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Biomedical subjects

D H Winship

Publications and source records attributed to D H Winship.

At least 19 recordsLinked to original sources
PubMed1999

Determination of protein carbonyl groups by immunoblotting.

Free radical-mediated oxidation of proteins results in the formation of carbonyl groups in quantities that reflect the intensity of the oxidative stress. We have developed an immunochemical technique for the quantification of carbonyl groups in protein samples prepared from small tissue samples and cell cultures. Protein samples were slot-blotted onto a polyvinylidene difluoride membrane, which was sequentially treated with 2,4-dinitrophenylhydrazine (DNPH), a primary antibody specific for the 2,4-dinitrophenol group, and a peroxidase-labeled second antibody. After the blots were developed with a chemiluminescent substrate and exposed to X-ray film, the level of immunostaining was quantitated by densitometry. Using oxidized bovine serum albumin as a standard and loading 5 microg of protein per slot, the minimum detectable carbonyl content was approximately 60 pmol carbonyl/mg protein. When necessary, nonspecific staining by noncarbonyl constituents in complex sample matrices was accounted for by using sodium borohydride-treated blanks. Results by the new method were highly correlated (r = 0.932, P < 0.0001) with those of the standard DNPH-based spectrophotometric technique. The coefficient of variation at a carbonyl level of 1.5 nmol/mg protein was 9.7%. The utility of this new method was demonstrated by measuring protein oxidation in cultured human colon cells (SW620) that were briefly exposed to H2O2.

Cells, Cultured↗
PubMed1996

Restructuring medical schools to better manage their three missions in the face of financial scarcity.

The leaders of schools of medicine face a major financial and management challenge as they approach the end of the twentieth century. The new environment for the practice of medicine is diminishing the clinical income that schools have used for so long to supplement their operations. Deans and their staffs must discover new ways to manage their schools and their schools' finances. In particular, schools that continue to rely on subsidies from their health care operations will very likely face the prospect of having to defend themselves as pressures for more cost-effective operations increase and clinical and other subsidies dwindle. In sum, for deans to remain captains of their own ships, preserve their schools' three missions, and balance their books, it is essential that they lead their schools in change toward better administrative, information, and financial management systems. Stritch School of Medicine at Loyola University of Chicago is reinventing itself in response to this challenge. The organizational and management models being used there have been partially guided by the two approaches to redesigning schools of medicine described in detail in this article, the service line management matrix (SLMM) and the fractal management (FM) method. In turn, the experience of implementing the education and research service lines at Loyola has permitted a refinement of the approaches, reflected in the descriptions in this article. These approaches constitute a new model that provides for the development of three administrative service lines-teaching, research, and clinical service (not implemented at Loyola). Each service line has its own leaders and managers, who are responsible for balancing income against expenses. Each service line is a profit-and-loss center, an approach that highlights how effectively the service line is being managed and leads to greater accountability and productivity of faculty and staff. This new approach makes it possible for the school to answer the question, "Can research and teaching pay for themselves?" If they cannot, any subsidies that are needed from clinical income are identified as such. This businesslike approach supplants the traditional one of commingling all income streams to pay for operations, a strategy that worked well enough when research and clinical income constantly increased but now places medical schools in harm's way.

Administrative Personnel↗
PubMed1990

Gastrointestinal manifestations of mixed connective tissue disease.

We examined the gastrointestinal tract abnormalities in 61 patients with mixed connective tissue disease. The first 34 were part of a prospective longitudinal study that included manometric and radiographic evaluation of the esophagus. Heartburn (48%) and dysphagia (38%) were by far the most common gastrointestinal symptoms. Seventeen percent of patients undergoing manometry had distal esophageal aperistalsis, and 43% low-amplitude peristalsis (less than 30 mmHg). Studies in 10 patients before and after treatment suggested that esophageal dysfunction in mixed connective tissue disease may be responsive to corticosteroids. Upper esophageal sphincter hypotension was also common. One patient had marked upper esophageal sphincter hypotension and recurrent aspiration, which resolved with corticosteroid therapy. Findings on radiographic studies of the stomach and small bowel in 54 patients and barium enemas in 16 patients were reviewed. Our series included one case each of malabsorption, colonic and small bowel perforations due to vasculitis, chronic active hepatitis, and acute pancreatitis. In conclusion, any area of the gastrointestinal tract may be affected by mixed connective tissue disease, although the esophagus is the most common location. The gastrointestinal aspects of mixed connective tissue disease overlap with those of progressive systemic sclerosis, polymyositis, and systemic lupus erythematosus.

Adolescent↗
PubMed1980

Esophageal dysfunction in esophagopharyngeal regurgitation.

Esophageal manometry was performed in 20 patients with esophagopharyngeal regurgitation, in 20 patients with severe chronic heartburn but without regurgitation, and in 20 normal subjects. The purpose of the procedure was to identify possible differences between these groups in upper esophageal sphincter and lower esophageal sphincter resting pressures, and in amplitude of peristaltic contraction in the distal esophagus. The mean peak upper esophageal sphincter pressures in normal subjects and in patients with chronic heartburn were significantly greater than in the patients with esophagopharyngeal regurgitation (101 and 108 vs. 54 mmHg, respectively). In the normal subjects, the mean lower esophageal sphincter resting pressure (19 mmHg) was significantly greater than for the heartburn group (14 mmHg) and for the patients with esophagopharyngeal regurgitation (10 mmHg). The amplitude of peristalsis was significantly lower in the group with regurgitation than in both normal subjects and the group with chronic heartburn. Nine normal subjects responded to intraesophageal infusion of 0.9% NaCl and 0.1 N HCl with a significant increase in upper esophageal sphincter resting pressure, but the group with esophagopharyngeal regurgitation showed no significant change. Patients with esophagopharyngeal regurgitation have lower esophageal sphincter hypotension, diminished peristaltic amplitude, upper esophageal sphincter hypotension, and diminished upper esophageal sphincter response to intraesophageal fluid. We conclude there is in these patients a breakdown of several normal esophageal mechanisms which ordinarily serve as barriers to esophagopharyngeal regurgitation.

Adult↗
PubMed1979

National Cooperative Crohn's Disease Study: study design and conduct of the study.

The design and execution of the National Cooperative Crohn's Disease Study are described in this paper. The Study incorporated several noteworthy features developed to meet specific demands of the disease and its therapy. A standard clinical grading system, the Crohn's Disease Activity Index (CDAI) was developed to allow uniform decentralized clinical evaluation and decision-making throughout the 5 yr of the study. All three drugs in widespread clinical use in Crohn's disease were studied both for suppressive and prophylactic efficacy and for toxicity. The study employed a scheme for double-blind evaluation of patient progress which allowed adjustment of prednisone dose according to the degree of illness and ensured continuous monitoring for serious toxicity of any study drug. Results were analyzed primarily by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. Outcome was also analyzed by life-table methods. Eleven hundred nineteen patients were entered and 604 patients were randomized at 14 study centers during the 5-yr duration of the study. Twenty patients were eliminated from analysis as not meeting diagnostic criteria for Crohn's disease, and another 15 patients were eliminated as not meeting other preestablished criteria for analysis. Nine percent of randomized patients, equally distributed in the four treatment groups, withdrew as noncompliant. Ninety percent of patients completed all or all but one protocol-specified visits, and 95% completed the final radiologic and sigmoidoscopic evaluation.

Azathioprine↗
PubMed1979

A trial of sulfasalazine as adjunctive therapy in Crohn's disease.

The effect of the combination of sulfasalazine and prednisone has been compared with that of prednisone and placebo in 89 actively symptomatic patients with Crohn's disease in a double-blind, randomized, multicenter controlled trial. The combination was less effective than prednisone alone in treatment of active symptomatic disease. The probability of obtaining this result, if sulfasalazine truly has a clinically useful effect equal to or greater than that specified in the calculation, is less than 1%. Patients who were in remission at the end of 8 wk were rerandomized to receive either the two drugs together or prednisone plus placebo while repeated systematic attempts to withdraw prednisone were made over the next 6 mo. Sulfasalazine showed no prednisone-sparing effect as judged either by outcome ranking or total dose of prednisone consmed by the two treatment groups. However, in this comparison the probability is greater than 5% that, given the results observed, a clinically useful effect of sulfasalazine of specified minimum degree truly exists. It was possible to withdraw prednisone from 25% of patients at the first attempt and ultimately in 37%.

Adult↗
PubMed1978

Cimetidine in the treatment of duodenal ulcer: review and commentary.

The published world literature on the efficacy of cimetidine, a histamine H2-receptor antagonist, in the treatment of duodenal ulcer is reviewed. In eight prospective randomized double blind placebo-controlled studies, cimetidine was administered to 348 duodenal ulcer patients with an incidence of endoscopically verified healing incidence of 37 percent in 300 placebo-treated patients. Healing rates were similar in patients receiving cimetidine in doses ranging from 0.8 to 2.0 g per day. It appears that at least 3 to 4 weeks of cimetidine therapy are needed to achieve healing rates of about 70 percent. In most trials, cimetidine was superior to placebo in achieving symptom relief in patients with duodenal ulcer. The drug has not been shown to result in acid rebound after cessation of therapy. There are no published prospective studies on the question of whether treatment with cimetidine results in increased ulcer for the short term treatment of duodenal ulcer. More data are required for an assessment of long term therapy with cimetidine.

Antacids↗
PubMed1977

Lipolysosomes in human liver: distribution in livers with fatty infiltration.

In this study we investigated whether lipolysosomes--lysosomes containing large lipid droplets--were present in livers of patients with various forms of hepatic injury. Organelles which displayed the same morphological characteristics and enzymatic activity as those originally described in the hamster and those found in the hepatocytes of patients with Wolman's or Wilson's disease were also found in hepatocytes of 13 of 14 randomly selected biopsy specimens from patients with minimal to severe fatty infiltration of the liver. The numbers and sizes of the lipolysosomes seemed to increase with the degree of fatty infiltration while their proportion in relation to the total number of lipid droplets remained below 5%. Based on these observations of a virtually constant association of lipolysosomes with excess lipid accumulation in liver cells we suggest that lysosomes probably play an important role in hepatic lipid metabolism and that various pathogenetic mechanisms may trigger their proliferation.

Adolescent↗