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Biomedical subjects

M Browne

Publications and source records attributed to M Browne.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of residency program merger on undergraduate medical student education in obstetrics and gynecology.

OBJECTIVE: To evaluate the effect of residency program merger on third-year medical student clerkships using student evaluations of their experiences and standardized subject examination scores. METHODS: End-of-clerkship ratings from student evaluations and National Board of Medical Examiners standardized subject examination scores in obstetrics and gynecology were used from clerkship sites where three separate military residency programs in obstetrics and gynecology recently merged into two new programs. Mean student evaluation scores and subject examination scores for the year preceding and the year following the merger were compared. RESULTS: The mean differences in medical student evaluation scores before and after merger of the residency programs were 0.1 (Mann-Whitney rank sum, P = .1), -0.1 (Mann-Whitney rank sum, P = .8), and 0.2 (Mann-Whitney rank sum, P = .3). The mean differences for subject examination scores before and after merger of the residency programs were -3.5 (95% confidence interval [CI] -33.2, 26.2; paired t test), -30.1 (95% CI -58.9, -1.4; paired t test), and -35.3 (95% CI -74.8, 4.3; paired t test). CONCLUSION: Merger of residency programs in obstetrics and gynecology does not appear to have a deleterious effect on medical students' satisfaction with the clerkship or their performance on standardized subject examinations at our institution.

Clinical Clerkship↗
PubMed1999

Reliability theory for load bearing biomedical implants.

At present, load-bearing implants are designed on a deterministic basis in which the structural strength and applied loading are given fixed values, and global safety factors are applied to (i) cover any uncertainties in these quantities, and (ii) to design against failure of the component. This approach will become increasingly inappropriate as younger and more active patient demands become more exacting and as devices become more complex. The present work describes a preliminary investigation in which a scientific and probabilistic technique is applied to assess the structural integrity of the knee tibial tray. It is envisaged that by applying such a technique to other load bearing biomedical devices, reliability theory may aid in future lifing procedures and materials/design optimisation.

Models, Theoretical↗
PubMed1999

Vascular actions of 17beta-oestradiol in rat aorta and mesenteric artery.

1. It has been proposed that the cardiovascular protective actions of 17beta-oestradiol may involve calcium antagonistic actions. We have examined the effects of 17beta-oestradiol on contractions to noradrenaline and KCl in male rat small mesenteric artery and aorta. 2. In rat mesenteric artery, 17beta-oestradiol (10 microM) significantly reduced the maximum contraction to noradrenaline (67.7 +/- 5.8% of control) and KCl (38.8 +/- 3.1% of control) without affecting potency. 3. In rat aorta, 17beta-oestradiol (10 microM) also significantly reduced contractions to noradrenaline (77.5 +/- 4.8% of control), and the effects were mimicked by droloxifene (10 microM). The effect of oestrogen was not prevented by the protein synthesis inhibitor cycloheximide (10 microM). In experiments carried out in calcium-free solution in which calcium stores were depleted, 17beta-oestradiol (10 microM) significantly reduced the contraction to calcium restoration in rat aorta. 4. In aorta from female rats, 17beta-oestradiol (10 microM) significantly reduced contractions to noradrenaline (73.6 +/- 10.8% of control), but this effect of oestrogen was not prevented by cycloheximide (10 microM). 5. In summary, 17beta-oestradiol diminishes the maximum contractile response to noradrenaline in both rat small mesenteric artery and aorta, an effect which at least in the aorta is mimicked by the oestrogen receptor antagonist/partial agonist droloxifene, and may be due to restriction of calcium entry by a nongenomic action.

Animals↗
PubMed1999

Bone marrow and recombinant human bone morphogenetic protein-2 in osseous repair.

Bone marrow stem cells and recombinant human bone morphogenetic protein-2 each has the capacity to repair osseous defects. Recombinant human bone morphogenetic proteins require the presence of progenitor cells to function. It is hypothesized that a composite graft of recombinant human bone morphogenetic protein-2 and marrow would be synergistic and could result in superior grafting to autogenous bone graft. Syngeneic Lewis rats with a 5-mm critical sized femoral defect were grafted with recombinant human bone morphogenetic protein-2 and marrow, recombinant human bone morphogenetic protein-2, marrow, syngeneic cancellous bone graft, or carrier alone (control). Serial radiographs (3, 6, 9, 12 weeks) and torque testing (12 weeks) were performed. Bone formation and union were determined. The recombinant human bone morphogenetic protein-2 and marrow composite grafts achieved 100% union at 6 weeks. Recombinant human bone morphogenetic protein alone achieved 80% union by week 12. Both groups yielded a higher union rate and superior mechanical properties than did either syngeneic bone graft (38%) or marrow (47%) alone. The superior performance of recombinant human bone morphogenetic protein-2 combined with bone marrow in comparison with each component alone strongly supports a biologic synergism. This experimentation shows the clinical importance of establishing operative site proximity for the osteoinductive factors and responding progenitor cells.

Animals↗
PubMed1998

Alkaline phosphatase activity measurement in the UK by AMP-buffered methods: an appraisal of current practice.

Most UK clinical laboratories use alkaline phosphatase (ALP) methods similar to that proposed by the International Federation of Clinical Chemistry (IFCC), based on the use of 2-amino-2-methyl-1-propanol (AMP) buffer. We present evidence of significant differences in results produced by apparently similar commercial ALP methods using an AMP buffer. We compared Bayer DAX, Dade Dimension and Boehringer Mannheim Hitachi 717 methods. Boehringer and Dade results were higher than Bayer results (Bland and Altman analysis, log transformed data): Boehringer (+23.0%, limits of agreement 1.16-1.31 times Bayer); Dade (+21.9%, limits of agreement 1.13-1.32 times Bayer). Biases were predominantly due to differences in reagents rather than analyser characteristics. Compared to a reagent system prepared exactly as described by the IFCC, Bayer was sub-optimal and Dade and Boehringer methods produced results higher than the IFCC method. Reference ranges and results on patients' samples by the various methods showed large differences but no clinically significant difference was observed in external quality assessment schemes either between Bayer and Boehringer or against method means. Apparently similar methods produce different results in patients' sera: external quality assessment schemes are not useful in highlighting these differences.

Alkaline Phosphatase↗
PubMed1997

Porphyria cutanea tarda and hematologic malignancy--a report of 4 cases.

Porphyria cutanea tarda has been reported in association with a variety of myeloproliferative and lymphoproliferative disorders, suggesting a possible association between these conditions. We describe four patients presenting within a 12 month period with sporadic porphyria cutanea tarda shortly following the diagnosis of hematologic malignancy. A review of the literature and evidence supportive of a causal association are presented.

Aged↗
PubMed1996

Quantitative EEG in the prediction of antidepressant response to imipramine.

The purpose of this study was to examine the utility of quantitative electroencephalography (QEEG) in the prediction of response to imipramine in depressed patients. Forty patients with a diagnosis of unipolar depression were subjected to a placebo washout and were assessed at pre-drug, 3 h after their first dose of imipramine, and again 2 weeks into treatment. Following 4 weeks of open imipramine treatment, patients were separated into responder (R) and non-responder (NR) groups. Statistical analysis of the 29 patients who completed the study focused on group comparisons of power spectral estimates in four frequency bands from multi-channel recordings. Results showed that theta power differentiated R and NR groups prior to treatment, in response to an acute test dose, as well as after 2 weeks of active drug treatment. Results based on this exploratory study suggest that QEEG may be a useful early predictor of response to imipramine.

Adult↗
PubMed1996

Phase II study of 5-fluoruracil leucovorin and azidothymidine in patients with metastatic colorectal cancer.

The primary objective of this study was to determine the response rate of patients with metastatic colorectal cancer to combined therapy with 5-fluorouracil (5-FU), leucovorin, and intravenous azidothymidine (AZT), a thymidine nucleoside analog. By itself, AZT has limited antineoplastic efficacy. However, experimental studies indicate that 5-FU enhances the antitumor activity of AZT by inhibiting synthesis of normal thymidine nucleotides with which AZT competes for incorporation into nucleic acids. A phase I study defined the maximum tolerated dose of AZT as 7 g/m2 with hypotension during the infusion being the dose-limiting toxicity. A phase II study was performed with oral leucovorin (100 mg p.o. hourly for 4 h prior to 5-FU and 4 h and 8 h after 5-FU), bolus 5-FU (400 mg/m2) followed 1 h later by a 2-h infusion of AZT (7 g/m2). Treatment was given weekly for 4 weeks followed by a 1-week break, which constituted a cycle of therapy. Responses were evaluated after every two cycles. Patients continued on therapy as long as they tolerated treatment and did not have progressive disease. Of 15 evaluable patients who had received no chemotherapy there was 1 complete response and 4 partial responses (a 33% response rate), whereas only 1 of 6 patients who had received prior adjuvant chemotherapy had a partial response (17%). An additional 10 patients had stable disease lasting 2-14 months. Therapy was well tolerated with the only one instance each of grade 3 nausea and vomiting, diarrhea, anemia, and hypotension. Approximately 50% of treatments were accompanied by mild hypotension, which was easily corrected by increasing the rate of normal saline infusion. There was no difficulty administering this regimen in the outpatient setting. While the overall response rate (29%) is comparable to that seen with combinations of 5-FU and leucovorin alone, in most reported series a considerably higher dose of 5-FU was utilized than in this study. Since patients in the present study experienced relatively little 5-FU toxicity, increasing the dose of 5-FU in this regimen would appear to be feasible and might result in a higher response rate.

Adenocarcinoma↗
PubMed1996

Use of bone morphogenetic protein-2 in the rabbit ulnar nonunion model.

The ability of the osteoinductive protein and recombinant human bone morphogenetic protein-2, combined with polylactic glycolic acid porous microspheres and autologous blood clot to heal a large segmental defect was tested in a rabbit diaphyseal defect model. Two centimeter nonuniting defects were surgically created in the bilateral ulnae of 50 male New Zealand white rabbits. Each defect was then implanted with a pastelike polylactic glycolic acid/blood clot combination that was mixed with 5 different concentrations of recombinant human bone morphogenetic protein-2. The forearms were radiographically assessed on a biweekly schedule for 8 weeks. At 8 weeks, all animals were sacrificed and forearms radiographed. Radiographs were then scored by 3 independent observers for bone formation and union rates. United limbs were tested in torsion for mechanical strength using a Burstein torsion tester. All nonunited limbs were analyzed histologically as were 2 united limbs from each dosage group. Radiographic evaluation revealed that there was a dose dependent response in healing of the ulnar defect with a higher bone formation rate in the 2 higher dose limbs than in the lower dose limbs. Union was achieved in 100% of the highest dose limbs, whereas only 50% of the lowest dose limbs achieved bony union. No defects implanted with carrier alone achieved union. Biomechanical studies revealed significantly stiffer bone than age matched controls. Histologic analysis demonstrated normal bone formation with abundant normal appearing osteoid. These dose response data further support the role of recombinant human bone morphogenetic protein-2 as a potent morphogen in bone regeneration.

Animals↗
PubMed1996

Characterization of the helicase and ATPase activity of human papillomavirus type 6b E1 protein.

Human papillomavirus type 6b (HPV-6b) is one of the most common causes of human genital warts, an important sexually transmitted disease. Discovery of antiviral therapies for this condition has been hampered by the inability to propagate the virus using standard tissue culture techniques and through difficulties in expressing sufficient recombinant viral proteins in vitro. Replication of papillomavirus DNA requires two viral proteins, E1 and E2. In an effort to establish assays to discover compounds active against this virus, we have co-expressed HPV-6b E1 and E2 proteins in insect cells. We demonstrate that the two proteins form a heteromeric complex which can be purified by sequence-specific DNA affinity chromatography. We also demonstrate that the complex has both E1-associated ATPase and ATP-dependent DNA helicase activity and report further characterization of these functions.

Adenosine Triphosphatases↗
PubMed1996

Multipurpose high sensitivity luminescence analyzer (LUANA): use in gel electrophoresis.

Many applications in molecular biology require the rapid and high-sensitivity detection of biological macromolecules. Here we describe a luminescence analyzer (LUANA), featuring xenon lamp-based illumination and a cooled CCD camera as detector. Luminescent samples (gels, membranes or microplates) are placed in a light-tight chamber, and computer software is used to control the camera and to display and analyze the images. LUANA can be used with a broad spectrum of excitation and emission wavelengths (200-1000 nm), allowing a choice of many fluorescent dyes and facilitating multicolor imaging. We show that LUANA is readily applicable to gel electrophoresis and highly sensitive; on gels we could detect < 100 fg of Cy5TM-labeled protein and 0.1 ng of plasmid DNA labeled with a fluorescent intercalator. We observed a linear response for sample concentrations differing by two orders of magnitude using a single acquisition time. This range could be further extended by using different acquisition times. We have also used LUANA in two-color imaging of DNA and for screening of antigen-antibody and peptide-protein complexes by gel bandshift.

Cloning, Molecular↗
PubMed1994

Surface modification of titanium alloy implants.

Hip replacement stems manufactured from Ti6Al4V titanium alloy were surface treated in one of four ways and tested for dissolution resistance in bovine serum. Those stems treated thermally were found to have significantly lower metal ion release compared with those receiving standard commercial treatments. The improved dissolution behaviour is associated with a change in the surface oxide structure from mixed titanium oxides to a more stable rutile structure.

Adsorption↗
PubMed1994

Alprazolam and amitriptyline in the treatment of moderate depression.

Forty-three out-patients with depression of a moderate degree were enrolled in a randomized, double-blind parallel group study comparing amitriptyline and alprazolam for 6 weeks of treatment. Patients were evaluated at the end of placebo washout and at Weeks 1, 2, 3 and 6 of drug therapy using the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI) and Clinical Global Impression (CGI). Drug dosage was determined in a fixed-flexible design resulting in mean final doses of alprazolam 3.2 mg/day and of amitriptyline 115 mg/day. Although both drug groups improved there were statistically significant differences in favour of amitriptyline at the end of the study on the HAM-D, BDI and HAM-A scales. Patients on amitriptyline reported more side effects overall than patients taking alprazolam with significantly more reports of dry mouth in the amitriptyline group.

Adolescent↗
PubMed1993

Combined modality therapy for stage IIIA non-small cell carcinoma of the lung.

53 patients with stage IIIA non-small cell carcinoma of the lung (NSCCL) were treated with multimodality therapy consisting of induction radiotherapy (55.8 Gy) and two cycles of concurrent chemotherapy with cisplatin, 25 mg/m2 for 4 days by continuous infusion and bolus etoposide, 100 mg/m2 on days 2 and 4 of each cycle followed by surgery and adjuvant chemotherapy. Of 53 evaluable patients, 47 achieved clinical responses (9 complete response, 38 partial response) after induction therapy for a response rate of 89%. 47 patients were resectable after induction therapy, but 8 patients refused surgery and 6 patients were not eligible for surgery based on poor pulmonary function (medical contraindications). 33 patients underwent thoracotomy and in 6 patients, resection was technically unfeasible. Thus complete surgical resection was accomplished in 27 patients. After all therapy, 28 patients achieved a complete response (53%) and 19 patients a partial response (36%). Toxicities were mild. At a maximum of 75 months (median, 28 months) of follow-up, the median survival of the entire group is 24 months. The median survival of resected patients has not been reached; their 6-year survival rate is 55%. Unresected patients survived for a median of 11 months. This multimodality regimen is well-tolerated, induces a high response and resectability rate and prolongs survival in resected patients.

Adult↗
PubMed1993

Ritanserin, imipramine, and placebo in the treatment of dysthymic disorder.

Fifty outpatients with dysthymic disorder (DSM-III) were divided by double-blind randomized assignment into three groups given ritanserin, imipramine, and placebo, respectively. The trial was of 7 weeks' duration; by week 6, imipramine was clearly superior to placebo, whereas by week 7, both drugs caused significantly more improvement than the placebo. Although imipramine had slightly greater efficacy than ritanserin, it also had significantly more side effects. This was particularly evident in the higher dropout rate with imipramine. The efficacy and side effect profile of ritanserin makes it well tolerated and acceptable with dysthymic patients who, although they do not respond as quickly as patients with major depressive disorder, do show significant improvement, given sufficient time.

Adult↗
PubMed1992

Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex.

The pharmacokinetics of stavudine (d4T; 2',3'-didehydro-3'-deoxythymidine) were studied in patients with AIDS-related complex or AIDS enrolled in a dose-ranging phase I/II study. Twenty-two patients were studied after the first oral dose of 0.67, 1.33, 2.67, or 4 mg/kg of body weight; 17 of them underwent an additional steady-state pharmacokinetic evaluation after thrice-daily dosing of the above doses. Stavudine absorption was rapid, with mean peak concentrations of 1.2-4.2 mg/L over the four dose levels studied. From 34% to 41% of an oral dose was excreted as unchanged drug in the urine. The mean values for plasma elimination half-life ranged from 1 to 1.6 h. The absolute bioavailability of a 4 mg/kg oral dose exceeded 80%. There was no change in pharmacokinetic parameters measured after the first dose and after chronic dosing. Stavudine is a new dideoxynucleoside with more complete and less variable oral absorption than existing nucleosides used for treatment of human immunodeficiency virus infection.

AIDS-Related Complex↗