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Biomedical subjects

J Baker

Publications and source records attributed to J Baker.

At least 73 records · Page 4Linked to original sources

Training in hypoxia: modulation of metabolic and cardiovascular risk factors in men.

PURPOSE: This study was designed to determine changes in metabolic and cardiovascular risk factors following normobaric hypoxic exercise training in healthy men. METHODS: Following a randomized baseline maximal exercise test in hypoxia and/or normoxia, 34 physically active subjects were randomly assigned to either a normoxic (N = 14) or a hypoxic (N = 18) training group. Training involved 4 wk of cycling exercise inspiring either a normobaric normoxic (F(IO2) = approximately 20.9%) or a normobaric hypoxic (F(IO2) = approximately 16.0%) gas, respectively, in a double-blind manner. Cycling exercise was performed three times per week for 20-30 min at 70-85% of maximum heart rate determined either in normoxia or hypoxia. Resting plasma concentrations of blood lipids, lipoproteins, total homocysteine, and auscultatory arterial blood pressure responses at rest and in response to submaximal and maximal exercise were measured before and 4 d after physical training. RESULTS: Total power output during the training period was identical in both normoxic and hypoxic groups. Lean body mass increased by 1.4 +/- 1.5 kg following hypoxic training only (P < 0.001). While dietary composition and nutrient intake did not change during the study, both normoxic and hypoxic training decreased resting plasma concentrations of nonesterified fatty acids, total cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) (P < 0.05 - < 0.001). Apolipoproteins AI and B decreased following normoxic training only (P < or = 0.001). Plasma concentrations of resting total homocysteine decreased by 11% following hypoxic training (P < or = 0.05) and increased by 10% (P < 0.05) following normoxic training. These changes were independent of changes in serum vitamin B12 and red cell folate which remained stable throughout. A decreased lactate concentration during submaximal exercise was observed in response to both normoxic and hypoxic training. Hypoxic training decreased maximal systolic blood pressure by 10 +/- 9 mm Hg (P < 0.001) and the rate pressure product by 14 +/- 23 mm Hg x beats x min(-1)/100 (P < or = 0.001) and increased maximal oxygen uptake by 0.47 +/- 0.77 L x min(-1) (P < 0.05). CONCLUSION: Normoxic and hypoxic training was associated with significant improvements in selected risk factors and exercise capacity. The stimulus of intermittent normobaric hypoxia invoked an additive cardioprotective effect which may have important clinical implications.

Adult↗

A cardiac evoked response algorithm providing threshold tracking: a North American multicenter study. Clinical Investigators of the Microny-Regency Clinical Evaluation Study.

The purpose of this study was to evaluate a pacing system using the recognition of cardiac evoked response for the automatic adjustment of pacing output. Patients were prospectively followed after primary implantation of VVIR pacemakers using AutoCapture (St. Jude Medical CRMD). Sensing and pacing thresholds, polarization signal, evoked response, and AutoCapture performance were evaluated with serial visits and 24-hour Holter monitoring. Three hundred ninety-eight patients (mean age 71 +/- 15 years) were followed for an average duration of 1 year (3 days-1.75 years) with the algorithm functional in > 90% of patients. Backup pacing in the event of exit block was confirmed in all patients. Pacing thresholds remained stable at 0.89 +/- 0.34 V with a pulse width of 0.31 ms (with chronic output autoset at 0.3 V above the actual threshold). Evoked response exhibited a small but statistically significant increase with time (8.92 mV at implant, 9.60 mV at 12 months), however, this finding did not result in any change in AutoCapture function during our follow-up period. The polarization signal remained stable with minimal variation (1.12 mV at implant, 1.18 at 12 months). No clinical adverse events were observed using the AutoCapture algorithm. In this initial experience with the AutoCapture algorithm the evoked response and polarization measurements remained adequate, allowing the system to function in the majority of patients with safe, low output pacing. High energy backup pacing provided an added safety feature over fixed output devices in cases of unexpected threshold rises. Longer follow-up is required for continued long-term validation of the algorithm.

Aged↗

Study of IgM aggregation in serum of patients with macroglobulinemia.

The effect of solvent conditions on the aggregation of IgM in serum specimens from patients with macroglobulinemia was studied by a turbidimetric procedure. Aggregation of IgM varied considerably among the samples and was affected by a number of experimental parameters. In general, IgM aggregation was more pronounced under acidic conditions and in solvents with low ionic strength. The presence of water-miscible organic solvents also promoted aggregation. Based on these studies, it was concluded that the major force involved in the formation of immunoglobulin aggregates in the serum of patients with macroglobulinemia was electrostatic, rather than hydrophobic, interactions. A number of additives known to prevent protein aggregation were evaluated for their effectiveness in inhibiting IgM aggregation. The only additives that were shown to inhibit or reduce IgM aggregation were charged molecules, such as arginine, sodium chloride, ethylenediamintetraacetic acid and quaternary ammonium beta-cyclodextrin. Some of these charged additives were also effective in dissociating the IgM aggregates once they were formed, even in the presence of detergent.

Anions↗

Prodrugs of CL316243: a selective beta3-adrenergic receptor agonist for treating obesity and diabetes.

CL316243 is a highly selective and potent beta3-adrenergic receptor agonist, and has been shown in rodent models to be an effective agent for treating obesity and Type II diabetes. To improve the oral absorption and pharmacokinetic profiles of CL316243, a number of prodrugs have been synthesized and evaluated. Several ester-type prodrugs show significant improvements in oral bioavailability in both rodent and primate models.

Adrenergic beta-Agonists↗

Development and preliminary clinical tests of an impedance sensing VDD recording pacemaker for diagnosis and research.

Episodes of serious but infrequently occurring cardiac arrhythmias can be difficult to detect and analyse, even with modern Holter monitoring. A previous diagnostic pacemaker developed by this group provided VVI pacing therapy and recorded intracardiac ECG signals but had no atrial sensing or impedance measuring capability. A new external diagnostic pacemaker system is described that has been developed to assist in diagnosing intermittent arrhythmias by selectively recording intracardiac signals. Unlike other ambulatory monitors, in addition to recording ECG, the device combines VDD pacing therapy with the capability of monitoring and recording intracardiac impedance and pressure waveforms through a temporary intracardiac lead. A PCMCIA memory card allows storage of 48 arrhythmic events of 21 seconds each. Twelve seconds of waveform are retained before the event occurs and nine seconds after. Data retrieval and processing is performed with a PC which reconstructs each waveform for display. The ECG provides data on cardiac rhythm while cardiac function is inferred from the haemodynamic signals. During simulated trials, 14 event types were presented to the system. All events were successfully detected and recorded. During in vivo clinical tests 83 waveform recordings were made. Impedance fluctuations with typical peak-to-peak values of 64 ohms were successfully recorded.

Arrhythmias, Cardiac↗

The effect of one injection of Depo-Provera on the human vaginal epithelium and cervical ectopy.

Two studies in rhesus monkeys have shown that progesterone implants, Depo-Provera and Norplant, were associated with vaginal thinning. Progesterone implants have also been associated with an increased risk of simian immunodeficiency virus (SIV) acquisition. This study in 16 women was done to assess vaginal epithelial thickness and number of cell layers from biopsies taken in the untreated follicular and luteal phases, and at 1 month and 3 months after administration of Depo-Provera. There was no significant change over time in either parameter from biopsies obtained in the luteal phase compared with those at either time after Depo-Provera administration. There was also no change in the mean number of Langerhans cells in vaginal wall specimens and no change in cervical ectopy. It appears that women do not respond to exogenous progestins with the dramatic vaginal thinning seen in rhesus monkeys.

Adult↗

Expression of proopiomelanocortin (POMC)-derived melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) peptides in skin of basal cell carcinoma patients.

We proposed that local expression and production of proopiomelanocortin (POMC) peptides may play a role in human skin physiology and pathology, including the development and progression of skin cancers. Reverse transcription polymerase chain reaction (RT-PCR) and Northern blotting hybridization techniques were used to study gene expression. Reversed-phase (RP) high-pressure liquid chromatography (HPLC) separation with subsequent radioimmunoassays were used to identify alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) peptides. Immunocytochemistry (IHC) was used to localize ACTH, alpha-MSH, and beta-MSH antigens in skin. RT-PCR, RP-HPLC, and IHC analyses documented the expression of POMC mRNA and production of ACTH and alpha-MSH peptides in lesional and perilesional skin of basal cell carcinoma (BCC) patients and in cultured keratinocytes, which was accompanied by the expression of the MC1-R gene encoding the receptor activated by MSH and ACTH. Thirty specimens were analyzed by IHC. Immunoreactive alpha-MSH, beta-MSH, and ACTH were detected, in 21 of 21, in 11 of 20, and in 6 of 8 of lesional skin, and in 6 of 6, in 5 of 7, and in 6 of 8 perilesional skin specimens analyzed, respectively. Antigen distribution was heterogenous and present in BCC, epidermis, hair follicles, dermal mononuclear cells, and extracellular matrix. We conclude that messenger RNA for POMC, MC1-R, and the peptides MSH and ACTH are produced in skin of BCC patients. Because keratinocytes are a target for MSH and ACTH bioregulation, the production of these peptides is stimulated by UVB, and the peptides can act as immunosupressors, we suggest that MSH and ACTH may facilitate development of BCC.

Adrenocorticotropic Hormone↗

A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.

BACKGROUND: Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few. OBJECTIVE: We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma. METHODS: Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards. RESULTS: Fluticasone propionate treatment resulted in significantly (P </=.034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use (P </=.010) and asthma symptoms (P </=.027). Both low-dose (88 micrograms twice daily) and medium-dose (220 micrograms twice daily) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate (P =. 006). Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications. CONCLUSION: Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile.

Adolescent↗

A report on alterations to the speaking and singing voices of four women following hormonal therapy with virilizing agents.

Four women aged between 27 and 58 years sought otolaryngological examination due to significant alterations to their voices, the primary concerns being hoarseness in vocal quality, lowering of habitual pitch, difficulty projecting their speaking voices, and loss of control over their singing voices. Otolaryngological examination with a mirror or flexible laryngoscope revealed no apparent abnormality of vocal fold structure or function, and the women were referred for speech pathology with diagnoses of functional dysphonia. Objective acoustic measures using the Kay Visipitch indicated significant lowering of the mean fundamental frequency for each woman, and perceptual analysis of the patients' voices during quiet speaking, projected voice use, and comprehensive singing activities revealed a constellation of features typically noted in the pubescent male. The original diagnoses of a functional dysphonia were queried, prompting further exploration of each woman's medical history, revealing in each case onset of vocal symptoms shortly after commencing treatment for conditions with medications containing virilizing agents (eg, Danocrine (danazol), Deca-Durabolin (nandrolene decanoate), and testosterone). Although some of the vocal symptoms decreased in severity with the influences from 6 months voice therapy and after withdrawal from the drugs, a number of symptoms remained permanent, suggesting each subject had suffered significant alterations in vocal physiology, including muscle tissue changes, muscle coordination dysfunction, and propioceptive dysfunction. This retrospective study is presented in order to illustrate that it was both the projected speaking voice and the singing voice that proved so highly sensitive to the virilization effects. The implications for future prospective research studies and responsible clinical practice are discussed.

Adult↗

The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study.

It has been postulated that hypertonic saline (HS) might impair the antimicrobial effects of defensins within the airways. Alternative non-ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance (BMC) in patients with cystic fibrosis (CF). This study reports the effect of inhalation of another osmotic agent, dry powder Mannitol (300 mg), compared with its control (empty capsules plus matched voluntary cough) and a 6% solution of HS on BMC in 12 patients with cystic fibrosis (CF). Mucus clearance was measured using a radioaerosol/gamma camera technique. Post-intervention clearance was measured for 60 min, followed by cough clearance for 30 min. Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls. However during the post-intervention measurement there was a significant improvement in BMC for both the mannitol (8.7+/-3.3% versus 2.8+/-0.7%) and HS (10.0+/-2.3% versus 3.5+/-0.8%). There was also a significant improvement in cough clearance with the Mannitol (9.7+/-2.4%) compared with its control (2.5+/-0.8%). Despite premedication with a bronchodilator, a small fall in forced expiratory volume in one second (FEV1) was seen immediately after administration of both the mannitol (7.3+/-2.5%) and HS (5.8+/-1.2%). Values of FEV1 returned to baseline by the end of the study. Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients. Further studies are required to establish the optimal dose and the long-term effectiveness of mannitol.

Administration, Inhalation↗

Evidence-based guidelines for the management of genital chlamydial infection in general practice. (Leicestershire Chlamydia Guidelines Group).

BACKGROUND: Valid clinical guidelines can be effective in improving patient care. Genital Chlamydia trachomatis infection is the commonest curable sexually transmitted disease (STD) in England and Wales and is an important cause of pelvic inflammatory disease (PID), tubal infertility and ectopic pregnancy. No published guidelines exist on managing genital chlamydial infection in British general practice. OBJECTIVE: We aimed to develop valid guidelines for the management of genital chlamydial infection for use in British general practice. METHODS: A district-wide postal questionnaire survey was used to document current clinical practice. A critical review of the evidence concerning the management of genital chlamydial infection as it relates to British general practice was performed. The information gained from the critical review and survey was used to develop evidence-based guidelines within a multidisciplinary guideline recommendation group. RESULTS: The guidelines covered the diagnosis, investigation, drug treatment and referral of adult male and female patients with genital chlamydial infection in general practice. CONCLUSION: Valid guidelines for the management of genital chlamydial infection have been developed for use in British general practice. Appropriate dissemination and implementation of the guidelines should lead to earlier detection and treatment of men and women with chlamydial infection and thereby reduce the incidence of PID, tubal infertility and ectopic pregnancy in women.

Adult↗

Campylobacter species in cats and dogs in South Australia.

BACKGROUND: Campylobacter enteritis was the most frequently notified infectious disease in Australia in 1996 and Campylobacter species have been associated with extra-intestinal infections such as purulent arthritis and Guillian-Barré syndrome. Dogs and cats are known to carry campylobacteria and contact with household pets have been implicated as possible sources of human infection. OBJECTIVE: To provide information on the species of campylobacter carried by cats and dogs in South Australia. METHODS: Faecal samples were collected from stray and owned cats and dogs and feral cats. Campylobacter-like organisms were isolated using selective media and filtration methods. They were then characterised by biochemical tests, antibiotic resistance and growth patterns under various conditions. Husbandry factors that could have influenced the carriage rates were examined both as single variables and in a multivariate logistic regression. RESULTS: Campylobacter upsaliensis and C jejuni were found in 11% and 4% of cats, respectively, whereas 34% dogs carried C upsaliensis, 7% C jejuni and 2% C coli. Intensive housing and open drains were found to be significant risk factors and increased the carriage rate by 2 and 2.6 times, respectively. CONCLUSION: Dogs and cats are a potential reservoir for human enteric infections with campylobacters.

Animals↗

Comparison of 1% ropivacaine and a mixture of 2% lignocaine and 0.5% bupivacaine for peribulbar anaesthesia in cataract surgery.

The purpose of the study was to compare 1% ropivacaine and hyaluronidase 75 units/ml with a 1:1 mixture of 2% lignocaine and 0.5% bupivacaine and hyaluronidase 75 units/ml for peribulbar anaesthesia in cataract surgery. We conducted a double-blind randomized trial involving 100 patients. Group 1 received a peribulbar injection of 8 ml of 1% ropivacaine and hyaluronidase 75 units/ml. Group 2 received a peribulbar injection of 8 ml of a 1:1 mixture of 2% lignocaine and 0.5% bupivacaine and hyaluronidase 75 units/ml. Parameters measured were ocular and eyelid movement scores, time suitable for surgery, need for supplementary injections, verbal pain score and complications. No statistical differences were found between the two groups regarding any of the study parameters. Both groups had excellent surgical analgesia and akinesia. We conclude that 1% ropivacaine is a suitable agent for single injection peribulbar anaesthesia for cataract surgery.

Aged↗

Herpesvirus 8 inclusions in primary effusion lymphoma: report of a unique case with T-cell phenotype.

We describe a case of primary effusion lymphoma with T-cell phenotype, mixed genotype, and intranuclear herpesvirus inclusions visible with the light microscope. Cells were studied by immunohistochemical analysis, in situ hybridization, immunoglobulin and T-cell receptor gene rearrangement, and polymerase chain reaction. Primary effusion lymphoma cells with T-cell phenotype revealed herpesvirus 8 inclusions predominantly seen in apoptotic cells, suggesting that productive viral infection is associated with cell death. Clinical features were typical of primary effusion lymphoma. Cytologic, molecular genetic, and phenotypic features demonstrated a unique variant of primary effusion lymphoma.

Adult↗