Search

Jaundice in an adult patient can be caused by a wide variety of benign or life-threatening disorders. Organizing the differential diagnosis by prehepatic, intrahepatic, and posthepatic causes may help make the work-up more manageable. Prehepatic causes of jaundice include hemolysis and hematoma resorption, which lead to elevated levels of unconjugated (indirect) bilirubin. Intrahepatic disorders can lead to unconjugated or conjugated hyperbilirubinemia. The conjugated (direct) bilirubin level is often elevated by alcohol, infectious hepatitis, drug reactions, and autoimmune disorders. Posthepatic disorders also can cause conjugated hyperbilirubinemia. Gallstone formation is the most common and benign posthepatic process that causes jaundice; however, the differential diagnosis also includes serious conditions such as biliary tract infection, pancreatitis, and malignancies. The laboratory work-up should begin with a urine test for bilirubin, which indicates that conjugated hyperbilirubinemia is present. If the complete blood count and initial tests for liver function and infectious hepatitis are unrevealing, the work-up typically proceeds to abdominal imaging by ultrasonography or computed tomographic scanning. In a few instances, more invasive procedures such as cholangiography or liver biopsy may be needed to arrive at a diagnosis. [ABSTRACT FROM AUTHOR]

Ten percent of the population abuses drugs or alcohol, and 20 percent of patients seen by family physicians have substance-abuse problems, excluding tobacco use. These patients can be identified by relying on regular screening or a high index of suspicion based on 'red flags' that can be noted in various clinical situations. The modified CAGE questionnaire is an excellent screening instrument, but several alternatives are available. The best screening test is one that the physician will routinely use well. Laboratory indicators such as gamma-glutamyl transpeptidase, mean corpuscular volume, and carbohydrate-deficient transferrin are nonspecific but can add to the evidence of alcohol abuse. If problem alcohol use is diagnosed, even brief physician advice can be helpful. If the problem has progressed to addiction, referral to an addiction specialist or treatment center is recommended. Special issues arise in dealing with substance abuse in adolescents, elderly patients, and patients with mental illness, but the family physician can play an important role in recognizing this common problem. [ABSTRACT FROM AUTHOR]

Context: Practice guidelines play an important role in medicine. Methodological principles have been formulated to guide their development.Objective: To determine whether practice guidelines in peer-reviewed medical literature adhered to established methodological standards for practice guidelines.Design: Structured review of guidelines published from 1985 through June 1997 identified by a MEDLINE search.Main Outcome Measures: Mean number of standards met based on a 25-item instrument and frequency of adherence.Results: We evaluated 279 guidelines, published from 1985 through June 1997, produced by 69 different developers. Mean overall adherence to standards by each guideline was 43.1% (10.77/25). Mean (SD) adherence to methodological standards on guideline development and format was 51.1% (25.3%); on identification and summary of evidence, 33.6% (29.9%); and on the formulation of recommendations, 46% (45%). Mean adherence to standards by each guideline improved from 36.9% (9.2/25) in 1985 to 50.4% (12.6/25) in 1997 (P<.001). However, there was little improvement over time in adherence to standards on identification and summary of evidence from 34.6% prior to 1990 to 36.1 % after 1995 (P = .11). There was no difference in the mean number of standards satisfied by guidelines produced by subspecialty medical societies, general medical societies, or government agencies (P = .55). Guideline length was positively correlated with adherence to methodological standards (P = .001).Conclusion: Guidelines published in the peer-reviewed medical literature during the past decade do not adhere well to established methodological standards. While all areas of guideline development need improvement, greatest improvement is needed in the identification, evaluation, and synthesis of the scientific evidence. [ABSTRACT FROM AUTHOR]

Background: In preparation for potential clinical development of Ab-01, an antagonistic antibody directed against the IL21R, studies were undertaken to address translational medicine needs that fall into four categories: 1) development of a pharmacodynamic biomarker assay suitable for use in the clinic, 2) demonstration that Ab-01 has the desired biological activity in vitro and in vivo in cynomolgus monkeys, the preferred safety study species, 3) pre-clinical in vivo proof-of-concept that the assay can be used to detect Ab-01 pharmacodynamic (PD) activity in treated subjects, and 4) comprehensive assessment of the agonistic potential of Ab-01 when cross-linked. This report and a recently published companion report address the first three of these needs. The fourth has been addressed in a separate study.Methods: Genes that change RNA expression upon ex vivo rhIL21 stimulation of whole blood were identified in human and cynomolgus monkey. The inhibitory effects of exogenously added Ab-01 were measured ex vivo in human and monkey, and the in vivo inhibitory effects of Ab-01 treatment were measured in monkey.Results: Stimulation of whole human blood for 2 hours with rhIL21 induced robust increases in RNA expression of 6 genes. This response was blocked by Ab-01, indicating that the assay is suitable for measuring Ab-01 activity in blood. rhIL21 induced expression of a similar set of genes in cynomolgus monkey blood. This response was blocked with Ab-01, thus demonstrating that Ab-01 has the desired activity in the species, and that safety studies done in cynomolgus monkeys are relevant. Proof -of-concept for using this assay system to detect PD activity in vivo was generated by measuring the response in monkey blood to ex vivo rhIL21 stimulation before and 5 minutes following in vivo Ab-01 administration.Conclusions: A robust PD biomarker assay suitable for clinical use has been developed in human whole blood. The successful adaptation of the assay to cynomolgus monkeys has enabled the demonstration of Ab-01 activity both in vitro and in vivo in monkey, thus validating the use of this species in safety studies and establishing proof-of-concept for using this PD assay system to aid in dose selection in clinical studies. [ABSTRACT FROM AUTHOR]

The article reports that sedative hypnotic agents reduce mortality and duration of delirium in the alcohol withdrawal syndrome. Prospective controlled trials on the management of patients meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for alcohol withdrawal delirium. Of 4 trials comparing sedative-hypnotic agents with neuroleptic drugs for duration of delirium, 3 trials showed a benefit with sedative-hypnotic agents with decreases in duration ranging from 22 to 48 hours.

Background: Magnetic resonance (MR) imaging of the neonate has been restricted by the need to transport the sick baby to the large magnetic resonance scanners and often the need for sedation or anaesthesia in order to obtain good quality images. Ultrasound is the reference standard for neonatal imaging.Objective: To establish a dedicated neonatal MR system and compare the clinical usefulness of MR imaging with ultrasound imaging.Design: Prospective double blind trial.Setting: Neonatal intensive care unit, Sheffield.Main Outcome Measures: Imaging reports.Patients: 134 premature and term babies.Results: In 56% of infants with pathology suspected on clinical grounds, MR provided additional useful clinical information over and above that obtained with ultrasound.Conclusion: Infants can be safely imaged by dedicated low field magnetic resonance on the neonatal intensive care unit without the need for sedation at a cost equivalent to ultrasound. [ABSTRACT FROM AUTHOR]