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Biomedical subjects

M A Turner

Publications and source records attributed to M A Turner.

At least 19 recordsLinked to original sources

Nutrition measures for managed care report cards.

Health plan "report cards," that is, published summaries of health plan performance, are a new way to help consumers select a health plan on the basis of cost and quality. The Health Plan Employer Data and Information Set (HEDIS) includes a set of health plan performance measures, standardized definitions, and methods for data collection. HEDIS is used as the basis for many report card initiatives and is the preferred tool of the managed care industry for measuring health plan performance. Nevertheless, the current list of HEDIS performance measures omits many health services, including medical nutrition therapy. Nutrition measures have the potential for wide appeal among health care stakeholders (ie, payers, consumers, and providers). Four measures related to medical nutrition therapy are proposed for managed care report cards: staffing for nutrition services and medical nutrition therapy for high cholesterol level, gestational diabetes, and cardiovascular disease. Barriers to adopting medical nutrition therapy measures in HEDIS include the need to address technical issues before considering new measures and competition from other potential measures. Steps to create support for medical nutrition therapy measures in HEDIS should focus on influencing representatives of health plans and employers to include these measures. The involvement of registered dietitians in the dynamic process of health plan evaluation is an important extension of ongoing efforts for strategic positioning in the managed care market.

Dietary Services

Gastrointestinal tract involvement by gynecologic diseases.

Involvement of the gastrointestinal tract by gynecologic disease processes-endometriosis, gynecologic neoplasms, inflammatory processes, and complications from radiation therapy or surgery for gynecologic tumors-may mimic primary gastrointestinal carcinoma on radiologic images. Endometriosis most often involves the anterior wall of the rectosigmoid colon, adjacent to the pouch of Douglas, and typically produces extrinsic mass effect on the serosa, with the overlying mucosa left intact. Direct extension of ovarian cancer to the colon through the subperitoneal space produces mass effect with serosal spiculation, tethering, and fixation; annular constriction; or partial or complete obstruction. Intraperitoneal seeding of ovarian carcinoma most frequently involves the colon and is seen as extrinsic masses, often with serosal spiculation and tethering. Cervical carcinoma, which most commonly spreads by direct invasion of the pelvic side wall and adjacent structures, produces serosal spiculation and circumferential narrowing. Benign ovarian or uterine tumors are purely extrinsic and have a smooth interface with the colonic wall. Tubo-ovarian abscesses are difficult to differentiate from cystic ovarian neoplasms or endometriomas. Radiation colitis causes narrowing of the rectum with intact mucosa and can be differentiated from recurrent tumor, unlike radiation-induced injury of the small bowel, which may be difficult to distinguish. Surgical adhesions produce a discrete transition point between dilated bowel proximally and nondilated distal bowel. Familiarity with the varied patterns of gastrointestinal tract involvement is important for accurate interpretation of imaging studies.

Diagnosis, Differential

Percutaneous drainage of enteric-related abscesses.

Percutaneous drainage is a routinely performed radiologic procedure used in the management of abdominal abscesses. This technique has become the preferred method of treatment for most abdominal and pelvic abscesses, specifically those of enteric origin related to surgical procedures, appendicitis, diverticulitis, and Crohn disease. The well-documented safety and therapeutic efficacy of percutaneous abscess drainage (PAD) lead to the acceptance of this procedure as the primary means of managing abdominal abscesses, obviating the need for surgery in many instances. PAD may provide definitive therapy or may serve as a temporizing measure before delayed surgical treatment. Although PAD was originally reserved for treatment of unilocular, relatively superficial fluid collections, the role of PAD has evolved such that it is now used to manage complex multilocular fluid collections and abscesses that lie deep within the abdomen or pelvis. Although the standard transabdominal approach is preferred, a variety of approaches, including transgastric, transrectal, transvaginal, and transgluteal, may be used. PAD is performed using CT or sonographic guidance.

Abdominal Abscess

Structures of partridge egg-white lysozyme with and without tri-N-acetylchitotriose inhibitor at 1.9 A resolution.

The three-dimensional structures of native partridge egg-white lysozyme (PEWL) and PEWL complexed with tri-N-acetylchitotriose inhibitor have been determined crystallographically and refined at 1.9 A resolution. Crystals of native and complexed protein are isomorphous and have space group and cell dimensions that are identical to those of hen egg-white lysozyme (HEWL) under similar crystallization conditions. Full occupancy of the trisaccharide in the inhibitor complex has allowed definitive modeling and refinement of all three sugar residues, located at subsites A, B, and C in the PEWL active site. A comparison has been made with HEWL/inhibitor complexes in which coordinates were either not refined (Blake CCF, et al., 1967, Proc R Soc B 167:378-388) or were refined at partial occupancy (Cheetham JC, Artymiuk PJ, Phillips DC, 1992, J Mol Biol 224:613-628). Although the loop comprising residues 70-75 is located on the surface of the protein and not near the active site, it appears to be affected indirectly by trisaccharide binding such that the loop shifts toward the active site and becomes relatively immobilized. The source of this loop movement appears to be the anchoring of Trp62, located in the active site cleft, as it forms a hydrogen bond with O6 of the N-acetylglucosamine at site C. Good electron density for the trisaccharide in the PEWL complex structure shows that Asp 101 is involved in hydrogen bonding interactions with the terminal sugar residue.

Animals

Urokinase plasminogen activator expression by primary and HPV 16-transformed keratinocytes.

The molecular events underlying progression of human papillomavirus (HPV) 16-associated intraepithelial neoplasia to invasive cancer have not been studied in detail. Penetration of the basement membrane is an early, but poorly understood step in this process and probably involves the action of one or more metallo- and serine proteinases. Urokinase-type plasminogen activator (uPA) is a serine proteinase that has been implicated in the pathogenesis of several epithelial tumors, but its role in HPV-associated tumors is not known. To examine uPA expression by HPV 16-transformed keratinocytes in vitro, primary foreskin keratinocyte cultures were transfected by HPV 16 DNA. The primary parental cells and the HPV 16-transformed keratinocytes were studied using substrate gel zymography, Western blot analysis and an in vitro assay measuring penetration of a Matrigel artificial basement membrane. Both uPA and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), were overexpressed in the HPV 16-transformed cells relative to the parental cell line. The transformed cells, but not the parental cells, were able to degrade and penetrate the Matrigel membrane and penetration was blocked by both PAI-1 and by antibodies to uPA. Our data suggest that HPV 16-induced transformation of keratinocytes is associated with upregulation of uPA expression. In conjunction with other proteinases, uPA plays an important role in the ability of HPV 16-transformed keratinocytes to penetrate artificial basement membranes.

Basement Membrane

Congenital abnormalities of the pancreas and biliary tree in adults.

Congenital abnormalities of the pancreaticobiliary tree may go undetected until adulthood. In adult patients with persistent and unexplained signs and symptoms, such as cholangitis, pancreatitis, jaundice, recurrent abdominal pain, and nausea and vomiting, a congenital anomaly of the pancreatic or bile duct must be considered and a low threshold for performing cholangiopancreatography is recommended. The most common congenital pancreaticobiliary abnormalities seen in adults are choledochal cyst, anomalous junction of the pancreatic and common bile ducts, aberrant biliary ducts, and pancreas divisum, with the following entities being more rarely seen: choledochoceles, multiple communicating intra- and extrahepatic duct cysts, Caroli disease, pancreaticobiliary abnormalities associated with situs anomalies, annular pancreas, and aberrant pancreatic ducts associated with enteric duplication cysts. Cholangiopancreatography allows confirmation of diagnosis and may demonstrate associated abnormalities such as choledocholithiasis or tumor. Recognition of congenital anomalies may aid in surgical planning and prevent inadvertent ductal injury. Although congenital pancreaticobiliary abnormalities are relatively uncommon, the increased prevalence of cholangitis, gallstones, and cholangiocarcinoma seen with the various types of biliary cystic disease and junctional anomalies and the increased association of pancreatitis seen with pancreatic anomalies make recognition of variant anatomy clinically important.

Adult

Benign bronchial stenosis treated with balloon bronchoplasty and metal stents.

We report a case of a benign bronchial stenosis that presented clinically with recurrent respiratory infections and increasing dyspnoea. This was associated with transradiancy and oligaemia of the ipsilateral lung. Treatment with balloon bronchoplasty and self-expanding metal stents prevented recurrent pneumonia and led to a sustained improvement in exercise tolerance.

Aged

Cardiac hypertrophy impairs recovery from ischaemia because there is a reduced reactive hyperaemic response.

OBJECTIVE: The aim was to investigate whether impaired coronary flow reserve associated with cardiac hypertrophy could significantly limit the flow debt repayment following short periods of coronary occlusion and exacerbate or prolong episodes of myocardial ischaemia. METHODS: Left ventricular hypertrophy was induced in guinea pigs by aortic constriction and the hearts were isolated six weeks later for Langendorff perfusion. Sham operated animals served as controls. The reactive hyperaemic response was studied following various lengths of occlusion of flow and the extent of aerobic and anaerobic metabolism was assessed in each group. RESULTS: Heart weight/body weight ratio was increased by approximately 25% (P < 0.001) with aortic constriction. The reactive hyperaemic flow response in isolated hearts was impaired by hypertrophy in both magnitude (P < 0.05) and duration. The repayment of flow debt was also significantly reduced, suggesting an inadequate recovery of the myocardium following the occlusion. The total amount of O2 consumed by the heart throughout the duration of hyperaemia was less in hypertrophy than in sham operated controls, suggesting a decrease in aerobic metabolism. Total lactate discharge expressed as a ratio of O2 consumed, which provides an estimation of the degree of anaerobic in relation to aerobic metabolism, was greater in hypertrophy than in sham operated controls. CONCLUSIONS: The hypertrophied heart is more vulnerable to brief periods of ischaemia because of an impaired reactive hyperaemic response which results in delayed metabolic recovery. These abnormalities may contribute to the increased morbidity associated with cardiac hypertrophy.

Animals

Crystallization and preliminary X-ray analysis of a mutant duck delta II crystallin.

A duck delta II crystallin mutant, where histidine 178 has been replaced by an aspartic acid residue, has been purified from a bacterial expression system and subsequently crystallized. The crystals grow as flat plates, with unit cell dimensions a = 94.1 A, b = 99.9 A, c = 108.7 A and beta = 102 degrees. The crystals exhibit the symmetry of space group P2(1) and diffract to a minimum d-spacing of 2.8 A resolution. On the basis of density calculation four monomers (one tetramer) are estimated to be present in the asymmetric unit (Vm = 2.5 A3/Da). Self-rotation functions clearly show the presence of 222 non-crystallographic symmetry.

Animals

Expression, purification, crystallization and preliminary X-ray analysis of human argininosuccinic acid lyase.

Human argininosuccinic acid lyase (ASAL) has been expressed, purified and crystallized in several distinct crystal morphologies. At present only one form is suitable for X-ray diffraction analysis. These crystals grow as hexagonal prisms, with unit cell dimensions a = b = 104.6 A, c = 185.3 A and alpha = beta = 90 degrees, gamma = 120 degrees. The crystals exhibit the symmetry of space group P3(1)21 or its enantiomorph, P3(2)21 (indistinguishable crystallographically) and diffract to a minimum d-spacing of approximately 3.5 A.

Argininosuccinate Lyase

Synthetic, structural and biological studies of the ubiquitin system: chemically synthesized and native ubiquitin fold into identical three-dimensional structures.

The solid-phase chemical synthesis of ubiquitin produced a molecule with physicochemical properties similar to those of the natural protein. We have grown crystals of this synthetic ubiquitin and performed an X-ray analysis at 1.8 A resolution in order to compare the synthetic protein with the known natural structure. The crystals were isomorphous with those of the natural protein, the R-factor between them being 7.1%. Difference Fourier analysis shows that the synthetic and natural structures are indistinguishable. The co-ordinates of the natural ubiquitin (1UBQ) were used as the starting point for restrained least-squares refinement (TNT program) against the synthetic X-ray data. The refinement converged to R = 16.5% and the resulting model did not change when refined against natural ubiquitin X-ray data (R = 18.7%). From both the refinement and featureless difference Fourier synthesis, we conclude that the synthetic and natural protein structures are identical. A short discussion about the uses of proteins with 'non-standard' amino acid residues is included.

Crystallography, X-Ray

Copper complexation by 3-hydroxypyridin-4-one iron chelators: structural and iron competition studies.

Clinical trials of 1,2-dimethyl-3-hydroxypyridine-4-one (1) as an orally available iron chelator are presently underway in several centers. Discrepant reports of toxicity in human and animal studies have stimulated debate on the role of iron status and the availability of iron for chelation relative to other essential elements like copper in determining the clinical effects of 1. Therefore, we investigated the ability of 1, its 1,2-diethyl analog 2, and their iron chelates to complex copper. Both compounds formed tetracoordinate 2:1 Cu(II) complexes which X-ray structure analysis showed to be planar and coordinated through the oxygen atoms of the hydroxy ketone functionality. Potentiometric analysis revealed that these complexes dominated at physiological pH, although between pH 6 and 7 approximately equal amounts of the mono and bis complexes of Cu with 1 were present at equilibrium. Comparing the stepwise formation constants deduced from the stability constants of these complexes (log beta 2 = 21.7 +/- 0.8 (1) and 20.2 +/- 2.0 (2)) with those of their Fe(III) complexes (Motekaitis,R.J.;Martell,A.E.Inorg.Chim.Acta 1991, 183,71-80) leads to a prediction of insignificant copper complexation when equimolar iron is present and dissociation products are thermodynamically unimportant. However, displacement of Fe3+ occurred from both complexes with stoichiometric amounts of Cu2+, implicating the participation of metal hydrolysis products in the equilibria. We conclude that Cu(II) complexes of the 3-hydroxypyridin-4-one chelators are stable under physiological conditions and that copper can effect displacement of iron by these agents under circumstances where hydrolysis of the metals is important.

Antithyroid Agents

Sequence and crystallization of Escherichia coli dethiobiotin synthetase, the penultimate enzyme of biotin biosynthesis.

The enzyme dethiobiotin synthetase (EC 6.3.3.3) has been cloned and over-expressed in Escherichia coli in such a way that milligram quantities are available. The purified enzyme has been subjected to a number of physical and chemical studies, sequenced and most notably it has been crystallized in a form that is suitable for X-ray structure determination. The cell dimensions are a = 72.8 A, b = 49.2 A, c = 61.4 A, beta = 106.2 degrees. The systematic absences are consistent with the monoclinic space group C2 with one polypeptide chain in the asymmetric unit.

Amino Acid Sequence

Hypertrophy causes delayed conduction in human and guinea pig myocardium: accentuation during ischaemic perfusion.

OBJECTIVE: The aim was to investigate why cardiac hypertrophy causes increased vulnerability to arrhythmias during myocardial ischaemia. METHODS: The electrophysiological basis for this increased vulnerability was studied in isolated perfused guinea pig hearts obtained 50 and 150 d after aortic constriction, and in sham operated controls. Cellular electrophysiology, conduction, and refractory periods were examined during control perfusion and during low flow (coronary flow reduced to 10% of control) and zero flow ischaemia. ECGs in patients with left ventricular hypertrophy and in controls matched for age and heart rate were also studied. RESULTS: Aortic constriction increased heart weight:body weight ratio by 33% at 50 d and by 69% at 150 d. Action potentials were unchanged in hypertrophied hearts. Significant conduction delay occurred in 150 d hypertrophied hearts [conduction time index 23(SEM 4) ms v 18(3) ms, p < 0.001; QRS width 40(1) ms v 35(1) ms, p < 0.01], but not in 50 d hypertrophied hearts. Conduction delay was also present in humans with left ventricular hypertrophy [QRS width 96(13) ms v 87(8) ms, p < 0.01]. Although the QTc interval was increased in humans, at 422(23) ms v 411(17) ms in controls, p < 0.05, this could be explained by the increased QRS duration. During ischaemia, ventricular arrhythmias tended to occur earlier in hypertrophied hearts. Hypertrophy was also associated with a greater increase in conduction delay. Ischaemia reduced action potential duration and refractory periods; the reduction in action potential duration was attenuated by hypertrophy (p < 0.01), although the reverse was apparent during low flow ischaemia at 50 d. CONCLUSIONS: Delayed conduction is an important feature of severe cardiac hypertrophy in guinea pigs and man. Hypertrophy is associated with accentuated conduction delay and altered repolarisation during ischaemia.

Animals

Proximal row carpectomy: a multicenter study.

Twenty patients underwent proximal row carpectomy and were retrospectively evaluated for pain, motion, grip strength, functional activity, and x-ray changes at a mean follow-up of 3 1/2 years. For nonrheumatoid patients, motion decreased 15% after surgery, mean grip strength improved 22%, and 82% believed their conditions were improved and said they would repeat the procedure. The procedure failed in all three patients with rheumatoid arthritis. Patients with mild preoperative arthritic changes had better results than those with advanced disease.

Adult

Manifestations of gastrointestinal disease on chest radiographs.

Diseases of the gastrointestinal tract may result in radiographic changes in the thorax. An abnormal chest radiographic finding is often the initial clue to the diagnosis of gastrointestinal disease. This article presents the commonly recognized and some unusual thoracic manifestations of significant primary esophageal diseases including achalasia, diverticula, carcinoma, duplication cysts, varices, esophageal perforation, and postoperative changes. Intraabdominal gastrointestinal processes such as pancreatitis or pseudocysts, gastric and colonic abnormalities, pneumoperitoneum, liver abnormalities, intraabdominal abscesses, and diaphragmatic hernias, which are frequently associated with intrathoracic abnormalities, are also reviewed. Awareness of changes on the chest radiograph produced by gastrointestinal disease allows prompt diagnosis and facilitates the appropriate confirmatory diagnostic study, such as esophagography or computed tomography.

Digestive System Diseases