Biomedical subjects

R Segal

Publications and source records attributed to R Segal.

At least 37 records · Page 2Linked to original sources

PubMed2001

Clinical, radiologic, demographic, and occupational aspects of hand osteoarthritis in the elderly.

OBJECTIVE: Osteoarthritis (OA) of the hand is common in elderly patients. The aim of this study was to characterize OA frequency, severity, and distribution and to trace interrelationships between these findings and the demographic, occupational, and medical data from elderly Jewish nonrheumatologic patients. METHODS: Study participants were 253 consecutive patients admitted to a geriatric center for a variety of nonrheumatic medical conditions. Excluded patients were those with rheumatoid arthritis; neurologic, orthopedic, or other conditions that would interfere with symmetric hand function; and mental or medical states that would interfere with history taking and radiographic studies. Patient occupations were graded as workload degree (on a scale of 1 to 3) and as the total occupational score (workload degree multiplied by the duration of each job). Clinical findings of Heberden nodes, Bouchard nodes, and malignment, graded on a scale of 0 to 3, were summed as the clinical OA score. Hand radiographs were independently read (modified Altman method), grading 5 parameters in each joint on a scale of 0 to 3, summed as a radiologic OA score. Statistical analyses included the Student t test, chi(2) test, ANOVA, Pearson correlation, and partial correlation coefficients. RESULTS: Among 253 elderly patients (171 women, 82 men; mean age, 79 years) OA was frequent (occurring in about 80% of patients), involving most severely the second and third distal interphalangeal, right first interphalangeal, and both first carpometacarpal joints. The prevalence of OA was similar in women and men, with higher scores in women, and reached significance only in the distal interphalangeal joints. Metacarpophalangeal joints were more involved in men. Age had a clear influence on OA scores. Ethnicity affected OA severity, with Ashkenazi Jews having significantly higher scores than Sepharadi Jews. Dominant hands had significantly higher global OA scores as well as isolated joint scores (except for the first carpometacarpal joint). Occupational load, housekeeping tasks, and the number of children did not influence the total or specific joint OA scores. Associated conditions such as obesity, diabetes, hypothyroidism, and chondro calcinosis were not associated with more pronounced OA. CONCLUSIONS: Hand OA was prevalent in our elderly cohort, and its severity was influenced by inherent traits such as age, female gender, ethnicity, and handedness. In contrast, acquired factors such as workload, number of children, and associated diseases did not appear to influence OA expression.

Age Factors↗

PubMed2001

Age-associated neovasculopathy with recurrent bleeding.

We hypothesize the existence of an age-associated neovasculopathy with recurrent bleeding. It could be the result of age-related defects in the regulation of the angiogenetic process creating pathologic small vessels with a bleeding tendency. Conditions like subdural hematoma, ocular angiopathies, intestinal angiodysplasia, coronary atherosclerotic plaques and others, may be the clinical expression of such a neovasculopathy.

Aging↗

PubMed2001

Retention and use of patient-centered interviewing skills after intensive training.

PURPOSE: Studies show that residents trained in patient-centered interviewing (PCI) are more effective in handling patients' emotions and are more skillful in gathering patients' data. This study evaluated the long-term use of PCI skills. METHOD: Fourteen residents received PCI training during internship, and their skills were evaluated before, immediately after, and two years after their training through directly observed patient interviews. A confidential survey evaluated the residents' actual use of PCI two years after the intensive training. Control groups of 14 interns prior to PCI training and 14 residents from another program not trained in PCI were also surveyed. RESULTS: Residents' use of PCI skills (optimization of setting, establishment of narrative thread, open-to-closed-ended questioning cone, avoid asking more than one question at a time, and (facilitation) were significantly improved, even two years after their training in PCI. The residents who received intensive block training reported using PCI techniques more frequently than did those in the control groups. However, the only significant difference in use of PCI skills between the intervention and control groups was found in reflection of patient's emotions. CONCLUSION: Medical residents retained PCI skills for two years. Further studies are needed to determine whether successful postgraduate training of physicians in PCI translates into a change in behaviors during their professional lives.

Case-Control Studies↗

PubMed2001

Sustained signaling by phospholipase C-gamma mediates nerve growth factor-triggered gene expression.

In contrast to conventional signaling by growth factors that requires their continual presence, a 1-min pulse of nerve growth factor (NGF) is sufficient to induce electrical excitability in PC12 cells due to induction of the peripheral nerve type 1 (PN1) sodium channel gene. We have investigated the mechanism for this triggered signaling pathway by NGF in PC12 cells. Mutation of TrkA at key autophosphorylation sites indicates an essential role for the phospholipase C-gamma (PLC-gamma) binding site, but not the Shc binding site, for NGF-triggered induction of PN1. In concordance with results with Trk mutants, drug-mediated inhibition of PLC-gamma activity also blocks PN1 induction by NGF. Examination of the kinetics of TrkA autophosphorylation indicates that triggered signaling does not result from sustained activation and autophosphorylation of the TrkA receptor kinase, whose phosphorylation state declines rapidly after NGF removal. Rather, TrkA triggers an unexpectedly prolonged phosphorylation and activation of PLC-gamma signaling that is sustained for up to 2 h. Prevention of the elevation of intracellular Ca2+ levels using BAPTA-AM results in a block of PN1 induction by NGF. Sustained signaling by PLC-gamma provides a means for differential neuronal gene induction after transient exposure to NGF.

Animals↗

PubMed2001

Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNFalpha monoclonal antibody and by pentoxiphylline.

We have previously shown that the clinical manifestations of experimental systemic lupus erythematosus (SLE) correlate with an early increased secretion of TNFalpha and IL-1. In the present study, we examined the efficacy of two therapeutic modalities which lower TNFalpha production or activity, on the clinical manifestations of the disease. Experimental SLE was induced in naive C3H.SW mice by injection of the human anti-DNA monoclonal antibody (mAb) bearing the common idiotype, 16/6 Id. Two weeks after booster injections, treatment with either an anti-TNFalpha mAb, or pentoxiphylline (PTX) was started, for a period of 6 weeks. Production of TNFalpha (by splenocytes) and IL-1 (by peritoneal macrophages) was determined 3 and 7 months after disease induction. The experimental mice were also followed for disease manifestations. Both treatment protocols, with anti-TNFalpha mAb and with PTX, reduced the production of the two pro-inflammatory cytokines. TNFalpha and IL-1, in mice with experimental SLE. Anti-DNA antibodies were significantly lower in the mice treated with either protocol. In addition, a significantly lower rate of leukopenia, proteinuria and immune complex deposition was observed in treated mice. Abrogation of TNFalpha and IL-1 production in the early stages of experimental SLE by an anti-TNFalpha mAb or by PTX improves the clinical status of mice afflicted with this autoimmune disease.

Animals↗

PubMed2001

Changing patterns of presentations of patients with HIV-related disease at a tertiary referral centre and its implications for physician training.

Highly active antiretroviral therapy (HAART) has been shown to be highly effective in controlling HIV-related disease progression. Our objective was to determine whether HAART had altered the spectrum of HIV-related disease presentations at a tertiary medical referral centre and if a change in the clinical presentations of HIV-infected individuals to the hospital had impacted on physicians' training. A retrospective study which examined all admissions of HIV-infected patients identified between 1 October 1996 to 30 September 1998 using a hospital-designed computer database was undertaken at the Beth Israel Deaconess Medical Center (BIDMC) tertiary medical referral centre. All medical residents were surveyed in order to assess their knowledge of HIV-associated admissions and their confidence treating HIV-infected patients. There were significant changes in the admitting diagnosis for HIV-related illness between 1996 and 1998. Admissions for opportunistic infections (OIs) declined whereas admissions with bacterial infections increased significantly. Use of HAART remained stable between the 2 years of the study. Physicians' overestimated the use of HAART and only 8% of residents felt very comfortable taking care of an HIV-infected patient. In conclusion, the spectrum of presentations with HIV-related disease to a tertiary referral centre continues to change in the HAART era and impacts on physicians' experience of the management of HIV disease.

AIDS-Related Opportunistic Infections↗

PubMed2001

Surveillance programs for early stage non-seminomatous testicular cancer: a practice guideline.

BACKGROUND AND PURPOSE: To identify an appropriate surveillance program for men with clinical stage I non-seminomatous germ cell tumors of the testis (NSGCT). MATERIALS AND METHODS: A systematic review of the published literature was combined with a consensus process, around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. RESULTS: No randomized controlled trials (RCTs) comparing surveillance schedules were found, but data from 12 case series and one RCT which compared radiotherapy with surveillance were reviewed. Variations in the schedules were not associated with observed variations in relapse, salvage, or survival rates. CONCLUSIONS: Men with clinical stage I testicular cancer, as defined by a normal physical examination, normal radiological scans (computed tomography [CT]) and serum markers (alpha-fetoprotein [AFP] and beta-subunit of human chorionic gonadotropin (betaHCG) which are normal or fall within normal limits during their expected half-lives, are eligible for surveillance. A recommended surveillance schedule is as follows: 1) Physical examination, blood serum marker tests (AFP and HCG), and chest x-rays should be conducted every month in the first year, every 2 months in the second year, every 3 months in the third year, and every 6 months in the fourth and fifth years; and 2) CT scans of the abdomen and pelvis should be conducted every 3 months in the first year, every 4 to 6 months in the second year and every 6 months in the third year, and once a year in the fourth and fifth year.

Germinoma↗

PubMed2001

[Malaria in Israel--a preventable disease].

This article deals with five cases of imported malaria among Haifa District citizens in 1999. Two patients died from multi-organ failure secondary to the infection. Malaria continues to be a serious health risk for travelers returning from endemic areas. Travelers require detailed advice on appropriate chemoprophylaxis against malaria and personal protection against mosquito bites. There has, however, been poor compliance to drug prophylaxis. Physicians should encourage travelers to seek advice from an accredited travelers clinic in advance of the trip. It is advisable for the physician to stress the importance of taking the recommended chemoprophylaxis.

Adult↗

PubMed2000

Skeletal muscle deformity and neuronal disorder in Trio exchange factor-deficient mouse embryos.

Dbl-homology guanine nucleotide exchange factors (DH-GEFs) regulate actin cytoskeletal reorganization, cell adhesion, and gene transcription via activation of Rho GTPases. However, little is known about the physiological role of mammalian DH-GEFs during development. The DH-GEF family member Trio is of particular interest because it is a multifunctional protein possessing two GEF domains, as well as a protein serine/threonine kinase domain, and trio-like genes in Caenorhabditis elegans and Drosophila were shown to function in neural migration and axon guidance. To determine the role of Trio during mammalian development, we generated a mouse trio loss-of-function mutation (trio(-/-)). Trio function is essential during late embryonic development as genotype analysis indicated that trio(-/-) embryos died between embryonic day (E)-15.5 and birth, or shortly thereafter. In the trio(-/-) embryos, primary skeletal myofibers were relatively normal at E14.5, but by E18.5 highly unusual spherical myofibers accumulated. Trio deficiency may cause a defect in secondary myogenesis, as the appearance of the abnormal trio(-/-) skeletal myofibers temporally coincided with the onset of secondary myogenesis, and smaller secondary myofibers located adjacent to the primary myofibers were absent. The proliferation of trio(-/-) secondary myoblasts appeared normal, suggesting that Trio may regulate secondary myoblast alignment or fusion. trio(-/-) embryos also displayed aberrant organization in several regions within the brain, including the hippocampal formation and olfactory bulb. We thus conclude that Trio is essential for late embryonic development, and that Trio functions in fetal skeletal muscle formation and in the organization of neural tissues.

Animals↗

PubMed2000

The impact of a rotation in geriatrics during the internship on young doctors.

We initiated a study aimed to evaluate the impact of a rotation in geriatrics during the internship (Preregistration Year-PY). A total of 46 young doctors who completed a month's rotation in geriatrics during the 5 year period 1993-1997 were located and sent a mail questionnaire. It included queries on how they appreciate the contribution of the rotation on their training. A total of 36 doctors (78%) responded, 94% mentioned they learned new skills and ranked them as highly important, and 91% affirmed that the experience in the geriatric ward contributed to a more positive attitude toward elderly patients. A total of 86% stated they would recommend young graduates to elect a geriatric rotation, 56% believe it should be included as an obligatory rotation during the PY. Based on this survey we concluded that a month's rotation in geriatrics is an important contribution to young graduates' medical education before entering practice. In view of the increasing number of elderly patients in most medical fields such experience should be fostered.

Journal Article↗

PubMed2000

Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II.

BACKGROUND: The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients, compared with captopril, an angiotensin-converting-enzyme (ACE) inhibitor. We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated. METHODS: We undertook a double-blind, randomised, controlled trial of 3,152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less. Patients, stratified for beta-blocker use, were randomly assigned losartan (n=1,578) titrated to 50 mg once daily or captopril (n=1,574) titrated to 50 mg three times daily. The primary and secondary endpoints were all-cause mortality, and sudden death or resuscitated arrest. We assessed safety and tolerability. Analysis was by intention to treat. FINDINGS: Median follow-up was 555 days. There were no significant differences in all-cause mortality (11.7 vs 10.4% average annual mortality rate) or sudden death or resuscitated arrests (9.0 vs 7.3%) between the two treatment groups (hazard ratios 1.13 [95.7% CI 0.95-1.35], p=0.16 and 1.25 [95% CI 0.98-1.60], p=0.08). Significantly fewer patients in the losartan group (excluding those who died) discontinued study treatment because of adverse effects (9.7 vs 14.7%, p<0.001), including cough (0.3 vs 2.7%).

Aged↗

PubMed2000

The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients.

OBJECTIVE: Aspirin is known to have a bimodal effect on the renal handling of uric acid (UA). High dosages (>3 gm/day) are uricosuric, while low dosages (1-2 gm/day) cause UA retention. Although very-low-dose (mini-dose) aspirin is used increasingly as a platelet aggregation inhibitor, no studies have been published on whether aspirin's renal effects occur at dosages of <0.5 gm/day. The aim of the present study was to evaluate the effects of commonly used mini-dosages of aspirin on renal function and UA handling in elderly patients. METHODS: The study included 49 elderly inpatients (age 61-94). Patients were excluded if they had renal failure, hyperuricemia, gout, or a history of bleeding, or if they were receiving anticoagulants, aspirin, or nonsteroidal antiinflammatory drugs. Previous medications and diet were kept unchanged. Aspirin was administered as follows: 75 mg/day (week 1), 150 mg/day (week 2), 325 mg/day (week 3), and 0 mg/day (week 4). Baseline and weekly samples of blood and urine were evaluated for UA, creatinine, blood urea nitrogen, creatinine clearance, UA excretion, UA clearance, and plasma levels of aspirin. RESULTS: At the lowest dosage, aspirin caused a 15% decrease in the rate of UA excretion (P = 0.045 by t-test), which was associated with a slight but significant increase in serum levels of UA (P = 0.009). These effects on UA levels were gradually reduced with increasing dosages of aspirin (multivariate analysis of variance with repeated measures showed no statistically significant difference in the rate of UA excretion between weeks 1-3 and week 0 [baseline], but the difference in serum UA levels for the same comparison was statistically significant [P = 0.038]). Generally, creatinine and UA clearance rates paralleled each other during aspirin treatment. However, 1 week after aspirin was discontinued, creatinine clearance remained decreased while UA clearance returned to baseline. Plasma aspirin concentrations were low and variable. However, patients with above-median aspirin levels had significantly greater changes in serum creatinine levels, urinary UA excretion rates, and UA clearance rates following the first week of aspirin treatment. Hypoalbuminemia and concomitant treatment with diuretics enhanced the effects of aspirin on renal function and UA retention. CONCLUSION: Mini-dose aspirin, even at a dosage of 75 mg/day, caused significant changes in renal function and UA handling within 1 week in a group of elderly inpatients, mainly in those with preexisting hypoalbuminemia. Given the widespread (and often unmonitored) use of mini-dose aspirin, especially among the elderly, these findings call for clinician alertness as well as for further studies to clarify the mechanisms underlying these phenomena.

Age Factors↗

PubMed2000

Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus-afflicted mice.

Aging mice of strains susceptible to the induction of experimental systemic lupus erythematosus (SLE) develop a milder disease than young animals. To find out whether the decrease in susceptibility to disease is due to age-associated changes in cytokine profile, we first examined the secretion of cytokines by healthy mice aged 2-15 months. A gradual age-related decline in the levels of interleukin (IL)-2 and interferon (IFN) gamma, and an increase in IL-4, IL-10, IL-1, and tumor necrosis factor (TNF) alpha were observed. Experimental SLE was induced in 2- and 10-month-old mice by immunization with the monoclonal anti-DNA antibody bearing the 16/6 Id. Early increased production of pro-inflammatory cytokines (TNFalpha and IL-1), followed by a peak of the Th1-type cytokines (IL-2, IFNgamma) were observed in young mice. The Th2-type cytokines (IL-4, IL-10) peaked later. In contrast, only a mild increase in all of the above cytokines was determined in 10-month immunized mice. It thus appears that the decline in susceptibility to SLE induction in older mice may be related to changes in the capacity to produce cytokines.

Aging↗

PubMed2000

Immune response of SLE patients to peptides based on the complementarity determining regions of a pathogenic anti-DNA monoclonal antibody.

We have examined the humoral and cellular responses of SLE patients to peptides based on the complementarity-determining regions (CDR) of a monoclonal anti-DNA antibody with a major idiotype- 16/6 Id, in comparison to their responses to the whole 16/6 Id-bearing antibody. Sera of 63% of the SLE patients had antibodies that bound the 16/6 Id, 80% had antibodies to one of the CDR-based peptides, and 40% of the patients reacted with both CDRs. Sera of only a few controls reacted with either the 16/6 Id (6%) or the CDR based peptides (4%) (P < 0.01). Peripheral blood lymphocytes (PBL) of 39% of the patients proliferated in response to the 16/6 Id or to one of the CDR-based peptides (37%), while in the control group the proliferation rates were 66% to the 16/6 Id and 59% to one of the CDR-based peptides (P < 0.05). The correlation between (both) the humoral and cellular immune responses to the CDR-based peptides and to the 16/6 Id suggests the relevance of these peptides to the 16/6 Id and provides additional information on the pathogenic moiety of the latter antibody.

Amino Acid Sequence↗

PubMed2000

Randomised comparison of losartan vs. captopril on quality of life in elderly patients with symptomatic heart failure: the losartan heart failure ELITE quality of life substudy.

OBJECTIVE: To measure health-related quality-of-life (HRQoL) in elderly symptomatic heart failure patients following treatment with an angiotensin II receptor antagonist (losartan) vs. an angiotensin-converting-enzyme (ACE) inhibitor (captopril). METHODS: Patients (age > or = 65 years) were randomised to losartan, titrated to 50 mg once daily, or captopril, titrated to 50 mg three times daily, as tolerated. Sickness Impact Profile (SIP) and Minnesota Living with Heart Failure (LIhFE) questionnaires were administered at baseline, weeks 12 and 48. Composite hypothesis testing of change in HRQoL from baseline for completers, and withdrawal for unfavourable events (death, clinical/laboratory adverse experience) was used to account for differential dropout rates. RESULTS: In 203 patients completing the substudy (week 48), significant and comparable improvements in HRQoL from baseline were observed for both treatment groups (p < or = 0.001). Although there was a trend favouring losartan vs. captopril for the composite HRQoL endpoint (unadjusted p = 0.018, one-sided), this was not considered significant after adjusting for multiple testing. Significantly more captopril patients in the substudy subset withdrew for unfavourable reasons (19.6 vs. 10.9%, p = 0.038). CONCLUSIONS: Significant improvements in HRQoL were observed in elderly patients with symptomatic heart failure treated with losartan and captopril long-term. A trend favouring losartan in the composite measure of drug tolerability/quality of life was not significant, but losartan was generally better tolerated than captopril in that significantly fewer losartan patients discontinued therapy.

Aged↗

PubMed2000

The frequency of Candida parapsilosis in onychomycosis. An epidemiological survey in Israel.

Candida albicans is regarded as the major pathogen in yeast-induced onychomycosis. Based on our impression of an increasing prevalence of Candida parapsilosis in this disease, we examined the data of two mycology laboratories in the same geographic location, from 1994 to 1996 in one (centre A) and for 1995 (6 months) in the other (centre B). A total of 954 and 230 toenails and 621 and 190 fingernails, respectively, underwent KOH microscopy and culture studies in each centre. Positive findings were noted in 45 and 65% of the toenails and 44 and 72% of the fingernails, respectively. In the toenails, Candida spp. were found in 22 and 15%, respectively, and in the fingernails, in 77 and 63%, respectively. The most frequent Candida species was C. parapsilosis (39.5% in toenails, 36.7% in fingernails), followed by C. albicans (19.5% in toenails, and 34.4% in fingernails). These results demonstrate a higher frequency of isolation of C. parapsilosis compared with C. albicans in onychomycosis. This might have important therapeutic implications.

Candida↗

PubMed2000

Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: results of the ELITE ventricular function substudy.

BACKGROUND: The mechanism by which angiotensin-converting enzyme inhibitors reduce mortality rates and disease progression in patients with heart failure is likely mediated in part through prevention of adverse ventricular remodeling. This study examined the effects of the angiotensin-converting enzyme inhibitor captopril and the angiotensin II type 1 receptor antagonist losartan on ventricular volumes and function in elderly patients with heart failure and reduced left ventricular ejection fraction (< or =40%). METHODS: Patients underwent radionuclide ventriculograms (RVG) at baseline and were randomized to either captopril (n = 16) or losartan (n = 13). After 48 weeks, another RVG was obtained. Therapy was then withdrawn for at least 5 days, and the RVG was repeated while the patient was not receiving the drug. RESULTS: At 48 weeks both captopril and losartan significantly reduced left ventricular (LV) end-diastolic volume index (135 +/- 26 to 128 +/- 23 mL/m(2) for losartan, P <.05 vs baseline; 142 +/- 25 to 131 +/- 20 mL/m(2) for captopril, P <.01; mean (SD). Captopril also reduced LV end-systolic volume index (98 +/- 24 to 89 +/- 21 mL/m(2), P <.01 vs. baseline), whereas a nonsignificant trend was observed for the losartan group (97 +/- 23 to 90 +/- 16 mL/m(2), P = not significant). The between-group differences in the changes in LV volumes were not statistically significant. After drug withdrawal, LV end-diastolic volume index remained significantly lower than baseline in the captopril group (P <.01). CONCLUSIONS: Both captopril and losartan prevent LV dilation, representing adverse ventricular remodeling, previously seen with placebo treatment. Reverse remodeling was observed in the captopril group. On the basis of these results, the relative effects on LV remodeling do not provide a rationale for a survival benefit of losartan over captopril.

Aged↗

PubMed2000

Designing An electronic patient record with multiple real time decision support modules for managing diseases

Physician compliance with clinical guidelines varies between 30% and 50% despite knowledge of and acceptance of guidelines. In an attempt to improve the use of guidelines there is increasing interest in the development of clinical decision support systems. We are interested in designing a system that is intended for interdisciplinary use in primary, secondary, and tertiary level situations. Since 1995 we have been developing an electronic oral health record containing a decision support system for caries management. As the addition of different decision support modules was contemplated, the ability to scale up the environment became important. We decided to use Authorware (Macromedia, San Francisco, CA), which is a multi-media program generator capable of generating code for PCs, Macs, and streaming interactively across the internet. Authorware uses SQL calls to an open architecture database that is essential for easy access by multiple users. Our system has modules for demographics, medical-, dental-, social-histories, head and neck physical exam, vital signs, chief complaints, caries and periodontal disease recording graphics, automatic surveillance of input data to identify risk factors for caries with automatic classification of risk level into low, medium, or high. A suggested management strategy at the systemic and local lesion level is automatically generated for the clinician. The system is currently undergoing beta testing with Delta Dental Insurance (Boston, MA) and the Veterans' Administration (Gainesville, FL).

Journal Article↗