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Biomedical subjects

H Reuveni

Publications and source records attributed to H Reuveni.

At least 19 recordsLinked to original sources
PubMed2004

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes.

AIMS/HYPOTHESIS: G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes. METHODS: Synthetic peptides derived from a kinase-substrate interaction site in GRK2/3 were initially screened for their effect on in vitro melanogenesis, a GRK-mediated process. The most effective peptides were administered intraperitoneally, utilising a variety of dosing regimens, to Psammomys obesus gerbils, Zucker diabetic fatty (ZDF) rats, or db/db mice. The metabolic effects of these peptides were assessed by measuring fasting and fed blood glucose levels and glucose tolerance. RESULTS: Two peptides, KRX-683(107) and KRX-683(124), significantly reduced fed-state blood glucose levels in the diabetic Psammomys obesus. In animals treated with KRX-683(124) at a dose of 12.5 mg/kg weekly for 7 weeks, ten of eleven treated animals responded with mean blood glucose significantly lower than controls (4.7+/-0.4 vs 16.8+/-0.8 mmol/l, p</=0.0001). Significant reductions in blood glucose compared with controls were also seen in ZDF rats administered KRX-683(124) and in db/db mice, which had significantly reduced fasting and 2-hour postprandial glucose levels after the treatment. CONCLUSIONS/INTERPRETATION: Sequence-based peptides derived from GRK2/3 have an antidiabetic effect demonstrated in three different animal models of Type 2 diabetes. By modulating GRK2/3 activity, these peptides enhance GPCR-initiated signal transduction, resulting in improved glucose homeostasis. Sequence-based peptide modulation of GRK could prove useful in the treatment of Type 2 diabetes.

Animals↗
PubMed2001

The need for routine pre-operative coagulation screening tests (prothrombin time PT/partial thromboplastin time PTT) for healthy children undergoing elective tonsillectomy and/or adenoidectomy.

In some medical centers, the routine pre-operative evaluation of healthy children undergoing elective tonsillectomy and/or adenoidectomy (T and A) includes coagulation screening tests (PT, prothrombin Time; PTT, partial thromboplastin time; and INR, international normalized ratio). In this retrospective study, we determined whether there is a positive correlation between prolonged PT/PTT/INR tests in healthy children, with no prior medical history of coagulation problems, and bleeding during surgery and/or bleeding in the month following surgery. We reviewed the records of 416 elective T and A surgeries performed at the Soroka University Medical Center in Beer-Sheva, Israel, over the course of 1999. One hundred and twenty-one (29.1%) patients had preoperative prolonged PT values but only four (3.3%) of these patients experienced light bleeding during surgery. Seven (5.8%) of the 121 patients with prolonged PT tests experienced bleeding episodes during the 1st month subsequent to the surgery. Of the 65 (15.6%) patients who had prolonged pre-operative INR values, only three (4.6%) experienced light bleeding during surgery. Two (3.1%) patients with prolonged INR values experienced light bleeding during the 1st month subsequent to surgery. Sixty-one (14.7%) patients had prolonged first preoperative PTT values, only five of whom (8.2%) experienced light bleeding during surgery. Two (3.3%) of the 61 with prolonged PTT values experienced light bleeding during the 1st month subsequent to surgery. We therefore concluded that pre-operative coagulation screening tests provide low sensitivity and low bleeding predictive value. As such, routine coagulation tests before T &A are not indicated unless a medical history of bleeding tendency is suspected.

Adenoidectomy↗
PubMed2001

The prescription pattern of oral nitrates in coronary artery disease. Appropriateness and cost considerations.

OBJECTIVES: To evaluate the prescription patterns of oral nitrates in terms of appropriateness and cost in a community setting. METHODS: A period prevalence, descriptive, applied study. Data including age, gender, type of medication, dosage and cost were extracted from the database of the largest health maintenance organisation (HMO) in Israel. The study population included enrollees over 35 years of age who received oral nitrates at least once during the 12-month study period. RESULTS: Oral nitrates were prescribed for 8007 patients (mean age 72.85+/-9.59 years, male:female ratio 1:1). A total of 52,694 prescriptions were issued for 56,553 medications, of these 88.1% for mononitrates, which constituted 95% of the annual cost for patients and the HMO. The mean prescribed daily dose for the various drugs ranged from 30% less than to 50% more than the recommended dose. Combination therapy with at least two nitrates, which is not the recommended treatment, was given to 5% of the patients. The recommended alternative treatment will alleviate the financial burden for providers and patients. CONCLUSIONS: Improved prescription habits can provide enhanced quality as well as cost savings for patients and providers.

Administration, Oral↗
PubMed2001

Effects of a fundholding discontinuation. An Israeli health maintenance organization natural experiment.

OBJECTIVE: To evaluate the effects of fundholding on cost containment and after termination of the project. DESIGN AND SETTING: Primary care practices participating in the project were allocated an itemized budget. Practices assumed authority for hospitalization, drugs, ambulatory medical diagnostic, consultant services and acquisition of minor equipment. Financial incentives were offered, but no penalties were imposed on practices where expenditure exceeded budget. SUBJECTS: Nine primary care practices in southern Israel. MAIN OUTCOME MEASURE: Total expenditure and a breakdown of expenditure per capita. RESULTS: Fundholding practice expenditure was compared with expenditure in the district as a whole. During the study period, total expenditure in fundholding practices rose by 12%, whereas that of the district rose by 37%. With discontinuation of the project, expenditure of the designated practices returned to the original levels, equivalent to those of the district. CONCLUSION: Fundholding is an efficient method of cost-containment. The effect will be long lasting only if motivation is maintained.

Budgets↗
PubMed2001

A screening process predicts success rates in residency re-training among new immigrant physicians in Israel.

OBJECTIVES: To evaluate predictors of success in training programs for Israeli international medical graduates (IMGs) from the former USSR. SUBJECTS: IMGs up to the age of 45 who passed a national licensing examination and a Hebrew knowledge exam were eligible for participation. INTERVENTION: Each IMG participated in one of three programs that offered similar academic activities. In two programs there was a preliminary selection process and one program had supplementary teaching hours. MAIN OUTCOME MEASURES: Resident's self-evaluation of skills compared with evaluation by department heads. The evaluation included eight clinical skills, a general evaluation, and the passing rate for Phase I of the National Certification Exam. FINDINGS: A total of 176 IMGs, all graduates from medical schools in USSR who immigrated to Israel from 1990 to 1996, and 20 heads of the participating departments completed the questionnaires. The response rate was 64% among the residents and 71% among the department heads. All residents had a similar level of self-esteem regarding clinical skills and considered themselves equal to or better than Israeli-trained residents. The department heads did not concur with this assessment, particularly for residents who participated in the program with no preliminary selection. Participants in the programs with preliminary selection received better evaluations from department heads than those in the program without and had significantly greater success in the written part of the board certification examination (p < 0.05). DISCUSSION AND CONCLUSIONS: Re-training programs for IMGs should include a preliminary process for participant selection. The training program should be implemented in academic departments, in which case supplementary teaching hours are not required.

Journal Article↗
PubMed2001

Newspaper advertising by health maintenance organizations during the reform of healthcare services in Israel.

BACKGROUND: On 1 January 1995 a new mandatory National Health Insurance Law was enacted in Israel. The new law fostered competition among the four major Israeli healthcare providers (HMOs or sick funds) already operating in the market due to the possibility that an unlimited number of patients and the relative budget share would shift among the HMOs. This led them to launch advertising campaigns to attract new members. OBJECTIVES: To examine newspaper advertising activities during the early stages of healthcare market reform in Israel. METHODS: Advertising efforts were reviewed during a study period of 24 months (July 1994 to June 1996). Advertisements were analyzed in terms of marketing strategy, costs and quality of information. RESULTS: During the study period 412 newspaper advertisements were collected. The total advertising costs by all HMOs was approximately US$4 million in 1996 prices. Differences were found in marketing strategy, relative advertising costs, contents and priorities among the HMOs. CONCLUSIONS: The content of HMOs' newspaper advertising was consistent with their marketing strategy. The messages met the criteria of persuasive advertising in that they cultivated interest in the HMOs but did not provide meaningful information about them. Future developments in this area should include consensus guidelines for advertising activities of HMOs in Israel, instruction concerning the content of messages, and standardization of criteria to report on HMO performance.

Advertising↗
PubMed2000

Reversal of the Ras-induced transformed phenotype by HR12, a novel ras farnesylation inhibitor, is mediated by the Mek/Erk pathway.

We have used the selective farnesylation inhibitor HR12 [cysteine-N(methyl)valine-N(cyclohexyl) glycine-methionine-O-methyl-ester] to study the role of oncogenic Ras in cytoskeletal reorganization in Ha-ras(V12)-transformed Rat1 cells (Rat1/ras). Application of HR12 resulted in complete restoration of the cytoskeleton and associated cell adhesions disrupted by oncogenic Ras. This included an increase in the number and size of focal adhesions, accompanied by massive stress fiber formation and enhanced tyrosine phosphorylation. Furthermore, HR12 induced assembly of adherens junctions and dramatically elevated the level of the junctional components, cadherin and beta-catenin. HR12 was unable to restore the nontransformed phenotype in cells expressing farnesylation-independent, myristylated Ras. Examination of the main Ras-regulated signaling pathways revealed that HR12 induced a dose- and time-dependent decline in Erk1&2 activation (t(1/2) approximately 6 h), which correlated with the accumulation of nonfarnesylated oncogenic-Ras. Inhibition of the Mek/Erk pathway in Rat1/ras cells, using the Mek inhibitor, PD98059, resulted in complete cytoskeletal recovery, indistinguishable from that induced by HR12. Moreover, a constitutively active Mek mimicked the effect of ras transformation in Rat1 cells, and prevented HR12-induced cytoskeletal effects in Rat1/ras cells. No such effects were observed after treatment of Rat1/ras cells with the phosphatidylinositol 3-kinase inhibitor LY294002. These findings establish the Mek/Erk pathway as the dominant pathway involved in conferring the cytoskeletal and junctional manifestations of the Ras-induced transformed phenotype.

3T3 Cells↗
PubMed2000

Signal transduction by a nondissociable heterotrimeric yeast G protein.

Many signal transduction pathways involve heterotrimeric G proteins. The accepted model for activation of heterotrimeric G proteins states that the protein dissociates to the free G(alpha) (GTP)-bound subunit and free G(betagamma) dimer. On GTP hydrolysis, G(alpha) (GDP) then reassociates with G(betagamma) [Gilman, A. G. (1987) Annu. Rev. Biochem. 56, 615-649]. We reexamined this hypothesis, by using the mating G protein of the yeast Saccharomyces cerevisiae encoded by the genes GPA1, STE4, and STE18. In the absence of mating pheromone, the G(alpha) (Gpa1) subunit represses the mating pathway. On activation by binding of pheromone to a serpentine receptor, the G(betagamma) (Ste4, Ste18) dimer transmits the signal to a mitogen-activated protein kinase cascade, leading to gene activation, arrest in the G(1) stage of the cell cycle, production of shmoos (mating projections), and cell fusion. We found that a Ste4-Gpa1 fusion protein transmitted the pheromone signal and activated the mating pathway as effectively as when Ste4 (G(beta)) and Gpa1 (G(alpha)) were coexpressed as separate proteins. Hence, dissociation of this G protein is not required for its activation. Rather, a conformational change in the heterotrimeric complex is likely to be involved in signal transduction.

Blotting, Western↗
PubMed2000

Variations in referrals to consultants: a study of general practitioners' characteristics in southern Israel.

The rate at which primary physicians refer patients to consultants varies considerably, not only within different regions, but also among practices within defined areas. Differences also have been identified between doctors within the same practice. This variation in referral rates is a source of concern because of the costs generated and implications for quality and quantity of care. Many studies that tried to identify the sources for this variation explained only part of it; however, these studies were based on small numbers.

Age Distribution↗
PubMed1999

Sleep fragmentation in children with atopic dermatitis.

OBJECTIVE: To characterize the sleep pattern of children with atopic dermatitis in clinical remission. METHODS: Fourteen children with atopic dermatitis, with a mean+/-SD age of 6+/-2 years, were recruited consecutively from a pediatric dermatology clinic. No participant had any other medical or psychiatric illness. The control group (n = 9, mean age 7+/-1.8 years) was composed of children with mild "benign" snoring and no evidence of respiratory disturbance during sleep. All participating children were evaluated by formal all-night polysomnography, scratch electrodes, and self-reported questionnaires filled in by their parents. RESULTS: The patients were studied when their skin condition was in remission. Sleep latency, total sleep time, and sleep efficiency were similar to the control group. The atopic dermatitis group had an average of 24.1+/-8.1 events per hour of arousals and awakenings, compared with 15.4+/-6.2 events per hour in the control group (P<.001). Direct observation, video monitoring, and scratch electrodes provided evidence of between 1 to 19 bouts of scratching per night, accounting for only 15% of the arousals and awakenings. The rest of the arousals and awakenings were not associated with any specific, identifiable polysomnographic event, such as apnea or jerks. CONCLUSION: Children with atopic dermatitis in clinical remission have sleep disturbances that are not related to scratching per se.

Case-Control Studies↗
PubMed1999

Alpha-cyanocinnamide derivatives: a new family of non-peptide, non-sulfhydryl inhibitors of Ras farnesylation.

Farnesylation of Ras and other proteins is required for their membrane attachment and normal function. Here we report on the synthesis of alpha-cyanocinnamide derivatives, a new family of farnesyltransferase inhibitors. These compounds are nonpeptidic and do not contain sulfhydryl groups. The most potent compound is a pure competitive inhibitor with respect to the Ras protein and mixed competitive with respect to farnesyl diphosphate. Selectivity studies against geranylgeranyltransferase and biological activities of selected compounds are described.

3T3 Cells↗
PubMed1999

A model of efficient and continuous quality improvement in a clinical setting.

OBJECTIVE: To establish a system of Continuous Quality Improvement (CQI) which does not require substantial resources in a clinical setting. SETTING: A busy department of obstetrics and gynaecology. METHODS: The system is based on seven elements: (i) comprehensive accumulation of data; (ii) involvement of all faculty members and the majority of residents; (iii) continuous monitoring of processes within the organization; (iv) application of clinical indicators; (v) file review system; (vi) task force approach for evaluation of processes within the organization; and (vii) intervention measures. MAIN OUTCOME MEASURES: Quality of contents of files and documentation, satisfaction of customers (patients, family members), trends of clinical indicators, effect of task force work, incidence of complaints. RESULTS: Inadequate documentation was noted in 14.6% before, and 4% 1 year after the initiation of the CQI program. Task force work in a variety of projects led to a substantial improvement in measured outcome. The absolute and relative numbers of complaints against the department decreased from 44 in 1993, to 27 in 1994, 20 in 1995 and 16 in 1996. In terms of the percentage of complaints directed against the hospital these figures represent 12.4, 9.6, 6.9 and 5.4% for 1993, 1994, 1995 and 1996 respectively. CONCLUSION: Our proposed CQI system has proved to be highly efficient and requires only minimal additional resources.

Data Collection↗
PubMed1998

[Comparison between every-day and every-3-days fluoxetine in young, moderately depressed out-patients].

Fluoxetine is now a well-known and often-used specific serotonin reuptake inhibitor (SSRI) and antidepressant. It has a very long active half-life, from 2-16 days. Our hypothesis was that sufficient therapeutic effectiveness would be achieved by prescribing the drug less frequently than once a day. To establish whether there is a difference between fluoxetine given daily or every 3 days, we assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV) to receive fluoxetine (20 mg), either each day or every 3 days. The study was open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and clinical judgment questionnaires. Follow-up lasted 6 months. Results indicated no differences in the clinical outcomes, except for slightly fewer side-effects in the study group. Although the open label design limits drawing definitive conclusions, our preliminary results provide more information, and support our hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive, double-blind studies are necessary to confirm our preliminary results.

Adult↗
PubMed1998

780 nm low power diode laser irradiation stimulates proliferation of keratinocyte cultures: involvement of reactive oxygen species.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine irradiation parameters of a 780 nm low power CW diode laser (6.5 mW) leading to enhanced proliferation of cultured normal human keratinocytes (NHK). The possible role of reactive oxygen species (ROS) in this response was evaluated. STUDY DESIGN/MATERIALS AND METHODS: NHK were exposed to a single dose of 0 to 3.6 J/cm2 (0-180 sec) of irradiation. Proliferation parameters studied were: incorporation of 3H-thymidine during 6-24 hr following irradiation; percentage of dividing cells and number of cells, 24 hr and 48 hr following irradiation, respectively. RESULTS: Proliferation of NHK exposed to 0.45-0.95 J/cm2 was significantly enhanced by 1.3-1.9-folds relative to sham-irradiated controls, as inferred from parameters studied. Exposure to other energy densities was considerably less effective in enhancing proliferation parameters. Added enzymatic antioxidants, superoxide dismutase or catalase, scavenging superoxide anions and H2O2, suppressed this enhanced proliferation. Added scavengers (alpha-tocopherol acetate, scavenging lipid peroxidation, or sodium azide, histidine, mannitol, scavenging singlet oxygen, superoxide anions, and hydroxyl radicals, respectively), or N-acetyl cysteine, the thiol-reducing agent, suppressed the response, but to different extents. CONCLUSIONS: The results indicate that 780 nm low power diode laser irradiation enhanced keratinocytes proliferation in vitro, with an apparent involvement of ROS in this response, and comparably, might be used to promote their proliferation in vivo to enhance wound healing.

Acetates↗
PubMed1997

Synthesis and biological activity of semipeptoid farnesyltransferase inhibitors.

Semipeptoids derived from the Ras farnesyl transferase inhibitor, CVFM, were synthesized by the Simultaneous Multiple Analogue Peptide Synthesis methodology. The semipeptoids were screened for their in vitro inhibition potency towards farnesyl transferase and geranylgeranyl transferase. Structure-activity relationship studies led to a potent and selective inhibitor, HR-11, which blocks Ras farnesylation in vitro with an IC50 of 1.2 nM. The cell permeable methyl ester derivative of HR-11, HR-12, inhibits Ras farnesylation in intact cells with an IC50 of 10 microM and with no detectable inhibition of Rap1A/K-rev geranyl-geranylation.

3T3 Cells↗
PubMed1996

Antiproliferative effect of pentoxifylline on psoriatic and normal epidermis. In vitro and in vivo studies.

Psoriasis is characterized by abnormal cell proliferation, inflammation and increased biosynthesis of various cytokines. The inhibitory effect of pentoxifylline on some cell functions has been reported widely. This property of pentoxifylline prompted an investigation of its possible role in controlling psoriasis. In the in vitro study normal human keratinocytes proliferation was determined and formation of cornified envelopes was assayed following treatment with pentoxifylline. The in vivo experiment consisted of nude mice grafted with psoriatic or normal skin treated with tetradecanyl phorbol 13 acetate. At the end of the treatment period, the grafts were excised and assessed for acanthosis and labelling index. The in vitro study showed that continuous exposure of normal human keratinocyte cultures to pentoxifylline resulted in a significant dose-dependent inhibition of proliferation, and in induction of cornified envelope formation. The in vivo experiments showed a significant reduction of epidermal thickness and of labeling index in psoriatic and tetradecanyl phorbol 13 acetate-treated normal skin, as compared to the initial values.

Adult↗
PubMed1995

[Seasonal variation in hospital admissions for cardiorespiratory diseases in the Negev].

Characteristics of patients admitted to the general medical wards of this hospital during the 21 months between January 1990 and September 1991 were analyzed. Cardiovascular and respiratory disease-related (CR) admissions accounted for 46.8% of the 18,774 admissions. Using a linear model, we examined the relationship between season and clinical characteristics of the patients admitted with CR diagnoses. They were admitted more often during the winter (December-February) than the summer (June-August). The ratio of CR admissions to other causes of admission was 0.75 in the summer, 0.93 in the spring, 1.01 in the winter, and 0.82 in the autumn (p < 0.0001). Seasonality affected more patients with coronary heart disease, noncoronary cardiac disease, and chronic pulmonary disease than those with pneumonia or other pulmonary diseases, or cerebrovascular events. Those admitted during the winter were older, had more than 1 CR condition, and their hospital stays were longer. This pattern of hospitalization partly explains the increase in admissions to medical wards in the winter with increase in work load.

Cardiovascular Diseases↗