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Biomedical subjects

C Wright

Publications and source records attributed to C Wright.

At least 19 recordsLinked to original sources

A newly recognized, likely autosomal recessive syndrome comprising agammaglobulinemia, microcephaly, craniosynostosis, severe dermatitis, and other features.

We present a novel, likely autosomal recessive, multi-system disorder seen in three siblings, two males and one female, born to nonconsanguineous parents. The disease manifests as agammaglobulinemia with marked microcephaly, significant developmental delay, craniosynostosis, a severe dermatitis, cleft palate, narrowing of the choanae, and blepharophimosis. The constellation of clinical signs seen in this family likely represents a new and recognizable form of agammaglobulinemia due to a defect in early B-cell maturation.

Abnormalities, Multiple↗

Impact of formulation on the abuse liability, safety and regulation of medications: the expert panel report.

A scientific meeting was held in April 2005 to consider how the formulation of medications might impact on their potential for abuse. The background papers prepared for this meeting, as well as abstracts of volunteered presentations, are published in this supplemental issue of Drug and Alcohol Dependence. This paper is the Expert Panel Report summarizing the discussions held following the formal presentations and including the suggested recommendations for additional research that emerged from these discussions. There was overwhelming consensus that formulation does play a role in prescription drug abuse, i.e., a formulation of an abused substance can be developed that will decrease its abuse potential, and several examples were cited. Nevertheless, it is imperative that new formulations have similar efficacy and in no way compromise medication access to doctors and patients. However, there was also consensus that a great deal of research and discussion was needed to fully implement a program of risk management through reformulation of existing products or tailoring the formulation of new products to retain clinical efficacy and safety while minimizing potential for abuse. Those who need to take part in this discussion include scientific groups, pharmaceutical companies, as well as governmental and regulatory agencies. The areas where more research is needed include development of standards for assessing tamper-resistance, improved animal models that can address formulation-related variables (e.g., onset, duration), the redesign of human laboratory studies providing appropriate models for comparing formulations, and improved post-marketing surveillance. Finally, knowledge and experience are needed to translate scientific work into a predictable, transparent and reliable regulatory process.

Chemistry, Pharmaceutical↗

Intraepidermal animal-type melanoma.

Animal-type melanoma is a rare variant of melanoma in humans.1 Its name is derived from its histological appearance, which is similar to that described in melanomas occurring in white or gray horses.2 All tumors are dermally located, and characterized by a proliferation of deeply pigmented elongated or rounded cells, showing moderate atypia and a low mitotic rate. In some tumors, secondary infiltration of the epidermis has been noted. More than half of the patients are younger than 30 years, and prognosis seems to be much better than that expected for a superficial spreading or nodular melanoma of the same size. We report the first case of animal-type melanoma in situ.

Adult↗

De-constructing home-based care for mental illness: can one identify the effective ingredients?

OBJECTIVE: Home-based care for severe mental illness has been the focus of intense research over the last 30 years and has produced mixed results. Replications of Assertive Community Treatment (ACT) in Europe have consistently failed to find these differences and various explanations have been advanced for this. METHOD: Studies were compared in context of health care, and then identifying and rating the components of the differing teams rather than simply their designation. Cluster analysis was used for the identification of common service characteristics and regression analysis to test for correlation with reduction in hospitalization. RESULTS: The nature of the control service may significantly explain the international variation in results. Six regularly occurring features of experimental services were identified from the examination of the components - smaller case loads, regularly visiting at home, a high percentage of contacts at home, responsibility for health and social care, multidisciplinary teams and a psychiatrist integrated in the team. Two of these, regularly visiting at home and responsibility for health and social care, are significantly associated with a reduction in hospitalization. CONCLUSIONS: It is premature to define an optimal configuration for home based care services. The need for introducing differing components of such care will depend on what is currently available locally. Where regular home visiting to psychotic patients plus a broad service model incorporating health and social care objectives are provided, major reductions in in-patient care are not currently to be anticipated by service re-configurations.

Cluster Analysis↗

Rheometrical and computational studies of blood viscoelasticity during coagulation.

The rheological behaviour of coagulating human blood has been measured using multiple strain wave frequencies. The results indicate that coagulating blood, prior to the point of incipient clot formation, can be modelled by a modified form of the Gross-Marvin 'ladder' model, and the benefits of such modeling for blood coagulation are discussed.

Blood Coagulation↗

Macroorchidism in two unrelated prepubertal boys with a normal FSH receptor.

BACKGROUND: Macroorchidism in prepuberty is an uncommon condition which we hypothesised might reflect constitutive activation of the FSH receptor (FSHR). PATIENTS AND METHODS: Patient 1 was found to have macroorchidism (15 ml testicular volume) at the time of orchidopexy when 3.7 years of age. A gonadal biopsy was obtained at the time of surgery. Patient 2 developed macroorchidism (5 ml) when 8.8 years old. Despite a testicular volume >4 ml, morning testosterone levels were unrecordable with no measurable gonadotrophin production in either patient. Patient 2 had prepubertal gonadotrophin levels 3 years later despite a testicular volume that was 8 ml bilaterally. Inhibin B was measured and the FSHR sequenced in both patients. RESULTS: Inhibin B levels were age and pubertal stage appropriate. Gonadal biopsy (patient 1) demonstrated areas of Sertoli cell hyperplasia. Sequence analysis of all 10 exons of the FSHR was normal. There was significant, presumed gonadotrophin-dependent testosterone production in both boys by 15 years of age. CONCLUSIONS: The cause of prepubertal macroorchidism in our patients is unclear but the pronounced difference in phenotype suggests that there may be more than one underlying mechanism. This mechanism was not constitutive activation of a mutated FSHR.

Child↗

Inter-laboratory comparison of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in bleaching earth used in the refinement of edible oils.

Bleaching earth (dried, powdered, bentonite-montmorillonite clay) is commonly used as a processing aid in edible oil refinement. Used bleaching earth may be incorporated into animal feed indirectly, for example because it is included into seed meal, or directly (e.g., as a binding agent). Control must be demonstrated to ensure that the levels of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in feed ingredients do not infringe European Community regulations. The low legislative action level assigned is analytically challenging and may be at or below the limits of quantification achievable by many laboratories. A statistical comparison (following the IUPAC/ISO/AOAC protocol) was made of analyses of PCDDs and PCDFs in selected bleaching earth samples by laboratories from Europe and the USA to assess the comparability of data. Of 19 sets of results submitted by laboratories for replicate samples, 11 demonstrated acceptable agreement.

Aluminum Silicates↗

Home blood glucose prediction: validation, safety, and efficacy testing in clinical diabetes.

BACKGROUND: Patients with diabetes do daily self-monitoring of blood glucose (SMBG). For such patients, we devised an engine that predicts not only the expected blood glucose level at the next meal but also the pending risks of hypoglycemia. The purpose of this study was to validate the predictions and provide evidence of the safety and efficacy of using predicted data in dosing decision support for routine patient care. RESEARCH DESIGN AND METHODS: The prediction engine is a computer program that accesses a central database into which daily records of self-monitored blood glucose data are captured by direct access either across the WWW or by an interactive voice response service on-line 24/7. Validation was done by comparison of predicted values to the subsequently observed data using a Clarke Error Grid. Safety focused on body weight and the frequency of hypoglycemia. Efficacy was judged according to glycated hemoglobin and daily insulin dosages. The experimental design contrasted patients in the tight control (TC) group who had been recently converted to intensified (basal-bolus) therapy with patients in the poor control (PC) group on conventional therapy and who were referred to begin intensified therapy. Both groups accessed the remote database to report their daily SMBG. Predicted glucose values were used in dosing decision support for the PC but not the TC group. RESULTS: Over the 6-month study period a total of 30,129 blood glucose levels were reported by the 54 study patients, and some 24,953 blood glucose predictions were made. Of these, 83% were in the clinically acceptable zones of the Clarke Error Grid. When these data were used for dosing decision support in the PC group, glycated hemoglobin levels fell significantly from 9.7 +/- 1.7% to 7.9 +/- 1.2%, and hypoglycemia dropped fourfold. Total daily insulin doses declined 22%, while body weight remained constant. In the parallel TC group (n = 24), glycated hemoglobin also fell, but only slightly from 7.6 +/- 0.9% to 7.2 +/- 1.1%, while daily insulin doses, rates of hypoglycemia and body weight remained constant. CONCLUSIONS: A novel engine is capable of generating meaningful predictions of blood glucose levels. Use of these validated predictions in decision support for managing medication doses proved safe and efficacious.

Algorithms↗

Sildenafil in neonatal pulmonary hypertension due to impaired alveolarisation and plexiform pulmonary arteriopathy.

We report a case of severe pulmonary hypertension in a neonate associated with impaired alveolarisation and plexiform pulmonary arteriopathy. Treatment with oral sildenafil in addition to inhaled nitric oxide (NO) resulted in recovery from the pulmonary hypertensive crisis. Long term sildenafil therapy was associated with complete resolution of the pulmonary hypertension.

3',5'-Cyclic-GMP Phosphodiesterases↗

Atomic force microscopy study of cellulose surface interaction controlled by cellulose binding domains.

Colloidal probe microscopy has been used to study the interaction between model cellulose surfaces and the role of cellulose binding domain (CBD), peptides specifically binding to cellulose, in interfacial interaction of cellulose surfaces modified with CBDs. The interaction between pure cellulose surfaces in aqueous electrolyte solution is dominated by double layer repulsive forces with the range and magnitude of the net force dependent on electrolyte concentration. AFM imaging reveals agglomeration of CBD adsorbed on cellulose surface. Despite an increase in surface charge owing to CBD binding to cellulose surface, force profiles are less repulsive for interactions involving, at least, one modified surface. Such changes are attributed to irregularity of the topography of protein surface and non-uniform distribution of surface charges on the surface of modified cellulose. Binding double CBD hybrid protein to cellulose surfaces causes adhesive forces at retraction, whereas separation curves obtained with cellulose modified with single CBD show small adhesion only at high ionic strength. This is possibly caused by the formation of the cross-links between cellulose surfaces in the case of double CBD.

Cellulose↗

Toxicity of the entomopathogenic fungus, Metarhizium anisopliae (Deuteromycotina: Hyphomycetes) to adult females of the blowfly Lucilia sericata (Diptera: Calliphoridae).

The fungus Metarhizium anisopliae (Metchnikoff) (Deuteromycotina: Hyphomycetes) is a natural component of soil flora world-wide and is a causal agent of the green muscardine diseases of insects. The use of this pathogen as a potential biocontrol agent against adult females of the blowfly, Lucilia sericata (Meigen) (Diptera: Calliphoridae) was considered. The blowfly L sericata is an economically important agent of cutaneous myiasis of sheep, particularly in northern Europe. Exposure of flies to suspensions of fungal spores by immersion, topical application or tarsal contact with treated surfaces all resulted in high levels of fatal infection. Spores suspended in silicone oil resulted in higher levels of infection (50-70%) than those formulated in a 0.3 glitre(-1) solution of the detergent Tween 80 (10-20%). Spore concentration had a significant effect on levels of infection of flies, with the highest levels of mortality (64%) resulting from a suspension of 1 x 10(7) conidia ml(-1). The duration of tarsal contact had a significant effect on levels of infection. Mean infection levels of 30% were observed following exposure of free-flying adults to a single spore-treated, 5 x 15 cm2 cloth surface suspended from the roof of a cage (30 cm cube). The implications of the results for the potential use of M anisopliae in the biocontrol of blowflies are discussed.

Animals↗

Effects of Soy-derived diets on plasma and liver lipids, glucose tolerance, and longevity in normal, long-lived and short-lived mice.

We examined the effects of diets based on a low isoflavone or a high isoflavone soy protein isolates in normal, growth-hormone receptor knockout and Ames dwarf, and Prop 1 (df) mice that are hypoinsulinemic, insulin-sensitive, and exceptionally long-lived, as well as in growth hormone transgenic mice that are hyperinsulinemic, insulin-resistant, dyslipidemic, and short-lived. Soybean diets tended to normalize plasma cholesterol levels in dwarf and transgenic mice, while low isoflavone diet reduced plasma triglycerides in most of the examined genotypes. The effects of low isoflavone and high isoflavone diets on the levels of free and esterified cholesterol in the liver were strongly genotype-dependent. Fasting blood glucose levels were reduced and glucose tolerance improved by both low isoflavone and high isoflavone diets in growth hormone-transgenic mice and in their normal siblings. Glucose tolerance was also improved by high-isoflavone diet in growth hormone receptor knockout mice. Lifespan was increased by low isoflavone diet in normal mice from two of the examined stocks. High isoflavone diet increased lifespan in normal animals from one line, but reduced lifespan of normal mice from a different line. We conclude that dietary soy protein intake can improve plasma and hepatic lipid profiles, reduce fasting glucose, enhance capacity for glucose tolerance, and prolong life, but all of these effects are strongly genotype-dependent.

Animals↗

Characteristics of women who deliver with no prenatal care.

OBJECTIVE: To compare the characteristics, morbidities and pregnancy outcomes of women with no prenatal care and women receiving some care. METHODS: Medical records were abstracted for demographic variables as well as information concerning substance abuse, sexually transmitted diseases and perinatal outcome. Bivariate associations of descriptive data were tested using odds ratios or Fisher's exact test. Multivariate analysis determined adjusted odds ratios. Significance was set at alpha=0.05. RESULTS: Women who received no prenatal care were more likely to be multiparous, living with at least one child, less educated, uninsured, smoke, use cocaine and have a prior history of substance abuse. Preterm labor, preterm delivery, low birth weight and stillbirth were more common. Syphilis and HIV were found in nearly 5% of women without care. CONCLUSION: Intensive interventions are needed for women who fail to receive prenatal care so as to link these high-risk women to needed services.

Adult↗

Day case management of sickle pain: 3 years experience in a UK sickle cell unit.

A day centre was established to determine whether an alternative approach to the management of uncomplicated sickle pain would improve the quality of care and reduce hospital admissions in patients with sickle cell disease. Since the centre opened there has been a 43% decrease in hospital admissions and 49% decrease in occupied bed days. In the third year, 84% of patients treated for severe sickle pain were managed without the need for hospital admission. A centre offering day case management of painful crisis reduced unnecessary hospital admissions for uncomplicated pain. This approach is safe and cost-effective.

Ambulatory Care↗

Acinar dysplasia: a rare cause of neonatal respiratory failure.

UNLABELLED: Acinar dysplasia is a rare cause of death in the first few hours of life, due to an absence of alveoli. This report presents the first case associated with additional major renal malformations. The diagnosis of acinar dysplasia was unexpectedly made at autopsy. CONCLUSION: Even in the presence of antenatally diagnosed severe anomalies, autopsy may reveal diagnostically important information.

Fatal Outcome↗