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Biomedical subjects

A W Nelson

Publications and source records attributed to A W Nelson.

At least 19 recordsLinked to original sources

The relationship between serum creatinine and estimated glomerular filtration rate: implications for clinical practice.

INTRODUCTION: A new classification of chronic kidney disease (CKD) has been widely adopted that stratifies patients into 5 'stages' according to estimated glomerular filtration rate (eGFR). In adults the most commonly used formulae to calculate eGFR are the Cockcroft and Gault (C and G) and Modification of Diet in Renal Disease (MDRD) formulae. The UK Renal Association has recommended calculation of MDRD eGFR to screen for reduced kidney function in primary and secondary care. AIM: The aim of this study was to explore the implication of using these predictive formulae. METHODS: We searched for patients currently attending a renal clinic who have ever had a serum creatinine (SCr) of exactly 100 micromol/L, 150 micromol/L or 200 micromol/L. The C and G and MDRD eGFRs corresponding to that SCr were calculated. The proportion of patients in each stage of the CKD classification was determined. RESULTS: For a SCr of 100 micromol/L mean eGFR was 86.5 ml/min (range 31.0 - 192.8) by C and G and 63.8 ml/min (range 39.7 - 99.9) by MDRD (p < 0.0001; t-test of mean). For SCr 150 micromol/L mean eGFR was 51.7 ml/min (18.0 - 110.4) by C and G and 38.0 ml/min (20.7 - 54.8) by MDRD (p < 0.0001). For SCr of 200 micromol/L mean eGFR was 34.4 ml/min (12.6 - 89.5) by C and G and 27.3 ml/min (16.7 - 41.3) by MDRD (p < 0.0001). Using MDRD eGFR 46.5% patients with a SCr of 100 micromol/L have stage 3 CKD (GFR 30-60 ml/min) and all patients with a SCr of 150 micromol/L or 200 micromol/L have CKD 3 or worse. 8.6% of males with SCr 100 micromol/L had stage 3 CKD or worse compared with 86.8% females. 70.2% patients > 65 years old with SCr 100 micromol/L had stage 3 CKD. CONCLUSIONS: Targeted screening of patients at-risk for CKD will identify a large number of patients who require management of CKD and potential referral to nephrology services even at levels of SCr regarded as 'normal' or mildly.

Aged↗

Identity of Saccharomyces cerevisiae tRNA(Trp) is not changed by an anticodon mutation that creates an amber suppressor.

A C35-->T mutation in an Escherichia coli tRNA(Trp) gene creates an amber suppressor which efficiently inserts glutamine in response to UAG codons in vivo (Soll, L., and Berg, P. (1969) Nature 223, 1340-1342). We have introduced the same change in a yeast tRNA(Trp) gene and demonstrated that the tRNA acts as an efficient amber suppressor in vivo. Amino acid sequence analyses were performed on chitinase produced by cells carrying the corresponding gene with a UAG codon at position 8 of the mature protein plus the mutant tRNA(Trp) gene. In contrast to comparable experiments with E. coli, tryptophan is inserted at a frequency > or = 80% by the yeast suppressor tRNA(Trp). Furthermore, in vitro charging experiments with the mutant tRNA(Trp) reveal no detectable increase in glutamine acceptor activity results from the C35-->T transition. The identity elements in E. coli tRNA(Gln) are well characterized (Jahn, M., Rogers, J., and Soll, D. (1991) Nature 352, 258-260). Sequence comparisons of the tRNA(Trp) and tRNA(Gln) molecules from E. coli reveal that the amber suppressor tRNA(Trp) has four of five identity elements required for glutaminyl-tRNA synthetase recognition. A similar comparison in the yeast system shows only two of the five potential identity elements are present. We conclude that, in spite of substantial structural similarities between yeast and E. coli aminoacyl-tRNA synthetases, fundamental differences can exist with regard to tRNA recognition.

Amino Acyl-tRNA Synthetases↗

Exocrine pancreatic function following intraoperative irradiation of the canine pancreas.

Twenty-four beagles received intraoperative irradiation (IORT) with 6 meV electrons to the pancreas and the duodenum. Intraoperative irradiation doses of 17.5 to 40 Gy were given. Billroth II gastrojejunostomy was done to bypass the irradiated duodenum. Six control dogs received only the Billroth II surgery. Two weeks postoperatively, irradiated dogs were given 50 Gy of 6 MV X radiation (external-beam radiation [EBRT]) to the pancreas and duodenum in 2 Gy fractions over a 5-week period. Dogs were monitored clinically and exocrine pancreatic function was evaluated using an N-benzoyl-l-tyrosyl-para-aminobenzoic acid (BT-PABA) test between 3 and 135 days postoperatively. Necropsies were performed on the dogs at 135 days postoperatively. The degree of gross pancreatic atrophy in the irradiated group was dose related. The mean percentage of normal acinar cells correlated with IORT doses and para-aminobenzoic acid (PABA) values (P less than 0.1). Weight loss was significantly greater in the irradiated dogs compared to the control (P less than 0.05) and the mean percentage of body weight loss correlated with the mean PABA values (P less than 0.01). In this study, the use of the BT-PABA test to evaluate progressive exocrine pancreatic function following IORT and EBRT showed an expected trend. A progressive decrease in exocrine pancreatic function in the irradiated dogs as indicated by plasma PABA levels may have been partly due to late radiation damage to acinar cells, secondary to vascular and ductular damage. At 135 days postoperatively none of the dogs showed clinical signs of exocrine pancreatic insufficiency and the plasma PABA levels were within the normal presurgical range. The progressive decrease in plasma PABA levels indicated a potential for the late development of exocrine pancreatic insufficiency. The BT-PABA test could be useful for evaluating the progressive decrease in exocrine pancreatic function and residual radiation injury to the pancreas. Because the exocrine deficiency can be managed with replacement therapy, pancreatic injury may not be a serious complication after doses of less than 30 Gy IORT with 50 Gy EBRT. Data from this study are in agreement with previous clinical and experimental reports that the duodenum is dose-limiting for IORT. Doses of 20 Gy IORT or less plus 50 Gy EBRT for treatment of carcinoma of the pancreas may not result in serious long-term complications due to radiation injury of the duodenum.

Adenocarcinoma↗

Pathologic response of the pancreas and duodenum to experimental intraoperative irradiation.

The pancreas and duodenum of 24 beagle dogs were given intraoperative irradiation (IORT) with 6 MeV electrons. The dose range was 17.5 Gy to 40 Gy. Billroth II gastrojejunostomy was performed on all dogs prior to irradiation. Six control dogs received only Billroth II surgery. Starting 2 weeks after surgery, dogs in the irradiation groups were given 50 Gy 6 MV X rays external beam radiation therapy (EBRT) to the pancreas and duodenum. The total dose of 50 Gy was given in 2 Gy fractions over 5 weeks. Dogs were monitored for 135 days then necropsied. Gross and histopathologic changes in the pancreas and duodenum were evaluated and quantitative analysis of pancreatic lesions done. Duodenal ulcers were found following 32.5 Gy and 40 Gy IORT. The pancreases were atrophic in irradiated dogs and exocrine pancreatic insufficiency occurred in one dog given 25 Gy. Gross pancreatic atrophy correlated with IORT dose. Histopathologic evidence of radiation damage to the pancreas was observed in acinar cells. Islet cell lesions were not apparent. There was pancreatic fibrosis and damage to blood vessels and ducts. Dose-response relationships were observed for the index of damage to the pancreas as a whole, for pancreatic fibrosis and a decrease in normal acinar cells. Although 25 Gy IORT plus 50 Gy EBRT was tolerated by the duodenum to 135 days, these doses may cause later pancreatic injury as an expression of damage to blood vessels and ducts. Exocrine pancreatic insufficiency and diabetes mellitus may thus represent potential late complications of IORT following 25 Gy or higher doses.

Animals↗

Aorticopulmonary window in a dog.

An aorticopulmonary window was diagnosed in an 18-month-old dog that had progressive exercise intolerance, hyperpnea, and cyanosis since birth. The dog was euthanatized and necropsied. Microscopic lesions in the lungs were compatible with chronic pulmonary hypertension.

Animals↗

The diagnosis of acute acalculous cholecystitis: a comparison of sonography, scintigraphy, and CT.

The clinical and laboratory diagnosis of acute acalculous cholecystitis is difficult, and the reliability of various diagnostic imaging techniques has not been established. The results of several imaging procedures performed over a 6-year period on 56 patients with clinically suspected acute acalculous cholecystitis were evaluated retrospectively. Sonography and CT were both highly sensitive (92% and 100%, respectively) and specific (96% and 100%, respectively). Hepatobiliary scintigraphy was compromised by frequent false-positives; the result was a specificity of only 38%. Percutaneous bile aspiration was insufficiently sensitive (33%) for diagnosis. Sonography was as sensitive as hepatobiliary scintigraphy and was more specific in establishing the diagnosis. Because sonography is relatively inexpensive and can be performed at the bedside, it should be regarded as a satisfactory screening procedure. However, CT is a good alternative in an easily transported patient when other intraabdominal disease is suspected.

Accidents↗

Gray-scale (B-mode) sonography of the maxillary sinus.

Gray-scale sonographic examination of the maxillary sinuses of five normal volunteers and 12 patients with maxillary sinus disease was performed and correlated with other radiologic imaging modalities, clinical follow-up, and, in two cases, surgical findings. B-mode scanning is a rapid, potentially useful, nonionizing diagnostic modality for determining whether the maxillary sinuses contain fluid or are normally aerated. Sonography may also demonstrate mucosal thickening, focal soft tissue masses, and complex collections.

Adolescent↗

Histochemical study of the anulus fibrosus in normal canine caudal cervical intervertebral discs.

A qualitative assessment of glycosaminoglycans (GAGs) in the non-chondrodystrophoid canine cervical anulus fibrosus was performed using the Alcian blue/critical electrolyte concentration staining technique. Estimates of GAG concentration were deduced for two groups of dogs (average age four and eight years) by determining the hyaluronic acid, chondroitin sulphates and keratan sulphate 'alcianophilic indices'. Keratan sulphate was the predominant GAG in the four-year-old group of dogs. The concentration of keratan sulphate was equal to that of chondroitin sulphates in the eight-year-old group and the total GAG concentration was decreased. This qualitative assessment indicated that the concentrations of keratan sulphate decreased and chondroitin sulphates increased between four and eight years of age. Similar conclusions have not been reported for anuli in the thoracic and lumbar regions of the canine spine.

Aging↗

Portacaval shunt as treatment for hypercholesterolemia. Metabolic and morphological effects in a swine model.

Since 1973 the portacaval shunt has been used as a treatment for homozygous familial hypercholesterolemia. Favorable results have been reported, but the mechanism or reduction of cholesterol is not clear. The objective of this research was to evaluate mechanisms of lipid alterations after portacaval shunting in Yucatan miniature swine. The animals were fed a high-fat diet, similar in composition to the average American diet, with or without added cholesterol. Controls were fed the atherogenic diet (+ cholesterol) for 8 months. Pigs were fed atherogenic or American diets for 8 months, then surgery (shunt or sham) was performed. They were continued on the diets for another 8 months. The vascular system was examined for the distribution and severity of atherosclerotic disease. Blood lipids and numerous biochemical indices were measured. Progression of atherosclerosis was slowed by portacaval shunting. Low density lipoprotein (LDL) concentrations were positively and high density lipoprotein (HDL) concentrations were negatively correlated with severity of atherosclerosis. Serum insulin concentrations were positively correlated with atherosclerosis. Cholesterol synthesis was increased by the shunting and decreased by cholesterol feeding. The cholesterol-fed swine is not an adequate model for familial hypercholesterolemia, but the results are consistent with inhibition of the atherosclerotic process and the involvement of lipoproteins and insulin in the mechanisms.

Animals↗

An audit of investigational services within general medical units.

Over a period of a year data was collected on the utilisation of investigational services by three general medical units. The pattern of practice was found to be very similar between the units. The average calculated daily test cost per patient ranged from +12-23 and the average dialy number of tests per patient was less than two. The services contributing most to costs were the relatively cheap but frequently-performed laboratory and radiological investigations. The implications of these findings in relation to hospital costs and to the education of medical staff is discussed.

Australia↗

The effect of ethanol and/or acetaldehyde on the incorporation of U14C-glucose into human umbilical artery lipids.

The effect of ethanol, acetaldehyde and a combination of ethanol and acetaldehyde added in vitro was determined on their abilities to alter conversion of glucose to lipid. When human umbilical arteries were perfused with acetaldehyde at a 0.5% concentration, a significant reduction (p less than 0.05) of 14C incorporation into lipid was observed. This reduction was found to be the result of depressed incorporation of glucose into phospholipid (PL) and triacylglycerides (TG). Acetaldehyde at a concentration of 0.25% appeared to depress incorporation; however, this was not significant. Acetaldehyde plus ethanol at final equal concentrations of 0.25%, 0.5% and 1.0% had no effect on incorporation of U14 C-glucose into lipid. Ethanol at concentrations of 0.5%, 0.25% and 0.125% had no effect on the incorporation of U14 C-glucose into lipid. The study suggests that acetaldehyde can depress the conversion of glucose into umbilical artery lipids. However, acetaldehyde in the presence of equal concentrations of ethanol does not exhibit this ability to depress conversion of glucose to lipids suggesting some cellular counter effect of these two agents.

Acetaldehyde↗

Evaluation of gamma radiation therapy in experimentally induced hemorrhagic pancreatitis in dogs.

Acute bile-trypsin pancreatitis was induced in two groups of six dogs each. One group was given supportive treatment only; the second group was treated with irradiation of the pancreas (400 rad). A third group of six dogs was irradiated, but pancreatitis was not induced. A 13-fold increase in survival time was observed in the dogs with pancreatitis which had been irradiated. Irradiation alone was found to reduce the volume of pancreatic secretion with a relative increase in trypsin content. Modification of the inflammatory reaction by irradiation and reduction in pancreatic secretion probably account for the therapeutic effect.

Acute Disease↗