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Biomedical subjects

M John

Publications and source records attributed to M John.

At least 55 records · Page 3Linked to original sources
PubMed2000

Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection.

BACKGROUND: Progressive subcutaneous fat wasting, fat accumulation, dyslipidaemia and insulin resistance in HIV-infected patients on antiretroviral therapy has been attributed to the long-term toxicity of HIV protease inhibitors (PI). More recently, fat wasting has been observed in patients who have never taken a PI, implicating an independent effect of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy. OBJECTIVES: To determine the relative contribution of NRTI and PI, as well as any other factors, to fat wasting in HIV-infected patients. DESIGN: Longitudinal cohort study involving 277 participants of the Western Australian HIV Cohort Study. METHODS: The time to onset of clinically apparent fat wasting in patients receiving different antiretroviral regimens was compared using standardized clinical criteria. Regional fat measured by dual energy X-ray absorptiometry (DEXA) in 161 patients was also compared. The average rate of percentage fat reduction was estimated in 70 patients who had consecutive DEXA scans at approximately 6-monthly intervals. Multiple confounding factors were considered in the analyses. RESULTS: Progressive subcutaneous fat wasting, indistinguishable from that described in PI-treated patients, does occur in PI-naive, NRTI-treated patients. In patients taking triple combination antiretroviral therapy, age (relative risk = 1.052 per year; P < 0.0001), white race (relative risk = 3.9; P = 0.023), longer duration of dual NRTI therapy prior to addition of PI (relative risk = 1.021 per month; P = 0.0046) and increased cumulative time on stavudine-containing regimens compared with time on zidovudine-containing regimens (relative risk = 1.085 per month; P < 0.0001) are associated with increased risk of fat wasting. Stavudine increases the risk of fat wasting by 265% per year compared with zidovudine. However PI therapy is associated with faster progression to clinically apparent wasting compared with dual NRTI therapy without PI. The results of DEXA scanning supports these clinical data and suggest a non-linear decline in fat over time. CONCLUSIONS: NRTIs do have an independent contribution to fat wasting, but PI are the predominant influence and may act synergistically with NRTIs. NRTIs appear to predispose individuals to slowly progressive fat loss, which is markedly accelerated when a PI and NRTIs are combined. Of the NRTIs, stavudine leads to an earlier onset of clinically apparent fat wasting compared with zidovudine. Fat wasting associated with NRTI use may be a manifestation of mitochondrial toxicity, which may be exacerbated by PI use.

Absorptiometry, Photon↗
PubMed2000

[Recommendations for the standardized evaluation and classification of patients with painful temporomandibular disorders].

INTRODUCTION: Due to the considerable degree of variation that exists among care providers with respect to the assessment of patients suffering from painful temporomandibular disorders (TMDs), an interdisciplinary working group for the study of orofacial pain aimed at developing recommendations for the evaluation and diagnostic classification of such patients. METHODS: Following an extensive literature search (computer-based search and handsearch), several working sessions were needed to develop a standardized diagnostic protocol. It was a prerequisite that recommended measures and instruments should have acceptable reliability and validity. Three independent reviewers - well-known experts in the pain field - critically reviewed the contents of our recommendations. RESULTS: A two-axis approach is recommended to assess the somatic and psychosocial parameters of the pain experience. Our concept closely follows the Research Diagnostic Criteria for Temporomandibular Disorders. In addition, we distinguish a minimal, a standard, and an extended evaluation. CONCLUSIONS: The recommendations appear to be useful to enhance the diagnostic quality in the evaluation of patients with painful TMDs.

English Abstract↗
PubMed2000

Value of bronchial artery embolisation with platinum coils in tumorous pulmonary bleeding.

We performed bronchial artery embolizations (BAE) using platinum coils with Dacron fibres in 30 consecutive patients with haemoptysis due to bronchial carcinoma. The aim of the study was to compare immediate results of bleeding cessation, recurrence and survival rates with a historical control group of 15 patients with tumorous pulmonary bleeding who were treated conservatively (non-BAE-group). Bronchial artery embolisation with platinum coils stopped active bleeding in all patients immediately. Comparing the BAE group and controls the cessation of first time haemoptysis (BAE 100% versus non-BAE 93%) and the rates of bleeding recurrence (BAE 50% versus non-BAE 47%) were similar in either group. In case of recurrent bleeding, repeated BAE led to a definite cessation of pulmonary haemorrhage in every case. In contrast, all patients with recurrent haemoptysis without a repeated BAE (8 patients, 27%) and all patients with bleeding recurrence in the non-BAE group died from pulmonary haemorrhage (8 patients, 53%). The mean survival time of the BAE group was significantly longer compared with the non-BAE group, 139 (range: 1-818) days versus 62 (range: 1-186) days (P<0.05). We conclude that consistent BAE proved beneficial in tumorous pulmonary bleeding, particularly with regard to the permanent arrest of haemorrhage in case of recurrence.

Aged↗
PubMed2000

Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy.

BACKGROUND: To determine if infectious disease events in HIV-infected patients treated with highly active antiretroviral therapy (HAART) are a consequence of the restoration of pathogen-specific immune responses, a single-centre retrospective study of all HIV-infected patients commencing HAART prior to 1 July 1997 was undertaken to determine the incidence, characteristics and time of onset of disease episodes in HAART responders (decrease in plasma HIV RNA of > 1 log10 copies/mL). METHODS: Baseline and post-therapy changes in CD4 T-cell counts and HIV RNA were compared in patients with and without disease and delayed-type hypersensitivity responses to mycobacterial antigens were measured in selected patients. RESULTS: Thirty-three of 132 HAART responders (25%) exhibited one or more disease episodes after HAART, related to a pre-existent or subclinical infection by an opportunistic pathogen. Disease episodes were most often related to infections by mycobacteria or herpesviruses but hepatitis C virus (HCV), molluscum contagiosum virus and human papilloma virus were also implicated. They were most common in patients with a baseline CD4 T-cell count of < 50/uL and occurred most often during the first 2 months of therapy and when CD4 T-cell counts were increasing. Mycobacteria- and HCV-related diseases were associated with restoration of pathogen-specific immune responses. CONCLUSIONS: We conclude that improved immune function in immunodeficient patients treated with HAART may restore pathogen-specific immune responses and cause inflammation in tissues infected by those pathogens.

AIDS-Related Opportunistic Infections↗
PubMed2000

Nephrotic syndrome in a patient with IgA deficiency-associated mesangioproliferative glomerulonephritis.

A case of mesangioproliferative glomerulonephritis in a 55-year-old woman with selective IgA deficiency and serum antinuclear antibodies who presented with nephrotic syndrome is described. The patient did not have clinical or laboratory features of systemic lupus erythematosus (SLE) other than antinuclear antibodies. Histology of the patient's renal biopsy revealed a mesangioproliferative glomerulonephritis and direct immunofluorescence showed that paramesangial deposits contained predominant IgM with lesser IgG, C3 and C1q. These findings are identical to those previously described in a form of glomerulonephritis associated with IgA deficiency and would be atypical for lupus nephritis. Glomerulonephritis is not a well recognized complication of IgA deficiency, though it has been rarely reported in the literature. This case provides further evidence that IgA deficiency is associated with a unique immune complex-mediated glomerulopathy with characteristic immunopathological and ultrastructural features. It is the first reported case to present with nephrotic syndrome.

Antibodies, Antinuclear↗
PubMed2000

Social support and personal models of diabetes as predictors of self-care and well-being: a longitudinal study of adolescents with diabetes.

OBJECTIVES: To examine whether peer support and illness representation mediate the link between family support, self-management and well-being. METHOD: Fifty-two adolescents (12-18 years old) with Type I diabetes were recruited and followed over 6 months, completing assessments of self-management, well-being, and social support. RESULTS: Perceived impact of diabetes and supportive family and friends were prospectively predictive of participants' well-being measures. Although support from family and friends was predictive of better dietary self-care, this relationship was mediated by personal model beliefs. In particular, beliefs about the effectiveness of the diabetes treatment regimen to control diabetes was predictive of better dietary self-care. CONCLUSIONS: Both friends and family are important to support adolescents as they live with and manage their diabetes. Personal models of diabetes are important determinants of both dietary self-care and well-being. In addition, personal models may serve to mediate the relationship between social support and dietary behavior.

Adolescent↗
PubMed2000

Enhanced expression of iNOS in inflamed colons of IL-2-deficient mice does not impair colonic epithelial barrier function.

On the basis of recently observed high levels of iNOS expression that correlated with intestinal inflammation in interleukin-2-deficient [IL-2(-/-)] mice, it was postulated that nitric oxide may damage colonic epithelial cells or impair intestinal epithelial barrier function. This damage may result in an increased permeability of the colonic epithelium leading to high antigenic exposure of the intestinal immune system, which may perpetuate chronic inflammation. Our data demonstrate that high expression of iNOS in IL-2(-/-) mice is correlated with the length/weight ratio (L/W ratio), a widely accepted marker for intestinal inflammation. However, no reduction of epithelial resistance was observed, as would be expected in case of a damaged, leaky epithelium. Our results suggest that enhanced formation of NO in IL-2(-/-) mice does not cause impairment of epithelial barrier function.

Animals↗
PubMed2000

Development of a DeltaglnA balanced lethal plasmid system for expression of heterologous antigens by attenuated vaccine vector strains of Vibrio cholerae.

We have previously shown that more prominent immune responses are induced to antigens expressed from multicopy plasmids in live attenuated vaccine vector strains of Vibrio cholerae than to antigens expressed from single-copy genes on the V. cholerae chromosome. Here, we report the construction of a DeltaglnA derivative of V. cholerae vaccine strain Peru2. This mutant strain, Peru2DeltaglnA, is unable to grow on medium that does not contain glutamine; this growth deficiency is complemented by pKEK71-NotI, a plasmid containing a complete copy of the Salmonella typhimurium glnA gene, or by pTIC5, a derivative of pKEK71-NotI containing a 1. 8-kbp fragment that directs expression of CtxB with a 12-amino-acid epitope of the serine-rich Entamoeba histolytica protein fused to the amino terminus. Strain Peru2DeltaglnA(pTIC5) produced 10-fold more SREHP-12-CtxB in supernatants than did ETR3, a Peru2-derivative strain containing the same fragment inserted on the chromosome. To assess immune responses to antigens expressed by this balanced lethal system in vivo, we inoculated germfree mice on days 0, 14, 28, and 42 with Peru2DeltaglnA, Peru2DeltaglnA(pKEK71-NotI), Peru2(pTIC5), Peru2DeltaglnA(pTIC5), or ETR3. All V. cholerae strains were recoverable from stool for 8 to 12 days after primary inoculation, including Peru2DeltaglnA; strains containing plasmids continued to harbor pKEK71-NotI or pTIC5 for 8 to 10 days after primary inoculation. Animals were sacrificed on day 56, and serum, stool and biliary samples were analyzed for immune responses. Vibriocidal antibody responses, reflective of in vivo colonization, were equivalent in all groups of animals. However, specific anti-CtxB immune responses in serum (P </= 0.05) and bile (P </= 0. 001) were significantly higher in animals that received Peru2DeltaglnA(pTIC5) than in those that received ETR3, confirming the advantage of higher-level antigen expression in vivo. The development of this balanced lethal system thus permits construction and maintenance of vaccine and vector strains of V. cholerae that express high levels of immunogenic antigens from plasmid vectors without the need for antibiotic selection pressure.

Administration, Oral↗
PubMed2000

Optimizing the germfree mouse model for in vivo evaluation of oral Vibrio cholerae vaccine and vector strains.

The germfree mouse model of Vibrio cholerae infection can be used to judge immune responses to V. cholerae vaccine and vector strains. In the original model, a single oral inoculation was administered on day 0, a booster oral inoculation was administered on day 14, and immune responses were analyzed with samples collected on day 28. Unfortunately, immune responses in this model frequently were low level, and interanimal variability occurred. In order to improve this model, we evaluated various primary and booster V. cholerae inoculation schedules. The most prominent systemic and mucosal antibody responses were measured in mice that received a multiple primary inoculation series on days 0, 2, 4, and 6 and booster inoculations on days 28 and 42. These modifications result in improved preliminary evaluation of V. cholerae vaccine and vector strains in mice.

Administration, Oral↗
PubMed2000

In vitro and in vivo analyses of constitutive and in vivo-induced promoters in attenuated vaccine and vector strains of Vibrio cholerae.

The optimal promoter for in vivo expression of heterologous antigens by live, attenuated vaccine vector strains of Vibrio cholerae is unclear; in vitro analyses of promoter activity may not accurately predict expression of antigens in vivo. We therefore introduced plasmids expressing the B subunit of cholera toxin (CtxB) under the control of a number of promoters into V. cholerae vaccine strain Peru2. We evaluated the tac promoter, which is constitutively expressed in V. cholerae, as well as the in vivo-induced V. cholerae heat shock htpG promoter and the in vivo-induced V. cholerae iron-regulated irgA promoter. The functionality of all promoters was confirmed in vitro. In vitro antigenic expression was highest in vaccine strains expressing CtxB under the control of the tac promoter (2 to 5 microgram/ml/unit of optical density at 600 nm [OD(600)]) and, under low-iron conditions, in strains containing the irgA promoter (5 microgram/ml/OD(600)). We orally inoculated mice with the various vaccine strains and used anti-CtxB immune responses as a marker for in vivo expression of CtxB. The vaccine strain expressing CtxB under the control of the tac promoter elicited the most prominent specific anti-CtxB responses in vivo (serum immunoglobulin G [IgG], P </= 0.05; serum IgA, P </= 0.05; stool IgA, P </= 0.05; bile IgA, P </= 0.05), despite the finding that the tac and irgA promoters expressed equivalent amounts of CtxB in vitro. Vibriocidal antibody titers were equivalent in all groups of animals. Our results indicate that in vitro assessment of antigen expression by vaccine and vector strains of V. cholerae may correlate poorly with immune responses in vivo and that of the promoters examined, the tac promoter may be best suited for expression from plasmids of at least certain heterologous antigens in such strains.

Animals↗
PubMed2000

Increased interleukin-10 and macrophage inflammatory protein-1 alpha release from blood monocytes ex vivo during late-phase response to allergen in asthma.

BACKGROUND: We determined the effect of late-phase responses to allergen challenge of mildly allergic asthmatic patients on the expression and release of the cytokines IL-10 and MIP-1alpha from peripheral blood monocytes. METHODS: Sixteen mildly allergic asthmatics were exposed to increasing concentrations of allergen aerosol. Nine demonstrated an early response alone (single responders), while seven had an early followed by a late response (dual responders). Monocytes were isolated from venous blood before and 24 h after allergen challenge, and placed in short-term culture for determination of IL-10 mRNA expression by reverse-transcription polymerase chain reaction and protein release. MIP-1alpha protein release was measured by radioimmunoassay. RESULTS: IL-10 mRNA expression was significantly higher in dual responders than early responders alone, for unstimulated monocytes or for monocytes exposed to lipopolysaccharide or IL-1beta. In addition, the release of IL-10 and MIP-1alpha from monocytes of dual responders was also enhanced. CONCLUSIONS: Circulating monocytes are primed to release more of the cytokines, IL-10 and MIP-1alpha, in dual but not in single responders, at 24 h after allergen. They may contribute to allergen-induced inflammatory responses in the airways.

Adult↗
PubMed2000

U.S. clinical investigation of the Artisan myopia lens for the correction of high myopia in phakic eyes. Report of the results of phases 1 and 2, and interim phase 3.

PURPOSE: The purpose of this article is to present the results of the U.S. Clinical investigation of the Artisan anterior chamber iris fixed lens implant for the correction of myopia in phakic eyes. METHODS: A prospective, multi-center, FDA-supervised trial was designed and undertaken in the United States by Ophtec USA, Inc., Boca Raton, Florida to determine the safety and efficacy of the Artisan lens as a potential refractive treatment for patients with high myopia. During the trial, two different models of the Artisan lens were used: one with a 5-mm optical zone (model 206) and the other with a 6-mm optical zone (model 204). RESULTS: The data presented comprise 176 enrolled subjects and 264 implant procedures. The most frequently chosen Artisan lens power was -13.00 D (average, -12.76 D; SD, 3.24). The postoperative results at 6 months for all eyes (n = 135) showed 100% of patients were 20/40 or better best-corrected while 72% gained one or more lines and 22% gained two or more lines regardless of degree of astigmatism or postoperative goal. Through the course of the study, intraocular pressure maintained a level with a mean below 16 mmHg. In general, total reported complications in the patient cohort decreased over time, dropping from 39% at the initial visit to 10% at visit four and 0% at visit seven. CONCLUSIONS: On the basis of the interim results of the U.S. Clinical Investigation of the Artisan Myopia Lens for the Correction of High Myopia in Phakic Eyes, the Artisan anterior chamber phakic IOL may offer an option for correction of high degrees of myopia. Refractive outcomes were exceptional and complications were minimal and amenable to treatment.

Adult↗
PubMed1999

Molecular dissection of regulated secretory pathways in human gastric enterochromaffin-like cells: an immunohistochemical analysis.

Enterochromaffin-like (ECL) cells regulate gastric acid secretion through vesicular release of histamine. Until now, the molecular machinery of human ECL cells involved in the formation and release of vesicles is largely unknown. We analyzed tissue samples obtained from normal human gastric mucosa (n=4) and ECLomas (n=5) immunohistochemically using the APAAP method or double immunofluorescence confocal laser microscopy. Human pheochromocytomas (n=5) were investigated in parallel and compared to ECL cells. Secretory pathways were characterized using antibodies specific for marker proteins of large dense-core vesicles (LDCVs; islet cell antigen 512, chromogranin A, pancreastatin, and vesicular monoamine transporter 2) and small synaptic vesicle (SSV) analogues (synaptophysin). Tissues were also analyzed for expression of the peptide hormone processing enzymes, carboxypeptidase E and prohormone convertase 1, as well as the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, 25-kDa synaptosome-associated protein (SNAP25), syntaxin, and synaptobrevin. Immunoreactivity for markers of LDCVs and SSV analogues were detected in normal ECL cells and ECLomas. Both tissues also showed expression of carboxypeptidase E and prohormone convertase 1. Analysis of vesicular SNARE (v-SNARE) and target membrane SNARE (t-SNARE) proteins revealed the presence of SNAP25, syntaxin, and synaptobrevin in normal and neoplastic ECL cells. Our data suggest that ECL cells possess the two vesicle types of regulated neuroendocrine secretory pathways, LDCVs and SSV analogues. Since ECL cells also contain typical SNARE proteins, the molecular machinery underlying secretory processes in this cell type appears to be identical to the secretory apparatus of neuroendocrine cells and neurons. In addition, our findings suggest that the secretory apparatus of ECL cells is maintained during neoplastic transformation.

Aspartic Acid Endopeptidases↗
PubMed1999

Temporary tracheobronchial stenting in malignant lymphoma.

BACKGROUND: Temporary stenting is a new strategy in the treatment of malignant airway stenoses. Patients receive stents as primary palliation followed by tumor-specific therapy in order to reduce the stenosis and subsequently remove the stent. METHODS: We investigated this strategy of temporary airway stenting in 5 consecutive patients with malignant lymphoma (Non-Hodgkin's lymphoma, n = 3; Hodgkin's lymphoma, n = 2) who presented with severe dyspnoea. Nine stents (six Strecker, three Dumon stents) were implanted into the trachea or main bronchi. After stenting, patients underwent tumor-specific therapy (chemotherapy, n = 4; percutaneous radiotherapy, n = 1). RESULTS: Clinical improvement of dyspnoea and stridor was observed in each patient after stent implantation. In 4 patients (80%), stents could easily be removed after successful tumor-specific therapy, which led to reduction of stenosis after a mean interval of 26 days (14 to 52 days). One patient died during chemotherapy 6 days after stenting. CONCLUSIONS: The results show that temporary stenting is a valuable strategy in chemo- and radiosensitive malignancies, as it ameliorates the patients' respiratory condition until tumor-specific therapy is effective, and prevents poststenotic complications. It integrates stent implantation in a multi-therapy concept.

Adolescent↗