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Biomedical subjects

D Feldman

Publications and source records attributed to D Feldman.

At least 73 records · Page 4Linked to original sources

The effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling.

BACKGROUND: Patients with angina after a Q-wave myocardial infarction benefit from elective revascularization, but it is not known whether asymptomatic patients, including those with a totally occluded infarct-related artery, improve after revascularization. OBJECTIVE: To determine the effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling. METHODS: We prospectively studied 31 consecutive asymptomatic patients (aged 57 +/- 2 years, 24 with anterior infarcts) after Q-wave myocardial infarction with > or = 70% stenosis of the infarct-related artery (IRA) who underwent early elective revascularization (days 4-10 after myocardial infarction). Group I consisted in patients with a totally occluded IRA (n = 10), and group II consisted in patients with a patent, though stenosed, IRA (n = 21). Resting echocardiography and low-dose dobutamine echocardiography were performed at baseline (day 3 +/- 1), and rest echocardiography was repeated after an 8-week follow-up. Significant myocardial viability was defined as > or = 2 wall segments improved (in a 16-segment model of left ventricle) versus baseline, and significant functional recovery as > or = 2 segments improved versus baseline on follow-up examination. Left ventricular end-systolic volume indices (ESVI) and end-diastolic volume indices and ejection fractions were measured by using a modified version of Simpson's rule (using apical two-chamber and four-chamber views). RESULTS: The left ventricular ESVI of patients in group I had decreased by 4.2 +/- 1.9 ml/m2, whereas for patients in group II the left ventricular ESVI had increased by 4.2 +/- 1.7 ml/m2 (P = 0.006). Similarly, the left ventricular end-diastolic volume index had decreased by 0.7 +/- 2.4 ml/m2 versus baseline at follow-up for patients in group I and increased by 7.8 +/- 2.1 ml/m2 for patients in group II (P = 0.02). The left ventricular ejection fraction increased by 7.3 +/- 3% for patients in group I and decreased by 0.4 +/- 2% for patients in group II (P = 0.04). CONCLUSION: There is less global left ventricular remodeling, a potentially deleterious process, after elective revascularization early after Q-wave myocardial infarction in asymptomatic patients who had had a totally occluded IRA before revascularization than there is in patients who had already had a patent, though stenosed, IRA before revascularization. These results suggest that restoration of patency of IRA after a Q-wave myocardial infarction is beneficial even for asymptomatic patients.

Coronary Disease↗

Adolescent growth is not associated with changes in flexibility.

OBJECTIVE: To determine whether adolescent growth is associated with a decrease in flexibility. DESIGN: Longitudinal cohort study of urban high school students. MAIN OUTCOME MEASURES: Flexibility of hamstring muscles (popliteal angle), quadriceps muscles (quadriceps angle), lumbar extensor muscles (Schober test), and combined lower extremity-trunk muscles (Sit and Reach test). RESULTS: There was no relation between growth and changes in flexibility for the lumbar flexor muscles, hamstring muscles, or muscles involved in the Sit and Reach test. Although there was a slight decrease in flexibility of the quadriceps muscle with increases in growth, the very low r2adj value (0.01-0.06) strongly suggests that growth plays only a small role in determining the flexibility of individuals. CONCLUSION: These results strongly suggest that growth is not a cause of decreased flexibility during the peripubescent period.

Adolescent↗

Results of complete soft tissue clubfoot release combined with calcaneocuboid fusion in the 4-year to 8-year age group following failed clubfoot release.

A subset of postoperative recurrent clubfeet was isolated in a group of patients 4 to 8 years old. Twenty-seven consecutive patients who underwent redo surgery consisting of complete soft tissue clubfoot release combined with a calcaneocuboid fusion were reviewed for this study. Twenty-six feet of 27 feet in 20 patients had a long-term good result, suggesting that this procedure is the one of choice for this age group.

Algorithms↗

Conventional and molecular cytogenetic identification of a variant klinefelter syndrome patient with a deleted X chromosome.

We report on the case of a 34-year-old patient with the Klinefelter syndrome and an unusual cytogenetic finding of a deletion involving the short arm of the X chromosome. This was confirmed with fluorescent in situ hybridization (FISH) using an X chromosome-specific whole chromosome painting probe. The patient presented with infertility. The only abnormal physical findings were atrophic testes with azoospermia and elevated levels of follicle-stimulating hormone and luteinizing hormone. This case represents a relatively mild manifestation of the Klinefelter syndrome. Previous reported cases were often associated with more severe phenotypes such as variable degrees of mental retardation and facial dysmorphism, hypothesized as due to the failure of X inactivation. The X inactivation center, located on Xq13, is presumably intact in our patient, who had a deletion involving only the short arm. The mild phenotype observed in our patient was found to be consistent with the conventional and molecular cytogenetic findings.

Adult↗

The goals and limitations of Israel's psychiatric case register.

The Israeli Ministry of Health maintains a psychiatric case register that includes basic demographic and clinical information for all psychiatric hospital admissions since 1950. Currently, the case register includes information about some 130,000 people who have been hospitalized. The case register is an important tool in many aspects of mental health care planning, such as delineating problem populations, developing interventions, assessing the ramifications of policies, enacting programs for quality control, and conducting research. In certain situations stipulated by law, some information in the case register is shared with other authorities. Although the full potential of the psychiatric case register has not been exploited so far, creation of additional linkages with other databases and increased application of case register data in field studies could enhance its usefulness.

Databases as Topic↗

Induction of androgen receptor by 1alpha,25-dihydroxyvitamin D3 and 9-cis retinoic acid in LNCaP human prostate cancer cells.

We have recently shown that 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits proliferation of LNCaP cells, an androgen-responsive human prostate cancer cell line. Also, 1,25-(OH)2D3 increases androgen receptor (AR) abundance and enhances cellular responses to androgen in these cells. In the current study, we have investigated the mechanism by which 1,25-(OH)2D3 regulates AR gene expression and the involvement of AR in the 1,25-(OH)2D3- and 9-cis retinoic acid (RA)-mediated growth inhibition of LNCaP cells. Northern blot analyses demonstrated that the steady-state messenger RNA (mRNA) level of AR was significantly increased by 1,25-(OH)2D3 in a dose-dependent manner. Time-course experiments revealed that the increase of AR mRNA by 1,25-(OH)2D3 exhibited delayed kinetics. In response to 1,25-(OH)2D3, AR mRNA levels were first detected to rise at 8 h and reached a maximal induction of 10-fold over the untreated control at 48 h; the effect was sustained at 72 h. Furthermore, the induction of AR mRNA by 1,25-(OH)2D3 was completely abolished by incubation of cells with cycloheximide, a protein synthesis inhibitor. 1,25-(OH)2D3 was unable to induce expression of an AR promoter-luciferase reporter. Together, these findings indicate that the stimulatory effect of 1,25-(OH)2D3 on AR gene expression is indirect. Western blot analyses showed an increase of AR protein in 1,25-(OH)2D3-treated cells. This increased expression of AR was followed by 1,25-(OH)2D3-induced inhibition of growth in LNCaP cells. Similar to 1,25-(OH)2D3, 9-cis RA also induced AR mRNA expression, and the effect of both hormones was additive. Moreover, 1,25-(OH)2D3 and 9-cis RA acted synergistically to inhibit LNCaP cell growth. These antiproliferative effects of 1,25-(OH)2D3 and 9-cis RA, alone or in combination, were blocked by the pure AR antagonist, Casodex. In conclusion, our results demonstrate that growth inhibition of LNCaP cells by 1,25-(OH)2D3 and 9-cis RA is mediated by an AR-dependent mechanism and preceded by the induction of AR gene expression. This finding, that differentiating agents such as vitamin D and A derivatives are potent inducers of AR, may have clinical implications in the treatment of prostate cancer.

Alitretinoin↗

Liarozole acts synergistically with 1alpha,25-dihydroxyvitamin D3 to inhibit growth of DU 145 human prostate cancer cells by blocking 24-hydroxylase activity.

1Alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits the proliferation of many cancer cells in culture, but not the aggressive human prostate cancer cell line DU 145. We postulated that the 1,25-(OH)2D3-resistant phenotype in DU 145 cells might result from the high levels of expression of 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) induced by treatment with 1,25-(OH)2D3. As this P450 enzyme initiates 1,25-(OH)2D3 catabolism, we presumed that a high level of enzyme induction could limit the effectiveness of the 1,25-(OH)2D3 antiproliferative action. To examine this hypothesis we explored combination therapy with liarozole fumarate (R85,246), an imidazole derivative currently in trials for prostate cancer therapy. As imidizole derivatives are known to inhibit P450 enzymes, we postulated that this drug would inhibit 24-hydroxylase activity, increasing the 1,25-(OH)2D3 half-life, thereby enhancing 1,25-(OH)2D3 antiproliferative effects on DU 145 cells. Cell growth was assessed by measurement of viable cells using the MTS assay. When used alone, neither 1,25-(OH)2D3 (1-10 nM) nor liarozole (1-10 microM) inhibited DU 145 cell growth. However, when added together, 1,25-(OH)2D3 (10 nM)/liarozole (1 microM) inhibited growth 65% after 4 days of culture. We used a TLC method to assess 24-hydroxylase activity and demonstrated that liarozole (1-100 microM) inhibited this P450 enzyme in a dose-dependent manner. Moreover, liarozole treatment caused a significant increase in 1,25-(OH)2D3 half-life from 11 to 31 h. In addition, 1,25-(OH)2D3 can cause homologous up-regulation of the vitamin D receptor (VDR), and in the presence of liarozole, this effect was amplified, thus enhancing 1,25-(OH)2D3 activity. Western blot analyses demonstrated that DU 145 cells treated with 1,25-(OH)2D3/liarozole showed greater VDR up-regulation than cells treated with either drug alone. In summary, our data demonstrate that liarozole augments the ability of 1,25-(OH)2D3 to inhibit DU 145 cell growth. The mechanism appears to be due to inhibition of 24-hydroxylase activity, leading to increased 1,25-(OH)2D3 half-life and augmentation of homologous up-regulation of VDR. We raise the possibility that combination therapy using 1,25-(OH)2D3 and liarozole or other inhibitors of 24-hydroxylase, both in nontoxic doses, might serve as an effective treatment for prostate cancer.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Stress and intervention strategies in mental health professionals.

There is growing evidence to show that mental health professionals by the nature of their work are particularly vulnerable to stress with all its detrimental effects on service delivery and quality of care. This comes at a time when mental health services in many countries are under considerable strain. The present paper examines the multifaceted stressors encountered by the mental health team and recommends possible ways of reducing burnout through innovative intervention strategies. The detection of emotional distress and psychological dysfunctioning in mental health providers is outlined and their management carefully considered.

Burnout, Professional↗

[Characteristics of adults with emotional distress in Israel-- patterns of mental health services used].

We sought firsthand data on the extent of perceived mental health needs and on patterns of use of mental health services among Israelis aged 22 and over. The data are from a national survey conducted in 1995. A random sample of phone numbers from the telephone company's computerized listings yielded 1,395 completed questionnaires (response rate, 81%). At some point in their lives, 27% had experienced emotional distress or mental health problems with which they had difficulty coping alone; 13.4% reported that they had such an experience during 1995. According to multivariate analysis, those more likely to report mental health problems were women, those with a chronic disease, Russian immigrants, divorced or widowed adults, those with a low level of education, and members of the Clalit sick fund. 38% of those who had ever had emotional or mental health problems had asked for help. The proportion of those seeking help was high among respondents aged 35-55, Hebrew speakers (compared to speakers of Russian or Arabic), and city dwellers, and the rate was low among members of the Clalit sick fund. Of those who did seek help, 39% went to a psychologist or a psychiatrist, 25% to their family doctor, 19% to a family member or friend, 7% to a social worker or social service agency, 6% to other medical personnel, and 4% to a psychiatric hospital. 30% turned for assistance to the private sector and 70% to the public sector. These findings have special significance in view of the impending reform of the mental health services. As mandated by the new National Health Insurance Law, mental health services are to be included in the basket of health services provided by the sick funds. The data can be of use in the management of sick funds and for physicians working in the community, as they prepare for this change. In addition, the data will be of aid to national policy makers in planning services suited to the needs of different population groups and to allocate resources more rationally.

Adult↗

Vitamin D receptor gene polymorphisms: analysis of ligand binding and hormone responsiveness in cultured skin fibroblasts.

Recent reports have suggested that polymorphisms in the gene encoding the vitamin D receptor (VDR) determine a portion of the genetic contribution to bone mineral density (BMD). Individuals homozygous for the allele lacking the Bsm I restriction site in the intron between exons 8 and 9 (BB genotype) have been found to have lower BMD than individuals homozygous for the allele having the Bsm I site (bb genotype). Interestingly, this polymorphism has also been associated with prostate cancer risk. The observed changes in BMD and prostate cancer risk might be due to an alteration in the function or abundance of the VDR leading to differential responsiveness of target cells to the action of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. To test this hypothesis, we cultured dermal fibroblasts from donors with BB, Bb, and bb genotypes and determined the level of VDR expression and the cellular responsiveness to 1,25(OH)2D3 treatment. VDR abundance, affinity for [3H]1,25(OH)2D3, and VDR mRNA levels were not detectably different in BB cells compared to bb cells. Moreover, equal expression of both VDR gene alleles was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) on mRNA from Bb fibroblasts. Fibroblast responsiveness to 1,25(OH)2D3, assessed by induction of 24-hydroxylase mRNA, was similar between BB and bb cell types in dose-response experiments. Although there were individual variations in the parameters we measured, there were no detectable or consistent differences in mean values from our small sample of cultured dermal fibroblasts. In conclusion, we did not detect significant differences in VDR properties or cellular responsiveness to 1,25(OH)2D3 that correlated with VDR genotype. Our findings suggest that these polymorphisms do not affect VDR function, but rather may be a marker for a nearby gene that is responsible for the genotype-associated variation in osteoporosis and prostate cancer risk.

Blotting, Northern↗

Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol)

PURPOSE: Substantial experimental and epidemiological data indicate that 1,25-dihydroxyvitamin D3 (calcitriol) has potent antiproliferative effects on human prostate cancer cells. We performed an open label, nonrandomized pilot trial to determine whether calcitriol therapy is safe and efficacious for early recurrent prostate cancer. Our hypothesis was that calcitriol therapy slows the rate of rise of prostate specific antigen (PSA) compared with the pretreatment rate. MATERIALS AND METHODS: After primary treatment with radiation or surgery recurrence was indicated by rising serum PSA levels documented on at least 3 occasions. Seven subjects completed 6 to 15 months of calcitriol therapy, starting with 0.5 microg. calcitriol daily and slowly increasing to a maximum dose of 2.5 microg. daily depending on individual calciuric and calcemic responses. Each subject served as his own control, comparing the rate of PSA rise before and after calcitriol treatment. RESULTS: As determined by multiple regression analysis, the rate of PSA rise during versus before calcitriol therapy significantly decreased in 6 of 7 patients, while in the remaining man a deceleration in the rate of PSA rise did not reach statistical significance. Overall the decreased rate of PSA rise was statistically significant (p = 0.02 Wilcoxon signed rank test). Dose dependent hypercalciuria limited the maximal calcitriol therapy given (range 1.5 to 2.5 microg. daily). CONCLUSIONS: This pilot study provides preliminary evidence that calcitriol effectively slows the rate of PSA rise in select cases, although dose dependent calciuric side effects limit its clinical usefulness. The development of calcitriol analogues with decreased calcemic side effects is promising, since such analogues may be even more effective for treating prostate cancer.

Aged↗

Pediatric anesthesia and postoperative analgesia.

Children are not "small adults," particularly when it comes to anesthesia and pain management. The psychological and physiologic uniqueness of children must not be forgotten. Cooperation and communication between the anesthesiologist, surgeon, and pediatrician are essential for successful anesthesia and pain management. Pediatric anesthesiologists involved in the perioperative management of infants and children are very much a part of the "continuity of care" concept.

Adult↗

Investigation of acidic fibroblast growth factor delivered through a collagen scaffold for the treatment of full-thickness skin defects in a rabbit model.

In this study the wound healing response of full-thickness skin defects was enhanced through the use of acidic fibroblast growth factor using a collagen scaffold. The objectives of this study were (1) to compare the facilitatory effects of acidic fibroblast growth factor on the cellular response (fibroblast, neutrophil, macrophage, epithelial), tissue response (angiogenesis, collagen) and mechanical properties in a healing wound; and (2) to determine the effect of a collagen scaffold on wound healing when compared with the control. Three 3 x 3 cm full-thickness defects were created on the dorsi of 15 New Zealand White rabbits. Each rabbit had a control (no treatment), collagen scaffold, and collagen scaffold with FGF-1 (100 microg/cm2). All the wounds were covered with a transparent polyurethane dressing. There were three periods of study (1, 2, and 3 weeks) with five rabbits in each period. The volume fraction of the tissue and cells was histomorphometrically determined for each wound. The acidic fibroblast growth factor/collagen system showed promise in enhancing the healing process. Acidic fibroblast growth factor/collagen treatment increased angiogenesis, enhanced epithelialization, and reduced contraction rate over the control. A higher inflammatory response was indicated in the collagen scaffold treated group. Hence acidic fibroblast growth factor delivered through a collagen scaffold shows promise in future clinical applications.

Analysis of Variance↗

Which primary care physicians treat depression?

The study attempted to determine the proportion of primary care physicians who treat depression and their characteristics. Data were from 677 respondents to a national survey of primary care physicians in Israel. Twenty-two percent always treated depression, 36.6 percent usually did, 28.6 percent sometimes did, and 12.6 percent never did. Logistic regression found that, compared with physicians who sometimes or never treated depression, those who always or usually treated depression treated more medical conditions, regarded themselves as the medical system's first contact for patients with psychosocial problems, had more frequent contact with social workers, and were more likely to have specialized in family medicine.

Adult↗

Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal French women: the OFELY study.

Previous studies have demonstrated an association between bone mineral density (BMD) and a start codon polymorphism (SCP) of the vitamin D receptor (VDR) gene in pre- and postmenopausal Caucasian and Japanese women. The SCP can be determined by a restriction fragment length polymorphism defined by the FokI restriction endonuclease. VDR alleles containing the FokI site are denoted by f and alleles lacking the site by F. In this study, the association between BMD and the SCP was examined in a group of 174 premenopausal French women who previously had been studied for a relationship between BMD and the VDR BsmI polymorphism. The SCP genotypes of the French women were FF 40%, Ff 44%, and ff 16% and they were independent of the BsmI genotype. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, proximal femur, forearm, and total body. In contrast to previous reports, there was no association of BMD with SCP genotype in this group of Caucasian women at any site. We also measured several biochemical indices of calcium homeostasis and bone turnover. We found no statistically significant associations between SCP genotype and calcium, parathyroid hormone, or vitamin D levels. There was a 33.5% higher level of the skeletal resorption marker N-telopeptides of type I collagen in the women with the ff genotype when compared with women with the FF genotype (p = 0.004). Other bone turnover markers failed to show an association with SCP genotype. In summary, the SCP genotype may not be associated with reduced BMD in all geographical or ethnic populations.

Adult↗