Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 73 records · Page 4Linked to original sources

PubMed2001

Cessation of secondary prophylaxis in patients with cryptococcosis.

Cryptococcal disease in HIV-positive individuals is usually a consequence of advanced immunosuppression. Treatment consists of long period of induction therapy followed by long-term secondary prophylaxis, usually with fluconazole. The introduction of highly active antiretroviral therapy has resulted in improvements in immunological function such that the cessation of primary and secondary prophylaxis against several opportunistic infections has become possible. We report our experience of the cessation of secondary antifungal prophylaxis in patients responding to highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

PubMed2001

Response to HBV vaccine in relation to vaccine dose and anti-HCV positivity: a New South Wales correctional facilities' study.

Currently, about two-thirds of inmates in NSW correctional facilities have a history of injection drug use, and about half have serological evidence of exposure to hepatitis C virus. The introduction of an accelerated hepatitis B vaccination program (0-1-2 months) in 1998, using a 20 microg/dose vaccine was necessitated by the need to vaccinate eligible inmates in this high-risk environment characterised by rapid client mobility. Since 1999, both 10 and 20 microg doses of vaccine were introduced. We found that sero-response rates were not significantly influenced by HCV antibody status, but were significantly lower in cohorts of inmates vaccinated with the 10 microg dose of vaccine.

Dose-Response Relationship, Immunologic↗

PubMed2001

Endothelin-1 and monocyte chemoattractant protein-1 modulation in ischemia and human brain-derived endothelial cell cultures.

Brain tissue damage due to ischemia/reperfusion has been shown to be caused, in part, by activated macrophages infiltrating into the post-ischemic brain. Using the Middle Cerebral Artery Occlusion (MCAO) mouse model, this study demonstrated that, in vivo, both endothelin-1 (Et-1), a potent vasoconstrictor, and the macrophage chemokine, monocyte chemoattractant factor-1 (MCP-1) are induced in ischemia. Further studies, using human brain-derived endothelial cells (CNS-EC), showed that in vitro, Et-1 can directly stimulate MCP-1 mRNA expression and MCP-1 protein; and this Et-1-induced MCP-1 production is mediated by the ET(A) receptor. Inflammatory cytokines, tumor necrosis factor alpha and interleukin-1beta, functioned additively and synergistically, respectively, with Et-1 to increase this MCP-1 production. Partial elucidation of the signal transduction pathways involved in Et-1-induced MCP-1 production demonstrated that protein kinase C-, but not cAMP-dependent pathways are involved. These data demonstrate that Et-1, functioning as an inflammatory peptide, increased levels of MCP-1, suggesting a mechanism for chemokine regulation during ischemia/reperfusion injury.

Animals↗

PubMed2001

Long-term follow-up of antiretroviral-naive HIV-positive patients treated with nevirapine.

This article reports on the extended follow-up of 125 antiretroviral (ARV)-naive patients treated with nevirapine (NVP) in the United Kingdom. The patients have been observed for a median of 1.8 years after starting NVP (range, 4 days-2.7 years). Baseline CD4 counts and HIV RNA levels were 210 (interquartile range, 130 - 335) cells/mm3 and 4.86 (range, 4.52-5.26) log10 copies/ml, respectively. Eleven patients (9.0%) developed a rash thought to be related to NVP, of whom 4 permanently discontinued NVP. Twenty-four months after starting NVP, RNA levels had dropped by a median of 2.32 log10 copies/ml and CD4 counts increased by a median of 143 cells/mm3. In all, 96 patients had at least one viral load measured <500 copies/ml, a median of 2.8 months after starting NVP. RNA levels rebounded >500 copies/ml in 37 of these patients, on average 2 years after initial response. In conclusion, in ARV-naive patients, NVP is generally well tolerated and long-term response rates are good.

Adult↗

PubMed2001

Parental medical neglect in the treatment of adolescents with anorexia nervosa.

OBJECTIVE: Although childhood sexual abuse has been a frequent focus of research on eating disorders, other forms of maltreatment have been less commonly reported. Parental medical neglect is examined in this study as having serious consequences for the treatment and prognosis of patients with anorexia nervosa. METHOD: Two case studies illustrate parental interference with treatment in which Child Protective Services (CPS) had to be involved in compliance with state law. Two adolescent females who were admitted for treatment for anorexia nervosa are presented. RESULTS: In both cases, the parents refused to comply with the recommendations of the treatment team, placing their children's health in jeopardy. In compliance with reporting guidelines, CPS was notified in both cases. CONCLUSIONS: Clinicians who treat minors with anorexia nervosa must consider parental compliance with treatment. Indications for the involvement of CPS are outlined. Optimally, this notification can ensure that the patient and family receive the requisite treatment.

Adolescent↗

PubMed2001

Detection of specific Bacillus anthracis spore biomarkers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was applied for the characterization of Bacillus anthracis spore biomarkers. B. anthracis spores were extracted under a simple procedure, followed by linear mode analysis, using sinapinic acid as the matrix. Several markers with a mass range of 4-7 kDa were detected in three B. anthracis strains: Vollum, Sterne and V770-NP1-R. Similar spectra were also obtained for spore extracts of two members of the B. cereus group: B. thuringiensis and B. cereus, but not for B. mycoides, B. subtilis or B. licheniformis, suggesting that these markers are specific to closely related members of the B. cereus group. When alpha-cyano-4-hydroxycinnamic acid was used as the matrix, at least four additional new markers within a mass range of 2-4 kDa could be detected in all B. anthracis spore extracts. These markers, corresponding to a molecular weight of 2528.3, 2792.4, 3077.4, and 3590.7 Da, have not been observed in extracts of the three closely related Bacillus species - B. cereus, B. thuringiensis and B. mycoides. These unique B. anthracis biomarkers, which were isotopically resolved and reproducibly detected in the highly accurate MALDI-TOFMS reflectron mode, may be useful as a basis for rapid and specific identification of B. anthracis strains.

Bacillus anthracis↗

PubMed2001

Alterations in CD30(+) T cells in monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of unknown significance (MGUS) is a monoclonal B cell expansion characterized by high levels of circulating monoclonal antibody that affects 3% of individuals over the age of 70. Although this is considered benign, a high percentage of MGUS patients develop a debilitating peripheral autoimmune neuropathy and have a significantly increased risk for progression to multiple myeloma. Here we show that the relative numbers of the CD30(+) T cell subset and levels of CD30 expression are elevated in activated lymphocytes from normal aged individuals (> or =60 years) and in MGUS patients, when compared to younger controls. PBL from MGUS patients and age-matched controls produced comparable levels of IL-6 when activated with anti-CD3 plus IL-2, and costimulation with a soluble form of CD30 ligand (sCD30L/CD8alpha) augmented anti-CD3 inducible IL-6 production similarly in both groups. However, MGUS PBL also produced measurable IL-6 when activated with sCD30L/CD8alpha alone. This capability was associated with the unique presence of CD30(+) T cells in the peripheral blood of MGUS patients. Furthermore, a higher percentage of activated MGUS T cells express CD30 when activated by incubation with idiotype-expressing autologous serum (68 +/- 13) than those activated by anti-CD3 plus IL-2 (43 +/- 7). These results indicate that quantitative alterations in CD30(+) T cells accompany aging and MGUS and that these cells may contribute to the chronic activation of B cells though the production of IL-6.

Aged↗

PubMed2001

Monoclonal antibody to polycyclic aromatic hydrocarbons based on a new benzo[a]pyrene immunogen.

Benzo[a]pyrenebutyric acid (B[a]PBA) has been synthesized and covalently coupled to bovine serum albumin to generate monoclonal antibodies (Mab). A competitive indirect enzyme-linked immunosorbent assay (ELISA) for polycyclic aromatic hydrocarbons (PAH) has been developed with Mab B[a]P-13. It was shown by testing with 21 parent PAH and 10 compounds carrying methyl, hydroxy, or butyric acid functions that the antibody had broad specificity. Highest affinity was found for four- to six-ring PAH. Different organic co-solvents were tested. No loss in sensitivity, compared with controls in PBS, were found with methanol, dimethyl sulfoxide, and glycerol at final concentrations of 5 to 10%. Further, an observation was made that a modification (fine-tuning) of the affinity and specificity of the antibodies was possible by changing the type of the added organic co-solvent. The high susceptibility of the ELISA with regard to inorganic ions might be an indication of a more hydrophilic binding pocket e.g. involving a pi-cation interaction. Investigation of the effect of pH revealed that for pH between 6 to 9 there was no noticeable impairment. With an LOD as low as 30 pg per well for B[a]P the sensitivity of the ELISA is sufficient for analyses of solvent extracts of many environmental samples. As an example, the determination of a PAH sum parameter, given as B[a]P-equivalents, in crude aerosol extracts by both ELISA and HPLC revealed good correlation (r2=0.717) but approximately five-fold overestimation by the immunochemical method, obviously as a result of cross-reacting analytes.

Air Pollutants↗

PubMed2001

Downregulation of the ERK 1 and 2 mitogen activated protein kinases using antisense oligonucleotides inhibits proliferation of porcine vascular smooth muscle cells.

The current model of the arterial response to injury suggests that proliferation of vascular smooth muscle cells is a central event. Mitogen activated protein kinases are part of the final common pathway of intracellular signalling involved in cell division and thus constitute an attractive target in attempting to inhibit this proliferation. We hypothesised that antisense oligonucleotides to mitogen activated protein kinase would inhibit serum induced smooth muscle cell proliferation by downregulating the protein. Porcine vascular smooth muscle cells were cultured and an antisense oligonucleotide sequence against the ERK family of mitogen activated protein kinases (AMK1) was introduced by liposomal transfection. Sense oligonucleotides and a random sequence were used as controls. Proliferation was inhibited by AMK1 versus the sense controls, as assessed by tritiated thymidine incorporation (P<0.01). Immunoblots revealed downregulation of the target protein by AMK1 by 63% versus the sense control (P<0.05). In conclusion, antisense oligonucleotides specifically inhibited proliferation and downregulated the target protein. This is consistent with a central role for mitogen activated protein kinases in vascular smooth muscle cell proliferation in the porcine model. In addition, the data suggest a possible role for antisense oligonucleotides in the modulation of the arterial injury response.

Analysis of Variance↗

PubMed2001

Differences between adolescents and young adults at presentation to an eating disorders program.

OBJECTIVE: To describe differences between adolescents and adults in clinical presentation of eating disorders. METHODS: Data from the charts of 622 female patients treated for an eating disorder in a division of adolescent medicine between 1980 and 1994 were coded and computerized. General categories included demographic and family factors, weight loss and weight changes, eating-related behaviors, diagnosis and severity, and treatment issues. Differences between the 438 patients who were aged 9-19 years (adolescents) and 184 patients who were aged 20-46 years (adults) were analyzed. RESULTS: Adolescents were more likely than adults (p <.05) to have a diagnosis of "eating disorder not otherwise specified," lower global severity score, greater denial and less desire for help, weight loss > or = 3 lb/month, lower original and maximum weights, and history of fasting and elimination of junk food from their diets. Adults were more likely than adolescents (p <.05) to have >1 year of weight loss, greater total weight loss, history of binge eating and laxative use, history of diuretic and ipecac use, diagnosis of bulimia nervosa, and prior use of psychiatric medications. Adolescents and adults did not differ (p >.05) in parents' occupational level; height, weight, and percent ideal body weight at presentation; original percent ideal body weight; use of diet pills, elimination of meat and use of a low-fat diet; daily calorie intake; prior eating disorder hospitalizations; and hospitalization during the course of treatment. CONCLUSIONS: The findings in this study document and confirm that there are important differences between adolescents and adults that must be taken into account in the evaluation and treatment of patients with eating disorders.

Adolescent↗

PubMed2001

Increases in renal epsilon-(gamma-glutamyl)-lysine crosslinks result from compartment-specific changes in tissue transglutaminase in early experimental diabetic nephropathy: pathologic implications.

Diabetic nephropathy (DN) is characterized by an early, progressive expansion and sclerosis of the glomerular mesangium leading to glomerulosclerosis. This is associated with parallel fibrosis of the renal interstitium. In experimental renal scarring, the protein cross-linking enzyme, tissue transglutaminase (tTg), is up-regulated and externalized causing an increase in its crosslink product, epsilon-(gamma-glutamyl)-lysine, in the extracellular space. This potentially contributes to the extracellular matrix (ECM) accumulation central to tissue fibrosis by increasing deposition and inhibiting breakdown. We investigated if a similar mechanism may contribute to the ECM expansion characteristic of DN using the rat streptozotocin model over 120 days. Whole kidney epsilon-(gamma-glutamyl)-lysine (HPLC analysis) was significantly increased from Day 90 (+337%) and peaked at Day 120 (+650%) (p < 0.05). Immunofluorescence showed this increase to be predominantly extracellular in the peritubular interstitial space, but also in individual glomeruli. Total kidney transglutaminase (Tg) was not elevated. However, using a Tg in situ activity assay, increased Tg was detected in both the extracellular interstitial space and glomeruli by Day 60, with a maximal 53% increase at Day 120 (p < 0.05). Using a specific anti-tTg antibody, immunohistochemistry showed a similar increase in extracellular enzyme in the interstitium and glomeruli. To biochemically characterize glomerular changes, glomeruli were isolated by selective sieving. In line with whole kidney measurement, there was an increase in glomerular epsilon-(gamma-glutamyl) lysine (+361%); however, in the glomeruli this was associated with increases in Tg activity (+228%) and tTg antigen by Western blotting (+215%). Importantly, the ratio of glomerular epsilon-(gamma-glutamyl) lysine to hydroxyproline increased by 2.2-fold. In DN, changes in the kidney result in increased translocation of tTg to the extracellular environment where high Ca(2+) and low GTP levels allow its activation. In the tubulointerstitium this is independent of increased tTg production, but dependent in the glomerulus. This leads to excessive ECM cross-linking, contributing to the renal fibrosis characteristic of progressive DN.

Animals↗

PubMed2001

Clenbuterol in the horse: urinary concentrations determined by ELISA and GC/MS after clinical doses.

Clenbuterol is a beta2 agonist/antagonist bronchodilator marketed as Ventipulmin and is the only member of this group of drugs approved by the US Food and Drug Administration (FDA) for use in horses. Clenbuterol is a class 3 drug in the Association of Racing Commissioners International (ARCI) classification system; therefore, its identification in postrace samples may lead to sanctions. Recently, the sensitivity of postrace testing for clenbuterol has been substantially increased. The objective of this study was to determine the 'detection times' for clenbuterol after administration of an oral clinical dose (0.8 g/kg, b.i.d.) of Ventipulmin syrup. Five horses received oral clenbuterol (0.8 g/kg, b.i.d.) for 10 days, and urine concentrations of clenbuterol were determined by an enhanced enzyme-linked immunoabsorbent assay (ELISA) test and gas chromatography/mass spectrometric (GC/MS) analysis by two different methods for 30 days after administration. Twenty-four hours after the last administration, urine concentrations of apparent clenbuterol, as measured by ELISA, averaged about 500 ng/mL, dropping to about 1 ng/mL by day 5 posttreatment. However, there was a later transient increase in the mean concentrations of apparent clenbuterol in urine, peaking at 7 ng/mL on day 10 postadministration. The urine samples were also analysed using mass spectral quantification of both the trimethylsilyl (TMS) and methane boronic acid (MBA) derivatives of clenbuterol. Analysis using the TMS method showed that, at 24 h after the last administration, the mean concentration of recovered clenbuterol was about 22 ng/mL. Thereafter, clenbuterol concentrations fell below the limit of detection of the TMS-method by day 5 after administration but became transiently detectable again at day 10, with a mean concentration of about 1 ng/mL. Derivatization with MBA offers significant advantages over TMS for the mass spectral detection of clenbuterol, primarily because MBA derivatization yields a high molecular weight base peak of 243 m/z, which is ideal for quantitative purposes. Therefore, mass spectral analyses of selected urine samples, including the transient peak on day 10, were repeated using MBA derivatization, and comparable results were obtained. The results show that clenbuterol was undetectable in horse urine by day 5 after administration. However, an unexpected secondary peak of clenbuterol was observed at day 10 after administration that averaged approximately 1 ng/mL. Because of this secondary peak, the detection time for clenbuterol (0.8 g/kg, b.i.d. x 10 days) is at least 11 days if the threshold for detection is set at 1 ng/mL.

Administration, Oral↗

PubMed2001

Non-reassuring fetal status in the prolonged pregnancy: the impact of fetal weight.

OBJECTIVE: To evaluate the incidence of abnormal fetal findings and Cesarean delivery for non-reassuring fetal status as a function of birth weight in the uncomplicated prolonged pregnancy. METHODS: Seven hundred and ninety-two patients at or beyond 41 weeks' gestation were managed expectantly. Population-specific birth-weight percentiles were calculated. Fetuses were retrospectively categorized as small (birth weight < 10th percentile), average (10th percentile < or = birth weight < or = 90th percentile) or large (birth weight > 90th percentile). The incidences of abnormal antepartum fetal testing results (i.e. oligohydramnios and/or abnormal non-stress testing) and Cesarean delivery for intrapartum non-reassuring fetal status were calculated for these three birth-weight categories. RESULTS: There was a significant inverse relationship between the incidence of abnormal fetal testing and birth-weight category (36%, 14% and 9% for small, average and large fetuses, respectively, P < 0.001). Small fetuses were more likely to require a Cesarean delivery for non-reassuring fetal status during labor than were all other fetuses (12.3% vs. 5.3%, P = 0.024). CONCLUSIONS: The frequency of oligohydramnios and abnormal non-stress testing is inversely related to birth weight in the expectantly managed prolonged pregnancy. In addition, small fetuses born at or beyond 41 weeks' gestation have an increased rate of Cesarean delivery for intrapartum non-reassuring fetal status.

Birth Weight↗

PubMed2001

Employee response to major organizational redesign.

A number of health care organizations are currently undergoing major organizational redesign. Despite these efforts, little is known about how these changes are affecting the employees participating in the redesign process. In response to this, a study was undertaken to determine the perceived impact of organizational redesign on nursing staff at 2 acute care hospitals that were undergoing major organizational change. Data were collected through semi-structured focus group interviews conducted on all 3 shifts (days, evenings, and nights). Findings suggest the early redesign period is highly turbulent and difficult for staff. Nurses expressed concern over changes in roles and responsibilities, disruption in work group relationships, loss of resource availability, reduction in quality of care, and alterations in physical and psychological state.

Attitude of Health Personnel↗

PubMed2001

Development of a self-directed learning readiness scale for nursing education.

Self-directed learning is a method of instruction used increasingly in adult education. A scale was developed in response to a need for a valid and reliable instrument to measure self-directed learning readiness. Such a scale will allow nurse educators to diagnose students' attitudes, abilities and personality characteristics, necessary for self-directed learning. This study was undertaken in two stages. In the first, the Delphi technique utilizing a panel of 11 nurse educator experts was used to assess the content and construct validity of a number of items perceived to reflect self-directed learning readiness. Each panel member was asked to independently rate the relevance of each item on a Likert scale. The second stage involved the administration of the questionnaire to a convenience sample of 201 undergraduate nursing students. The questionnaire was analysed using principal components factor analysis with varimax rotation, Chronbach's coefficient alpha, and item-to-total correlations to measure the scale's construct validity, internal consistency (reliability), and unidimensionality, respectively.The resulting self-directed learning readiness scale appears homogeneous and valid. The scale will assist nurse educators in the diagnosis of student learning needs, in order for the educator to implement teaching strategies that will best suit the students. Furthermore the development of this scale will provide valuable data for curriculum development.

Attitude of Health Personnel↗

PubMed2001

Monitoring a clinical trial conducted under the Food and Drug Administration regulations allowing a waiver of prospective informed consent: the diaspirin cross-linked hemoglobin traumatic hemorrhagic shock efficacy trial.

In 1996, the US Food and Drug Administration (FDA) enacted Rule 21 CFR section 50.24, which allows a narrow exception to the requirement for prospective informed consent from human research subjects in clinical trials investigating potentially beneficial therapies for acute, life-threatening conditions. The first clinical trial to be conducted under this rule was sponsored by Baxter Healthcare Corporation and approved by the FDA on November 21, 1996. This large, multicenter, randomized clinical trial was designed to compare the addition of diaspirin cross-linked hemoglobin (DCLHb) with standard care in the initial resuscitation of adults experiencing severe, uncompensated, traumatic hemorrhagic shock. Before the first planned interim analysis of the data, review of fatal adverse events revealed an imbalance in mortality between the 2 treatment groups. The Data Monitoring Committee (DMC) recommended suspension of patient enrollment 24 days later. Additional data collection and analyses confirmed the excess number of deaths in patients treated with DCLHb but failed to reveal the cause of these deaths. The trial was formally terminated after only 112 of the planned 850 patients had been enrolled. We review the events leading up to and the rationale behind the DMC recommendations for suspension of patient enrollment and trial termination. Although the DCLHb trial was unsuccessful in achieving its goals, the monitoring process worked well. Emergency research was facilitated by DMC oversight, and the interests of research subjects were protected by the actions of the DMC.

Aspirin↗

PubMed2001

Rocuronium: high risk for anaphylaxis?

Patients suspected of anaphylaxis during anaesthesia have been referred to the senior author's clinic since 1974 for investigation. Since release of rocuronium on to the worldwide market, concern has been expressed about its propensity to cause anaphylaxis. We identified 24 patients who met clinical and laboratory (intradermal, mast cell tryptase and morphine radioimmunoassay) criteria for anaphylaxis to rocuronium. The incidence of rocuronium allergy in New South Wales, Australia has risen in parallel with sales, while there has been an associated fall in reactions to other neuromuscular blocking drugs. Data from intradermal testing suggested that rocuronium is intermediate in its propensity to cause allergy in known relaxant reactors compared with low-risk agents (e.g. pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium, succinylcholine).

Anaphylaxis↗

PubMed2001

Surfing with spirochaetes: an ongoing syphilis outbreak in Brighton.

BACKGROUND/OBJECTIVES: There has been a recent shift in the epidemiology of early syphilis in the developed world with sporadic outbreaks on a historic low level of background disease. Here we describe an ongoing outbreak of syphilis in Brighton. METHODS: Data collected on all patients with a diagnosis of early infectious syphilis at Brighton GUM clinic. RESULTS: 30 cases of early syphilis were diagnosed over a 25 month period beginning in July 1999. 28 were homosexual or bisexual men, giving a rate of 134 cases per 100 000 homosexual men. The cases reported a median of three sexual contacts (range 1-50) in the preceding 6 months and 77% had concurrent regular and casual partners. 83% of contacts were casual and untraceable. Over one third (11) of these cases reported oral sex as their only risk factor for syphilis acquisition and were unaware of this transmission route. 70% were diagnosed with primary or secondary infection, the remaining 30% being asymptomatic with early latent infection. Eight of the cases were HIV positive and a further eight remain untested for HIV. At least one concurrent STI was found in 40% of cases. Regular outbreak control meetings, involving relevant healthcare professionals, were held to plan appropriate interventions. CONCLUSION: The high rate of casual and untraceable contacts in this outbreak suggest that alternative control measures are necessary, including on-site testing and further health education regarding the oral transmission of syphilis. Continued vigilance for syphilis is essential, especially in those patients who are HIV positive.

Adult↗