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Biomedical subjects

M Friedberg

Publications and source records attributed to M Friedberg.

At least 19 recordsLinked to original sources
PubMed2004

Hypothalamic regulation of adiposity: the role of 11beta-hydroxysteroid dehydrogenase type 1.

Following extensive suprasellar operations for excision of hypothalamic tumors, some patients develop morbid obesity despite receiving replacement doses of glucocorticoids. Urine analysis of cortisol and cortisone metabolites show that 11-OH/11-oxo ratios are significantly higher in patients with hypothalamic obesity, indicating enhanced 11beta-HSD1 activity. This correlates with the visceral-to-subcutaneous fat ratio. The consequence of increased 11beta-HSD1 activity and a shift of the steroid inter-conversion towards cortisol may contribute to the effects of the latter in adipose tissue. The message from the hypothalamus to adipocyte 11beta-HSD-1 involves hormones, the sympathetic nervous system and cytokines. CRH and ACTH downregulate 11beta-HSD-1 activity and induce lipolysis. Tumor necrosis factor-alpha and interleukin-1beta upregulate 11beta-HSD-1 expression and activity, while enhancing lipolysis. The sympathetic nervous system exerts its effects through beta-adrenergic upregulation and alpha-adrenergic downregulation of 11beta-HSD-1 activity. Inhibition of 11beta-HSD-1 suppresses preadipocyte differentiation into mature adipocytes, and may provide a therapeutic tool.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2001

Long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products.

BACKGROUND: Glucose degradation products (GDPs) are cytotoxic in vitro and potentially toxic in vivo during peritoneal dialysis (PD). We are presenting the results of a two-year randomized clinical trial of a new PD fluid, produced in a two-compartment bag and designed to minimize heat-induced glucose degradation while producing a near neutral pH. The effects of the new fluid over two years of treatment on membrane transport characteristics, ultrafiltration (UF) capacity, and effluent markers of peritoneal membrane integrity were investigated and compared with those obtained during treatment with a standard solution. DESIGN: A two-group parallel design with 80 continuous ambulatory peritoneal dialysis patients was used. The patients were randomly assigned to either the new fluid (N = 40) or to a conventional one (N = 40), and were stratified with respect to age, diabetes, and time on PD. Peritoneal transport characteristics were assessed by the Personal Dialysis Capacity (PDCtrade mark) test at 1, 6, 12, 18, and 24 months after inclusion and by weighing the overnight bag daily. Infusion pain and handling were evaluated using a questionnaire. Peritoneal mesothelial and interstitial integrity were evaluated by analyzing overnight effluent dialysate concentrations of CA 125, hyaluronan (HA), procollagen-1-C-terminal peptide (PICP), and procollagen-3-N-terminal peptide (PIIINP) at 1, 6, 12, 18, and 24 months. RESULTS: The handling of the new two-compartment bag was considered easy, and there were no indications of increased discomfort with the new system. Furthermore, no changes in peritoneal fluid or solute transport characteristics were observed during the study period for either fluid, and neither were there any differences with regard to peritonitis incidence. However, significantly higher dialysate CA 125 (73 +/- 41 vs. 25 +/- 18 U/mL), PICP (387 +/- 163 vs. 244 +/- 81 ng/mL), and PIIINP (50 +/- 24 vs. 29 +/- 13 ng/mL) and significantly lower concentrations of HA (395 +/- 185 vs. 530 +/- 298 ng/mL) were observed in the overnight effluent during treatment with the new fluid. CONCLUSIONS: We conclude that the new fluid with a higher pH and less GDPs is safe and easy to use and has no negative effects on either the frequency of peritonitis or peritoneal transport characteristics as compared with conventional ones. Our results indicate that the new solution causes less mesothelial and interstitial damage than conventional ones; that is, it may be considered more biocompatible than a number of conventional PD solutions currently in use.

Adult↗
PubMed2000

Choosing a career in primary care: the road not taken.

CONTEXT: Despite a mission statement and curriculum that are unique in our country in proposing to direct physicians to primary care (PC), the proportion of doctors graduating from Ben Gurion University (BGU) who choose PC is similar to that of other Israeli medical schools. OBJECTIVES, METHODS AND STUDY POPULATION: To investigate factors underlying our graduates' career choices we sent a questionnaire to six consecutive classes that had graduated from this medical school. We hypothesized that medical school was not the decisive factor influencing career choice. RESULTS: Returns were received from 135 graduates (54%). The nature of a specialty was the most important factor in choosing a career and in rejecting PC. Differences between primary care physicians (PCPs) and non-primary care physicians (NPCPs) were identified. PCPs emphasized factors relating to their personal lives. NPCPs emphasized the nature of a specialty in career choice. The most important factor in choosing PC was the physician-patient relationship and human aspects of medicine. Medical school was viewed as playing a minor role in career choice. PROPOSED INTERVENTIONS: Graduates proposed methods to increase the proportion of doctors choosing PC. These included: economic incentives; changing work conditions; strengthening contact with tertiary care; continuing medical education; and changing PC clerkships in medical school. CONCLUSION: The inherent nature of a specialty is central to career choice. In PC, the patient-physician relationship is central to physicians' career choice.

Journal Article↗
PubMed1999

[Congenital syphilis: need for adequate antenatal care].

Congenital syphilis is well-known and treatable with penicillin. Diagnosis in the neonate and young child may be difficult and consequently morbidity and mortality can be high. Prevention in children is of utmost importance and can be achieved by proper antenatal care and adequate follow-up of pregnant women. This includes identification of pregnant women at risk for contracting syphilis. The case presented demonstrates this need.

Female↗
PubMed1999

Evaluation of conflict of interest in economic analyses of new drugs used in oncology.

CONTEXT: Recent studies have found that when investigators have financial relationships with pharmaceutical or product manufacturers, they are less likely to criticize the safety or efficacy of these agents. The effects of health economics research on pharmaceutical company revenue make drug investigations potentially vulnerable to this bias. OBJECTIVE: To determine whether there is an association between pharmaceutical industry sponsorship and economic assessment of oncology drugs. DESIGN: MEDLINE and HealthSTAR databases (1988-1998) were searched for original English-language research articles of cost or cost-effectiveness analyses of 6 oncology drugs in 3 new drug categories (hematopoietic colony-stimulating factors, serotonin antagonist antiemetics, and taxanes), yielding 44 eligible articles. Two investigators independently abstracted each article based on specific criteria. MAIN OUTCOME MEASURE: Relationships between funding source and (1) qualitative cost assessment (favorable, neutral, or unfavorable) and (2) qualitative conclusions that overstated quantitative results. RESULTS: Pharmaceutical company-sponsored studies were less likely than nonprofit-sponsored studies to report unfavorable qualitative conclusions (1/20 [5%] vs 9/24 [38%]; P = .04), whereas overstatements of quantitative results were not significantly different in pharmaceutical company-sponsored (6/20 [30%]) vs nonprofit-sponsored (3/24 [13%]) studies (P = .26). CONCLUSIONS: Although we did not identify bias in individual studies, these findings indicate that pharmaceutical company sponsorship of economic analyses is associated with reduced likelihood of reporting unfavorable results.

Biomedical Research↗
PubMed1998

Insulin stacking for capillary electrophoresis.

Stacking methods are very important in overcoming the poor detection limits in capillary electrophoresis. Human insulin, a polypeptide, was concentrated on the capillary (stacked) based on three different and simple treatment methods to the sample: dilute buffers, high salt content, and acetonitrile (66%) were added to the sample to induce stacking. A dilute buffer in the sample caused a limited stacking, while acetonitrile treatment and high salt content in the sample caused much greater (approximately 20-fold) stacking. High salt concentration in the sample caused stacking presumably by a transient isotachophoretic method. In addition to stacking, the acetonitrile treatment removed the excess proteins in the sample. Insulin did not denature or precipitate in 66% acetonitrile as confirmed by high-performance liquid chromatography (HPLC) and immunoassays. Acetonitrile treatment enabled one-third of the capillary to be loaded with sample thus increasing the detection signal greatly. The insulin peak after acetonitrile treatment and separation by capillary electrophoresis (CE) was confirmed by HPLC and by CE fraction collection followed by immunoassay. Based on acetonitrile treatment, insulin detection in pancreatic tissue homogenates is shown to be feasible.

Animals↗
PubMed1997

Analysis of urinary N-acetyl-beta-glucosaminidase by capillary zone electrophoresis.

N-Acetyl-beta-glucosaminidase (NAG), a glycosidase enzyme, present in serum, urine and the renal lysosomes is utilized clinically as an early marker for renal damage preceding the elevation of both blood urea nitrogen and creatinine. NAG is analyzed by CE after incubation of urine samples with the synthetic substrate methylumbelliferyl-beta-D-glucosaminide. The reaction mixture is introduced directly into the instrument without further treatment. The released reaction product, 4-methyl-umbelliferone, is separated at 13.2 kV in a 400 mM borate buffer, pH 8.1. Detection was achieved with either ultraviolet absorption or with fluorescence. The fluorescence detection was more sensitive and gave cleaner electropherograms. The CZE method correlated well with an automated kinetic fluorescent assay. 4-Methyl-umbelliferone conjugated to different substrates is used in the analysis of many enzymes involved in the inborn errors of metabolism.

Acetylglucosaminidase↗
PubMed1997

Ketoprofen analysis in serum by capillary electrophoresis.

A method for the quantification of ketoprofen, a new non-prescription non-steroidal anti-inflammatory drug, in serum, by capillary zone electrophoresis for therapeutic monitoring and emergency toxicology is described. Serum is deproteinized with acetonitrile in the presence of an internal standard, to remove serum proteins and to induce sample stacking. The migration time was about 10 min. The assay was linear between 1-10 mg/l without any interferences. The method compared well to an HPLC assay. The HPLC afforded a better detection limit, but the CE was less expensive to operate. This method demonstrates that capillary electrophoresis is a simple and effective method for determination of ketoprofen as well as other drugs in human serum at levels close to 1 mg/l.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Cancer risk after renal transplantation in the Nordic countries, 1964-1986.

The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow-up. Information on 5,692 Nordic recipients of renal transplants in 1964-1982 was linked with the national cancer registries (1964-1986) and population registries. Person-years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age- and calender-specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10-fold to 30-fold above expectation, were associated with cancers of the lip, skin (non-melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva-vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer.

Adult↗
PubMed1987

Eosinophilia in hemodialysis patients.

Thirteen percent of 99 patients undergoing maintenance hemodialysis showed an increased predialysis peripheral blood eosinophil count (mean value of 828 cells/mm3, range 410-2,710). Patients with eosinophilia were predominantly male and evidenced more frequent elevation of total plasma IgE levels. Otherwise, no differences were found between patients with and without eosinophilia.

Adolescent↗
PubMed1986

Effect of sunlight exposure on circulating 1,25-dihydroxyvitamin D in hemodialyzed patients and of exogenous parathyroid hormone in anephric patients.

Sunshine exposure increased the serum concentration of 25-hydroxyvitamin D (25-OHD) in 9 hemodialyzed patients. Mean 1,25-dihydroxyvitamin D (1,25-(OH)2D) was unchanged, but in two patients with low initial 25-OHD values this increase was accompanied by a rise in circulating 1,25-(OH)2D, although not to normal levels. One hemodialyzed patient developed liver insufficiency with a resultant reduction of serum 25-OHD concentration accompanied by a decrease in serum 1,25-(OH)2D concentration. The results indicate that the circulating levels of 1,25-(OH)2D in patients with end-stage renal failure are to some extent regulated by the serum 25-OHD concentrations. Injection of parathyroid hormone (PTH) induced minor increases in serum concentrations of 1,25-(OH)2D in patients with end-stage renal failure and even in anephric patients, suggesting the existence of an extrarenal PTH-sensitive 1-alpha-hydroxylase. However, the enzyme was stimulated by supraphysiological concentrations of PTH, and therefore not necessarily of importance in the normal regulation of calcium metabolism.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

Hepatobiliary scanning in cholecystitis.

To validate the use of 99mTc-PIPIDA in the diagnosis of biliary tract disease, 117 patients with clinical symptoms of acute cholecystitis were prospectively scanned as an initial screening test. The accuracy of the test was evaluated on the basis of surgical pathology in 59 patients. Three groups were defined: cystic duct obstruction, common duct obstruction, and normal scan. The diagnostic accuracy of the test for acute cholecystitis was 97%. Complete common duct obstruction was confirmed at surgery in 12 patients (100%). A normal scan helped to rule out acute cholecystitis. Jaundice did not influence the reliability of the method. Hepatobiliary scanning is an accurate, safe, and rapid diagnostic test for acute cholecystitis.

Acute Disease↗