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Biomedical subjects

A Adler

Publications and source records attributed to A Adler.

At least 37 records · Page 2Linked to original sources
PubMed2002

Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.

BACKGROUND AND STUDY AIMS: Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort. PATIENTS AND METHODS: Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain). RESULTS: Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy. CONCLUSIONS: Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.

Adolescent↗
PubMed2001

Association of tobacco smoke exposure and respiratory syncitial virus infection with airways reactivity in early childhood.

Exposure to infectious agents and environmental tobacco smoke are thought to induce bronchial hyperresponsiveness (BHR). This study was undertaken to determine the effects of passive exposure to tobacco smoke and respiratory syncitial virus (RSV) lower respiratory infection (LRI) during infancy on the occurrence of BHR in the first 2 years of life. Eighty-six cases of documented RSV (mean age, 188 days) and 78 controls (mean age, 162 days) were enrolled from the clinic and in-patient service of a single hospital. None had a history of prior LRI. Subjects were studied at 6-month intervals up to 19 months of age with a standardized respiratory illness and parental smoking questionnaire, partial expiratory flow-volume curves by the "hug" (rapid thoracic compression) technique, and methacholine challenge. Exposure to maternal and paternal cigarette smoking, maternal history of asthma, and mold exposure were associated with decreased levels of length-corrected maximal flow at functional residual capacity (V'(maxFRC)). RSV-LRI was not related to V'(maxFRC). After adjustment of V'(maxFRC) for these factors, V'(maxFRC) was a significantly and positively correlated with a methacholine concentration provoking a 40% fall in V'(maxFRC) (PC40) and negatively correlated with dose-response slope. After adjustment for V'(maxFRC), there were no independent effects of tobacco smoke exposure or RSV-LRI on methacholine responses. These data do not support a role for RSV as a risk factor for airways reactivity in childhood and indicate that exposure to tobacco smoke affects airways reactivity through its effects on airways.

Bronchial Hyperreactivity↗
PubMed2001

Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51).

AIMS/HYPOTHESIS: To estimate the economic efficiency of intensive blood-glucose control with metformin compared with conventional therapy primarily with diet in overweight patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS: Cost-effectiveness analysis based on patient level data from a randomised clinical controlled trial involving 753 overweight (> 120% ideal body weight) patients with newly diagnosed Type II diabetes conducted in 15 hospital-based clinics in England, Scotland and Northern Ireland as part of the UK Prospective Diabetes Study. Subjects were allocated at random to an intensive blood-glucose control policy with metformin (n = 342) or a conventional policy primarily with diet (n = 411). The analysis was based on the cost of health care resources associated with metformin and conventional therapy and the estimated effectiveness in terms of life expectancy gained from within-trial effects. RESULTS: Intensive blood-glucose control with metformin produced a net saving of 258 Pounds per patient (1997 United Kingdom prices) over the trial period (median duration of 10.7 years) due to lower complication costs, and increased life expectancy by 0.4 years (costs and benefits discounted at 6%). CONCLUSIONS/INTERPRETATION: As metformin is both cost-saving in the United Kingdom and extends life expectancy when used as first line pharmacological therapy in overweight Type II diabetic patients, its use should be attractive to clinicians and health care managers alike.

Adult↗
PubMed2001

Risk factors for diabetic neuropathy and foot ulceration.

Peripheral sensory neuropathy (PSN) and foot ulcers are disabling and expensive complications of diabetes with few therapeutic options. Knowledge of risk factors for both complications, based on prospective observational studies, permits identification of individuals at high risk and provides options for intervention. Glycemia is the main modifiable risk factor for PSN, whereas PSN and trauma are the principal potentially modifiable risk factors for the development of foot ulceration.

Diabetic Foot↗
PubMed2001

Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial.

Novel therapies are needed for locally advanced pancreatic carcinoma. ONYX-015 (dl1520) is an E1B-55 kDa region-deleted adenovirus that selectively replicates in and lyses tumor cells with abnormalities in p53 function (eg gene mutation). We carried out a phase I dose escalation study of ONYX-015 in patients with unresectable pancreatic cancer. ONYX-015 was administered via CT-guided injection (n = 22 patients) or intraoperative injection (n = 1) into pancreatic primary tumors every 4 weeks until tumor progression. Interpatient dose escalation was carried out with at least three patients per dose level from 10(8) p.f.u. up to the 10(11) p.f.u. dose level (two patients treated at this dose). The majority of patients had abnormally low cellular immunity (CD4 counts and hypersensitivity skin testing). Injection of ONYX-015 into pancreatic carcinomas was well-tolerated. Mild, transient pancreatitis was noted in only one patient. Dose-escalation proceeded to the highest dose level. Neutralizing antibodies rose post-treatment in all patients. After injection, ONYX-015 was detectable in the blood 15 min later, but not between 1 and 15 days later. Viral replication was not documented, however, in contrast to trials in other tumor types. No objective responses were demonstrated. Intratumoral injection of an E1B-55 kDa region-deleted adenovirus into primary pancreatic tumors was feasible and well-tolerated at doses up to 10(11) p.f.u. (2 x 10(12) particles), but viral replication was not detectable.

Adenoviridae↗
PubMed2001

An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54).

AIMS: To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or beta blocker (atenolol) in patients with Type 2 diabetes. DESIGN: A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. SETTING: Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. SUBJECTS: Hypertensive patients (n = 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the beta blocker atenolol. MAIN OUTCOME MEASURES: Life expectancy and mean cost per patient. RESULTS: There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was 6485 UK pounds in the captopril group, compared with 5550 UK pounds in the atenolol group, an average cost difference of 935 UK pounds (95% confidence interval 188 UK pounds, 1682 UK pounds). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. CONCLUSIONS: Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438-444 (2001)

Adrenergic beta-Antagonists↗
PubMed2001

Insulin-sensitizing effect of rosiglitazone (BRL-49653) by regulation of glucose transporters in muscle and fat of Zucker rats.

Thiazolidinediones (TZDs), a class of antidiabetic agents, are specific agonists of peroxisome proliferator activator receptor (PPARgamma). However, their mechanisms of action, and the in vivo target tissues that mediate insulin sensitization are not well understood. The aim of this study was to investigate the role of glucose transporters (GLUT-1 and GLUT-4) in the TZD insulin-sensitizer action. The effects of rosiglitazone treatment were studied using Zucker (fa/fa) rats after 7 days of oral dosing (3.6 mg/kg/d). Rosiglitazone lowered (approximate 80%) basal plasma insulin levels in obese rats and substantially corrected (approximately 50%) insulin resistance based upon results from hyperinsulinemic euglycemic clamp studies. GLUT-4 protein levels were reduced (approximately 75%) in adipose tissue of obese rats and treatment with rosiglitazone normalized them. Interestingly, GLUT-1 protein content was increased in adipose tissue ( thick approximate 150%) and skeletal muscle (approximately 50%) of obese rats and treatment with rosiglitazone increased it even more by 5.5-fold in fat and by 2.5-fold in muscle. Consistent with these results, basal (GLUT-1-mediated) transport rate of 3-O-methyl-D-glucose into isolated epitrochlearis muscle was elevated in response to rosiglitazone. Incubation of fully differentiated 3T3-L1 adipocytes with the drug for 7 days increased the levels of GLUT-1 protein, but did not affect GLUT-4 levels. In conclusion, rosiglitazone may improve insulin resistance in vivo by normalizing GLUT-4 protein content in adipose tissue and increasing GLUT-1 in skeletal muscle and fat. While the drug has a direct effect on GLUT-1 protein expression in vitro without a direct effect on GLUT-4 suggests that direct and indirect effects of rosiglitazone on glucose transporters may have an important role in improving insulin resistance in vivo.

3T3 Cells↗
PubMed2001

The laparoscopic Janeway gastrostomy. An alternative technique when percutaneous endoscopic gastrostomy is impractical.

BACKGROUND AND STUDY AIMS: Today, percutaneous endoscopic gastrostomy (PEG) is the standard procedure for ensuring safe feeding access. In the case of advanced hypopharyngeal and esophageal carcinomas, it may not be feasible to pass an existing stenosis by endoscopy. The aim of this prospective study was to investigate the laparoscopic Janeway gastrostomy as an alternative technique for guaranteeing feeding access in these instances. PATIENTS AND METHODS: Between May 1993 and December 1999, 21 patients underwent laparoscopic Janeway gastrostomies. Indications were extended incurable tumors of the hypopharnyx (n = 12) and esophagus (n = 9) which rendered oral nutrition impossible and did not allow passage by the endoscope. RESULTS: The mean operative time was 38 minutes (range 24-50). No procedure-related intraoperative or postoperative complications were observed. All patients recovered quickly from surgery and the gastrostomies functioned well in all cases until the death of the patients. CONCLUSION: The laparoscopic Janeway gastrostomy is a safe and simple technique for palliative feeding access, avoiding a laparotomy in patients in whom percutaneous endoscopic placement is impractical.

Aged↗
PubMed2001

Magnetic resonance cholangiopancreatography-guided unilateral endoscopic stent placement for Klatskin tumors.

BACKGROUND: Advanced and incurable Klatskin tumors of Bismuth-type III and IV cause obstructive jaundice. Palliation of patients with Klatskin tumors is usually carried out by bilateral endoscopic stent placement. Endoscopic retrograde cholangiography (ERC) in such patients is associated with a comparatively high morbidity and mortality mainly due to postprocedure bacterial cholangitis. To reduce ERC-related complications the outcome of replacing ERC with magnetic resonance cholangiopancreatography (MRCP) was investigated. Subsequently, unilateral contrast injection and stent placement were performed, thus avoiding bilateral contrast injection and stent insertion. METHODS: Patients thought to have a Klatskin tumor underwent clinical evaluation, laboratory, and noninvasive imaging studies before ERC. Patients were enrolled in this feasibility study if investigators agreed with the clinical diagnosis of an advanced and incurable Klatskin tumor. MRCP images were used to determine the predominate ductal drainage for the liver segments thus directing stent placement. Based on these findings, unilateral ERC and subsequent unilateral stent placement were performed. Antibiotics were not given before ERC. Amsterdam-type stents (10F) were placed and replaced routinely at 2 months. In cases of earlier occlusion, the stents were replaced immediately. RESULTS: Thirty-five patients underwent MRCP, ERC, and unilateral stent deployment. Two further patients enrolled after MRCP were withdrawn because ERC could not be carried out. In 35 patients with unilateral stents bilirubin levels decreased (18.9 +/- 6.3 mg/dL to 3.2 +/- 2.3 mg/dL) and jaundice resolved in 86%. After first stent deployment, post-ERC bacterial cholangitis occurred in 6% (2 of 35) of patients. CONCLUSIONS: This new method of MRCP-guided endoscopic unilateral stent placement could reduce ERC-related complications caused by initial stent deployment. The results of this study justify a randomized prospective comparative trial.

Bile Duct Neoplasms↗
PubMed2001

The Spanish National Institutes of Health-Chronic Prostatitis Symptom Index: translation and linguistic validation.

PURPOSE: The prominence of health related quality of life end points in international clinical research underscores the importance of well validated and translated measures to enable cross-cultural comparison. The National Institutes of Health (NIH)-Chronic Prostatitis Symptom Index (CPSI) assesses symptoms and health related quality of life in men with chronic nonbacterial, NIH type III prostatitis. To expand its use to Spanish speaking patients we performed a translation and linguistic validation. MATERIALS AND METHODS: The 9-item NIH-CPSI was translated into Spanish according to a standard methodology of 2 forward translations, 1 reconciled version, back translation of the reconciled version and 3 independent reviews by bilingual experts. The purpose of this methodology was to create a single universal Spanish version that would be acceptable to native Spanish speakers inside and outside of the United States. After the translation process the Spanish version was pre-tested in Argentina, Mexico, Spain and the United States. Patient responses were analyzed to identify necessary modifications. The internal consistency of the CPSI was evaluated using Cronbach's alpha. Pearson's product moment correlations were used to evaluate construct validity. RESULTS: Data were collected from chronic prostatitis patients, including 15 in Argentina, 15 in Mexico, 4 in the United States and 3 in Spain. The translation had high reliability overall and in all subscales (Cronbach's coefficient alpha = 0.81 to 0.94), and the subscales correlated well with each other (r = 0.76 to 0.97). However, patients expressed difficulty in distinguishing the response categories "a menudo" ("often") from "normalmente" ("usually") in question 3. We revised "a menudo" to "muchas veces" ("much of the time") and "normalmente" to "casi siempre" ("almost always") to improve the distinctiveness of response categories. CONCLUSIONS: The Spanish NIH-CPSI has high reliability as well as face and construct validity in Spanish speaking men from various countries. The Spanish NIH-CPSI permits cross-cultural comparisons of men with chronic nonbacterial prostatitis.

Adult↗
PubMed2000

Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group.

OBJECTIVE: To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes. DESIGN: Incremental cost effectiveness analysis alongside randomised controlled trial. SETTING: 23 UK hospital clinic based study centres. PARTICIPANTS: 3867 patients with newly diagnosed type 2 diabetes (mean age 53 years). INTERVENTIONS: Conventional (primarily diet) glucose control policy versus intensive control policy with a sulphonylurea or insulin. MAIN OUTCOME MEASURES: Incremental cost per event-free year gained within the trial period. RESULTS: Intensive glucose control increased trial treatment costs by pound 695 (95% confidence interval pound 555 to pound 836) per patient but reduced the cost of complications by pound 957 (pound 233 to pound 1681) compared with conventional management. If standard practice visit patterns were assumed rather than trial conditions, the incremental cost of intensive management was pound 478 (-pound 275 to pound 1232) per patient. The within trial event-free time gained in the intensive group was 0.60 (0.12 to 1.10) years and the lifetime gain 1.14 (0.69 to 1.61) years. The incremental cost per event-free year gained was pound 1166 (costs and effects discounted at 6% a year) and pound 563 (costs discounted at 6% a year and effects not discounted). CONCLUSIONS: Intensive blood glucose control in patients with type 2 diabetes significantly increased treatment costs but substantially reduced the cost of complications and increased the time free of complications.

Adult↗
PubMed2000

[Classification and treatment of bile duct injuries after laparoscopic cholecystectomy].

Iatrogenic bile duct lesions are serious complications during laparoscopic cholecystectomy and include biliary leakage and major bile duct injury. The incidence of biliary lesions following laparoscopic cholecystectomy is up to threefold higher than that of the open procedure. A total of 108 patients with bile duct lesions after laparoscopic cholecystectomy were treated at our institution. Endoscopic treatment was successful in 68 cases, 6 patients were treated by external drainage, and 34 patients required surgical therapy. Selection criteria for the type of treatment included the etiology, anatomical situation, and diagnostic interval of the biliary lesion. We suggest a classification of bile duct injury and a proposal for diagnosis and treatment of these complications.

Adult↗
PubMed2000

Life-expectancy projection by modelling and computer simulation (UKPDS 46).

A method is described for estimating the life-expectancy of cohorts of type 2 diabetic patients, based on computer simulation from a parametric model. The method can be used where non-parametric methods, such as the Kaplan-Meier estimate, fail due to lack of the data. The simulation algorithm combines observed and modelled information to estimate the life-expectancy implications of event rates observed within a study. The use of bootstrap methods to estimate confidence intervals is discussed. The methods are illustrated with results that have been previously published, without derivation, in a health economic analysis of tight blood pressure (BP) control in the UK Prospective Diabetes Study (UKPDS), and the application to other health economic analyses of UKPDS data is discussed.

Algorithms↗
PubMed2000

Preimplantation genetic diagnosis in two families at risk for recurrence of Herlitz junctional epidermolysis bullosa.

The Herlitz type of junctional epidermolysis bullosa (H-JEB) is a severe inherited bullous disease which leads to the early demise of the affected newborn. Mutations in the genes encoding the 3 polypeptides of the anchoring filament protein laminin 5 underlie this condition. We studied 2 families with affected children who previously died from H-JEB. Mutation screening using heteroduplex analysis and direct sequencing of the PCR products revealed a previously described hotspot mutation in LAMB3 (R635X), and a novel delayed termination codon in LAMB3 in the first proband. In the second proband, we found a novel initiation codon mutation in LAMB3, and a novel 2 bp deletion in LAMB3. For preimplantation genetic diagnosis (PGD) in these families, we developed nested multiplex PCR assays, amplifying the mutations and informative intragenic polymorphisms in the probands. Single embryonic cells were biopsied from 8-cell embryos using standard techniques, and subjected to the multiplex PCR assay followed by restriction enzyme digestion. Embryos found not to carry either mutation were transferred to the mothers, and a pregnancy was established in the second family as evidenced by the elevated level of HCG, although the pregnancy did not persist. This study illustrates the feasibility of PGD for an inherited skin disorder for the first time.

Base Sequence↗
PubMed2000

A micromechanical model of airway-parenchymal interdependence.

The forces of parenchymal interdependence in the lung are potent inhibitors of airway smooth muscle shortening, as evidenced by the marked dependence of bronchial responsiveness on lung volume. In this study we developed a mathematical-computer model of the effects of parenchymal interdependence on airway smooth muscle shortening. A three-dimensional network of cuboidal alveolar walls was tethered at its boundaries and surrounded a single airway with mechanical properties identical to the alveolar parenchyma. The walls were assigned highly nonlinear properties so that the pressure-volume behavior of the model matched that measured in dogs. Constriction of the airway was achieved by increasing the circumferential tension in the airway wall, and then solving the force-balance equations of the model to calculate the equilibrium configurations of the airway wall and all the interconnecting alveolar walls. The changes in airway resistance predicted by the model at various transpulmonary pressures (P(tp)) were compared to those obtained by the alveolar capsule oscillator technique in dogs during induced bronchoconstriction at various P(tp) (Balassy et al., J. Appl. Physiol. 78:875-880, 1995). The model matched the data reasonably well at P(tp) values above about 0.5 kPa, but was too responsive at lower P(tp). We were able to make the model match the data at all P(tp) by including an additional stiffness term, such as might conceivably arise from the airway wall itself.

Airway Resistance↗
PubMed1999

Pyrrolidine-3-carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ET(B) selectivity.

When the dialkylacetamide side chain of the ET(A)-selective antagonist ABT-627 is replaced with a 2,6-dialkylacetanilide, the resultant analogues show a complete reversal of receptor selectivity, preferring ET(B) over ET(A). By optimizing the aniline substitution pattern, as well as the alkoxy group on the 2-aryl substituent, it is possible to prepare antagonists with subnanomolar affinity for ET(B) and with selectivities in excess of 4000-fold. A number of these compounds also show promising pharmacokinetic profiles; a useful balance of properties is found in A-192621 (38). Pharmacology studies with A-192621 serve to reveal the role of the ET(B) receptor in modulating blood pressure; the observed hypertensive response to persistent ET(B) blockade is consistent with previous postulates and indicates that ET(B)-selective antagonists may not be suitable as agents for long-term systemic therapy.

Acetanilides↗
PubMed1999

Enhancement or initiation of testicular sperm motility by in vitro culture of testicular tissue.

OBJECTIVE: To describe different techniques of testicular tissue culture and their effect on sperm motility, mainly in cases of totally immotile spermatozoa, and to compare the effect of in vitro culture with that of motility stimulants. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENT(S): Ten patients undergoing testicular biopsy for diagnostic purposes or for intracytoplasmic sperm injection. INTERVENTION(S): Dissected testicular biopsy samples and tissue blocks were cultured at 37 degrees C for up to 96 hours. Immediately after dissection, immotile testicular spermatozoa were incubated for 30 minutes in pentoxifylline and 2-deoxyadenosine. MAIN OUTCOME MEASURE(S): Sperm motility and vitality. RESULT(S): Overall, dissected samples showed improved sperm motility, which peaked within 48 hours of culture. Unlike motility, vitality declined linearly, from 56.3%+/-19% at initial assessment to 18.8%+/-11% at 96 hours. Five samples had initially immotile spermatozoa, of which four acquired motility at 48 hours. In vitro culture showed results comparable with those of incubation with pentoxifylline and 2-deoxyadenosine. Culture of tissue blocks did not improve motility or vitality compared with dissected tissue. CONCLUSION(S): The motility of testicular spermatozoa was enhanced or initiated after in vitro culture. Testicular biopsy culture may be an alternative to the use of motility stimulants to obtain motile spermatozoa for intracytoplasmic sperm injection, particularly when oocytes are not immediately available.

Adult↗