Search PubMed⌕ Search

Biomedical subjects

G M Murphy

Publications and source records attributed to G M Murphy.

At least 91 records · Page 5Linked to original sources
PubMed1998

Porphyria cutanea tarda and human immunodeficiency virus: two cases associated with hepatitis C.

Hepatitis C virus (HCV) was recently recognized as a probable etiologic factor for porphyria cutanea tarda (PCT). A review of the literature revealed 40 cases of PCT associated with the human immunodeficiency virus (HIV). In most of these cases, hepatitis C status was unknown. We describe two patients with PCT who were coinfected with HIV and HCV and discuss the interaction of these two viruses. A diagnosis of PCT, especially in a young patient, should prompt investigation for underlying HIV and HCV infection. Porphyrin studies should be performed in any patient with HIV and photosensitivity. Clinicians should be aware of the infectious risk associated with the vesicles and erosions in these patients.

Adult↗
PubMed1998

Low-dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients.

BACKGROUND: Renal transplant recipients have an increased incidence of skin cancers, which may be multiple and aggressive. OBJECTIVES: The purpose of this study was to examine the chemoprophylactic effects of low-dose etretinate (0.3 mg/kg/day) on skin cancer development in renal transplant recipients and to monitor retinoid toxic effects at this dose. METHODS: All skin lesions were counted and photographed prior to therapy with etretinate. Patients were assessed at monthly intervals for new skin lesions and for retinoid toxicity. RESULTS: Eleven renal transplant recipients participated. There was a significant reduction in the number of skin cancers which occurred during etretinate therapy compared with pre-treatment for 3 and 6 months of treatment, and a trend towards fewer skin cancers in the 12 and 18 month treatment periods. Side-effects were well-tolerated and no significant biochemical effects were observed. CONCLUSION: Low dose etretinate is safe, well-tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients.

Adult↗
PubMed1998

Langerhans cells in benign, premalignant and malignant skin lesions of renal transplant recipients and the effect of retinoid therapy.

BACKGROUND AND DESIGN: Langerhans cells (LC) are a unique population of antigen-presenting cells in the epidermis which may play a role in the defense mechanisms against skin tumors. Renal transplant recipients (RTRs) have a significantly increased incidence of premalignant and malignant skin lesions. Langerhans cells, which are important for local immune surveillance, may be depleted or downregulated in skin neoplasms of RTRs, facilitating their growth. We investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs), five basal cell carcinomas (BCCs), four Bowen's disease, eight dysplastic lesions (actinic keratoses), and three viral warts from 15 RTRs and compared these to the Langerhans cell densities in normal control skin. Eleven RTRs were receiving low-dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of low-dose retinoid therapy on Langerhans cell densities in SCCs from these patients was also assessed. Langerhans cells in frozen tissue sections were stained with the anti-human Leu-6 monoclonal antibody. RESULTS: There was no significant difference in LC numbers between normal skin from RTRs and normal skin from non-immunosuppressed individuals. There was a statistically significant reduction in LC/mm2 and LC/1000 K (keratinocytes) for SCC, BCC, dysplastic lesions and viral warts compared with normal skin (P < 0.001, P < 0.01, P < 0.001, P < 0.05, respectively). There was a trend for an increase in Langerhans cell density in SCCs which developed during etretinate therapy compared with pre-etretinate but the difference was not statistically significant. CONCLUSIONS: In this study of RTRs, a significant reduction in Langerhans cell densities was observed in SCCs, BCCs and dysplastic lesions compared with normal skin. A reduction in Langerhans cell density in viral warts from RTRs was also observed. A working hypothesis may include a multifactorial etiology for this reduction in Langerhans cell densities. It is possible that human papilloma virus (HPV) infection, by reducing intraepidermal Langerhans cell density, may decrease local immune surveillance and facilitate the development of skin cancers. Ultraviolet radiation and immune suppression may also play a role. The marked depletion of Langerhans cells in skin cancers, precursor lesions and viral warts suggests a central role for Langerhans cells in skin cancer promotion in RTRs.

Basal Cell Carcinoma↗
PubMed1997

Cholylglycine hydrolase and 7alpha-dehydroxylase optimum assay conditions in vitro and caecal enzyme activities ex vivo.

Increasing evidence implicates deoxycholic acid (DCA) in the pathogenesis of cholesterol-rich gallbladder stones. However, relatively little is known about the activities of the two intestinal bacterial enzymes (cholylglycine hydrolase and cholic acid 7alpha-dehydroxylase) responsible for the deconjugation and subsequent dehydroxylation of conjugated cholic acid (CA), to form DCA. We, therefore, established optimal reaction conditions for measuring the activities of these two enzymes in vitro, and applied these conditions to the determination of the enzymes in caecal aspirates from six subjects undergoing clinically-indicated colonoscopy. With respect to cholylglycine hydrolase activity: zero order kinetics were found over 20 min at 37 degrees C (pH optimum 4.0), with Km and Vmax values of 1.66 mmol/l and 0.90 mmol CA min(-1) mg prot(-1), respectively. For cholic acid 7alpha-dehydroxylation: zero order kinetics were found over 7.5 min at 37 degrees C, under anaerobic conditions (pH optimum 8.0), with Km and Vmax values of 5.23 x 10(-8) mol/l and 1.88 x 10(-7) mol DCA min(-1) mg prot(-1), respectively. Applying these reaction conditions to the caecal aspirates, endogenous cholylglycine hydrolase activities ranged from 0.49 to 2.43 units (mg protein[-1] min[-1]) and CA 7alpha-dehydroxylase activities from 1.75 to 5.82 x 10(-7) units (mg protein[-1] min[-1]). This study is unique in assaying quantitatively both the deconjugation and dehydroxylation enzyme activities in human caecal samples--an essential first step to further studies of intestinal bacterial enzymes in the pathogenesis of cholesterol gallstone disease.

Amidohydrolases↗
PubMed1997

p53 tumor suppressor gene protein expression in premalignant and malignant skin lesions of kidney transplant recipients.

BACKGROUND: Kidney transplant recipients have an increased incidence of skin cancer, the cause of which is likely multifactorial. Inactivation of the tumor suppressor gene p53 protein may be important. Chemoprophylaxis of skin cancer with retinoids is beneficial in these patients. OBJECTIVE: Our purpose was to investigate the immunohistochemical expression of p53 protein in premalignant and malignant cutaneous lesions in kidney transplant recipients and the effect of low-dose etretinate on p53 expression. METHODS: Paraffin sections were stained with the monoclonal antibody DO-7. RESULTS: Immunoreactivity of p53 was observed in 59% of basal cell carcinomas and more than 60% of squamous cell carcinomas, Bowen's disease, dysplastic lesions, and viral warts. No demonstrable effect of etretinate on p53 expression could be determined. CONCLUSION: The high prevalence of p53 immunoreactivity in premalignant and malignant skin lesions of kidney transplant recipients supports a role for p53 protein in skin cancer. This could be caused by mutation of the p53 gene, inactivation, or failure of degradation of p53 protein.

Adult↗
PubMed1997

Gallstone dissolution with oral bile acid therapy. Importance of pretreatment CT scanning and reasons for nonresponse.

In patients with cholesterol-rich gallbladder stones and a patent cystic duct, complete stone clearance rates of 65-90% have been reported with oral bile acids (OBAs) alone or with adjuvant lithotripsy (extracorporeal shock-wave lithotripsy; ESWL). The aims of the present study were to analyze pretreatment gallstone characteristics that predict the speed and completeness of dissolution with OBAs +/- ESWL, and to assess, in patients with incomplete dissolution, the reasons for the poor response. We compared pretreatment gallstone characteristics in 43 patients who became stone-free after a median of 9 months OBAs +/- ESWL with those in 43 age- and sex-matched patients whose stones failed to dissolve after two years of treatment. In those with incomplete gallstone dissolution, we repeated the oral cholecystogram and computed tomogram (CT) and, in selected patients, obtained gallbladder bile by percutaneous fine-needle puncture. In patients who became stone-free, those with stones that were isodense with bile and/or had CT scores of < 75 Hounsfield units had the fastest dissolution rates. In the 43 nonresponders, the main causes for treatment failure were impaired gallbladder contractility and acquired stone calcification. CT-lucent, noncholesterol stones, or failure of desaturation of bile with the prescribed bile acids, occurred in a minority. We conclude that the pretreatment CT attenuation score predicts both the speed and completeness of gallstone dissolution. In patients with incomplete stone dissolution, the combination of oral cholecystography, CT, and analysis of gallbladder bile will determine the underlying reasons for treatment failure in most, but not all, cases.

Administration, Oral↗
PubMed1997

Inhibition of beta-amyloid formation by haloperidol: a possible mechanism for reduced frequency of Alzheimer's disease pathology in schizophrenia.

Several reports have suggested that the frequency of Alzheimer's disease (AD) neuropathology is significantly reduced in elderly individuals with schizophrenia (SZ), and it has been proposed that medications used for treatment of SZ may be responsible. A central event in AD pathology is the formation of beta-amyloid (A beta) peptide, which is derived by enzymatic processing of its precursor protein. Haloperidol, an antipsychotic medication commonly used in the treatment of SZ, can act as an inhibitor of select proteinases; hence, we examined the ability of this compound to inhibit A beta formation by cultured cells. Haloperidol and, to a lesser extent, droperidol inhibited A beta in a dose-dependent manner. These results may explain the apparent reduction of AD neuropathological changes in elderly patients with SZ as well as provide a possible mechanism for this difference.

Alzheimer Disease↗
PubMed1997

Porphyria cutanea tarda and hematologic malignancy--a report of 4 cases.

Porphyria cutanea tarda has been reported in association with a variety of myeloproliferative and lymphoproliferative disorders, suggesting a possible association between these conditions. We describe four patients presenting within a 12 month period with sporadic porphyria cutanea tarda shortly following the diagnosis of hematologic malignancy. A review of the literature and evidence supportive of a causal association are presented.

Aged↗
PubMed1997

No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease.

OBJECTIVE: The relationship between number of apolipoprotein E epsilon 4 (APOE epsilon 4) alleles and the rate of cognitive decline in patients with Alzheimer's disease was examined. METHOD: Rate of decline in score on the Mini-Mental State was measured during the active phase of the decline curve between Mini-Mental State scores of 23 and 0. To characterize onset, the authors also estimated for each subject the age at which the Mini-Mental State score fell below 23 and obtained a retrospective report of age at onset from the caregiver. The number of APOE epsilon 4 alleles carried by each subject was determined from genomic DNA samples. The study included 86 subjects with probable Alzheimer's disease who had had at least two cognitive evaluations (a mean of 5.6 evaluations per subject over an average period of 3.6 years). RESULTS: The results did not support an association between APOE epsilon 4 dosage and rate of cognitive decline. Age at onset and age at which the Mini-Mental State score fell below 23 were also not related to APOE epsilon 4 dosage. The APOE allele frequencies were similar to those in other studies of subjects with Alzheimer's disease, showing an enrichment of the epsilon 4 allele. CONCLUSIONS: Although the APOE epsilon 4 allele is a risk factor for Alzheimer's disease, there is no support of a strong association between APOE epsilon 4 dosage and rate of cognitive decline. The epsilon 4 allele did not predict age at onset. Methodological inconsistencies may account for discrepancies between these results and previous findings.

Age of Onset↗
PubMed1997

No association between the alpha 1-antichymotrypsin A allele and Alzheimer's disease.

The alpha 1-antichymotrypsin (ACT) A allele was recently associated with Alzheimer's disease (AD), and the ACT AA genotype was reported to be more frequent in AD subjects with the apolipoprotein E (APOE) epsilon4 allele. We examined ACT and APOE genotypes in a sample of 160 subjects with probable AD and in 102 elderly control subjects. ACT A allele frequencies were similar in AD subjects (0.503) and elderly controls (0.519). In addition, we found no evidence that in AD the AA genotype is more frequent in subjects with the APOE epsilon4 allele than in those without it. Our results do not support an association between the ACT A allele and AD.

Adult↗
PubMed1997

Screening of patients with iron overload to identify hemochromatosis and porphyria cutanea tarda.

OBJECTIVE: To assess the importance of iron overload as a risk factor for porphyria cutanea tarda (PCT). DESIGN: Prospective study during a 4-month period. SETTING: Departments of emergency care, gastroenterology, and dermatology in a tertiary referral center. PATIENTS: Patients were deemed eligible for inclusion in the study if serum ferritin levels were greater than 500 micrograms/L (normal range: females, < 125 micrograms/L; males, < 325 micrograms/L). MAIN OUTCOME MEASURES: Porphyrin excretion profiles were analyzed on all patients included in the study, where clinically relevant. A diagnosis of PCT was confirmed biochemically in all cases. The HLA typing was then performed on newly diagnosed cases of PCT. RESULTS: Of 4127 patients tested, 240 patients with an elevated serum ferritin level were identified, of whom 74 had an elevated serum ferritin level of more than 500 micrograms/L. Of the latter group, 17.5% had hemochromatosis and 6.7% had PCT. The incidence of PCT in the hemochromatosis group was 23%; HLA typing revealed the presence of at least 1 of the hemochromatosis markers. CONCLUSIONS: A high serum ferritin level in the absence of evident cause should prompt investigation for both hemochromatosis and PCT. The HLA heterozygosity for hemochromatosis in some patients with PCT may be a cause of hepatic siderosis.

Adult↗