Elevated prothrombin level and shortened clotting times in subjects with type 2 diabetes.
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Blood Coagulation↗
Biomedical subjects
M Hoffman
Publications and source records attributed to M Hoffman.
Rates of complication in first-trimester manual vacuum aspiration abortion done by doctors and mid-level providers in South Africa and Vietnam: a randomised controlled equivalence trial.
BACKGROUND: We assessed whether the safety of first-trimester manual vacuum aspiration abortion done by health-care providers who are not doctors (mid-level providers) is equivalent to that of procedures done by doctors in South Africa and Vietnam, where mid-level providers are government trained and accredited to do first-trimester abortions. METHODS: We did a randomised, two-sided controlled equivalence trial to compare rates of complication in abortions done by the two groups of providers. An a-priori margin of equivalence of 4.5% with 80% power and 95% CI (alpha=0.05) was used. 1160 women participated in South Africa and 1734 in Vietnam. Women presenting for an induced abortion at up to 12 weeks' gestation were randomly assigned to a doctor or a mid-level provider for manual vacuum aspiration and followed-up 10-14 days later. The primary outcome was complication of abortion. Complications were recorded during the abortion procedure, before discharge from the clinic, and at follow-up. Per-protocol and intention-to-treat analyses were done. This trial is registered at with the identifier . FINDINGS: In both countries, rates of complication satisfied the predetermined statistical criteria for equivalence: rates per 100 patients in South Africa were 1.4 (eight of 576) for mid-level providers and 0 for doctors (difference 1.4, 95% CI 0.4 to 2.7); in Vietnam, rates were 1.2 (ten of 824) for mid-level providers and 1.2 (ten of 812) for doctors (difference 0.0, 95% CI -1.2 to 1.1). There was one immediate complication related to analgesics. Delayed complications were caused by retained products and infection. INTERPRETATION: With appropriate government training, mid-level health-care providers can provide first trimester manual vacuum aspiration abortions as safely as doctors can.
Abortion, Induced↗
Challenges in implementing a cervical screening program in South Africa.
BACKGROUND: The Cervical Health Implementation Project was initiated with the aim of developing and evaluating health system interventions for improving public sector cervical screening services. The project was conducted between January 2001 and May 2003 in three districts in South Africa. This paper describes the districts, interventions and their evaluation, and discusses the implications of these findings for the roll out of a national cervical screening program. METHODS: A pretest/post-test study design was employed. The following interventions were developed and implemented: health worker training workshops, health system tools and protocols and a community awareness program. Pre- and post-intervention facility audits, key informant interviews, staff knowledge, attitude and practice (KAP) surveys and client KAP surveys were conducted. Clinic records and cytology laboratory data were reviewed. RESULTS: Service organization, availability of screening equipment and education and communication materials improved. The proportion of staff who knew the screening policy increased from 43% to 82%; and 68% of staff agreed with the screening policy after, as opposed to 23% before the intervention. In two of the districts, cytology turnaround times continued to be long. Only 50% of women with a high-grade squamous intraepithelial lesion had a colposcopy and biopsy within 6 months of a Pap smear. Although the number of new smears performed in the three districts increased from 1544 in 2001 to 2801 in 2002, overall the coverage remained less than 4%. CONCLUSION: This project highlights the considerable challenges that need to be addressed to effectively implement the national screening policy.
Adult↗
The application of genomic and proteomic technologies in predictive, preventive and personalized medicine.
The long asymptomatic period before the onset of chronic diseases offers good opportunities for disease prevention. Indeed, many chronic diseases may be preventable by avoiding those factors that trigger the disease process (primary prevention) or by use of therapy that modulates the disease process before the onset of clinical symptoms (secondary prevention). Accurate prediction is vital for disease prevention so that therapy can be given to those individuals who are most likely to develop the disease. The utility of predictive markers is dependent on three parameters, which must be carefully assessed: sensitivity, specificity and positive predictive value. Specificity is important if a biomarker is to be used to identify individuals either for counseling or for preventive therapy. However, a reciprocal relationship exists between sensitivity and specificity. Thus, successful biomarkers will be highly specific without sacrificing sensitivity. Unfortunately, biomarkers with ideal specificity and sensitivity are difficult to find for many diseases. One potential solution is to use the combinatorial power of a large number of biomarkers, each of which alone may not offer satisfactory specificity and sensitivity. Recent technological advances in genetics, genomics, proteomics, and bioinformatics offer a great opportunity for biomarker discovery. The newly identified biomarkers have the potential to bring increased accuracy in disease diagnosis and classification, as well as therapeutic monitoring. In this review, we will use type 1 diabetes (T1D) as an example, when appropriate, to discuss pertinent issues related to high throughput biomarker discovery.
Biomarkers↗
Depot medroxyprogesterone versus norethisterone oenanthate for long-acting progestogenic contraception.
BACKGROUND: There are two injectable progestogen-only contraceptives (IPCs) that have been available in many countries in the world since 1983. They are both still extensively used in many developing countries, forming a large proportion of the health system's expenditure on contraception. These are depot medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-EN). These are both highly effective contraceptives that receive wide acceptance amongst women in their fertile years. They differ in frequency of administration that has implications on patient uptake. They also differ in cost that may significantly affect budgeting in the health system. A systematic comparison will aid to ensure their rational use. OBJECTIVES: To determine if there are differences between depot medroxyprogesterone acetate given at a dose of 150 mg IM every 3 months and norethisterone oenanthate given at a dose of 200mg IM every 2 months, in terms of contraceptive effectiveness, reversibility and discontinuation patterns, minor effects and major effects. SEARCH STRATEGY: We searched the computerized databases MEDLINE using PubMed, Popline, Cochrane Controlled Trials Register, Biblioline, LILACS, EMBASE and PASCAL for randomised controlled trials of DMPA versus NET-EN for long-acting progestogenic contraception. Studies were included regardless of language, and all databases were reviewed from the time that injectable progestogens have been in use. SELECTION CRITERIA: All randomised controlled comparisons of DMPA acetate given at a dose of 150 mg IM every 3 months versus NET-EN given at a dose of 200mg IM every 2 months, used for contraception, were included. Trials had to report on contraceptive efficiency and return to fertility, discontinuation risks and reasons for discontinuation, and clinical effects, both menstrual and non-menstrual. DATA COLLECTION AND ANALYSIS: BD and CM evaluated the titles and abstracts obtained through applying the search strategy and applied the eligibility criteria. BD attempted to contact authors where clarification of the data was required, and contacted all main manufacturers of the contraceptives. After inclusion of the two studies, the data was abstracted and analysed with RevMan 4.2. MAIN RESULTS: Two trials were included in this review. There was no significant difference between the two treatment groups for the frequency of discontinuation for either contraceptive, although the women on NET-EN were 4% more likely to discontinue for personal reasons than those on DPMA. Discontinuation because of accidental pregnancy did not differ between the groups. Although the duration of bleeding and spotting events was the same in each group, women on DPMA were 21% more likely to develop amenorrhoea. Mean changes in body weight at 12 and 24 months, and in systolic and diastolic blood pressure at 12 months did not differ significantly between the studies. AUTHORS' CONCLUSIONS: While the choice between DPMA and NET-EN as injectable progestogen contraceptives may vary between both health providers and patients, data from randomized controlled trials indicate little difference between the effects of these methods, except that women on DMPA are more likely to develop amenorrhoea. There is inadequate data to detect differences in some non-menstrual major and minor clinical effects.
Contraception↗
Discovery of a cool planet of 5.5 Earth masses through gravitational microlensing.
In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.
Journal Article↗
Circulating tissue factor accumulates in thrombi, but not in hemostatic plugs.
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Animals↗
The status of legal termination of pregnancy in South Africa.
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Abortion, Legal↗
Oral evaluation in rabbits of cyclosporin-loaded Eudragit RS or RL nanoparticles.
The hydrophobic cyclic undecapeptide cyclosporin A (CyA) used in the prevention of graft rejection and in the treatment of autoimmune diseases was encapsulated by nanoprecipitation within non-biodegradable polymeric nanoparticles. The effect of polymers (Eudragit RS or RL) and additives within the alcoholic phase (fatty acid esters and polyoxyethylated castor oil) on the size, zeta potential and the encapsulation efficiency of the nanoparticles was investigated. The mean diameter of the various CyA nanoparticles ranged from 170 to 310 nm. The size as well as the zeta potential increased by adding fatty acid ester and polyoxyethylated castor oil within the organic phase. No significant differences in surface potential were observed for all formulations tested. Probably due to the very low water solubility of the drug, high encapsulation efficiencies were observed in a range from 70 to 85%. The oral absorption of CyA from these polymeric nanoparticles was studied in rabbits and compared to that of Neoral capsule. Based on comparison of the area under the blood concentration-time curve values, the relative bioavailability of CyA from each nanoparticulate formulation ranged from 20 to 35%.
Acrylic Resins↗
Formulation of insulin-loaded polymeric nanoparticles using response surface methodology.
The objective of this work was to formulate new oral insulin-loaded nanoparticules using the response surface methodology. The insulin nanoparticles were prepared by a water-in-oil-in-water emulsification and evaporation method. The polymers used for the encapsulation were blends of biodegradable poly-epsilon-caprolactone (PCL) and of positively-charged, nonbiodegradable polymer (Eudragis RS). A central composite design has been built to investigate the effects of three controlled variables: ratio of polymers (PCL/RS ratio), volume, and pH of the aqueous solution of polyvinyl alcohol. The nanoparticles were characterized by measuring the amount of entrapped insulin, the particle size, the polydispersity of the obtained particles, the zeta potential, and the amount of insulin released after 7 hours. A second-order model was evaluated by multiple regression and was statistically tested for each of the studied controlled variable. The obtained polynomials proved efficient to localize an optimal operating area highlighted by the use of three-dimensional response surfaces and their corresponding isoresponse curves. An interesting formulation given by the models was selected, prepared, and evaluated. The corresponding quantity of entrapped insulin was 25 IU per 100 mg of polymer, and the particle size was 350 nm with a polydispersity of 0.21. The quantity of released insulin was 4.8 IU per 100 mg of polymer after 7 hours and the zeta potential was +44 mV. All these collected values were in perfect accordance with values estimated by the models. Finally, the results suggested that PCL/RS 50/50 nanoparticles might represent a promising formulation for oral delivery of insulin.
Administration, Oral↗
One more way that mice and men are different.
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Animals↗
The clinical bioinformatics ontology: a curated semantic network utilizing RefSeq information.
Existing medical vocabularies lack rich terms to describe findings that are generated by modem molecular diagnostic procedures. Most bioinformatics resources were designed primarily to support the needs of the research community. We describe the development of a curated resource, the Clinical Bioinformatics Ontology (CBO), a semantic network appropriate for describing clinically significant genomics concepts. The CBO includes concepts appropriate for both molecular diagnostics and cytogenetics. A standardized methodology based on consistent application of RefSeq information is applied to the curation of the CBO in order to provide a reproducible and reliable tool. Challenges related to this curation process are discussed in this paper. At the time of submission the CBO included 4,069 concepts, associated by 8,463 relationships.
Computational Biology↗
The Healthgrid White Paper.
Over the last four years, a community of researchers working on Grid and High Performance Computing technologies started discussing the barriers and opportunities that grid technologies must face and exploit for the development of health-related applications. This interest lead to the first Healthgrid conference, held in Lyon, France, on January 16th-17th, 2003, with the focus of creating increased awareness about the possibilities and advantages linked to the deployment of grid technologies in health, ultimately targeting the creation of a European/international grid infrastructure for health. The topics of this conference converged with the position of the eHealth division of the European Commission, whose mandate from the Lisbon Meeting was "To develop an intelligent environment that enables ubiquitous management of citizens' health status, and to assist health professionals in coping with some major challenges, risk management and the integration into clinical practice of advances in health knowledge." In this context "Health" involves not only clinical procedures but covers the whole range of information from molecular level (genetic and proteomic information) over cells and tissues, to the individual and finally the population level (social healthcare). Grid technology offers the opportunity to create a common working backbone for all different members of this large "health family" and will hopefully lead to an increased awareness and interoperability among disciplines. The first HealthGrid conference led to the creation of the Healthgrid association, a non-profit research association legally incorporated in France but formed from the broad community of European researchers and institutions sharing expertise in health grids. After the second Healthgrid conference, held in Clermont-Ferrand on January 29th-30th, 2004, the need for a "white paper" on the current status and prospective of health grids was raised. Over fifty experts from different areas of grid technologies, eHealth applications and the medical world were invited to contribute to the preparation of this document.
Computer Communication Networks↗
Passive stretch inhibits central corelike lesion formation in the soleus muscles of hindlimb-suspended unloaded rats.
Hindlimb suspension unloading (HSU) is a ground-based model simulating the effects of microgravity unloading on the musculoskeletal system. In this model, gravity causes the hind foot of the rat to drop, opening the front of the ankle to 90-105 degrees plantar flexion at rest. As HSU proceeds, the normal weight-bearing angle of 30 degrees dorsiflexion is achieved progressively less, and the contraction range of soleus is abbreviated. Our laboratory reported that 12 days of HSU caused central corelike lesions (CCLs) of myofibril breakdown (Riley DA, Slocum GR, Bain JL, Sedlak FR, Sowa TE, and Mellender JW. J Appl Physiol. 69: 58-66, 1990). The present study investigated whether daily stretch of the calf muscles prevents CCL formation. The soleus muscles of HSU Sprague-Dawley male rats (approximately 287 g) were lengthened by unilateral ankle splinting at 30 degrees. Compared with the nonsplinted side, splinting for 10 or 20 min per day in awake rats significantly decreased CCLs in soleus by 88 and 91%, respectively (P < 0.01). Compared with control muscle wet weight, 20-min splinting reduced atrophy by 33%, whereas 10-min splinting ameliorated atrophy by 17% (P < 0.01). Bilateral soleus electromyograph recording revealed higher levels of contractile activity on the splinted side during splinting. To isolate the effects of stretch from isometric contractile activity, contractions were eliminated by whole animal anesthesia with isoflurane during 10-min daily splinting. The percentage of fibers with CCLs was reduced by 57%, and the average lesion size was 29% smaller in the stretched muscle (P < 0.05). Soleus muscle wet weight and fiber area were unaltered by stretch alone. Loaded contractions during splinting are necessary to prevent muscle fiber atrophy. Passive muscle stretch acts to maintain myofibril structural integrity.
Animals↗
Outcomes of the peer-taught 12-week family-to-family education program for severe mental illness.
OBJECTIVE: Family-to-Family Education Program (FFEP) is a 12-week course for family members of adults with serious mental illness (SMI). This study evaluates the effectiveness of FFEP for several family member outcomes. METHOD: The FFEP enrollees on a > or =3-month waiting list were eligible; 95 consenting family members agreed to four interviews (waitlist, pre-FFEP, post-FFEP, and 6 months post-FFEP) regarding subjective and objective burden, empowerment, and depression. Mixed effects ANOVA models tested hypotheses of decreased burden and increased empowerment after FFEP. RESULTS: The FFEP was associated with reduced subjective burden (P < 0.01) and increased empowerment (P < 0.01) without changes in objective burden. Knowledge about SMI, understanding the mental health system, and self-care also improved. There was no significant decay at 6-month followup. CONCLUSION: This study provides evidence that FFEP is helpful to relatives of persons with SMI by reducing subjective burden and worry, and increasing empowerment, knowledge about SMI, understanding the mental health system, and self-care.
Baltimore↗
Lung cancer in patients with HIV infection: is it AIDS-related?
HIV-infected individuals have an increased risk of malignancy, especially non-Hodgkin's lymphoma and Kaposi's sarcoma. Recently, several workers have noted a raised prevalence of lung cancer in HIV-positive subjects. We describe the diagnosis and clinical course for four HIV-seropositive patients who presented with lung cancer. All of the patients were young and were heavy smokers. They were all on highly active antiretroviral therapy (HAART), although the adherence varied from poor to excellent. The CD4 cell counts of these patients ranged from 200 to 686 cells/microL and their viral loads ranged from undetectable to 29,000 HIV-1 RNA copies/mL. After initial diagnosis of HIV infection between 5 and 13 years previously, they all presented with advanced lung cancer, with a very short clinical course, and all four died within 2-9 months of diagnosis. A comparison of the incidence of lung cancer in patients with HIV infection at our centre with that in the general population suggests that there is an increased prevalence in the HIV-infected patients. We review the literature and discuss whether lung cancer in HIV infection is coincidental or related to the primary disease.
Adult↗
Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system.
Using a cell-based model system of coagulation, we performed a systematic examination of the effect of varying individual procoagulant proteins (over the range of 0-200% of pooled plasma levels) on the characteristics of thrombin generation. The results revealed a number of features unique to the different coagulation factors, as well as common features allowing them to be grouped according to the patterns observed. Variation of those factors contributing to formation of the tenase complex, factor (F)VIII, factor (F)IX and factor (F)XI, primarily affected the rate and peak of thrombin production, but had little to no effect on total thrombin production. The effect of decreased FXI was milder than seen with decreased FVIII or FIX, and more variable between platelet donors. In contrast, varying the concentration of factors that contribute to formation of the prothrombinase complex, prothrombin or factor (F)V (with FV-deficient platelets), significantly affected all three measures of thrombin production: rate, peak and total. Additionally, while no thrombin generation was observed with no factor X, only very small amounts (between 1% and < 10% of normal plasma levels) were required to normalize the measured parameters. Finally, our results with this cell-based system highlight differences in thrombin generation on cell surfaces (platelets) compared with phospholipids, and suggest that platelets contribute more than simply a surface for the generation of thrombin.
Blood Coagulation Factors↗
The remineralizing effect of an essential oil fluoride mouthrinse in an intraoral caries test.
BACKGROUND: The authors conducted a two-week clinical study to determine the remineralizing effect of an experimental mouthrinse containing both fluoride and essential oils in an intraoral caries test model. METHODS: The study used an observer-blinded, randomized, controlled, 3 x 3 crossover design. The authors enrolled in the study 153 subjects, each of whom had a mandibular removable partial denture. Two partially demineralized human enamel specimens were mounted on each subject's removable partial denture. Subjects used either a fluoride mouthrinse with essential oils (the test mouthrinse), a fluoride nonessential oils mouthrinse (the positive control) or an essential oil nonfluoride mouthrinse (the negative control) twice daily for 14 days. The researchers assessed specimens for mineral content change and fluoride uptake using surface microhardness, or SMH, testing and enamel fluoride analysis, respectively. RESULTS: Of the 153 subjects enrolled in the study, 125 subjects were evaluable at the study endpoint. The results after two weeks showed that percentage of SMH recovery was 42 percent in the test group, 36 percent in the positive control group and 16 percent in the negative control group. The fluoride uptake was 19 micrograms per square centimeter, 16 microg/cm2 and 3 microg/cm2 for the test mouthrinse, positive control and negative control groups, respectively. In terms of both percentage of SMH and fluoride uptake, the test mouthrinse and positive control mouthrinse were statistically higher than the negative control mouthrinse, and the test mouthrinse was "at least as good as" the positive control mouthrinse. CONCLUSIONS: This study provides evidence that an essential oil mouthrinse with 100 parts per million fluoride is effective in promoting enamel remineralization and fluoride uptake. CLINICAL IMPLICATIONS: The combination of fluoride and essential oils in a mouthrinse may provide anticaries efficacy, in addition to essential oils' previously established antigingivitis efficacy.
Cariostatic Agents↗