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Biomedical subjects

G Manley

Publications and source records attributed to G Manley.

At least 37 records · Page 2Linked to original sources

Treatment and recovery for sexual addicts.

Over the last 10 years, primary health care practitioners have seen an increase in their case loads of persons with chronic addictive illnesses (e.g., alcohol- and drug-related illnesses, eating disorders, spending addictions). The management of chronic illnesses usually is aimed at restoring a level of health and reinforcing a positive lifestyle so that a person can manage the illness rather than having it cured and its effects eradicated. Practitioners can apply the treatment modalities already being used in the management of chronic and addictive illnesses to treat the most newly emerging addictive illness--sexual addiction. Following the premise that a person needs to be involved with other people who have the illness, treatment and recovery are based on a 12-step recovery-group process. Additionally, sexually addicted clients need medical and emotional therapy. This article focuses on understanding the decision-making process involved in the care of patients with sexual addiction, and presents tools and resources to help in managing this illness.

Clinical Protocols↗

The isolation and characterization of glycosaminoglycans in normal human serum.

The optimization of conditions for the isolation and characterization of human serum glycosaminoglycans (GAG) is described, together with studies of the accuracy and reproducibility of the method. The principle of the method is proteolytic digestion of serum using papain followed by precipitation of GAGs from the digested sample with cetyl pyridinium chloride (CPC). The uronic acid level and electrophoretic separations can be obtained from a 5 ml serum sample. The mean CPC-precipitable uronic acid level in pooled normal serum was 10.8 mg l(-1) serum. Using enzymatic and chemical analysis the major serum GAG was shown to be chondroitin sulphate (CS). Two distinct electrophoretic fractions were identified both consisting of CS but differing in their degree of sulphation. Dermatan sulphate, heparan sulphate and hyaluronic acid were not detected.

Journal Article↗

Serum hyaluronic acid in patients with disseminated neoplasm.

Hyaluronic acid concentrations were measured by a laser nephelometric assay in serum samples from 50 patients with advanced disseminated neoplasm and 50 healthy controls matched for age and sex. The identity of hyaluronic acid was confirmed by a combination of electrophoretic and enzymatic techniques. The mean serum hyaluronic acid concentration for the control group was 1.09 mg/l, with a range of 0-4 mg/l. The mean concentration for patients with neoplastic disease was 10.38 mg/l, with a range of 0-100 mg/l. Sixty two per cent of the patients with disseminated neoplasm had serum hyaluronic acid concentrations above the control range. There was no correlation between the increased concentration of hyaluronic acid and tumour type, serum bilirubin, serum alkaline phosphatase, or serum urea concentrations. There was a higher incidence of hypercalcaemia in patients with increased hyaluronic acid concentrations, but the correlation between hyaluronic acid and calcium concentrations was not significant. In view of the possible role of hyaluronic acid in cellular differentiation and morphogenesis the finding of increased hyaluronic acid concentrations in patients with advanced neoplastic disease may be of fundamental importance in cancer biology.

Adult↗

Effect of inhibitors of the lipoxygenase pathway on mouse myoblast fusion.

In this study we examined the effects of inhibitors of the lipoxygenase and cyclooxygenase pathways on mouse myoblast fusion. The fusion of cloned mouse myoblasts was markedly inhibited, in a dose-dependent manner, when cells were cultured in medium supplemented with either phenidone (1-phenyl-3-pyrazolidione) or BW755c (3-amino-1-(3-tri-fluoromethylphenyl)-2-pyrazoline), drugs which have been reported to inhibit lipoxygenase and cyclo-oxygenase activities. Fusion was also inhibited when these cells were cultured in medium supplemented with esculetin (6,7-dihydroxycoumarin) which has been reported to inhibit lipoxygenase activity. Removal of the above inhibitors resulted in a return to control levels of fusion. Fusion was not demonstrably inhibited with aspirin (acetylsalicylic acid) and only inhibited to a minor extent with indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid); both of these drugs are inhibitors of cyclo-exygenase activity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

The binding of urate to plasma proteins determined by four different techniques.

Venous occlusion in healthy individuals showed no binding of urate under conditions when the expected increased levels of known bound species was demonstrated. Ultrafiltration of serum from 10 healthy controls and five gouty individuals also showed the absence of binding in all cases, as did electrophoretic and chromatographic studies.

Blood Proteins↗

Measurement of serum glycosaminoglycans by laser nephelometry.

A simple, sensitive micromethod for the assay of serum hyaluronic acid and chondroitin sulphates is presented. The method is based on the binding of the quaternary ammonium salt, cetylpyridinium chloride (CPC) to serum polyanions, and quantitation of the complexes by laser nephelometry. Measurement of the CPC complexes in serum before and after digestion with specific enzymes enables quantitation of hyaluronic acid and chondroitin sulphates in less than 100 microliters serum. Using this technique, hyaluronic acid is detectable in a small number of normal human sera at concentrations up to 4 mg/l, and chondroitin sulphates are consistently present at concentrations ranging from 2 to 25 mg/l.

Carbazoles↗

Acoustical responses and suppression-period patterns in guinea pigs.

Acoustic responses to short sound stimuli have been measured in the external ear canal of guinea pigs. Unequivocal responses had frequencies between 1.8 and 3.2 kHz, latencies (to their peak pressures) of 2.8 to 4.5 ms and sound pressures up to -10 dB SPL. A set of criteria was developed to clearly distinguish acoustical responses from after-resonances of the stimuli. Added phase-locked, very-low-frequency tones were able under some conditions to totally suppress the acoustical responses. The suppression-period pattern thus produced strongly resemble those obtained for man and the masking-period patterns obtained with human subjects.

Acoustic Stimulation↗

Urinary excretion of glycosaminoglycans and hydroxyproline in Paget's disease of bone, compared with neoplastic invasion of bone.

Urinary glycosaminoglycan and hydroxyproline excretion was studied in 11 patients with clear evidence of Paget's disease of bone. Urinary hydroxyproline, cetyl pyridinium chloride (CPC)-precipitable uronic acid and CPC-precipitable hexosamine were expressed as ratios to urinary creatinine. Urine samples were concentrated x 1000 by vacuum dialysis and the glycosaminoglycans examined by electrophoresis on cellulose acetate followed by staining with alcian blue. All the cases studied showed markedly raised hydroxyproline excretion, whereas the uronic acid excretion was normal or only slightly raised in 10 of the 11 cases studied. One patient who had a raised uronic acid and raised hydroxyproline concentration was shown to have osteosarcoma as a complication of Paget's disease. THE VERY HIGH HYDROXYPROLINE: creatinine ratio in all cases of Paget's disease (mean 241.8 mmol hydroxyproline/mol creatinine) contrasted sharply with the cases of disseminated neoplasm, where the ratio was either normal or slightly raised (mean 29.3 mmol hydroxyproline/mol creatinine). The ratio of hydroxyproline to CPC-precipitable uronic acid was also markedly raised in cases of Paget's disease (mean 77.3 mmol hydroxyproline/mmol uronic acid) and was lower in the neoplastic group (mean 14.1 mmol hydroxyproline/mmol uronic acid) but showed no advantage over the hydroxyproline: creatinine ratio in differentiating the two groups. THE URINARY HYDROXYPROLINE: creatinine ratio promises to be of value in differentiating between Paget's disease of bone and neoplastic invasion of bone. A marked rise in CPC-precipitable uronic acid excretion alone is more suggestive of neoplastic invasion of bone, and if associated with a marked increase in hydroxyproline excretion, it raises the possibility of neoplastic change in Paget's disease of bone. The results of this study also suggest that bone collagen, rather than bone tissue in general, is primarily affected in Paget's disease.

Aged↗

Urinary excretion of glycosaminoglycans in disseminated neoplasm.

Urinary glycosaminoglycan excretion was studied in 24 cases of disseminated neoplasm, 12 of which had unequivocal evidence of skeletal involvement. Urinary hydroxyproline, cetylpyridinium chloride (CPC)-precipitable uronic acid, and CPC-precipitable hexosamine were expressed as a ratio to urinary creatinine. Glycosaminoglycans contained in urine concentrated x 1000 by vacuum-dialysis were separated by electrophoresis on cellulose acetate and stained with alcian blue. Of the 12 cases with clear evidence of skeletal involvement, eight (66%) showed elevation of serum alkaline phosphatase, five (42%) showed elevation of urinary hydroxyproline, and three (25%) showed elevation of urinary uronic acid. It is concluded that urinary uronic acid is not a sensitive index of skeletal involvement in disseminated neoplasm. The most striking feature of the study was the identification of a well-defined fraction indist inguishable from hyaluronic acid in seven (58%) of the cases with evidence of skeletal involvement. Hyaluronic acid is not normally identifiable in adult human urine. The hyaluronic acid excretors showed more consistent biochemical evidence of bone disease (elevation of serum alkaline phosphatase and urinary hydroxyproline) than the non-excretors. The possibility that the urinary hyaluronic acid is derived from degradation of skeletal hyaluronic acid is discussed. An alternative explanation is that the hyaluronic acid is derived from neoplastic cells as part of a reversion of glycosaminoglycan synthesis to a more ;fetal' state, a glycosaminoglycan counterpart of the production of oncofetal antigens by neoplastic cells.

Adult↗

Properties of heparan sulphate and chondroitin sulphate from young and old human aortae.

1. Glycosaminoglycans were liberated from old and young human ascending aortae by digestion with papain. Heparan sulphate and chondroitin sulphate were separated by the different solubilities of their complexes with cetylpyridinium chloride in solutions of sodium chloride. Final fractionation was achieved by salt-gradient column chromatography on Dowex 1 (Cl(-)form). 2. Heparan sulphate from old aortae showed a slight, but consistent, increase in sulphation compared with heparan sulphate from young aortae. 3. The major amino acids associated with aortic heparan sulphate and chondroitin sulphate were serine, glycine, glutamic acid and aspartic acid. Heparan sulphate and chondroitin sulphate from old aortae contained about twice as much total amino acid as heparan sulphate and chondroitin sulphate from young aortae. Alkali hydrolysis resulted in the destruction of more serine in chondroitin sulphate from old, compared with young, aortae. 4. Molecular weights of glycosaminoglycans from old and young aortae were found to be similar, and in the region of 35000. 5. It is suggested that there is an increased degree of protein-glycosaminoglycan cross-linking in old aortae.

Adolescent↗

Urinary excretion of glycosaminoglycans in the various forms of gargoylism.

The urinary excretion of glycosaminoglycans in 28 cases of gargoylism, embracing the Hurler, Hunter, Sanfilippo, Morquio, and Scheie syndromes (McKusick, 1966), has been examined using the cetylpyridinium chloride (CPC) turbidity test, the uronic acid/creatinine ratio, and the electrophoretic pattern of urine concentrates, as routine procedures. Ion-exchange column chromatographic techniques were also employed for the fractionation of glycosaminoglycans and aminosugars. Molecular weights were investigated by gel filtration and ultracentrifugation. The CPC turbidity test was positive in every case. The uronic acid/creatinine ratio provided a sensitive index of increased glycosaminoglycan excretion. Cases of the Hurler syndrome showed the highest, and cases of the Morquio and Scheie syndromes the lowest, ratios. A correlation was observed between the uronic acid/creatinine ratio and the clinical severity of the disease. Cellulose acetate electrophoresis differentiated clearly between the two major forms of gargoylism, the Hurler and Sanfilippo syndromes, but differentiation between the Hurler, Hunter, and Scheie syndromes was more difficult on electrophoretic data alone. Results obtained with cases diagnosed as the Morquio syndrome were disappointing. The existence of formes frustes of the Sanfilippo syndrome among the mentally subnormal is predicted. Errors caused by bacterial contamination of urine samples are emphasized. The atypical behaviour of urinary glycosaminoglycans in analytical procedures is discussed. Molecular weight studies suggested heterogeneity. The nature of the basic defect in gargoylism is discussed.

Adolescent↗

Excretion patterns of glycosaminoglycans and glycoproteins in normal human urine.

Glycosaminoglycans and glycoproteins in the urine of 100 healthy, active, human subjects were examined by cellulose acetate electrophoresis and salt gradient, ion-exchange, column chromatography. The cetylpyridinium chloride (CPC) turbidity and uronic acid:creatinine ratio was also studied. Fractions were identified by electrophoretic mobility, staining reactions, susceptibility to enzyme digestion, identification of amino- and neutral sugars, hexosamine, uronic acid, and sulphate assays, and optical rotation. The CPC turbidity is relatively high in childhood, falling to lower levels in adults, but rising again to relatively high levels in old age. The uronic acid: creatinine ratio is high in children, falling to a low level in adult life, and rising only slightly in old age. Three major electrophoretic fractions, corresponding with glycoprotein, heparan sulphates, and chondroitin sulphates, were identified in every urine sample. Hyaluronic acid was identified in some samples. A small amount of keratan sulphate was present in the ;heparan sulphate' fraction. Chondroitin sulphate excretion is high in children. Adults excrete relatively less chondroitin sulphate and more heparan sulphate. In old age, the proportion of glycoprotein increases. The excretion pattern in the first few days of life resembles that of the adult. It is stressed that extreme caution must be exercised in interpreting the urinary glycosaminoglycan pattern of a child.

Adolescent↗