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Biomedical subjects

C M Williams

Publications and source records attributed to C M Williams.

At least 91 records · Page 5Linked to original sources

Comparison of the Q-switched alexandrite (755 nm) and Q-switched Nd:YAG (1064 nm) lasers in the treatment of benign melanocytic nevi.

BACKGROUND: A variety of pigmented lesions have been shown to be effectively treated with several pigment-specific laser systems currently available. There has been recent evidence to indicate that they may also be useful in the treatment of melanocytic nevi. OBJECTIVE: To compare the clinical and histologic effects of the Q-switched (QS) alexandrite (755 nm) and Nd:YAG (1064 nm) lasers in the treatment of melanocytic nevi. METHODS: Eighteen patients received three QS alexandrite and Nd:YAG laser treatments to either half of a large nevus or to two small adjacent nevi. Tissue biopsies were obtained for histologic examination. Degree of clinical improvement was determined by comparative photographic global assessment scores. The amount of melanin present within the nevi before and after laser irradiation was measured by reflectance spectrometry. RESULTS: Clinical global assessment scores were significantly reduced in all QS alexandrite and QS Nd:YAG laser-treated nevi after three treatments. Melanin reflectance spectrometry scores improved after the first laser treatment only. Histologically, a significant reduction in epidermal pigmentation and melanocytes were observed following laser irradiation with either QS system. CONCLUSION: Both the QS alexandrite and Nd:YAG laser systems resulted in significant improvement (lightening) of treated nevi. The QS alexandrite laser produced slightly better results using the parameters outlined.

Humans↗

Nutrition.

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Cholesterol↗

Quantitation of apolipoprotein B-48 in triacylglycerol-rich lipoproteins by a specific enzyme-linked immunosorbent assay.

This paper describes the use of an antiserum, specific for apolipoprotein (apo) B-48, in a competitive, enzyme-linked immunosorbent assay (ELISA) for apo B-48 in triacylglycerol-rich lipoprotein (TRL) fractions prepared from fasting and post-prandial plasma samples. Previously we showed the antiserum to act as an effective immunoblotting agent following sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Its use in this ELISA indicates that the antiserum recognises the C-terminal region of the protein on the surface of lipoprotein particles. The ELISA had a sensitivity of less than 37 ng/ml and intra- and inter-assay coefficients of variation of 3.8% and 8.6%, respectively. There was no cross-reaction in the ELISA against serum albumin, ovalbumin, thyroglobulin, or apo B-100 (purified by immunoaffinity chromatography), and high lipid concentrations (as Intralipid) did not interfere. A low density lipoprotein fraction reacted in the ELISA but SDS-PAGE-Western blot analysis confirmed the presence, in the fraction, of a small amount of apo B-48, indicating the existence of low density dietary-derived lipoprotein particles. ELISA and SDS-PAGE-Western blot analysis were used to measure apo B-48 in 12 series of postprandial samples collected from 4 diabetic and 8 normal subjects, following test meals of varying fat content. The mean correlation between the two methods was r = 0.74. The mean fasting concentration of apo B-48 in the TRL fractions from 15 healthy men was 0.46 microgram/ml of plasma.

Antibody Specificity↗

Nutritional status and clinical outcome in elderly female surgical orthopaedic patients.

The possible relationship between nutritional status and clinical outcome following orthopaedic hip surgery was investigated. The nutritional status of 60 elderly female patients admitted for elective total hip replacement (THR) and emergency fractured neck of femur surgery (FNF) was measured over time. Specific measures of clinical outcome, including well-being and functional status, were monitored during hospital stay and at 4, 8 and 26 weeks following discharge. Patients were allocated to a high nutritional risk group where any three of the following were less than the 5th percentile value: serum albumin, haemoglobin, triceps skinfold thickness, mid-upper arm muscle circumference and body weight. Using this definition, malnutrition was present in 4% of THR patients and 41% of FNF patients. It was found that the high risk patients had significantly longer convalescence periods, (median stay 27.5 days compared with 0 days, P < 0.0009), and a greater proportion were dependent upon walking frames at 6 months (46% compared with 11%, P < 0.01). Fifty percent of the high risk patients had been living independently prior to admission, in contrast only 29% had returned to their homes at 6 months after discharge. The results indicate an apparent link between clinical outcome and nutritional status based upon the allocation procedure employed, which has the potential for ensuring cost-effective nutritional intervention.

Journal Article↗

Meal frequency; does it determine postprandial lipaemia?

OBJECTIVE: To determine the effect of altering meal frequency on postprandial lipaemia and associated parameters. DESIGN: A randomized open cross over study to examine the programming effects of altering meal frequency. A standard test meal was given on three occasions following: (i) the normal diet; (ii) a period of two weeks on a nibbling and (iii) a period of two weeks on a gorging diet. SETTING: Free living subjects associated with the University of Surrey. SUBJECTS: Eleven female volunteers (age 22 +/- 0.89 y) were recruited. INTERVENTIONS: The subjects were requested to consume the same foods on either a nibbling diet (12 meals per day) or a gorging diet (three meals per day) for a period of two weeks. The standard test meal containing 80 g fat, 63 g carbohydrate and 20 g protein was administered on the day prior to the dietary intervention and on the day following each period of intervention. MAJOR OUTCOME MEASURES: Fasting and postprandial blood samples were taken for the analysis of plasma triacylglycerol, non-esterified fatty acids, glucose, immunoreactive insulin, glucose-dependent insulinotropic polypeptide levels (GIP) and glucagon-like peptide (GLP-1), fasting total, low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations and postheparin lipoprotein lipase (LPL) activity measurements. Plasma paracetamol was measured following administration of a 1.5 g paracetamol load with the meal as an index of gastric emptying. RESULTS: The compliance to the two dietary regimes was high and there were no significant differences between the nutrient intakes on the two intervention diets. There were no significant differences in fasting or postprandial plasma concentrations of triacylglycerol, non-esterified fatty acids, glucose, immunoreactive insulin, GIP and GLP-1 levels, in response to the standard test meal following the nibbling or gorging dietary regimes. There were no significant differences in fasting total or LDL-cholesterol concentrations, or in the 15 min postheparin lipoprotein lipase activity measurements. There was a significant increase in HDL-cholesterol in the subjects following the gorging diet compared to the nibbling diet. DISCUSSION: The results suggest that previous meal frequency for a period of two weeks in young healthy women does not alter the fasting or postprandial lipid or hormonal response to a standard high fat meal. CONCLUSIONS: The findings of this study did not confirm the previous studies which suggested that nibbling is beneficial in reducing the concentrations of lipid and hormones. The rigorous control of diet content and composition in the present study compared with others, suggest reported effects of meal frequency may be due to unintentional alteration in nutrient and energy intake in previous studies.

Adult↗

Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye laser.

Despite increasing knowledge of wound healing and collagen metabolism, hypertrophic scars and keloid scars are difficult to eradicate. Median sternotomy scars are often hypertrophic or keloidal. We treated them with a 585 nm flashlamp-pumped pulsed-dye laser, which selectively injures cutaneous microvessels without inducing scars. 16 adult patients with hypertrophic or keloidal median sternotomy scars after heart surgery received two treatments to one half of their previously untreated scars every 6-8 weeks and were reviewed at 6 months. Symptoms and clinical, histological, photographic, and surface texture assessments were obtained for treated and untreated areas of scar and evaluated independently by two observers blind to the treatment and by digital image analysis of skin surface casts. There was a significant improvement in erythema, scar height, skin surface texture, and pruritus in laser-treated scar areas; this improvement persisted for at least 6 months.

Adult↗

Effects of dietary fatty acid composition on basal and hormone-stimulated hepatic lipogenesis and on circulating lipids in the rat.

Thirty male rats were randomly assigned to one of three dietary groups in which the source of dietary fat was either a mixed oil, maize oil or fish oil. Effects of dietary fatty acid composition on in vitro rates of [U-14C]glucose incorporation into hepatic total lipids and into hepatic triacylglycerol were measured under basal, insulin (4 nM)-, gastric inhibitory polypeptide (GIP; 6 nM)- and insulin + GIP (4 nM + 6 nM)-stimulated conditions. Effects of the three diets on postprandial plasma triacylglycerol, cholesterol, insulin and GIP concentrations were also measured. The fish-oil diet decreased rates of basal glucose incorporation into hepatic total lipids (P < 0.05) and hepatic triacylglycerol, (P < 0.01) compared with the mixed-oil diet. The presence of insulin + GIP in the incubation medium stimulated glucose incorporation into hepatic total lipids in the maize-oil (P < 0.01) and fish-oil groups (P < 0.05), as well as into hepatic triacylglycerol in the maize-oil group (P < 0.005). In addition, the fish-oil diet decreased postprandial plasma triacylglycerol levels compared with both other dietary groups (P < 0.05 both cases), and the mixed-oil diet markedly increased postprandial plasma insulin levels compared with the other dietary groups (P < 0.001).

Animals↗

Treatment of nevus of Ota by the Q-switched alexandrite laser.

BACKGROUND: The Q-switched alexandrite laser (755 nm, 100 nanoseconds) selectively targets and destroys cutaneous pigment such as that found in dermal pigmented lesions and tattoos. The nevus of Ota is a benign dermal melanocytic lesion, which, due to its large size and periocular location, has been notoriously difficult to treat. Utilizing the principles of selective photothermolysis, the alexandrite laser could effect an excellent treatment for nevus of Ota. OBJECTIVE: To report the effectiveness of the Q-switched alexandrite laser in treating nevus of Ota. METHODS: Seven patients with nevus of Ota were treated with the Q-switched alexandrite laser (755 nm, 100 nanoseconds) with energy densities ranging from 4.75 to 7.0 J/cm2 at 8-12-week intervals. Response to therapy was evaluated through independent observation and rating of sequential photographs by two blinded observers. Histologic examinations of lesional skin biopsies before and after completion of laser treatments were performed. RESULTS: An average of two laser treatments were required to effect an average clinical improvement of 50%. Five patients showed 100% lesional clearance after an average of five treatments. No scarring, textural changes, or pigmentary side effects were observed in treated skin. Histology of laser-irradiated lesions revealed elimination of upper dermal pigmentation without epidermal disruption, and rare melanophages and pigmented spindle cells in the deep reticular dermis. No lesional recurrences were observed up to 1 year following treatment. CONCLUSION: The Q-switched alexandrite laser can effectively eliminate nevus of Ota without untoward side effects, such as scarring.

Adolescent↗

Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A.

We examined the capacity of purified rat peritoneal connective tissue-type mast cells (PMC) to express mRNA for several cytokines. Stimulation of PMC with anti-IgE for 4 hr induced the expression of mRNA encoding interleukin-5 (IL-5), IL-6, tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Unstimulated PMC expressed detectable mRNA for TNF-alpha but not for the other four cytokines. Incubation of PMC with cyclosporin A (CsA) or dexamethasone (DEX), each at 10(-6) M for 24 hr, significantly inhibited the induced expression of mRNA for each of the five cytokines, and also inhibited release of biologically active TNF-alpha. Throughout these experiments mRNA levels of the housekeeping gene G3PDH were not altered by stimulation with anti-IgE or incubation with CsA or DEX. We conclude that immunological activation of rat PMC induces gene expression of several cytokines and that expression of these genes can be inhibited by immunosuppressive drugs.

Animals↗

Postprandial lipid and hormone responses to meals of varying fat contents: modulatory role of lipoprotein lipase?

OBJECTIVE: Substrate and hormone responses to meals of differing fat content were evaluated in normal subjects in order to investigate mechanisms underlying the regulation of postprandial lipoprotein concentration. DESIGN: A randomised cross-over study with three different meals on three occasions. SETTING: Free-living subjects associated with Surrey University. SUBJECTS: Ten male volunteers (aged 18-23 years) were recruited. INTERVENTIONS: Three test meals containing 20, 40 or 80 g fat but identical carbohydrate and protein content were randomly allocated to volunteers. MAJOR OUTCOME MEASURES: Pre- and postprandial blood samples were taken for the analysis of plasma triacylglycerol, non-esterified fatty acids, glucose, immunoreactive insulin and glucose-dependent insulinotrophic polypeptide levels and postheparin lipoprotein lipase activity measurements. RESULTS: Peak triacylglycerol concentrations and lipoprotein lipase activity measurements were significantly higher following the 80 g than the 20 g fat meal (P = 0.009 and P = 0.049 respectively). Areas under the glucose-dependent insulinotrophic polypeptide time-response concentration curves were significantly higher following the 80 g compared with the 20 g fat meal (P = 0.04), but no differences in insulin response to the meals were seen. The 30-360 min decrease in the non-esterified fatty acid concentration was less following the 80 g than the 20 g meal (P = 0.001). CONCLUSIONS: The results suggest that glucose-dependent insulinotrophic polypeptide may mediate increased lipoprotein lipase activity in response to fat-containing meals and may play a role in circulating lipoprotein homeostasis. This mechanism may be overloaded with high fat meals with adverse consequences on circulating triacylglycerol and NEFA concentrations.

Adolescent↗

IL-4 enhances IL-3 and IL-8 gene expression in a human leukemic mast cell line.

We examined the capacity of interleukin (IL)-4 to induce or enhance the expression of certain cytokines in resting and activated cells of the HMC-1 human leukemic mast cell line. The HMC-1 mast cells were cultured with or without recombinant human IL-4 and then activated with the calcium ionophore ionomycin. Stimulation of non-IL-4-treated cells with ionomycin (10 microM) for periods of 30 min to 8 hr induced expression of mRNA encoding IL-3, IL-4 and IL-8 but was without effect on levels of mRNA for tumour necrosis factor (TNF)-alpha or beta-actin. Culture of the cells with IL-4 (100 ng/ml) for 24 hr led to a small increase in resting levels of mRNA for IL-3 and IL-8 but not for IL-4, TNF-alpha or beta-actin. More notably, the IL-4 treatment produced a pronounced elevation of mRNA for IL-3 and IL-8 when the cells were subsequently activated with ionomycin. The IL-4 treatment produced a negligible effect on IL-4 mRNA, and no effect on TNF-alpha or beta-actin mRNA levels in ionomycin-activated cells. Quantitation of cDNA by competitive polymerase chain reaction (PCR) revealed that the IL-4 treatment produced a sixfold increase in ionomycin-induced levels of cellular IL-3 mRNA, a fourfold increase in induced IL-8 mRNA and less than a twofold increase in induced IL-4 mRNA. The IL-4 treatment led to a 15- to 20-fold increase in ionomycin-induced secretion of IL-3 product and a doubling of induced IL-8 product. These effects of IL-4 were not associated with increased mast cell numbers. We conclude that IL-4 alone is a weak activator of IL-3 and IL-8 gene expression in mast cells, but is able to enhance activation signals in stimulated mast cells leading to transcription and secretion of these two cytokines.

Base Sequence↗

The safety and pharmacokinetics in adult subjects of an intravenously administered 99mTc-labeled 17 amino acid peptide (CYT-379).

A phase I study was designed to evaluate the safety and pharmacokinetics of a novel platelet reactive peptide, peptide acetyl-SYGRGDVRGDFKCTCCA-amide (CYT-379), which binds to the fibrinogen receptor of activated platelets and also binds to 99mTc. Eleven subjects with suspected deep venous thrombosis had 0.1, 0.5 or 1.0 mg of the peptide infused intravenously. Pharmacokinetics were determined by assaying blood samples in 6 of the 11 subjects and by urine sampling in 5 of these 6 subjects. Plasma and whole blood time-activity curves demonstrated an initial fast component with half-time clearance of 0.2 +/- 0.01 and 0.2 +/- 0.02 h and a slow component with half-time clearance of 2.8 +/- 0.3 and 2.7 +/- 0.2 h (mean +/- SEM for plasma and whole blood, respectively). Urine clearance was 22.6 +/- 3.3 and 10.8 +/- 1.6 mL/min when normalized to body surface area. The cumulative excretion of 99mTc-CYT-379 in the urine was 16.6 +/- 3.6, 45.6 +/- 16.9 and 45.6 +/- 1.8% of the administered dose over 0-2, 0-12 and 0-24 h after radiopharmaceutical injection, respectively. Images obtained in 11 subjects immediately, at 1-2, and 4-6 h after injection were evaluated for abnormalities and were compared with duplex Doppler ultrasonography. 99mTc-CYT-379 images were positive in only 3 of 7 subjects who had a positive duplex Doppler examination in at least one lower extremity. One subject with negative duplex Doppler had also negative 99mTc-CYT-379 scintigraphy. One subject with negative scintigraphy and two other subjects with positive scintigraphy had no other imaging studies of the deep venous system performed. No adverse reactions were observed during or after the infusion of 99mTc-CYT-379. 99mTc-CYT-379 appears to be a safe radiopharmaceutical and demonstrates rapid clearance from plasma in human subjects.

Adult↗