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Biomedical subjects

G M Murphy

Publications and source records attributed to G M Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1999

The cutaneous porphyrias: a review. The British Photodermatology Group.

Many patients with cutaneous porphyria have curable or controllable disease; untreated porphyria may prove fatal. The genetic defects and mechanisms underlying porphyria are steadily being delineated, treatments have become more appropriate and genetic counselling is now more accurate. A summary of the basic diagnostic features, management and recent advances in the cutaneous porphyrias is presented, based on a workshop held by the British Photodermatology Group.

Humans↗
PubMed1999

Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin.

Renal transplant recipients have an increased risk of developing skin cancers, which are often multiple and aggressive. Frequently, these tumours develop on a background of widespread epidermal dysplasia. Systemic retinoids are known inhibitors of skin cancer but reports of their use in renal transplant patients are limited. We describe our experience using 0.3 mg/kg daily of acitretin in 16 patients over a 5-year period. Overall, there was a significant reduction in the number of new tumours excised in 12 of 16 patients during treatment compared with the same pretreatment interval. A significant chemoprophylactic effect was shown for up to 4 years of treatment. Patients with five or more tumours prior to acitretin benefited most. Two patients discontinued treatment because of side-effects and two patients developed hyperlipidaemia. Two patients with end-stage graft failure proceeded to haemodialysis. The introduction of low-dose acitretin proved to be a useful strategy in the long-term reduction of skin cancer in renal transplant recipients with multiple skin cancers and extensive epidermal dysplasia.

Acitretin↗
PubMed1999

Is monochromatic irradiation testing useful in the differentiation of drug-induced photosensitivity from chronic actinic dermatitis?

Chronic actinic dermatitis (CAD) is an uncommon, eczematous photosensitive eruption affecting predominantly elderly men and to which drug-induced photosensitivity may sometimes appear clinically identical. This retrospective study compares the monochromatic irradiation results in 11 patients with CAD and 14 patients with drug-induced photosensitivity, to assess whether such testing is useful in the differentiation of these two conditions. Thus, the action spectra of the drug photosensitivity patients were plotted and compared with those of 12 nonphotosensitive control patients: 10 patients were found to be photosensitive in the UVA range; the implicated drugs included quinine, sparfloxacin, amiodarone, doxycycline, mefenamic acid, nalidixic acid, fenbrufen, diclofenac, enalapril, diltiazem and prochlorperazine maleate. One patient on doxycycline was photosensitive in both the UVA and UVB ranges. The remaining three patients were not tested until after discontinuation of their drug and their light tests were then normal. In the CAD group, five patients were photosensitive in the UVA, UVB and visible light ranges and six were photosensitive in the UVA and UVB ranges. Comparison of the mean minimal erythema dose responses then demonstrated dissociation of the drug-induced from the CAD group in the UVB region; the result was statistically significant. This suggests that UVA-sensitivity dissociated from UVB-sensitivity is a relative indicator of drug-induced photosensitivity and monochromatic irradiation testing may therefore be helpful in the differentiation of these two disorders.

Adult↗
PubMed1999

Home phototherapy: report on a workshop of the British Photodermatology Group, December 1996.

Phototherapy is a popular and effective treatment for many patients with skin diseases. However, repeated journeys to hospital for phototherapy can be inconvenient and expensive. If it were available, many patients might prefer home-based phototherapy as long as it was safe and effective. Indeed, many psoriasis patients already self-treat with ultraviolet A sunbeds at home. This report represents a consensus view from a British Photodermatology Group workshop held in December 1996, the purpose of which was to examine the potential role of home-based phototherapy in dermatological practice. We conclude that home-based therapy represents a suboptimal treatment with greater attendant risks than phototherapy in a hospital environment. The level of medical supervision of the home treatment is crucial to its safety and effectiveness. Until further studies are forthcoming, home phototherapy should be largely restricted to those with overwhelming difficulties in attending hospital.

Home Care Services↗
PubMed1999

Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones.

BACKGROUND: Treatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been proposed as the mechanism for the increase in the proportion of deoxycholic acid in bile. AIMS: To study the effects of octreotide on intestinal transit in acromegalic patients during octreotide treatment, and to examine the relation between intestinal transit and bile acid composition in fasting serum. METHODS: Mouth to caecum and large bowel transit times, and the proportion of deoxycholic acid in fasting serum were measured in non-acromegalic controls, acromegalic patients untreated with octreotide, acromegalics on long term octreotide, and patients with simple constipation. Intestinal transit and the proportion of deoxycholic acid were compared in acromegalic patients before and during octreotide. RESULTS: Acromegalics untreated with octreotide had longer mouth to caecum and large bowel transit times than controls. Intestinal transit was further prolonged by chronic octreotide treatment. There were significant linear relations between large bowel transit time and the proportion of deoxycholic acid in the total, conjugated, and unconjugated fractions of fasting serum. CONCLUSIONS: These data support the hypothesis that, by prolonging large bowel transit, octreotide increases the proportion of deoxycholic acid in fasting serum (and, by implication, in bile) and thereby the risk of gallstone formation.

Acromegaly↗
PubMed1999

Multiple perifollicular fibromas.

Perifollicular fibroma is a benign mesodermal tumour of the hair follicle. It can occur as a solitary papule or as multiple lesions that are clinically indistinguishable from other tumours of the pilar apparatus. Multiple perifollicular fibromas may be inherited although the pattern remains unclear. Adnexal tumours can be associated with internal malignancy and perifollicular fibromas have been linked with adenomatous colonic polyps. This report describes a patient with multiple perifollicular fibromas with no associated malignancy to date and a family pedigree suggestive of an autosomal dominant pattern of inheritance.

Adult↗
PubMed1998

Macrophage colony-stimulating factor augments beta-amyloid-induced interleukin-1, interleukin-6, and nitric oxide production by microglial cells.

In Alzheimer's disease (AD), a chronic cerebral inflammatory state is thought to lead to neuronal injury. Microglia, intrinsic cerebral immune effector cells, are likely to be key in the pathophysiology of this inflammatory state. We showed that macrophage colony-stimulating factor, a microglial activator found at increased levels in the central nervous system in AD, dramatically augments beta-amyloid peptide (betaAP)-induced microglial production of interleukin-1, interleukin-6, and nitric oxide. In contrast, granulocyte macrophage colony-stimulating factor, another hematopoietic cytokine found in the AD brain, did not augment betaAP-induced microglial secretory activity. These results indicate that increased macrophage colony-stimulating factor levels in AD could magnify betaAP-induced microglial inflammatory cytokine and nitric oxide production, which in turn could intensify the cerebral inflammatory state by activating astrocytes and additional microglia, as well as directly injuring neurons.

Alzheimer Disease↗
PubMed1998

No neuropathologic evidence for an increased frequency of Alzheimer's disease among elderly schizophrenics.

BACKGROUND: There is currently controversy as to the frequency of Alzheimer's disease (AD) in elderly persons with schizophrenia. Several studies have reported an increased frequency of AD in elderly schizophrenics, whereas others have found no increase. This issue is important because it has been hypothesized that medications used to treat schizophrenia may exacerbate AD histopathology. METHODS: We examined autopsy cases from a state psychiatric hospital and a Veterans Affairs medical center. Charts were reviewed on 166 subjects to determine if the history warranted a DSM-IV diagnosis of schizophrenia. All subjects had complete gross and microscopic neuropathologic evaluations, which were reviewed for evidence of Alzheimer's disease. RESULTS: Retrospective chart review identified 51 subjects over the age of 55 who met DSM-IV criteria for schizophrenia (mean age = 71.7 years, SD = 8.6, range 56-95 years). Of these 51, only I met neuropathologic criteria for AD, a frequency of 2%. CONCLUSIONS: The frequency of subjects meeting neuropathologic criteria for Alzheimer's disease in our sample of schizophrenics was equal to or less than that found in the general population. Because institutionalized populations may contain an excess of elderly schizophrenic patients with severe behavioral pathologies, which may in turn reflect the presence of neurodegenerative processes such as Alzheimer's disease, our results may actually overestimate the frequency of Alzheimer's in the entire schizophrenic population. The frequency of Alzheimer's disease in the elderly with schizophrenia may be less than that in the general population.

Aged↗
PubMed1998

Expression of vascular endothelial growth factor (VEGF) and its receptors is regulated in eyes with intra-ocular tumours.

The immunolocalization and gene expression of vascular endothelial growth factor (VEGF) and its cognate tyrosine kinase receptors, Flt-1 and KDR, has been studied in ocular melanomas and retinoblastomas using in situ hybridization and immunohistochemistry. Tumour-related alterations in VEGF/VEGF-receptor expression have also been examined in separate and uninvolved iris, retina and choroid of the same eyes. Although VEGF immunoreactivity in the normal retina was virtually absent, low-level VEGF expression was evident in the ganglion cell-bodies, Müller cells and in a distinct population of amacrine cells. VEGF gene expression was absent in the iris and choroid of normal eyes. In tumour-bearing eyes, high levels of VEGF protein and gene expression were observed within the vascularized regions of the tumours, while the adjacent retina and choroid showed increased VEGF levels when compared with normals. Flt-1 and KDR gene expression and immunolocalization occurred in VEGF-expressing ganglion, Müller and amacrine cells in normal eyes. Within the intra-ocular tumours, VEGF-receptor gene expression and protein was evident in the endothelial cells and also in cells close to the vessels, while in the adjacent retina, Flt-1 and KDR levels were elevated over normal, especially in the blood vessels. Flt-1 and KDR were both observed at elevated levels in the choroid and iris blood vessels. This study suggests that VEGF, Flt-1 and KDR are expressed by neural, glial and vascular elements within normal human retina. Intra-ocular tumours demonstrate a high level of VEGF and VEGF-receptor expression; within uninvolved, spatially separate retina, choroid and iris in the same eyes, expression is also elevated, especially within the vasculature. Retinal vascular endothelia may respond to high intra-ocular levels of VEGF by increasing expression of their VEGF receptors, a phenomenon which could have relevance to neoplasm-related ocular neovascularization.

Adolescent↗
PubMed1998

A validated technique for the analysis of biliary bile acid secretion in donor livers prior to transplantation.

Many parameters currently used for the pre-transplant assessment of liver allografts, are not reliable enough in predicting the likelihood of early graft dysfunction or non-function. It is generally accepted that bile secretion is a sign of hepatic function post-transplant and that bile flow shows a close linear relationship to the secretion of bile acids ("apparent choleretic activity"). We have studied bile flow, biliary bile acid concentrations and composition and measured apparent choleretic activity from hepatic bile collected with a new technique under controlled conditions at the time of retrieval from 18 donor livers. More than three samples were collected from each of 13 donors and a total of 65 samples of hepatic bile were analysed. Of these, ten showed typical apparent choleretic activity with a positive slope in the regression line analysis (correlation coefficient of 0.9), validating our collection technique.

Adolescent↗
PubMed1998

Altered expression of the p53-regulated proteins, p21Waf1/Cip1, MDM2, and Bax in ultraviolet-irradiated human skin.

The distribution of p21WAf1/CiP1, MDM2, and Bax/Bcl-2 proteins in ultraviolet (UV)-irradiated and nonirradiated human skin was examined immunohistochemically and compared with p53 protein levels. Sun-protected buttock skin from three volunteers was exposed to solar simulated irradiation, and biopsies were performed 0.5, 1, 2, 4, and 24 hours after irradiation as well as control unirradiated skin from the opposite buttock. A similar staining pattern was observed in each of the three volunteers. P53 protein was detectable in all skin samples examined. P21Waf1/CiP1 protein was visible in the nuclei of cells at 4 hours, and staining intensity increased at 24 hours. MDM2 protein expression was noted in isolated nuclei in the epidermis at 24 hours. Bax cytoplasmic staining was evident in the basal layer of the epidermis of all samples, and this staining appeared to increase in intensity in the 4- and 24-hour specimens. There was no Bcl-2 immunohistochemical staining in any sample. These results suggest that p53 and genes/proteins under the control of p53 are altered/ activated in normal human skin in response to UV exposure.

Aged↗
PubMed1998

Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?

1. One hypothesis for the link between inflammatory bowel disease and primary sclerosing cholangitis is that neutrophil activators, such as bacterial chemotactic peptides or neutrophil granule products themselves, pass from the inflamed colon to the liver via an enterohepatic circulation. However, there are no data on biliary concentrations of neutrophil granule products in patients with active and inactive inflammatory bowel disease.2. Gall bladder bile was obtained at laparotomy from 42 patients with ulcerative colitis and 21 patients with Crohn's disease. Biliary lactoferrin and myeloperoxidase concentrations were quantified by ELISA.3. In active ulcerative colitis, the mean lactoferrin concentration in gall bladder bile of 2.8+/-0.40 mg/l was higher than that seen after colectomy (1.2+/-0.11 mg/l; P<0.0001) or in patients with pouchitis (1.8+/-0.34 mg/l; P=0.06). In active Crohn's colitis, the mean lactoferrin concentration was 3.7+/-0.9 mg/l, compared with 1.1+/-0. 24 mg/l in the post-colectomy group (P<0.05) and 3.1+/-0.71 mg/l in those with active ileitis or ileocolitis. In contrast, biliary myeloperoxidase concentrations were low and comparable in all groups, with a mean concentration in the 42 patients with ulcerative colitis of 11.2+/-1.9 microgram/l.4. In contrast to myeloperoxidase, biliary lactoferrin concentrations are increased in active ulcerative colitis and Crohn's disease, and fall with colectomy and with disease remission. These findings indirectly support the hypothesis that bacterial chemotactic peptides (which induce selective degranulation of neutrophil secondary granules), and/or lactoferrin itself, undergo an enterohepatic circulation.

Acute Disease↗
PubMed1998

The APOE epsilon4 allele is associated with decline on delayed recall performance in community-dwelling older adults.

OBJECTIVE: This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults. DESIGN: Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype. SETTING: Aging Clinical Research Center, Stanford University. PARTICIPANTS: One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age. MEASUREMENTS: At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up. RESULTS: Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype. CONCLUSION: These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.

Adult↗