed1990

Quantitation of IgM antibodies to the M. leprae synthetic disaccharide can predict early bacterial multiplication in leprosy.

Quantitative enzyme-linked immunosorbent assays detecting IgM to the soluble Mycobacterium leprae crude sonicate (CD75) and the synthetic disaccharide antigen coupled to bovine serum albumin (ND-BSA) were assessed for their ability to determine early infection in families/household contacts of leprosy patients and employees of a leprosy center working in close contact with leprosy patients. Although IgM to both antigens (CD75 and ND-BSA) correlated with the bacterial index (BI) assessed histologically on skin-biopsy samples, the level of IgM antibodies to ND-BSA was a much more sensitive indicator of low bacterial loads. A 4.4-fold difference in antibody levels was observed between the mean group levels of endemic controls (N = 116) and tuberculoid leprosy patients with a BI of 0 (N = 88), increasing to sevenfold in tuberculoid leprosy patients with a BI of 1 (N = 20). Using a statistical cut off with endemic controls (mean + 2 S.D.), household/family contacts showed 30% seropositivity (N = 180) as compared to staff contacts who showed 17% seropositivity (N = 55). Percent seropositivity in family contacts was not related to the type of leprosy of the index case (lepromatous vs. tuberculoid) or the duration of treatment of the index case. Age of the individual in the family contact group had a significant influence on seropositivity. These results support the hypothesis that, in this community, factors other than the viable bacterial load of the index case, such as genetic susceptibility, may be influencing the high rate of seropositivity in family contacts. IgM ND-BSA antibodies seem to provide a good indicator of low antigenic loads and could prove to be useful in detecting subclinical infection before the onset of disease. Follow-up studies of these seropositive individuals are in progress to understand the relationship between seropositivity and the progress of clinical disease.

Antibodies, Bacterial↗
PubMed1989

Changes in nerves and neuropeptides in skin from 100 leprosy patients investigated by immunocytochemistry.

The cutaneous innervation is now known to contain neuropeptides including substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory nerves, and vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), principally in autonomic nerves. Skin biopsies from 100 leprosy patients and equivalent areas from 50 non-leprosy controls were fixed in p-benzoquinone solution for immunofluorescence staining and in Bouin's fluid for classification of leprosy type. Antisera to the neural markers, neurofilaments, and protein gene product 9.5 (PGP 9.5), and to neuropeptides were used. Cutaneous nerves and nerve endings immunoreactive for neuropeptides, neurofilaments, and PGP 9.5 were seen in all non-leprous control cases. In leprosy, PGP 9.5- and neurofilament-immunoreactive nerve fibres were seen in all 14 cases of the indeterminate (early) type and in the majority (33/43) of lepromatous cases, but in a smaller proportion (15/43) of tuberculoid cases. Neuropeptide immunoreactivity was seen in only 2/14 of the indeterminate leprosy specimens and was completely absent in other types. This early disappearance may be of diagnostic significance. Thus, cutaneous sensory and autonomic dysfunctions in leprosy are well reflected by changes in nerve fibres and neuropeptides.

Calcitonin↗
PubMed1989

T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis.

We sought to protect CBA mice against tuberculosis using in vivo transfer of a T-cell line previously shown to be capable of I-A-restricted recognition of peritoneal macrophages infected in vitro with Mycobacterium tuberculosis. This line induces total bacteriostasis in vitro. In mice that received 500 rads of irradiation 48 h before infection, the T-cell line caused significant prolongation of life when given intravenously with a challenge dose of 5 x 10(6) organisms. Similar experiments with two other T-cell lines showed that these lines offered no protection. Bacterial load at the time of death was inversely related to the time of survival. Thus, death occurred at a lower bacterial load in adoptively protected mice, implying the contribution of an immunopathological component in these animals. The protective T-cell line, which was CD4+ CD8-, had no effect on the rate of growth of strain BCG in CBA nu/nu mice or M. tuberculosis in fully T-cell-deprived mice. This could indicate that CD8+ cells play a role in this system or that there is a need for the recruitment of interleukin 2-producing cells in the recipient. Experiments with monoclonal antibodies to selectively deplete T-cell subsets in normal CBA mice showed that depletion of CD4+ cells strikingly shortened survival, whereas depletion of CD8+ cells did not. However, CD8-depleted mice died with a lower bacterial load than those found in nondepleted controls, and the lesions in CD8-depleted mice were histopathologically distinct. These results suggest that the CD8+ cells either down-regulate bacteriostasis or cause immunopathology in this model and that it is the CD4+ cells that are the major protective subset in long-term protection experiments.

Animals↗