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L Wolfe

Publications and source records attributed to L Wolfe.

At least 37 records · Page 2Linked to original sources

Multicenter, randomized, prospective trial of early tracheostomy.

OBJECTIVES: Determine the effect of early (days 3-5) or late (days 10-14) tracheostomy on intensive care unit length of stay (ICU LOS), frequency of pneumonia, and mortality, and evidence of short-term or long-term pharyngeal, laryngeal, or tracheal injury in head trauma, non-head trauma, and critically ill nontrauma patients. STUDY DESIGN: Randomized, prospective. SETTING: Five Level I trauma centers. METHODS: Data were obtained prospectively and included Acute Physiology and Chronic Health Evaluation III score (AIII), Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, type of endotracheal tube or tracheostomy, level of positive end-expiratory pressure, and peak inspiratory pressure. Patients were to undergo laryngoscopy for detection of injury according to the Lindholm criteria at the time of endotracheal tube or tracheostomy removal and be reevaluated at 3 to 5 months after discharge. RESULTS: One hundred fifty-seven patients were entered, 127 to early randomization (3-5 days) and 28 to late randomization (10-14 days); however, only 112 patients with early and 14 with late randomization had completed data forms for the primary study goals. An additional 22 patients from the early entry groups were rerandomized late. Early randomization data: the AIII score was higher (p < 0.05) in the head trauma tracheostomy (65 +/- 4) than in the nontracheostomy group (51 +/- 4) and in the nontrauma tracheostomy (92 +/- 6) than in the nontracheostomy group (68 +/- 7), but was equivalent in the non-head trauma group. Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, positive end-expiratory pressure, and peak inspiratory pressure were not significantly different in any of the groups. There were no significant differences in ICU LOS, frequency of pneumonia, or death in any of the groups after either early or late tracheostomy compared with continued endotracheal intubation. Only 83 patients underwent postextubation laryngoscopy. There were no significant differences between the groups; however, there were trends to more vocal cord ulceration and subglottic inflammation in the continued intubation group. No patient was seen in this study with late vocal cord or laryngeal stenosis; there were no tracheal-innominate artery fistulae. Seven of the patients with abnormal findings at extubation had normal 3- to 5-month postextubation laryngoscopy. CONCLUSION: Physician bias limited patient entry into the study. Although there were higher AIII scores in the head trauma early tracheostomy patients, there were no differences in the primary end points of ICU LOS, pneumonia, or death in any of the groups studied. Long-term endoscopic follow-up was poor, but no known late tracheal stenosis was seen.

APACHE↗

The impact of a positive crossmatch upon outcome after liver transplantation.

Recent reports have shown that liver allografts transplanted against a positive lymphocytotoxic crossmatch (CDC+) are susceptible to an increased frequency of rejection, and decreases in patient and graft survival. The implication of a positive flow cytometric crossmatch (FCXM+) in liver transplantation remains controversial. The purpose of this study was to determine what impact a pretransplant IgG crossmatch due to CDC+ or FCXM+ had upon the clinical outcome following liver transplantation. Preoperative crossmatch status was determined prospectively in 110 consecutive liver transplants performed between July 1991 and January 1995. Allografts were divided into three groups: negative crossmatch (NXM), positive flow cytometric crossmatch FCXM+, and positive lymphocytotoxic crossmatch CDC+. Crossmatch status did not impact patient or graft survival. Actuarial patient survival was similar between groups at 12 months (88% vs. 95% vs. 92%, NXM vs. FCXM+ vs. CDC+) and 24 months (81% vs. 93% vs. 92%, NXM vs. FCXM+ vs. CDC+) (P=0.1938). Actuarial allograft survival was similar between groups at 12 months (76% vs. 93% vs. 85%, NXM vs. FCXM+ vs. CDC+) and 24 months (76% vs. 89% vs. 85%, NXM vs. FCXM+ vs. CDC+) (P=0.0738). CDC+ allografts had a significant increase in early rejection episodes compared with NXM (46% vs. 7%, CDC+ vs. NXM) (P=0.003) or FCXM+ allografts (46% vs. 10%, CDC+ vs. FCXM+) (P=0.006). CDC+ allografts experienced significantly more rejection episodes per year than NXM (53% vs. 20%, CDC+ vs. NXM) (P=0.015) or FCXM+ allografts (53% vs. 23%, CDC+ vs. FCXM+) (P=0.02). CDC+ allografts had a significant increase in numbers of additional nonconventional therapeutic interventions compared to NXM allografts (0.9+/-0.5 vs. 0.2+/-0.1, CDC+ vs. NXM) (P=0.039). The presence of cytotoxic antibodies pretransplantation is associated with increased incidences of early rejection, and rejection episodes per year. With careful monitoring and aggressive therapeutic interventions the presence of cytotoxic antibodies are not deleterious to patient or liver allograft survival.

Adult↗

Significance of indeterminate third-generation hepatitis C virus recombinant immunoblot assay.

Indeterminate hepatitis C virus (HCV) third-generation recombinant immunoblot assay (RIBA3.0; Ortho Diagnostic Systems) patterns were arbitrarily defined by the manufacturer as the detection of only one antibody out of the four that were sought, namely, c100 (NS4 encoded), c22 (core encoded), c33c (NS3 encoded), and NS5 (NS5 encoded). The aims of the present study were (i) to determine the prevalence of indeterminate RIBA3.0 patterns in patients consecutively tested for anti-HCV antibodies in a university hospital; (ii) to evaluate the significance of these patterns in terms of viral replication, liver disease, and risk factors for HCV; and (iii) to get an insight into the mechanism underlying this peculiar immune response. Among 3,074 serum samples consecutively tested for anti-HCV antibodies, 588 were found to be positive by screening assays. Fifty-nine of them (10%) were RIBA3.0 indeterminate and were compared with 59 RIBA3.0-positive ones. Thirty-one RIBA3.0-indeterminate and 53 RIBA3.0-positive serum samples were HCV RNA positive by PCR (53 versus 90%; P < 10(-6). RIBA3.0-indeterminate and RIBA-3.0-positive patients with positive PCR results were not significantly different for the prevalence of risk factors for HCV infection and elevated serum alanine aminotransferase activities. Immunosuppression, attributable to coexisting human immunodeficiency virus infection, organ transplantation, or the administration of immunosuppressive drugs, was significantly more frequent in PCR-positive, RIBA3.0-indeterminate patients than in PCR-negative, RIBA3.0 indeterminate patients (P < 0.001) and PCR-positive patients with a positive RIBA3.0 result (P < 0.01). The distribution of HCV genotypes did not differ significantly between HCV RNA-positive patients with indeterminate or positive RIBA3.0 results. In conclusion, the prevalence of indeterminate RIBA3.0 patterns in virology laboratories is about 10%; in about half of these patients HCV replication is detected by PCR; the main factor responsible for indeterminate RIBA3.0 patterns could be immunosuppression, whereas HCV genotypes do not seem to play major role.

Antigens, Viral↗

Measuring defensive medicine using clinical scenario surveys.

For more than two decades, advocates of malpractice system reform have claimed that the most damaging and costly result of the U.S. medical malpractice system is the practice of defensive medicine, in which physicians order tests and procedures primarily because of fear of malpractice liability. In this article, we discuss the issues raised by different definitions of defensive medicine and propose a working definition to guide measurement of the concept. We also consider the strengths and weaknesses of available approaches for measuring defensive medicine. Finally, we describe an empirical approach to measuring defensive medicine using clinical scenario surveys. The results suggest that, if physicians actually practice as they say they would in these surveys, defensive medicine does exist, although not to the extent suggested by anecdotal evidence or direct physician surveys. The results also suggest that defensive medicine varies considerably across clinical situations. In all of the scenarios, many physicians chose aggressive patient management styles even though conservative management was considered medically acceptable by the expert panels that developed the scenarios. In most cases, medical indications, not malpractice concerns, motivated clinical choices. Our results highlight the limitations of surveys as a method of measuring the extent of defensive medicine. The implications of managed care and health care reform for defensive medicine are also discussed.

Attitude of Health Personnel↗

Assessing the characteristics of patients with oral lichen planus.

The authors assessed the medical history, lifestyles and health habits of 146 patients with oral lichen planus as confirmed by biopsy. The results support a relationship between stress and the development of oral lichen planus. Fifty-one percent of the subjects reported that they had experienced stressful events at the time of the lichen planus onset. Practitioners may want to consider the benefits of stress management and bereavement counseling in managing patients with oral lichen planus.

Adolescent↗

Mutual confounding and interactive effects between hepatitis C and hepatitis B viral infections in hepatocellular carcinogenesis: a population-based case-control study in Taiwan.

A population-based case-control study was conducted in Taiwan to determine the hepatitis C virus (HCV)-associated risk of hepatocellular carcinoma (HCC) in a hyperendemic area for hepatitis B virus (HBV) infection. A total of 58 recently diagnosed HCC patients and 225 matched community controls, who participated in a community-based liver cancer screening program, were recruited between March 1991 and March 1994. Control subjects were matched to HCC patients by age (+/- 5 years), sex, residence, and date of serum sample collection (+/- 3 months). Serum samples from all study subjects were tested for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCVs) by enzyme immunoassays, as well as HCV RNA by reverse transcription-PCR assays. Accordingly, patients with HCC were more likely than were controls to be positive for HBsAg (82.8% versus 12.9%, with an odds ratio (OR) of 22.9), anti-HCVs (13.8% versus 4.4%, with an OR of 3.9), and HCV RNA (13.8% versus 5.8%, with an OR of 2.7). After adjustment for anti-HCVs and HCV RNA positivities, the matched ORs associated with HBsAg increased to 27.6 and 28.1, respectively, whereas the corresponding adjusted ORs for anti-HCVs and HCV RNA after controlling for HBsAg status were increased to 8.8 and 6.2, respectively. In the meantime, interactive effects between HCV and HBV on risk were also observed. Compared with those who were negative for both anti-HCVs and HBsAg, the matched ORs associated with the sole positivity of anti-HCVs and HBsAg were 4.0 (95% confidence interval = 0.7-24.0) and 24.6 (95% confidence interval = 9.5-64.1), respectively, whereas 6 HCC cases but none of control subjects were positive for both anti-HCVs and HBsAg. These results indicate that there are mutual confounding and interactive effects between HCV and HBV with respect to their links to HCC in this endemic area of chronic HBV infections.

Adult↗

The fluctuations of hepatitis C virus RNA and IgM anti-HCV (core) serum levels correlate with those of alanine aminotransferases during the hepatitis relapses of patients treated with interferon.

Variations in the serum levels of hepatitis C virus (HCV) RNA. IgM antibody against the HCV 'core' structural protein (c22) and alanine amino-transferase (ALT) were measured in 23 patients with chronic hepatitis C who underwent therapy with interferon-alpha 2a (IFN alpha 2a). Low pretreatment levels of viraemia and undetectable IgM anti-core were significantly associated with a long-term response to treatment. In patients with hepatitis relapses after the end of treatment, HCV RNA levels increased before or at the same time as ALT in 29 out of 34 cases (85%). ALT flares occurred before or simultaneously with IgM anti-core elevations in 18 out of 20 cases (90%). Therefore, post-treatment hepatitis C exacerbations show the same sequence of events seen as in hepatitis B exacerbations (increases of viraemia followed by those of ALT and IgM anti-'core'). These findings underscore the diagnostic and prognostic usefulness of monitoring anti-HCV-positive patients with quantitative assays for HCV markers.

Alanine Transaminase↗

Induction with OKT3 and prostaglandin E1 in liver transplantation.

Forty-six consecutive adult patients underwent 51 orthotopic liver transplants in a prospective study to evaluate sequential induction with ORTHOCLONE OKT3 (muromonab-CD3), prostaglandin E1, cyclosporine, azathioprine, and methylprednisolone. Infection prophylaxis included preoperative bowel preparation and ganciclovir if cytomegalovirus was diagnosed in either donor or recipient. All rejection episodes were documented by liver biopsy before treatment. Seventy-four percent of patients evaluable beyond 1 year have had no rejection episodes. The retransplant rate was 10%, with a 4% primary nonfunction rate. There was no rejection of grafts that could not be retreated with OKT3. Forty-two percent (5 of 12) of rejection episodes responded to steroid recycling alone. The infection rates for all patients at 1 year were 54% bacterial, 17% fungal, and 22% viral. Three septic deaths were attributed to overimmunosuppression. Two-year patient and graft survival rates were 80% and 72%, respectively. This OKT3 induction protocol results in limited rejection episodes without increasing infections, yielding an acceptably low rate of graft loss.

Adult↗

Radioimmunoassay of ganirelix in plasma or serum.

A procedure for the radioimmunoassay (RIA) of ganirelix in plasma or serum at concentrations as low as 0.050 ng/ml is described. Antiserum was produced by coupling the N-terminus glycyl analog of ganirelix to BSA by a carbodiimide reaction and immunizing rabbits with this conjugate. The antiserum did not crossreact with LHRH or with various ganirelix peptide fragments. For RIA, 125I labeled ganirelix was used as the tracer and a double antibody procedure was used to separate the free and bound fractions. No purification of the analyte was required prior to RIA. Accuracy of the method was assessed by adding known quantities of ganirelix to ganirelix-free plasma and determining the ratio of measured to added analyte. Linear regression analysis for the concentration range 0.050-50.0 ng/ml yielded a regression equation of y = 0.97x + 0.18, r = 0.999, where x is the amount added and y is the amount measured. Additional validation was obtained from an in vivo study in which [3H]-ganirelix was administered to monkeys and plasma clearance profiles were determined by RIA and an HPLC-radiochemical method. The results were in agreement within experimental error of the two methods. Linear regression analysis of the comparative data gave the equation y = 0.92x + 33.7, r = 0.980, where x is the amount measured by RIA and y is the amount measured by HPLC-radiochemical analysis.

Amino Acid Sequence↗

Purification and characterization of a cytosolic insulin-stimulated serine kinase from rat liver.

A cytosolic insulin-sensitive serine kinase has been purified to apparent homogeneity in parallel from livers of control or acutely insulin-treated rats. The kinase is labile and requires rapid purification for stability. The kinase migrates as a band of apparent Mr = 90,000 on denaturing gels and elutes as a monomer on Superose 12 gel filtration. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis and renaturation, the 90-kDa band presumed to be the kinase shows kinase activity toward myelin basic protein in situ. Substrates of the kinase include Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide), ribosomal protein S6, S6 peptide, a proline-rich peptide substrate, microtubule-associated protein 2, and myelin basic protein. The kinase also phosphorylates histones H1 and H2B, but does not autophosphorylate to a significant stoichiometry. The activity of the kinase is inhibited by fluoride, glycerophosphate, p-nitrophenyl phosphate, p-nitrophenol, heparin, quercetin, poly-L-lysine, and potassium phosphate, but is unaffected by calcium, cAMP, spermine, protein kinase inhibitor peptide, phorbol myristate acetate, calcium plus phosphatidylserine, or vanadate. The kinase will utilize magnesium (10 mM) as well as manganese (1 mM) as a cofactor for maximal phosphotransferase activity. The kinase is not detected by immunoblotting with antibodies directed against protein kinase C or type II S6 kinase. Taken together, these properties distinguish this kinase from other insulin-sensitive kinases that have been described previously. The purified kinase from livers of insulin-treated rats shows a 5-20-fold higher specific activity compared to enzyme prepared from control rats, suggesting a covalent modification as the mechanism of activation. Incubation of purified, insulin-stimulated kinase with purified phosphatase 2A leads to deactivation of the kinase activity, and the phosphatase inhibitor nitrophenyl phosphate blocks this deactivation. The insulin-activated kinase fails to immunoblot with anti-tyrosine phosphate antibodies. Taken together, these results indicate that insulin activates this novel cytosolic protein kinase by a mechanism that causes its phosphorylation on serine or threonine residues.

Amino Acid Sequence↗

Gastric bypass for treating severe obesity.

Gastric bypass (RY-GBP) has a very small gastric pouch with a 1-cm diameter Roux-Y gastrojejunostomy. RY-GBP is associated with early satiety and an aversion to sweets secondary to dumping syndrome symptoms and has a significantly better weight loss than various gastroplasty procedures, including the vertical banded gastroplasty. However, it may be associated with vitamin B-12 deficiency and iron deficiency anemia in menstruating females, preventable with prophylactic oral iron and vitamin B-12. With an 80% 5 y follow-up, RY-GBP patients lose two-thirds of their excess weight within 2 y, 60% at 5 y, and greater than 50% at 9 y. The RY-GBP can be beaten by nibbling "junk foods" (potato or corn chips). Conversion to a malabsorptive procedure may cause severe malnutrition and fat-soluble vitamin deficiencies and should be used only for "superobese" patients who fail a standard RY-GBP and have severe comorbidity. RY-GBP is the most effective procedure for morbid obesity, especially in patients addicted to "sweets."

Gastric Bypass↗

Long-term effects of gastric surgery for treating respiratory insufficiency of obesity.

The Pickwickian syndrome can be divided into two primary breathing disorders, which can affect patients alone or in combination: sleep apnea syndrome (SAS) and obesity hypoventilation syndrome (OHS). Between 1980 and 1990, 126 patients with respiratory insufficiency underwent gastric surgery for morbid obesity, 12.5% of the entire series. These patients weighed more (164 +/- 36 vs 135 +/- 25 kg, P less than 0.0001) and were more often men (62% vs 14%, P less than 0.001) than those without pulmonary dysfunction. Sixteen had OHS alone, 65 had SAS alone, and 45 had both. Of those with OHS, 38 have been followed for 5.8 +/- 2.4 y since surgery and 29 are currently asymptomatic. In the 12 patients in whom arterial blood gases were available greater than 5 y since surgery, the PaO2 increased from 54 +/- 10 to 68 +/- 20 mm Hg (P less than 0.0001) and PaCO2 fell from 53 +/- 9 to 47 +/- 11 mm Hg (P = 0.05). Of the 110 patients with SAS, 57 were available for follow-up an average of 4.5 +/- 2.3 y since surgery and 38 were completely asymptomatic, 15 had mild SAS, and 4 had both SAS and OHS. In 40 patients with pre- and post-weight reduction sleep polysomnograms, the sleep apnea index fell from 64 +/- 39 to 26 +/- 26 (P less than 0.0001). Although respiratory insufficiency of obesity patients had a higher operative mortality than did patients without pulmonary dysfunction (2.4% vs 0.2% after gastric bypass), weight loss was associated with significant improvements in sleep apnea, arterial blood gases, pulmonary hypertension, left ventricular dysfunction, lung volumes, and polycythemia.

Adult↗

Relaxation of pig coronary arteries by new and potent cGMP analogs that selectively activate type I alpha, compared with type I beta, cGMP-dependent protein kinase.

Smooth muscle preparations of human aorta or pig coronary arteries contain nearly equal amounts of cGMP-dependent protein kinase isozymes (cGMP kinase I alpha and I beta). In order to understand the roles of these isozymes in relaxing vascular smooth muscle, several new cGMP analogs were synthesized and tested for potencies in activating each enzyme and in relaxing pig coronary arteries. Analogs modified with a derivatized phenylthio group at the 8-position were as much as 72-fold more potent in activating purified cGMP kinase I alpha than cGMP kinase I beta. Electron-donating substituents, such as hydroxy, amino, and methoxy, on the phenyl ring enhanced the potencies of these analogs in activating cGMP kinase I alpha. The most potent of these cGMP analogs [8-(4-hydroxyphenylthio)-cGMP] was 17 times more potent (EC50 = 1.1 microM) as a muscle relaxant than the most efficacious analog tested previously. Among derivatives with an 8-halo group, 8-iodo-cGMP was the most potent compound (Ka = 9 nM for I alpha and 122 nM for I beta) for both I alpha and I beta. Analogs modified at the 1,N2-position or at both the 1,N2-and 8-positions of cGMP were highly potent for activating both isozymes. Within this group, 8-I-beta-phenyl-1,N2-etheno-cGMP had Ka values of 22 nM and 17 nM for cGMP kinase I alpha and I beta, respectively, whereas the Ka values of cGMP were 110 nM and 250 nM for the two isozymes. 8-I-beta-phenyl-1,N2-etheno-cGMP was the most potent muscle relaxant tested, with EC50 of 0.4 microM. For all cGMP analogs tested, there was a positive correlation between potency for activation of cGMP kinase I alpha and that for relaxation of pig coronary arteries. Assuming that the kinase assay conditions yielded a cyclic nucleotide specificity similar to that which would exist in intact cells, it was concluded that the cGMP kinase I alpha isozyme mediates the relaxation of pig coronary artery smooth muscle caused by cGMP elevation. However, an additional role for cGMP kinase I beta in the relaxation process could not be ruled out.

Animals↗

Musculoskeletal tumors in childhood.

As treatment strategies improve, the ability to cure children with musculoskeletal tumors is growing. The stage of a given malignancy, representing the degree of spread of the tumor to its local surroundings or distant sites, is the best predictor of long-term survival. Unfortunately, the insidious nature of the presentation of these tumors leads to their late recognition in advanced stages. This review will present scenarios suggesting the need for consideration of malignancy in the differential diagnosis of clinical problems related to the musculoskeletal system. Pitfalls in diagnosis and therapeutic approaches will also be discussed.

Bone Neoplasms↗

Stomal complications of gastric bypass: incidence and outcome of therapy.

Gastric bypass is an effective treatment for morbid obesity. However, it is sometimes complicated by stenosis or ulceration of the gastrojejunal anastomosis. Stomal ulceration and stenosis developed in, respectively, 12.5% and 12% of 191 patients who underwent gastric bypass. Only 3% had both complications simultaneously. The risk of developing either complication was highest in the first 2 months after surgery. Stomal stenosis responded to endoscopic dilation in all instances, and appears to be a safe and effective method of treating this problem following gastric bypass. Stomal ulceration healed with an H2 blocker and sucralfate administration in all but one patient. Postoperative weight loss was similar in patients with or without stomal stenosis or ulceration. We conclude that, although stomal complications occur in about 20% of all patients undergoing gastric bypass, they can almost always be managed by conservative therapy.

Catheterization↗