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Biomedical subjects

M A French

Publications and source records attributed to M A French.

87 records · Page 5Linked to original sources
PubMed1984

Protein losing enteropathy due to systemic lupus erythematosus.

We report the case of a 29 year old woman with a protein losing enteropathy caused by systemic lupus erythematosus presenting with periorbital oedema. Only three other cases of protein losing enteropathy due to systemic lupus erythematosus have been described, two of which were thought to be because of a primary enteropathy, although the exact pathogenesis was unknown. We suggest that both the protein losing enteropathy and periorbital oedema in this patient were because of increased capillary permeability to serum albumin, as a result of products of plasma C3 conversion which were present in large amounts. It is also of interest that the antigen/antibody system in this patient was RNP/anti-RNP and that DNA antibodies were not detected. This patient falls into a subset of systemic lupus erythematosus in which anti-DNA antibodies are not present, some of which appear to have a more favourable prognosis.

Adult↗
PubMed1984

Antibody-dependent cellular cytotoxicity of human vascular endothelium in systemic sclerosis.

Sera from 39 patients with systemic sclerosis were examined for a cytotoxic effect on human umbilical vein endothelium. Although none of the sera produced direct cytotoxicity of 51Cr-labelled endothelial cells, even with added complement, nine sera did produce increased 51Cr release when co-cultured with endothelial cells and normal human peripheral blood mononuclear cells. The effector cells involved in this cytotoxicity possessed Fc receptors but were non-T and non-adherent while the responsible serum factor(s) was present in IgG containing fractions. This cytotoxicity tended to occur in patients with both circulating immune complexes and precipitating antibodies to nuclear and cytoplasmic antigens who, as a group, had more severe and extensive visceral disease than those without such serological abnormalities. Control studies using sera from both 27 normal controls and 19 patients with either diabetes or extensive athero-sclerotic vascular disease failed to reveal any similar cytotoxicity.

Adult↗
PubMed1984

Systemic antibody deficiency in patients without serum immunoglobulin deficiency or with selective IgA deficiency.

Serum IgG tetanus toxoid antibody (IgGTTab) concentrations were measured in patients with chronic chest infections or recurrent acute chest infections following immunization and compared with results obtained in a group of 43 controls. Apart from selective IgA deficiency in some patients, all had normal or high serum immunoglobulins. Using an enzyme linked immunosorbent assay (ELISA) for IgG TTab, antibody was present following one immunization in all controls who had previously been immunized and following two immunizations in those not previously immunized. Ninety-seven and a half per cent of controls had a serum antibody concentration of greater than 4 micrograms/ml. Following the same immunization schedule, eight of 45 (18%) patients with chronic chest infections and three of 11 (27%) patients with recurrent acute infections had a serum IgG TTab of less than 4 micrograms/ml. The three patients with a low IgG TTab concentration and recurrent acute infections all had selective IgA deficiency. Two of these patients have benefited from injections of normal human immunoglobulin. It is suggested that systemic antibody deficiency as a cause of chronic or recurrent respiratory tract infections cannot be excluded by measuring serum immunoglobulin concentrations alone and that it is of value to measure antibody responses following immunization.

Adult↗
PubMed1984

Serum IgG subclass concentrations in healthy adults: a study using monoclonal antisera.

IgG subclass concentrations have been measured in the sera of 172 healthy adults using monoclonal antisera. 'Normal ranges' are given. The findings were similar to those of previous studies of European populations but differed from the findings of the only other study of a large British population. In particular, low proportions of IgG4 in a British population have not been confirmed. IgG4 concentrations were higher in males than females (P = less than 0.00003) and IgG3 concentrations were higher in females than males (P = 0.034).

Adult↗
PubMed1983

Association of IgA deficiency with HLA A28 and B14.

HLA typing was performed in two groups of individuals with low serum IgA concentrations. These consisted of 44 individuals identified from a blood donor clinic and 37 individuals attending an Immunology clinic with disorders associated with IgA deficiency. Both groups showed an increase in the frequency of HLA B14 (p less than 0.0001), HLA-A28 (P = 0.0007) and the combinations HLA-A1, B14 and HLA-A28, B14. The previously reported increase in HLA-A1, B8 was not apparent in either group. These data suggest that there is a gene within the human major histocompatibility complex which is relevant in IgA deficiency.

Dysgammaglobulinemia↗
PubMed1983

Systemic lupus erythematosus and Klinefelter's syndrome.

A case of Klinefelter's syndrome presenting with systemic lupus erythematosus while receiving androgen replacement therapy is described. The association of systemic lupus erythematosus with Klinefelter's syndrome is discussed, particularly in terms of the effect of sex hormones.

Adult↗
PubMed1983

Primary immunoglobulin deficiency and haematological disorders.

Nine patients with immunoglobulin deficiency and various haematological disorders are presented. In all patients, recurrent infections had antedated the onset of the haematological disorder but, in most, the possibility of primary immunodeficiency had not been considered until after the haematological diagnosis had been established. The recognition of immunodeficiency is important since such patients may require steroids, immunosuppressive therapy or splenectomy. Gammaglobulin would appear to be the appropriate therapy in this situation. Infections were reduced in all 6 patients so treated.

Adult↗
PubMed1983

Immune complexes in systemic sclerosis; detection by C1q binding, K-cell inhibition and Raji cell radioimmunoassays.

Thirty-four patients with systemic sclerosis (SS) were investigated for the presence of circulating immune complexes by means of a fluid phase C1q binding assay, K-cell inhibition assay and a Raji cell radioimmunoassay and the results compared with those obtained in 21 patients with systemic lupus erythematosus (SLE) and 52 normal healthy controls. Patients with SS showed an incidence of circulating immune complexes comparable to that found in SLE, with 20 patients (58.5%), giving a positive result with at least one of the assays. The presence of circulating immune complexes in patients with SS was found to be associated with both elevation of serum IgG and IgA levels and extensive visceral involvement by the disease. These findings raise the possibility that circulating immune complexes could be involved in the pathogenesis of SS.

Adult↗
PubMed1983

Serum and tissue concentrations of cefoxitin and cefamandole in women undergoing hysterectomy.

To prevent infection in 40 patients who underwent vaginal or abdominal hysterectomy, each patient received a single 15-mg/kg dose of either cefoxitin or cefamandole by rapid (5-minute) intravenous injection before the operation. Samples of serum, myometrium, endometrium, ovaries, and tubes were obtained at various intervals after injection of the antibiotic and were assayed for cephalosporin concentration. Maximum tissue concentrations of 30 micrograms/g of both drugs were detected approximately 30 minutes after the dose, with levels dropping below 3 micrograms/g in approximately 2 hours. Although both antibiotics achieved closely similar concentrations in serum and tissues, the ratios of these levels to their usual mean minimum inhibitory concentrations for Bacteroides fragilis were appreciably higher for cefoxitin than for cefamandole. These pharmacokinetic observations support the current dosage recommendations for the use of cefoxitin in treating and preventing gynecologic infections, as well as the recommendation that it be administered shortly before the operation to maximize tissue levels during the perioperative period.

Adult↗
PubMed1982

Platelet monoamine oxidase activity and cigarette smoking.

Platelet MAO activity and plasma thiocyanate concentrations were determined in 72 normal volunteers (22 non-smokers and 50 smokers). Thiocyanate concentrations were used as an index of exposure to cigarette smoke. A significant negative correlation between MAO and thiocyanate concentration was observed for the group (rs = 0.35; P less than 0.005). When examined by sex, the correlation was significant for females but not for males. Mean MAO activity was significantly lower for female smokers than for female non-smokers. For males, no significant differences in MAO activity were observed between smokers and non-smokers. It is possible that smoking causes inhibition of MAO by a direct effect or by indirect effects such as altering hormone levels. Alternatively women with a low MAO activity have a greater innate tendency to smoke.

Adult↗
PubMed1982

Penetration of ceforanide and cefamandole into the right atrial appendage, pericardial fluid, sternum, and intercostal muscle of patients undergoing open heart surgery.

Doses of 30 mg of ceforanide or cefamandole per kg were administered intravenously to 26 patients just before their chests were opened for coronary artery bypass or cardiac valve replacement surgery. Samples of right atrial appendage, pericardial fluid, plasma, aortic wall, intercostal muscle, and sternum were obtained at different times after the antibiotic was injected, and these samples were assayed for cephalosporin concentration. For ceforanide the pre-bypass plasma half-life was 2.5 h, and the atrial appendage half-life was 2.1 h; for cefamandole the pre-bypass plasma half-life was 0.75 h and the atrial appendage half-life was 0.72 h. At 3 h the concentrations of ceforanide and cefamandole in atrial appendages were 28.0 and 5.0 micrograms/g, respectively. Ceforanide achieved higher and more sustained concentrations in other tissues than cefamandole. Considering the minimal inhibitory concentrations of these drugs for staphylococci, cefamandole and ceforanide should provide adequate protection against infection by these organisms for the duration of the surgical procedure.

Cardiac Surgical Procedures↗
PubMed1981

Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients.

Cimetidine induces reversible dose-related central nervous system (CNS) toxicity. Trough serum concentrations and the development of CNS toxicity correlate. We compared cimetidine kinetics in 12 healthy subjects and 31 patients. Six of the latter had normal renal and liver function, five had renal disease only, 12 had liver disease only, and eight had both renal and liver disease. Postmortem tissue distribution was assessed in 11 patients, and expressed as tissue:serum ratio. Average cimetidine total clearance (ClB) in milliliters per minute for each group was as follows: patients with renal and liver disease (182 +/- 105), renal disease only (193 +/- 24), liver disease only (463 +/- 145), normal patients (510 +/- 93), and healthy subjects (583 +/- 140). Renal function was the major determinant for ClB, and the relationship was described by ClB = 4.2(CCr) + 140, r = 0.87, where CCr is creatinine clearance. Cimetidine clearance was affected little by age. Tissue:serum ratios from highest to lowest were as follows: kidney greater than stomach greater than liver greater than bone greater than brain greater than fat. Central and steady-state distribution volumes were not influenced by age or disease. There was enchanced CNS penetration in liver disease patients; their cerebrospinal fluid (CSF):serum ratio was twice the normal. Our kinetic studies identify patient characteristics likely to result in elevated blood levels, and suggest that the greatest risk of CNS toxicity is in those with liver disease.

Adolescent↗
PubMed1981

Amikacin and gentamicin accumulation pharmacokinetics and nephrotoxicity in critically ill patients.

Twenty-five critically ill adults receiving blood level-adjusted doses of amikacin were prospectively studied with serum, urine, and, when possible, tissue amikacin concentrations. These data were fitted to a two-compartment pharmacokinetic model. Prolonged urine collections or postmortem tissues (or both) were used to confirm predicted tissue accumulation. Nephrotoxicity was also investigated. Patients were defined as having renal damage if they showed an increase in serum creatinine of greater than 0.5 mg/100 ml, an increase in urine beta 2-microglobulin of greater than 50 mg/day, and presence of urinary casts of greater than 500/ml. Renal damage was attributed to amikacin if there was, in addition to the above, tissue accumulation of amikacin of greater than 600 mg. These patients were matched with 25 patients treated with gentamicin during the same time period. There were no statistical differences between the gentamicin- and amikacin-treated patients in age, sex, weight, base-line creatinine clearance, concurrent cephalosporins or diuretics, treatment duration, site of infection, normalized (amikacin/gentamicin dosing ratio of 3:1) total dose, mortality, or tissue accumulation. More amikacin-treated patients (19 of 25) than gentamicin-treated patients (9 of 25) received prior aminoglycosides (P less than 0.01). The only pharmacokinetic parameter that differed between amikacin and gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin-treated patients (16%) and 5 amikacin-treated patients (20%). At a 3:1 dosing ratio, there were no significant differences between amikacin and gentamicin two-compartment pharmacokinetics and nephrotoxic potential in matched critically ill patients, but the trend of these data showed greater amikacin tissue accumulation. However, at an amikacin/gentamicin dosing ratio of 4:1, their tissue accumulation potential appeared to be almost identical.

Amikacin↗
PubMedDate not supplied

Combined analysis of two-year follow-up from two open-label randomized trials comparing efficacy of three nucleoside reverse transcriptase inhibitor backbones for previously untreated HIV-1 infection: OzCombo 1 and 2.

PURPOSE: To compare inhibition of HIV replication, improvements in CD4+ T-cell counts, metabolic parameters, and body shape changes after 2 years of assigned therapy in OzCombo patients. METHOD: Study participants were those who were recruited into the open-label OzCombo 1 (1996/1997) and OzCombo 2 (1997/1998) trials. Patients in OzCombo 1 were randomized to receive indinavir in combination with zidovudine+lamivudine (AZT+3TC; n = 35), stavudine (d4T)+3TC (n = 34), or d4T+didanosine (ddI) (n = 37). OzCombo 2 patients were randomized to the same nucleoside reverse transcriptase inhibitor (NRTI) backbones with nevirapine (n = 20, 22, 23, respectively). The mean time-weighted changes from baseline in CD4 T-cell count/mL, HIV RNA (log copies/mL plasma), and proportions with detectable viral load (<500 copies plasma HIV RNA/mL) between NRTI arms over 2 years were compared by formal meta-analysis. A cross-sectional study of metabolic and body shape complications was also undertaken. RESULTS: For the comparison of d4T+3TC and d4T+ddI to AZT+3TC, mean differences in time-weighted change from baseline in CD4 T-cell count/microL and log copies HIV RNA/mL adjusted for baseline CD4+ T-cell and HIV RNA counts were: -44 (p =.08) and -14 (p =.56) cells/microL and -0.1 (p =.40) and -0.1 (p =.6) copies/mL. Odds ratios for detectable viral load in the last study quarter were 0.6 (p =.44) and 1.0 (p =.95). The mean percent leg fat was lower in the d4T+3TC and d4T+ddI than the AZT+3TC arm (mean difference 5.1% [p =.07] and 7.6% [p =.02], respectively). CONCLUSION: For all regimens, virological control and immunological response were maintained over 2 years. Regimens containing d4T and particularly d4T+ddI were significantly associated with increased peripheral fat loss compared with AZT+3TC.

Adipose Tissue↗