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Biomedical subjects

W G Smith

Publications and source records attributed to W G Smith.

At least 19 recordsLinked to original sources
PubMed1991

Leiomyosarcoma of the small intestine presenting as a pelvic mass: four cases.

Four patients with leiomyosarcoma of the small intestine who presented with a pelvic mass are reviewed. The tumors had clinical and radiographic features resembling ovarian neoplasms. These patients develop sizable tumors and, yet, have relatively few symptoms which would necessarily direct the physician to the intestine as the site of origin. The clinicopathologic features and management of these tumors are reviewed.

Aged↗
PubMed1990

Effects of dideoxyforskolin on proteoglycan synthesis and structure in embryonic chick chondrocyte cultures.

1,9-Dideoxyforskolin inhibits proteoglycan synthesis and xyloside-initiated glycosaminoglycan (GAG) synthesis in chick embryo chondrocytes. Dideoxyforskolin does not affect the length of xyloside-initiated GAG chains secreted into the medium but chains from the dense proteoglycan secreted into the medium appear slightly longer. Incorporation of labeled serine into the dense proteoglycan and subsequent digestion with Pronase revealed a dramatic decrease in percent of total radioactivity associated with GAG chains in the proteoglycan from cultures treated with forskolin or dideoxyforskolin. These observations suggest that these diterpenes have a specific inhibitory effect on chain initiation reactions and thus may be useful tools in the study of proteoglycan synthesis and processing.

Animals↗
PubMed1990

Effect of forskolin on synthesis of xyloside-initiated glycosaminoglycans in embryonic chick chondrocytes.

The synthesis of sulfated glycosaminoglycan (GAG) chains has been studied in the presence of various concentrations of the artificial acceptor 4-methylumbelliferyl beta-D-xyloside and of forskolin. Sulfated GAG chains formed in the presence of forskolin had a smaller hydrodynamic radius than controls, as revealed by chromatography on Sepharose CL-6B. Sulfated GAGs from both control and treated cultures behaved identically when chromatographed on DEAE.

Animals↗
PubMed1990

Analysis of preoperative intracavitary cesium application versus postoperative external beam radiation in stage I endometrial carcinoma.

Two groups of patients with surgical Stage I endometrial carcinoma treated at the LDS Hospital in Salt Lake City are analyzed. Group 1 comprises 112 patients treated from 1974 through 1976, during which time preoperative intracavitary cesium was routinely used in all patients. Group 2 comprises 117 patients treated 1981 through 1983 under the treatment policy of hysterectomy without preoperative cesium. High risk patients from each group (grade 3 and/or deep myometrial invasion) generally received similar postoperative external beam pelvic radiotherapy (4500-5000 cGy). While 5-year actuarial disease-free survival rates were similar in each group (94% Group 1 vs 91% Group 2), multivariate analysis by the Cox Regression Method revealed that inclusion within treatment Group 2 carried independent adverse prognostic significance (p = 0.018). Other independent predictors of adverse 5-year disease-free survival included deep myometrial invasion and increasing histologic grade. Group 1 patients with grade 3 lesions had a superior 5-year actuarial disease-free survival (76% vs 53%) compared to those from Group 2. Group 1 patients with deep myometrial invasion also had a superior 5-year disease-free survival (84% vs 69%). The remaining low risk patients (grade 1 or 2, less than 1/3 myometrial invasion) had an excellent 5-year disease-free survival with or without preoperative cesium. Immediate preoperative intracavitary cesium was well tolerated, did not obscure pathologic findings and in our experience, reduced the probability of recurrence in high risk Stage I endometrial carcinoma patients.

Brachytherapy↗
PubMed1989

Metabolic effects of forskolin in chick chondrocytes.

The effects of forskolin on parameters of energy metabolism and proteoglycan synthesis have been investigated in chick embryo sternal chondrocyte cultures. After 8 h exposure to 100 microM forskolin, ATP levels and oxygen consumption were unaltered. Protein synthesis was unaffected up to 50 microM forskolin and protein degradation was unaffected by forskolin up to 100 microM. In contrast, incorporation of the proteoglycan precursors, 35SO4 and [3H]glucosamine, was more sensitive to forskolin. Inhibition was linear with dose between 10 and 100 microM, reaching 70% at 100 microM. Incorporation of 35SO4 into glycosaminoglycan chains initiated on an artificial beta-xyloside acceptor was inhibited in the same manner. cAMP accumulation was maximal at 10 microM forskolin, a concentration which did not alter proteoglycan synthesis. We conclude that a major, acute effect of forskolin in these short-term experiments is inhibition of proteoglycan synthesis in a cAMP-independent manner.

Adenosine Triphosphate↗
PubMed1989

Short-term effect of captopril on renal haemodynamics in chronic renal failure.

Glomerular filtration rate (GFR), effective renal plasma flow, and creatinine clearance were measured in ten patients with stable chronic renal failure (GFR less than 50 ml/min) before, during and after 1 month's treatment with captopril. Plasma angiotensin II decreased significantly during treatment (P less than 0.05) and increased after the drug was stopped. Renin concentration increased with captopril (P less than 0.02) and urine protein excretion decreased (P less than 0.05). Blood pressure did not change in any individual. There was no alteration in baseline GFR, effective renal plasma flow, or creatinine clearance, with or without captopril. Following a high-protein meal there was no increase in any of the measured renal haemodynamic parameters before, during, or after taking the drug. There was a significant increase in plasma creatinine while taking captopril (P less than 0.02) which reversed on cessation of the drug. These results suggest that in stable chronic renal failure the human renal microvasculature is unresponsive to inhibitors of angiotensin-converting enzyme.

Adult↗
PubMed1989

Glycosylated and carbamylated haemoglobin in uraemia.

Glycosylated and carbamylated haemoglobin were determined in patients with uraemia and/or diabetes mellitus. Glycosylated haemoglobin measured by ion-exchange chromatography (HbA1, HbA1c, HbA1a + b) was elevated in non-diabetic uraemic patients, while colorimetrically determined glycosylated haemoglobin was similar to controls. Patients with diabetes mellitus and normal renal function had similar glycosylated haemoglobin concentrations to those with renal failure. Both methods showed an excellent correlation, independent of renal function, in patients with diabetes mellitus. The HbA1c component was more influenced by diabetes and the HbA1a + b component was relatively more dependent on renal function. Carbamylated haemoglobin was detected in all subjects, but was grossly elevated in uraemia. Carbamylated haemoglobin significantly correlated with renal function and chromatographically determined glycosylated haemoglobin. Data from this study strongly suggests that the apparent elevation of chromatographically determined glycosylated haemoglobin in uraemia is due to the increased formation of carbamylated haemoglobin. However, in patients with diabetes mellitus, independent of renal function, both the chromatographic and colorimetric methods of determining glycosylated haemoglobin are equally valuable and reliable. The non-enzymatic formation of carbamylated haemoglobin in uraemia has several similarities to glycosylated haemoglobin in patients with diabetes mellitus. Carbamylated haemoglobin may have a clinical role as a marker of uraemia and may also have a pathophysiological relevance.

Adult↗
PubMed1988

Carbamylated haemoglobin in chronic renal failure.

Carbamylated haemoglobin was measured by quantifying the release of isopropyl hydantoin by the acid hydrolysis of globin using gas liquid chromatography. Carbamylated haemoglobin was evaluated in 167 subjects including patients with a wide spectrum of renal disease. Grossly elevated concentrations of isopropyl hydantoin (mean values greater than 80 ng IPH/mg globin) were found in chronic renal failure, dialysis and transplant patients with renal failure compared to healthy subjects (15-39 ng IPH/mg globin). The elevated carbamylated haemoglobin correlated with renal function. Carbamylated haemoglobin may act as an indicator of uraemic status and has a potential clinical usefulness and may also have a pathophysiological significance.

Adult↗
PubMed1988

Pancreatic beta-cell function in CAPD.

Pancreatic beta-cell function was evaluated in uraemic patients by measuring beta-cell peptides in the peripheral blood after intravenous glucagon (1 mg) stimulation. Patients in chronic renal failure, patients on haemodialysis, and both new and established subjects on continuous ambulatory peritoneal dialysis (CAPD) (10 in each group) were studied and compared to 8 healthy controls. Fasting glucose (3.6-4.4 mmol/l) and insulin concentrations (9.5-11.7 mU/l) were normal and did not differ between the uraemic groups, but c-peptide concentrations were markedly increased in uremia (1.84-2.38 nmol/l) compared to controls (0.48 nmol/l). Following glucagon stimulation an exaggerated blood glucose response with delayed glucose peak was observed, while the peak insulin response to glucagon was normal; however, the return to basal concentrations was delayed in uraemia. The c-peptide response was also exaggerated and peak concentrations in uraemic subjects (3.0-4.3 nmol/l) were significantly greater than controls (1.5 nmol/l). The response of CAPD patients was similar to those on haemodialysis and non-dialysed uraemic patients. The abnormalities seen were due to uraemia, and CAPD treatment had no specific adverse effect on beta-cell function. Thus, from this data there was no evidence that CAPD per se is detrimental to beta-cell integrity.

C-Peptide↗
PubMed1988

Effects of IGF-I on the synthesis and processing of glycosaminoglycan in cultured chick chondrocytes.

We have studied the effect of the somatomedin IGF-I on stimulation of synthesis of DNA, RNA, protein, and glycosaminoglycan in chick chondrocytes. Stimulation of RNA and protein synthesis was rapid, occurring within 10 min after addition of IGF-I. Stimulation of sulphation required a lag time of about 2 h, whether chains were initiated on native protein core or on the artificial acceptor 4-methyl-umbelliferyl-beta-D-xyloside. DNA synthesis was not stimulated until after 10 h of exposure to IGF-I. Investigation of the rate of processing of proteoglycan core protein after pulse-labelling chondrocytes with 35SO4 yielded data which were best described by a biexponential function. IGF-I had no effect on the t 1/2 of the initial phase (16.44 min in the absence of IGF-I and 20.38 min in the presence of IGF-I). However, addition of IGF-I resulted in a decrease in the t 1/2 of the terminal phase from 122.58 to 55.44 min, which may reflect an increase in synthesis in the enzymes necessary for polymerization and sulphation of proteoglycan.

Aggrecans↗
PubMed1987

Leprechaunism: in vitro insulin action despite genetic insulin resistance.

We recently identified a female leprechaun infant with marked hyperinsulinemia [as high as 10,975 microU/ml (78,746 pmol/liter)], presumably secondary to insulin resistance. She had two physical findings suggestive of possible insulin action: cystic ovarian enlargement with gonadotropin-independent steroid secretion and persistent, severe myocardial hypertrophy. To examine the pathophysiology of this disorder we measured the in vitro sensitivity to insulin and other growth factors of erythroid progenitors and a T-lymphoblast cell line derived from her peripheral blood. Resistance to insulin was demonstrated by failure of her circulating erythroid progenitor cells to augment proliferation in response to physiologic concentrations of insulin (1-10 ng/ml). An immortalized T lymphoblast cell line was established by transforming the cells with the human retrovirus human T cell leukemia virus II. This cell line showed little or no response to physiologic concentrations of insulin contrary to consistently observed stimulation of colony formation by cell lines similarly derived from normals. The patient's T lymphoblasts, however, showed normal sensitivity to insulin-like growth factor I. In response to supraphysiologic insulin concentrations (25-1000 ng/ml), leprechaun T lymphoblasts showed significant augmentation of colony formation (peak 189% above baseline at 50 ng/ml); normal T lymphoblasts also showed responsiveness at these high insulin concentrations. Preincubation with a monoclonal antibody against the insulin-like growth factor I receptor (alpha IR-3 at 5000 ng/ml) blocked the in vitro effect of physiologic concentrations of insulin-like growth factor and supraphysiologic concentrations of insulin on leprechaun and control T lymphoblast colony formation, but had no clear effect upon the response to physiologic insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Regulation of in vivo IgE biosynthesis in mice with complete Freund's adjuvant.

Complete Freund's adjuvant (CFA) administered before sensitization dampened the normal and cyclophosphamide-enhanced response of high and moderate IgE responder phenotype mice (CAF1 and C57B1/6J, respectively). CFA-induced suppression of IgE biosynthesis was effective in reducing anaphylactic histamine release from approximately 2,900 ng histamine per milliliter to background levels (less than 100 ng/ml). CFA-induced ascites fluid was able to reduce the cyclophosphamide-enhanced IgE response of low-responder phenotype SJL mice from 1:320 to less than 1:5 as determined by passive cutaneous anaphylaxis. Muramyl dipeptide, a mycobacterial cell wall component capable of eliciting effects similar to those seen with CFA, was shown to induce suppression of IgE production if incorporated in incomplete Freund's adjuvant. Muramyl dipeptide administered in saline was ineffective, while incomplete Freund's adjuvant alone had some immunoregulatory properties. Ongoing IgE responses were less susceptible to regulation. CFA administered to sensitized C57B1/6J mice was ineffective in inducing IgE suppression when animals were challenged with antigen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Continuous ambulatory peritoneal dialysis: a three year experience.

During a three year period 66 patients with end-stage renal failure were commenced on continuous ambulatory peritoneal dialysis (CAPD) at the Western Infirmary, Glasgow. The patient survival and the technique success rates were 86 per cent and 64 per cent at two years respectively. Biochemical and blood pressure control were very satisfactory on a relatively free diet and usually without the need for antihypertensive drugs. The complications next in frequency to peritonitis were catheter obstruction, postural hypotension and excessive weight gain. The mean hospitalisation period per patient per annum was 33 days, with half of this due to peritonitis. Despite selection criteria favouring older patients, diabetics and those with vascular complications, one third of the patients were able to work.

Adolescent↗
PubMed1986

Peritonitis in continuous ambulatory peritoneal dialysis.

The main complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis. This paper describes our experience in the diagnosis and management of this complication in 66 patients during the three years to October 1982. The overall incidence of peritonitis was one episode every 6.75 patient months. Staphylococcus albus and Staphylococcus aureus together accounted for 46 per cent of the episodes, and 24 per cent were culture negative. Catheter exit site infections due to Staphylococcus aureus were common and they may have predisposed to peritonitis with gram -ve organisms as well as to staphylococcal peritonitis. Antimicrobial therapy was effective in 60 per cent of peritonitis episodes. The culture negative episodes usually responded to treatment while those due to fungi, though uncommon, did not. Twenty-nine per cent of these CAPD patients were transferred to haemodialysis because of peritonitis which failed to respond to treatment or which recurred repeatedly.

Adolescent↗
PubMed1979

Systems of care and treatment outcomes for alcoholic patients.

All admissions to the Singer Mental Health Center, Rockford, Ill, with a diagnosis of alcoholism in a one-year period (N = 466) were randomly assigned to one of two inpatient programs. One program, "intensive incare," had a high staff-patient ratio with the operating assumption that intensive staff-patient interaction is significant in patient outcome. The other, "peer-oriented incare," was of low staff density with the assumption that patient-patient interaction is critical in rehabilitation. In addition, the patients resided in communities with outpatient services classified as either "network" (an organized set of community services) or "no-network" (no special funding or deliberate outreach effort). Thus, each patient could be treated in one of four systems of care. Data on treatment outcomes were collected via semistructured interviews at 3, 6, 12, and 18 months after admission. The "peer-oriented incare" system showed superiority to the "intensive incare" treatment approach in improved drinking behavior. There were no other significant differences among the four systems on the outcome criteria for alcoholic patients. Along with other recent studies, these findings have implications for policy planning, particularly with today's emphasis on cost effectiveness.

Adult↗