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Biomedical subjects

M Allen

Publications and source records attributed to M Allen.

At least 37 records · Page 2Linked to original sources

Compliance with prenatal care visits in substance abusers.

OBJECTIVE: We sought to determine whether pregnant, inner-city substance abusers, cared for in a multidisciplinary setting, had comparable numbers of missed appointments and similar outcomes in comparison with a low-risk patient population. METHODS: A retrospective review was conducted on a sample of 97 patients with uncomplicated prenatal care over a 7-year period (1994-2001). They were compared to a sample of 88 substance abusers cared for and delivered at Bellevue Hospital over the same period. Demographic information was recorded, as well as frequency of prenatal visits, number of missed appointments, birth weight, and gestational age at delivery. RESULTS: In our population, substance abusers were found to be significantly older (28.9 vs. 25.6 years, p < 0.0001), had had more pregnancies (4.3 vs. 2.4, p < 0.0001) and had had more children (2.0 vs. 0.7, p < 0.0001) than controls. Both substance abusers and control patients had a similar number of scheduled appointments (11.4 in each group, p = 0.99), but substance abusers missed more appointments (1.6 vs. 0.7, p < 0.0005). CONCLUSIONS: When cared for in a multidisciplinary setting, substance abusers will attend an adequate number of prenatal visits. However, they are still more likely than non-substance abusers to miss visits, although the difference may not be clinically significant.

Adult↗

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma.

BACKGROUND: Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin. PATIENTS AND METHODS: Chemotherapy naïve patients with EOC were treated with doxorubicin (50 mg/m(2) day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m(2)/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below. RESULTS: Twelve patients with advanced EOC received a median of six cycles (range 2-6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m(2)/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease. CONCLUSIONS: The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m(2)).

Adult↗

Fetal endoscopic telesurgery using an Internet Protocol connection: clinical and technical challenges.

Until recently, fetoscopic laser surgery to seal the placental anastomoses that cause severe twin-to-twin transfusion syndrome has been available in only a few centres worldwide. The technique typically takes a long time to learn. We have used a dedicated Internet Protocol (IP) connection for tele-education to assist the introduction of fetoscopic laser surgery to Australia. During the implementation of the international telemedicine link, there were multiple clinical and technical problems, which were eventually overcome. The quality of images and of video-sequences was comparable to that supported by an ISDN connection. Pictures of live surgery performed by an expert in Florida, USA, were transmitted and viewed by a novice team in Brisbane, Australia. The Australian team has performed 19 fetoscopic laser operations to date. Preliminary results are comparable to those from centres that have performed over 100 procedures.

Australia↗

MeV ion jets from short-pulse-laser interaction with thin foils.

Collimated jets of carbon and fluorine ions up to 5 MeV/nucleon ( approximately 100 MeV) are observed from the rear surface of thin foils irradiated with laser intensities of up to 5 x 10 (19)W/cm(2). The normally dominant proton acceleration could be surpressed by removing the hydrocarbon contaminants by resistive heating. This inhibits screening effects and permits effective energy transfer and acceleration of other ion species. The acceleration dynamics and the spatiotemporal distributions of the accelerating E fields at the rear surface of the target are inferred from the detailed spectra.

Journal Article↗

A phase I dose-finding study of a combination of pegylated liposomal doxorubicin (Doxil), carboplatin and paclitaxel in ovarian cancer.

Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease. A dose finding study of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first-line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(-2); doxil 20, 30, 40 and 50 mg m(-2). Schedules examined included treatment cycles of 21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with doxil being administered every other course (q 42). The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(-2) and doxil 30 mg m(-2) q 21. Reducing the paclitaxel dose to 135 mg m(-2) did not allow the doxil dose to be increased. Delivering doxil on alternate cycles at doses of 40 and 50 mg m(-2) also resulted in dose-limiting toxicities. The recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175 mg m(-2), doxil 30 mg m(-2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(-2), doxil 20 mg m(-2) q 21. Grade 3/4 haematologic toxicity was common at the recommended phase II doses but was short lived and not clinically important and non-haematologic toxicities were generally mild and consisted of nausea, paraesthesiae, stomatitis and palmar plantar syndrome.

Adult↗

Detection of biogenic CO production above vascular cell cultures using a near-room-temperature QC-DFB laser.

We report the first application of pulsed, near-room-temperature quantum cascade laser technology to the continuous detection of biogenic CO production rates above viable cultures of vascular smooth muscle cells. A computer-controlled sequence of measurements over a 9-h period was obtained, resulting in a minimum detectable CO production of 20 ppb in a 1-m optical path above a standard cell-culture flask. Data-processing procedures for real-time monitoring of both biogenic and ambient atmospheric CO concentrations are described.

Air Conditioning↗

Assessing the burden of respiratory disease in the UK.

This review explores the health and social burden of some of the main respiratory diseases (asthma, chronic obstructive pulmonary disease, cryptogenic fibrosing alveolitis, cystic fibrosis, lung cancer, mesothelioma, obstructive sleep apnoea and tuberculosis) in order to increase awareness of these diseases and highlight areas where improvements in care are required. The overall impact of respiratory diseases in the U.K. in terms of prevalence, mortality, morbidity and economic costs, with particular reference to secondary care has been considered and comparisons made with the rest of Europe where data are available. Respiratory diseases are responsible for a significant proportion of serious morbidity and premature death among the population of the U.K. and they will continue to present a growing challenge; special support is needed to tackle this burden.

Adolescent↗

Induction of donor-specific tolerance to islet allografts in nonhuman primates.

Pancreatic tissue grafting is by far the most physiological therapeutic solution to the insulin deficiency of diabetes. Recent clinical trials have indicated somewhat successful use of nonsteroidal immunosuppressive regimens and a successful nonhuman primate trial using CD154 for costimulation blockade was reported. However, these protocols need to be replaced with safe and efficacious ones in which long-term allotolerance would make these treatments routine in a clinical setting. With the specific objective of testing whether peripheral infusions of stem cells or stem cell fractions in conjunction with islet allografting would induce allograft tolerance, we have established a macaque diabetic model. The macaques were rendered diabetic by streptozotocin and required daily doses of insulin to maintain lower blood glucose levels. The diabetic macaques then received islets and stem cells from unrelated and MHC-mismatched donors without any immunosuppression. In our initial analysis, 5 of 7 macaques that received stem cell infusions at the time of islet allografting have shown allograft survival longer than the group of macaques that received islets without the stem cell infusion. One of these five macaques has been normoglycemic for 10 months, with no exogenous insulin. This macaque received stem cell population enriched for CD34+ cells with depletion of CD18 cells, which have shown low or no allostimulatory potential in mixed lymphocyte cultures. Increased levels in insulin and C-peptide levels were shown in the macaques after islet transplantation.

Animals↗

Induction of islet allotolerance in nonhuman primates.

Recent clinical trials have pioneered the successful use of a nonsteroidal immunosuppressive regimen and established a basis for application in a routine clinical setting. In this study, a single islet transplant was not sufficient to regulate blood glucose levels, and a second transplant became necessary. A similar observation was made in our macaque islet transplant study, where animals after the second transplantation have shown trends towards normoglycemia in the presence of mycophenolate mofetil. All five animals that received the second transplant have shown an initial rise in C peptide levels, which rapidly decreased as we tapered the MMF dose from 20 mg/kg BID to 5 mg/kg SID. Two animals of the five that were preconditioned with MMF one week prior to transplantation have shown significantly higher C peptide levels. We believe that it is very important to understand the relationship between the first graft failure and subsequent islet allograft success. Since graft success did not correlate with number of transplanted islets, the correction of blood glucose levels toward normoglycemia after the second transplantation suggests a mechanism by which the allotolerance to second transplant is facilitated by the first islet transplantation. These initial observations suggest approaches to "tolerize" the recipient to accept the second-transplant islets (a) through preconditioning the animal to improve the rate of success for the first transplant or (b) through tolerization to islets in the first transplant to facilitate better engraftment of the second-transplant islets.

Animals↗

Mitochondrial sequence analysis for forensic identification using pyrosequencing technology.

Over recent years, requests for mtDNA analysis in the field of forensic medicine have notably increased, and the results of such analyses have proved to be very useful in forensic cases where nuclear DNA analysis cannot be performed. Traditionally, mtDNA has been analyzed by DNA sequencing of the two hypervariable regions, HVI and HVII, in the D-loop. DNA sequence analysis using the conventional Sanger sequencing is very robust but time consuming and labor intensive. By contrast, mtDNA analysis based on the pyrosequencing technology provides fast and accurate results from the human mtDNA present in many types of evidence materials in forensic casework. The assay has been developed to determine polymorphic sites in the mitochondrial D-loop as well as the coding region to further increase the discrimination power of mtDNA analysis. The pyrosequencing technology for analysis of mtDNA polymorphisms has been tested with regard to sensitivity, reproducibility, and success rate when applied to control samples and actual casework materials. The results show that the method is very accurate and sensitive; the results are easily interpreted and provide a high success rate on casework samples. The panel of pyrosequencing reactions for the mtDNA polymorphisms were chosen to result in an optimal discrimination power in relation to the number of bases determined.

Base Sequence↗

In-utero treatment of fetal bladder-outlet obstruction by a ureterocele.

Fetal bladder-outlet obstruction by ureteroceles is usually treated at birth. However, such obstruction may be detrimental to the health of the fetus and so in-utero correction is preferable. We describe the successful cytoscopy guided laser incision, with no complications, of a uterocele that was causing bladder-outlet obstruction in a fetus of 19 weeks and 6 days gestation.

Adult↗

Trial-related discrimination in HIV vaccine clinical trials.

Participants in preventive HIV vaccine trials may experience negative social consequences of trial participation, including problems related to a vaccine-induced positive HIV antibody test, yet few vaccine studies have reported on this issue. From October 1995 through November 1998, 1516 AIDS Vaccine Evaluation Group (AVEG) volunteers were assessed for reports of trial-related discrimination (TRD). Ninety TRD events were reported by 76 (5%) of 1516 volunteers. The most commonly reported incidents (n = 52, 57.8%) were negative reactions of friends, family, and co-workers to the volunteer. Few incidents (approximately 10%) were reported as linked to HIV testing. The majority of events (n = 47, 52%) were described by volunteers as "resolved" at the time of reporting, 36 (40%) as "not resolved," and for 7 (8%) events volunteers did not report resolution status. Reported incidents were analyzed by logistic regression to determine their association with the volunteer's age, sex, race, sexual orientation, and HIV risk category. There was no association between volunteer characteristics and TRD. Logistic regression and analysis of variance (ANOVA) were used to analyze association of trial sites with the number of TRD events reported. After controlling for site variation in data collection and reporting, no significant differences were found between the sites in terms of the number or type of TRD reported. Fears that TRD would be widespread and severe have not been borne out by this analysis. While the results of this study are reassuring, they should be interpreted with caution, as it is unclear whether these results may be extended to phase III trials enrolling large numbers of individuals at higher risk of HIV acquisition.

AIDS Vaccines↗

In vitro and in vivo investigations into the biocompatibility of diamond-like carbon (DLC) coatings for orthopedic applications.

Diamond-like carbon (DLC) shows great promise as a durable, wear- and corrosion-resistant coating for biomedical implants. The effects of DLC coatings on the musculoskeletal system have not been investigated in detail. In this study, DLC coatings were deposited on polystyrene 24-well tissue culture plates by fast-atom bombardment from a hexane precursor. Two osteoblast-like cell lines were cultured on uncoated and DLC-coated plates for periods of up to 72 h. The effects of DLC coatings on cellular metabolism were investigated by measuring the production of three osteoblast-specific marker proteins: alkaline phosphatase, osteocalcin, and type I collagen. There was no evidence that the presence of the DLC coating had any adverse effect on any of the parameters measured in this study. In a second series of experiments, DLC-coated cobalt-chromium cylinders were implanted in intramuscular locations in rats and in transcortical sites in sheep. Histologic analysis of specimens retrieved 90 days after surgery showed that the DLC-coated specimens were well tolerated in both sites. These data indicate that DLC coatings are biocompatible in vitro and in vivo, and further investigations into their long-term biological and tribological performance are now warranted.

Alkaline Phosphatase↗

Lifelong learning in ethical practice: a challenge for continuing medical education.

BACKGROUND: Formal education in the identification, analysis, and resolution of ethical issues in clinical practice is now an essential component of undergraduate and postgraduate medical education. Physicians educated before the 1980s have had little or no formal education in ethics. This article describes a project for assessing the content and format appropriate for the continuing education needs of practicing physicians. METHODS: A questionnaire and follow-up facilitated small-group discussions with a physician ethicist around case-based problems were used to identify the ethical issues in practice where participants felt the need for continuing education. RESULTS: The project confirmed that practitioners had very little formal ethics in medical school and less since starting practice despite encountering ethical issues. The most frequently used method of learning about ethics was informal discussion among those who have the same lack of formal education. Physicians did not feel that they needed a "very high" level of confidence and competence in handling ethical issues, even those commonly encountered. Participants indicated strongly that they lacked a systematic approach to the identification and analysis of ethical issues and suggest incorporation of the ethical component into regular CME. FINDINGS: In spite of the small study population and the volunteer nature of the participants, the project demonstrated the identification of ethics content for CME similar to that used in medical education. Further work is needed to assess objective needs for ethics education in addition to the perceived needs of clinicians.

Education, Medical, Continuing↗

Pseudotumor deltoideus: a previously undescribed anatomic variant at the deltoid insertion site.

A spectrum of eccentric bone irregularities were observed in the humeral deltoid tuberosity region of five patients. Patients were referred for associated pain or for the incidental radiographic findings. The lesions are characterized radiographically by a relative lucency at or adjacent to the deltoid tuberosity, variably increased uptake on the bone scan, and mild cortical irregularity or adjacent eccentric marrow abnormality on MRI and CT. The term pseudotumor deltoideus is coined for these previously undescribed anatomic variants. Imaging studies and extended clinical follow-up in these patients support an inactive or indolent process that may be managed conservatively. The potential etiology and role of these cortical irregularities as tumor simulators is emphasized.

Adult↗

Genetic counseling impacts decision for prophylactic surgery for patients perceived to be at high risk for breast cancer.

BACKGROUND: This study addresses the impact a comprehensive genetic counseling program had on women considering prophylactic mastectomy or oophorectomy. METHODS: Sixty patients underwent detailed family evaluation and risk was estimated. Recommendations were made regarding testing. Ramifications of testing were discussed in detail. RESULTS: Thirty-one women (37%) were considering prophylactic surgery believing themselves to be at high risk. Of these, 23 had testing recommended. Seven patients proceeded with prophylactic surgery based solely on high-risk assessment. Ten women were tested; five were positive. Three patients proceeded with prophylactic surgery despite a negative test. One decided against surgery despite a positive test. After counseling, prophylactic surgery was performed in just over half the initial candidates. CONCLUSIONS: Breast cancer risk estimation and genetic evaluation can be complex. Comprehensive genetic risk assessment programs can play a significant role in the management of patients considering prophylactic surgery for perceived high risk.

Adolescent↗