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Biomedical subjects

R Wexler

Publications and source records attributed to R Wexler.

8 recordsLinked to original sources
PubMed2001

Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews.

G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on disease expression. Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The Netherlands (n=1), and the United States (n=1) were enlisted. All trace their ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208-D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the deletion was found to be 20 +/- 7 generations (the 95% confidence interval is 15-26 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 14th century. This corresponds with the founding of the Jewish community of Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ individuals in eastern Europe, which followed this settlement. The penetrance of mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no significant differences in the mean baseline lipid level of G197del carriers from different countries were found. Polymorphisms of apolipoprotein E and of scavenger-receptor class B type I were observed to have minor effects on the plasma lipid profile. With respect to determinative genetic influences on the biochemical phenotype, there is no evidence that could support the possibility of a selective evolutionary metabolic advantage. Therefore, the founder effect in a rapidly expanding population from a limited number of families remains a simple, parsimonious hypothesis explaining the spread of G197del-LDLR-linked FH in AJ individuals.

Adolescent↗
PubMed2001

Leprosy in Israel: an imported disease--the support of histopathological examination for its detection.

Leprosy is rare and non-endemic in Israel. Cases of leprosy are invariably imported by immigrants or foreign workers arriving from endemic areas. In view of the relative rarity of the disease, clinicians and pathologists are not always alert to the possibility of the disease or recognize potential symptoms. A case history is presented of a 31-year-old immigrant presenting symptoms of skin lesions and nodules on the hands and facial region, especially the ear lobe. Confirmation of the infection was provided by histopathology of suspected lesions stained for acid-fast bacilli (modified Fite-Faraco staining).

Adult↗
PubMed1996

Novel nonpeptide antiplatelet glycoprotein IIb/IIIa receptor antagonist, DMP754: receptor binding affinity and specificity.

OBJECTIVE: To define the antiplatelet efficacy and specificity of the glycoprotein IIb/IIIa complex (GPIIb/IIIa) antagonist prodrug DMP754 and its free acid form, XV459. METHODS AND MATERIALS: DMP754 has an IC50 > 1 mumol/l, and, upon its conversion with esterases to its free acid form, demonstrated high potency (IC50 20-45 nmol/l) in inhibiting human platelet aggregation induced by 10 mumol/l adenosine diphosphate, 20 micrograms/ml collagen, 1 mmol/l epinephrine, 10 mumol/l platelet activating factor or 0.5 IU/ml thrombin. The in-vitro rate of hydrolysis of DMP754 or XV459 is much faster with human or canine liver esterases (t 1/2 = 2.4-23 min) than with plasma esterases (t 1/2 = 5.5-7.6 h). Platelet GpIIb/IIIa integrin binding affinity and specificity for XV459 were determined using cell binding/adhesion assays. RESULTS: The range of IC50 values of XV459 in inhibiting platelet aggregation in platelet-rich plasma obtained from 12 subjects was 0.035-0.069 mumol/l with a mean IC50 of 0.050 +/- 0.003 mumol/l. Additionally, XV459 inhibited platelets obtained from mongrel dogs, baboons, sheep, guinea pigs, and mice with IC50 in the range 0.024-0.06 mumol/l, and IC50 in the range 0.16-5.8 mumol/l in pigs, rabbits, and rats. XV459 inhibited [125I]-fibrinogen binding to activated human platelets with an IC50 of 0.011 +/- 0.003 mumol/l. XV459 demonstrated a high degree of selectivity in specifically inhibiting fibrinogen binding to the platelet integrin, GPIIb/IIIa (IC50 = 0.00025 +/- 0.00005 mumol/l) compared with inhibiting other integrins (alpha v beta 3, IC50 > 10 mumol/l; or alpha v beta 5, alpha 5 beta 1, or alpha 4 beta 1, for which the IC50 exceeded 100 mumol/l). CONCLUSION: DMP754 is a potent antiplatelet agent in inhibiting platelet aggregation, and has a high specificity and affinity for human platelet GPIIb/IIIa receptors.

Amino Acids↗
PubMed1988

Patient anesthesia and monitoring at a 1.5-T MRI installation.

This paper describes the facilities successfully used to provide patient monitoring and anesthesia support in a 1.5-T imaging installation. The requirements for the MRI site for anesthetic gases, shielded power, and radiofrequency ports are outlined. Specific modifications in anesthesia machines, anesthesia cart, laryngoscope, mercury sphygmomanometer, oximeter, and remote blood pressure devices are described. Additional aspects of patient monitoring and support, e.g., electrocardiogram and pressure infusion, are also discussed.

Anesthesiology↗
PubMed1975

Lactose hydrolyzed milk.

Lactose intolerance is being reported in many populations. Yet, milk is highly nutritious and methods are being explored to use milk while limiting the lactose content. Thirty-two blacks 13-19 years of age were studied to determine a blood sugar rise with 8 ounces of the following test milks: 1) untreated whole milk (12 g/lactose); 2) 90% lactose hydrolyzed milk (1.2 g/lactose); and 3) 50% lactose hydrolyzed milk (6 g/lactose). In the 22 lactose malabsorbers, the peak blood sugars were: 1) untreated whole milk--4.4 mg/100 ml, 2) 90% lactose hydrolyzed milk--14.5 mg/100 ml, and 3) 50% lactose hydrolyzed milk--8.8 mg/100 ml. The 10 blacks with normal lactose absorption had a comparably high peak blood sugar on all three test milks. Differences between the blood sugar in the lactose absorbing and malabsorbing subjects when drinking untreated whole milk are significant (P less than 0.001); so are differences in the lactose malabsorbing subjects consuming untreated whole milk and 90% lactose hydrolyzed milk (P less than 0.001) as well as 50 and 90% lactose hydrolyzed milk. Symptoms were reported by three lactose malabsorbing subjects with untreated whole milk with two of the three symptomatic with 90% lactose hydrolyzed milk and none with 50% lactose hydrolyzed milk. No symptoms were reported by the lactose absorbers. Significant improvement in absorption with 90% lactose hydrolyzed milk is seen in low lactase subjects. Lactose hydrolyzed milk may serve as an important alternative for food planners wanting to provide milk to high risk populations with low lactase levels.

Adolescent↗