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Biomedical subjects

R Coleman

Publications and source records attributed to R Coleman.

At least 145 records · Page 8Linked to original sources
PubMed1997

Genetic studies of atopy and atopic dermatitis.

Atopy and the atopic disorders are likely to result from multifactorial inheritance, with interaction between genetic and environmental factors. It has been proposed that at least two major mechanisms, non-antigen specific (total IgE levels) and antigen specific (specific IgE antibodies and skin tests), regulate the immune response to allergens in humans: firstly, a gene/genes independent of the human leucocyte antigen system which is involved in the regulation of total IgE levels, and secondly, a specific immune response gene/genes associated with major histocompatibility complex class II genes which are involved in antigen-specific mechanisms. Candidate genes have been proposed for both mechanisms and linkage has been found between atopy and at least three different gene loci. This paper reviews the evidence supporting a genetic basis for atopy and atopic dermatitis and outlines recent advances in the molecular genetic mapping of genes associated with these disorders.

Dermatitis, Atopic↗
PubMed1997

Chronic mucocutaneous candidosis associated with hypothyroidism: a distinct syndrome?

Chronic mucocutaneous candidosis (CMC) is a rare, complex disorder characterized by chronic and recurrent candida infections of the skin, nails and oropharynx. In over 50% of cases there is an associated endocrine disease, the complex being described as the candida endocrinopathy syndrome. Inheritance of familial endocrine associated cases has been thought to follow an autosomal recessive pattern. In addition, autosomal recessive and autosomal dominant forms of CMC not associated with endocrinopathy have been described. We report a new syndrome in which there is vertical transmission of CMC within families associated with primary hypothyroidism. This suggests that the candida endocrinopathy syndrome can be subdivided into at least two types, one associated with hypoparathyroidism and/or hypoadrenalism which is inherited as an autosomal recessive trait, the other associated with hypothyroidism which is an autosomal dominant disease. We emphasize the importance of early and regular monitoring thyroid function in individuals with CMC and a need to provide appropriate genetic counselling to affected members.

Adult↗
PubMed1997

Ramipril-associated lichen planus pemphigoides.

We report the first case of lichen planus pemphigoides (LPP) secondary to ingestion of ramipril, an angiotensin-converting enzyme inhibitor. Clinical, histological and immunofluorescent findings were all consistent with a diagnosis of LPP. Linear basement membrane zone (BMZ) staining with IgG and C3 was only seen at the roof of split-skin preparations and circulating autoantibody to the BMZ was present at a titre of 1/100. Controlled immunoblotting of epidermal extracts detected the bullous pemphigoid antigens of 230 and 180 kDa.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Off-label drug use in human immunodeficiency virus disease.

We wished to determine the extent to which drugs used to treat HIV disease and its clinical manifestations are prescribed for conditions other than those listed on the U.S. Food and Drug Administration's approved drug label, how such "off-label" use varies by patient characteristics and type of HIV-related medical condition, and the extent to which physicians alter the way they treat HIV-related conditions because of reimbursement problems associated with off-label drug use. We surveyed 1,530 primary care providers for people with HIV disease between February and May 1993. A three-part survey instrument was used to obtain data on the drugs prescribed for the last three patients with HIV disease treated by the provider, the preferred choice of therapy for 32 specific HIV-related conditions, and the extent to which providers faced reimbursement problems regarding the use of drugs for off-label indications. Three drug compendia were used as cited sources of off-label drug uses. In all, 387 (32%) evaluable surveys were returned, yielding data on 1,148 patients. The majority (81%) of patients received at least one drug off-label, and almost half (40%) of all reported drug therapy was off-label. Most off-label drug use was for treatment and prevention of HIV-related opportunistic infections, which frequently represented the community standard of practice (e.g., trimethoprim/sulfamethoxazole for prevention of Pneumocystis carinii pneumonia), or the de facto standard of practice when no licensed therapies were available (e.g., drugs for treatment of Mycobacterium avium complex, MAC). More than 75% of off-label usage was cited in at least one of the three authoritative medical compendia. The use of drugs for off-label indications in HIV care is common and frequently represents community standards of care. Reliance on drug compendia for support of off-label drug use accounts for the majority of such uses, although many legitimate off-label uses may not be included because of compendia publication lag. The prevalence of off-label drug use in routine clinical practice and the development of newer and more costly drugs for treatment of HIV and its medical complications argues for the articulation of an explicit national reimbursement policy for off-label uses of prescription drugs so that medically appropriate therapies will be available to those with insurance in a rational, consistent way.

AIDS-Related Opportunistic Infections↗
PubMed1996

S-adenosyl-L-methionine prevents disruption of canalicular function and pericanalicular cytoskeleton integrity caused by cyclosporin A in isolated rat hepatocyte couplets.

Isolated rat hepatocyte couplets were used to study the effect of S-adenosyl-L methionine (SAMe) treatment on disruption of canalicular function caused by cyclosporin A (CyA). Canalicular function was assessed by counting the percentage of couplets that were able to accumulate the fluorescent cholephile choly-lysyl-fluorescein (CLF) into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA). Cotreatment with 1 mmol/L SAMe prevented the inhibition of canalicular vacuole accumulation caused by CyA (75 nmol/L and 100 nmol/L), whereas treatment with it after CyA was unsuccessful. SAMe prevented the dose dependent reduction caused by CyA (5 nmol/L-1 mumol/L) both on CVA and on retention of CLF preaccumulated within the canaliculus, the effect on retention being complete. No difference in intracellular content of reduced glutathione (GSH) between the control and any dose level of the immunosuppressor, with or without SAMe treatment was observed, suggesting that changes in intracellular reduced GSH levels are not involved in the effects of SAMe. F-actin was stained with fluorescein-isothiocyanate phalloidin and fluorescence measurements were performed by confocal microscopy. The ratio of the percanalicular area fluorescence/total couplet fluorescence, indicative of F-actin distribution, significantly decreased with CyA. However, cotreatment of CyA with SAMe protected the integrity of the pericanalicular cytoskeleton, suggesting that this beneficial effect on canalicular function may maintain canalicular contractions and/or preserve tight junction function. Results are discussed in relation to possible involvement of the transmethylation pathway, modifications in membrane fluidity, effects on bile acid transport, and of inhibition of uptake of CyA. They suggest that SAMe could be a good candidate for protecting against CyA-induced membrane dysfunction.

Actins↗
PubMed1996

A new cryosurgical device for controlled freezing.

A new cryosurgical device was developed in this study to facilitate examination of factors affecting the outcome of cryotreatment. Special emphasis was placed on the control of the cooling rate at the freezing front. In the new computer-controlled cryosurgical device, the controlling variable is the cryoprobe temperature, which is calculated to ensure prespecified cooling rates at the freezing front. Details of the new cryodevice, results of a validation test, and the system characteristics are presented in Part I of this study. In this part of the study initial results of 13 in vivo experimental cryotreatments, including histological observations, are presented. The in vivo pilot investigations include the normal, healthy skin and the underlying skeletal muscle of the thighs in rabbits. Using low cooling rate-controlled freezing, the new cryosurgical device is demonstrated here as an effective surgical tool. An in vivo temperature measurement technique is employed based on miniature thermocouples and X-ray images. Thermal analysis of the heat transfer in the cryotreated tissue is presented, based on the temperature measurements and on numerical heat transfer simulations. Cryotreated tissue was extracted either immediately or 4 or 7 days following the procedure. The histological observations on the skeletal muscle of the 4- and 7-day postcryoinjury were not substantially different. The effective penetration depth of the cryolesion was in the range of 5-15 mm, possibly extending up to 25 mm, depending on the specific area treated and operating parameters. The cryotreatment resulted in complete destruction of cells in the skin followed by rapid replacement by epithelial cells. Histological responses to cryotreatment of skeletal muscle were similar to those resulting from a range of traumatic episodes, e.g., crush damage. It was also found that most of the blood vessels in the cryotreated region remained intact without histological evidence of extravasation of erythrocytes.

Animals↗
PubMed1996

Comparison of the effects of redox cycling and arylating quinones on hepatobiliary function and glutathione homeostasis in rat hepatocyte couplets.

Menadione (2-methyl-1,4-naphthoquinone, a redox cycling and arylating quinone; 5-100 microM) inhibited the canalicular vacuolar accumulation (CVA) of a fluorescent bile acid, cholyl-lysyl-fluorescein (CLF), in rat hepatocyte couplets. This was associated with depletion of reduced glutathione and accumulation of oxidized glutathione, the latter indicating that the concentrations of menadione used were able to induce oxidative stress. There was no associated cytotoxicity as indicated by ATP content. Treatment of couplets with the redox cycling quinone 2,3-dimethoxy-1,4-naphthoquinone (up to 100 microM) had relatively little effect on CVA, suggesting that the magnitude of reactive oxygen formation induced by this compound was insufficient to disrupt canalicular integrity. In comparison, the arylation of protein thiol groups by p-benzoquinone (up to 100 microM) proved to be more potent in inhibiting canalicular vacuolar accumulation. The predominant mechanism of menadione-induced inhibition of couplet hepatobiliary function is therefore more likely to involve the arylation of critical thiol groups (such as those in the F-actin cytoskeleton) rather than their oxidation. The oxidative effects of menadione could, however, potentiate the deleterious effects induced by arylation, such as by reduced glutathione depletion.

Adenosine Triphosphate↗
PubMed1996

Patient reactions to met and unmet psychological need: a critical incident analysis.

Patients with cancer must deal with a variety of psychological and social difficulties, but the extent to which staff assist patients with these difficulties is not clear. Using the Critical Incident Technique (CIT), patients attending a Cancer Centre were asked to describe situations in which their emotional needs were, and were not, met by staff. Although most patients were able to describe a situation in which their needs were met by staff, 23% also described a situation in which this was not the case. These latter incidents were often related to anxiety, confusion and a wish to sever links with the hospital. Patients who reported that their needs were not met requested more staff time and further information about their diagnosis and treatment.

Adaptation, Psychological↗
PubMed1996

PK 11195 aggravates 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic porphyria in rats.

There is evidence to suggest that peripheral-type benzodiazepine receptors (PBR) are involved in porphyrin transport during erythroid differentiation, and it is possible that these receptors have an important role in heme biosynthesis. We examined the biochemical and ultrastructural alterations in rat liver following experimentally induced acute hepatic porphyria, as well as the effects of the administration of a selective PBR ligand, PK 11195. The most severe pathological conditions were found in rats that received a combined treatment of the porphyrinogenic agent 3,5-diethoxycarbonyl-1,4- dihydrocollidine (DDC) and PK 11195. Transmission electron microscopy showed a correlation between the ultrastructural pathology of the liver, the total porphyrin levels in urine and liver, and the porphobilinogen levels in urine. Hepatocytes in this acute porphyria showed the development of large secondary lysosomes containing crystalline aggregates of protoporphyrin. Bile canaliculi were grossly enlarged, contained aggregates of protoporphyrin crystals, and showed the presence of bile thrombi. In addition, prominent bundles of collagen fibers (fibrosis) were commonly found in livers of rats that had been treated with DDC or DDC and PK 11195. We conclude that the administration of PK 11195 to porphyric rats aggravates porphyrin accumulation and cellular damage in the liver. Perhaps this evidence suggests that PK 11195 blocks the binding of protoporphyrin IX to PBR, thus elevating the content of protoporphyrin IX in liver.

Animals↗
PubMed1996

Directional-tip endotracheal tubes for blind nasotracheal intubation.

OBJECTIVES: To compare initial success rates of blind nasotracheal intubation using directional-tip endotracheal tubes vs standard endotracheal tubes. METHODS: A prospective trial comparing directional-tip and standard endotracheal tubes during initial attempts at blind nasotracheal intubation (BNTI) at a university hospital ED. Using an alternating schedule, the directional-tip or standard tube was used for the first attempt at BNT1. An attempt was defined as beginning when the tube was placed through the nose into the posterior pharynx and ending when the patient was intubated or the tube was removed from the nares. After the intubation, the physician graded the difficulty of the technique (i.e., easy/routine, intermediate, difficult, or unable to intubate nasally). RESULTS: There were 49 patients entered over 5 months. Patient presentations for the intubations were trauma (45.8%), overdose (33.3%), respiratory/cardiac event (12.5%), seizure (2.1%), and other (6.3%). Intubation was successful on the first attempt in 18 of 21 patients (86%; 95% CI, 64% to 97%) for the directional-tip tube vs 16 of 28 patients (57%; 95% CI, 37% to 76%) for the standard tube (p = 0.03). The groups did not differ in age, sex, clinical presentation, or perceived difficulty of intubation. Only 1 patient could not be intubated nasally and was subsequently intubated orally. CONCLUSION: The use of directional-tip tubes may improve the success rate of the first attempt at BNTI.

Adolescent↗
PubMed1996

Plasma cell tumour in a renal transplant recipient.

We report the occurrence of a plasma cell tumour in an immunosuppressed renal allograft recipient. The lesion showed polyclonal proliferation of plasma cells with equal staining for kappa and lambda chains. Purely cutaneous plasma cell tumours are uncommon, few cases having been reported in immunosuppressed patients.

Anti-Inflammatory Agents↗