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Biomedical subjects

G M Murphy

Publications and source records attributed to G M Murphy.

At least 235 records · Page 13Linked to original sources

Hydroxychloroquine in polymorphic light eruption: a controlled trial with drug and visual sensitivity monitoring.

A double-blind controlled trial of oral hydroxychloroquine (HC) treatment in polymorphic light eruption (PLE) was completed in 13 patients on active treatment and 15 on placebo during June, July and August 1982. HC dose was 400 mg daily for the first month and 200 mg daily thereafter. Exposure to ambient solar ultraviolet radiation (UVR) was monitored throughout the trial by polysulphone film lapel badges. Patients scored their symptoms on a visual analogue scale. Drug concentration was monitored in plasma and hair, and oculotoxicity was assessed by visual contrast sensitivity. Moderate clinical improvement occurred, associated with a statistically significant improvement in skin rash (P less than 0.01).

Adult↗

Prophylactic PUVA and UVB therapy in polymorphic light eruption--a controlled trial.

A double-blind controlled trial of low-dose prophylactic oral psoralen photochemotherapy (PUVA) and ultraviolet-B (UVB) irradiation therapy was undertaken from April to September 1983 in 42 patients with polymorphic light eruption (PLE). Patients were randomly allocated to three groups, PUVA with oral 8-methoxypsoralen (8-MOP), UVB with oral placebo, and control low-dose UVA with oral placebo. The initial dose given to each active treatment group was a third of the predetermined minimal phototoxic or erythema dose, followed three times weekly for 6 weeks by doses incremented by an eighth on each occasion in the PUVA group and by a seventh in the UVB group. Ultraviolet radiation exposure was monitored throughout with polysulphone film lapel badges. Patients recorded their symptoms on a visual analogue scale. Symptoms of rash and itch in patients treated with PUVA and UVB were significantly less affected by increasing exposure to ultraviolet radiation than were these symptoms in control patients.

Clinical Trials as Topic↗

Role of polyamines in intestinal adaptation in the rat.

The cellular mechanisms controlling adaptive intestinal mucosal hypo- and hyperplasia are poorly understood but changes in tissue polyamine levels and in the activity of the key enzymes controlling their synthesis (ornithine decarboxylase: ODC) and degradation (diamine oxidase: DAO) have been implicated. Therefore, in two models of adaptive mucosal hyperplasia (pancreatico-biliary diversion, PBD, achieved by surgically transposing the jejunum to lie between pylorus and ampulla of Vater, and 90% small bowel resection, SBR-both studied 8 weeks after surgery) and in one model of hypoplasia (8 days total parenteral nutrition) we measured indices of mucosal mass (wet weight, protein and DNA per 10-cm intestine), the growth-associated polyamines (putrescine, spermidine and spermine per 10-cm intestine and per mg DNA) and DAO activity in the duodenum, five 10-cm segments of jejunum, five 10-cm segments of ileum and in the colon, and compared the results with those found in transected or unoperated controls. The results for the indices of mucosal mass confirmed that TPN led to a modest degree of small bowel mucosal hypoplasia whilst PBD, and particularly 90% SBR, stimulated marked adaptive hyperplasia. There were corresponding changes in the amounts of putrescine and spermidine (but not of spermine)-not only when the results were expressed per unit length but also when calculated per mg mucosal DNA and in the ratio of spermidine:spermine. There was an increasing proximal-to-distal gradient in mucosal DAO per unit length intestine in all experimental groups but when the results were expressed per mg DNA, the ileal DAO levels were significantly reduced in the PBD and resection groups, when compared with the controls. These data support the hypothesis that polyamines play a major, and perhaps a controlling, role in regulating adaptive intestinal mucosal growth.

Amine Oxidase (Copper-Containing)↗

Mucosal polyamine profile in normal and adapting (hypo and hyperplastic) intestine: effects of DFMO treatment.

The polyamines, putrescine, spermidine, and spermine, are believed to play an important role in modulating normal and adaptive intestinal mucosal growth. Polyamine synthesis is rate limited by ornithine decarboxylase (ODC) and ODC activity is specifically inhibited by -difluoromethyl ornithine (DFMO). To assess the importance of polyamines in adaptive growth we first measured mucosal polyamine profiles at different sites in the normal rat intestine and compared the results with those obtained in adaptive hypoplasia (seven days parental nutrition, TPN), in the adaptive hyperplasia of two weeks after 90% small bowel resection (SBR) or pancreatico biliary diversion (PBD). We then examined the effects of DFMO (2% in drinking water, daily from two days before surgery) on the polyamine concentrations and the adaptive response to PBD. The hyperplasia of SBR and PBD was associated with increases in all the polyamine concentrations particularly putrescine. TPN induced a modest degree of hypoplasia and little change in polyamine synthesis resulting in subnormal polyamine concentrations and significantly inhibited the mucosal adaptive response. Changes in polyamine metabolism are important in intestinal mucosal adaptation and by controlling these changes adaptive growth can be controlled.

Adaptation, Physiological↗

Volumetric asymmetry in the human amygdaloid complex.

The amygdaloid complex was parcellated into 15 nuclei based on cytoarchitecture in 19 human brains. The volumes of the nuclei were determined in the right and in the left hemisphere for each case. A multivariate analysis showed that the amygdaloid complex is asymmetrical between the hemispheres, with the lateral nucleus of the amygdala, which is larger in the right hemisphere, showing the strongest volumetric asymmetry. These findings are discussed in relation to the amygdala's role as a mediator between limbic and cortical processing, and in light of the right hemisphere's specialization for emotional behaviors.

Aging↗

Polyamine distribution in the rat intestinal mucosa.

As the first step in a study of mucosal polyamine metabolism during intestinal adaptation, we have measured mucosal polyamine concentrations at different sites along the normal rat intestine. Putrescine, spermidine, spermine and cadaverine were measured by spectrofluorometric analysis after thin-layer chromatography of their dansylated derivatives. Spermidine was present in the largest amounts at each of the sampling sites. The ratio of the concentration of spermidine to that of spermine paralleled the established pattern of cellular proliferation in the normal intestine as did the putrescine concentration (nmol per 10 cm) which decreased from duodenum to colon. These results provide the essential background to an assessment of the role of polyamines in the intestinal adaptive response.

Animals↗

The human medial amygdaloid nucleus: no evidence for sex difference in volume.

The volume of the medial nucleus of the amygdala was determined in the right and in the left hemispheres in 17 human brains ranging in age from 35 weeks of gestation to 94 years of age. An analysis of covariance which adjusted for differing age and brain size distributions in the male and female samples showed no significant sexual dimorphism in medial nucleus volume. This finding is discussed in relation to evidence for sexual dimorphism in the medial nucleus of the amygdala in animal brains.

Adolescent↗

Effect of obesity and weight reduction on biliary cholesterol saturation and the response to chenodeoxycholic acid.

Biliary cholesterol saturation indices (SI's) were measured in fasting duodenal bile from (i) obese and non-obese individuals with and without cholesterol gallstones, (ii) obese individuals undergoing weight reduction and (iii) obese gallstone patients receiving chenodeoxycholic acid (CDCA) therapy. Biliary lipid secretion rates were also measured in three obese subjects before and during 11 days starvation. The mean SI in fifteen non-obese controls (0.89 +/- SEM 0.06) was significantly lower than that in the twenty-four obese without (1.14 +/- 0.07; P less than 0.01), and in the twenty-nine non-obese with gallstones (1.30 +/- 0.05; P less than 0.001) while in sixteen obese gallstone patients, the mean SI of 1.55 +/- 0.06 was significantly higher than that seen in the other three groups (P less than 0.01-0.001). Although fifteen obese subjects lost 15% of their initial body weight during dieting, this did not change their SI's consistently. However in three obese individuals, total starvation did reduce the SI's and significantly lowered the biliary cholesterol secretion rate. Ten obese gallstone patients responded to 15.8 +/- 0.3 mg CDCA kg-1 day-1 by developing unsaturated fasting duodenal bile (SI 0.89 +/- 0.04). A further increase in CDCA dose to 19.0 +/- 0.7 mg kg-1 day-1, as a result of reducing body weight, was more effective in lowering SI's (0.75 +/- 0.06, range 0.51-1.0) than that achieved by increasing the dose to 18.9 +/- 0.46 mg kg-1 day-1 through more capsules per day (SI 0.89 +/- 0.03, range 0.67-1.25). These studies show that (i) biliary cholesterol SI's are greater when obesity and gallstones occur together than in either obesity or gallstones alone, and (ii) although weight loss in obese individuals does not consistently alter biliary cholesterol SI's, it may be beneficial in obese patients receiving CDCA therapy for gallstone dissolution.

Adolescent↗

Gall stone disease without gall stones--bile acid and bile lipid metabolism after complete gall stone dissolution.

Although bile acid and bile lipid metabolism have been studied in established cholelithiasis, little is known about them in patients destined to develop gall stones, but in whom the stones have not yet appeared (prestone gall stone disease). After confirmed complete gall stone dissolution and withdrawal of treatment, gall stones recur frequently. Before the stones reappear, these patients have 'poststone gall stone disease'. In 13 such patients we confirmed complete gall stone dissolution with two normal cholecystograms and in 11 of the 13 by normal ultrasonography, measured bile acid and bile lipid composition in fasting duodenal bile, bile acid synthesis from marker corrected three day faecal bile acid excretion, bile acid pool size using an abbreviated isotope dilution technique, 'steady-state' bile lipid secretion using a duodenal amino acid perfusion system and then calculated the enterohepatic cycling frequency of the bile acid pool and the relationship between pool size and body weight. The results confirm that after withdrawal of treatment the biliary cholesterol saturation index reverts to levels (1.6 +/- SEM 0.4) comparable with those before dissolution therapy first began (1.6 +/- 0.2; NS). The mean bile acid pool size in the 13 patients of 4.4 +/- 0.5 mmol was comparable with that in untreated gall stone patients. Pool size was significantly smaller in the nine non-obese patients (3.5 +/- 0.3), than in the four obese (6.0 +/- 0.8; p less than 0.05). It also correlated significantly with body weight (r = 0.72) and with %IBW (r = 0.79). The coefficients of variation for biliary bile acid, phospholipid and cholesterol secretion were high, but the mean hourly secretion rates were of the same order as those seen in untreated gall stone patients studied with the amino acid duodenal perfusion stimulus. These results provide a baseline for assessing the response to postdissolution treatment and may indicate metabolic events leading to gall stone formation.

Adult↗

Fasting and postprandial ileal function in adapted ileostomates and normal subjects.

The output of 11 established ileostomies was compared with ileal flow measured by intestinal perfusion in five normal volunteers when fasting and during the ileal passage of test meals containing different proportions of medium chain triglyceride and long chain triglyceride. Oroileal transit of the meal was the same in the two groups, but ileostomy output was less than ileal flow of normal persons both fasting (16.3 +/- 10.9 vs 62.4 +/- 24.7 ml/h, p less than 0.001) and after the long chain triglyceride rich meal (35.4 27.0 vs 96.1 +/- 20.2 ml/h, p less than 0.001). After ingestion of the medium chain triglyceride rich meal, ideal flow failed to increase in normal subjects but in ileostomates the changes in flow after medium chain triglyceride and long chain triglyceride rich meals were not significantly different. The fasting ileostomy effluent composition differed from that of normal fasting ileal content in having a higher concentration of potassium (8.0 +/- 2.9 vs 4.7 +/- 0.6 mmol/1, p less than 0.04) and a higher osmolality (353 +/- 63 vs 287 +/- 5 mosm/kg, p less than 0.05). Sodium concentration tended to be lower in ileostomy effluent, but in contrast to previous reports, ileostomy effluent was of consistently alkaline pH (7.2 +/- 0.3). These concentrations were not significantly altered by either type of meal. The long chain triglyceride rich meal increased the ileal flow of bile acids in both normal subjects and ileostomates, whereas the medium chain triglyceride rich meal increased bile acid flow in ileostomates but not in normal subjects, possibly reflecting a different amount of the bile acids in the ileum of the ileostomate. In the adapted ileostomate, the low volume and high potassium concentration of fasting effluent suggest that sodium and water absorption are continuously stimulated by chronic salt depletion.

Adaptation, Physiological↗

Sunscreens.

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Humans↗

Cyclosporine and experimental skin allografts: long-term survival in rats treated with low maintenance doses.

Although cyclosporine (CsA) is a powerful immunosuppressive agent in organ transplantation, its efficacy in skin transplantation has not been examined completely. We have tested it as primary immunosuppression in a rat skin allograft model. Histoincompatible Brown-Norway skin grafts are rejected in untreated Lewis hosts within 9 +/- 1 days but survive for 22 +/- 3, 34 +/- 2, or 41 +/- 8 days after 7, 14, or 21 days of CsA treatment (15 mg/kg per day subcutaneously), respectively (p less than 0.001). Animals treated daily for 4 weeks died from drug toxicity; however, an initial 2-week course followed by a low maintenance dose (15 mg/kg every fourth day) produced indefinite (greater than 150 days) graft acceptance without side effects. The long-surviving grafts were supple, grew long hair, and showed normal histology. When the drug was stopped at any time during this maintenance period, early signs of rejection (hair loss, epidermal breakdown, and localized ulceration) occurred, which could be reversed completely by a short CsA "pulse" (15 mg/kg per day for 7 days). These experimental data support the potential application of CsA immunosuppression in human skin allotransplantation.

Animals↗

On the brain of a scientist: Albert Einstein.

Neuron:glial ratios were determined in specific regions of Albert Einstein's cerebral cortex to compare with samples from 11 human male cortices. Cell counts were made on either 6- or 20-micron sections from areas 9 and 39 from each hemisphere. All sections were stained with the Klüver-Barrera stain to differentiate neurons from glia, both astrocytes and oligodendrocytes. Cell counts were made under oil immersion from the crown of the gyrus to the white matter by following a red line drawn on the coverslip. The average number of neurons and glial cells was determined per microscopic field. The results of the analysis suggest that in left area 39, the neuronal: glial ratio for the Einstein brain is significantly smaller than the mean for the control population (t = 2.62, df 9, p less than 0.05, two-tailed). Einstein's brain did not differ significantly in the neuronal:glial ratio from the controls in any of the other three areas studied.

Aged↗