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Biomedical subjects

A Jaffe

Publications and source records attributed to A Jaffe.

At least 37 records · Page 2Linked to original sources

Selections from current literature: minor depression.

The term "minor depression" has had several accepted definitions with differing diagnostic criteria. A review of papers published during the period 1991-1996, in which minor depression was a component of the study, demonstrates the extent of these differences. The heterogeneity of definitions of minor depression has been an obstacle to research on a mental disorder that appears to have a high prevalence and causes significant functional disability. As a result of these differing definitions, there is uncertainty about its natural history and prevalence, and whether therapy is beneficial. Agreement on a standard definition is necessary for investigations that are required to describe adequately these components of minor depression. This paper details the variety of definitions of minor depression and suggests use of the research diagnostic criteria published in the Diagnostic and Statistical Manual, fourth edition (DSM-IV) in future research.

Activities of Daily Living↗

Effects of gonadal steroids and their antagonists on DNA synthesis in human vascular cells.

The cardiovascular effect of estrogen is currently under intense investigation, but the role of androgens in vascular biology has attracted little attention. Because endothelial repair and vascular smooth muscle cell (VSMC) proliferation affect atherogenesis, we analyzed the effects of 17beta-estradiol (E2), dihydrotestosterone (DHT), and sex hormone antagonists on DNA synthesis in human umbilical VSMCs and in E304 cells (a human umbilical endothelial cell line). In VSMCs, both E2 and DHT had a biphasic effect on [3H]thymidine incorporation into DNA: low concentrations (0.3 nmol/L for E2, 3 nmol/L for DHT) stimulated [3H]thymidine incorporation (+35% and +41%, respectively), whereas high concentrations (30 nmol/L for E2, 300 nmol/L for DHT) inhibited [3H]thymidine incorporation (-40%). In contrast, E2 (0.3 to 300 nmol/L) and DHT (3 to 3000 nmol/L) dose-dependently enhanced [3H]thymidine incorporation in E304 cells (peak, +85% for both). In VSMCs, high concentrations of E2 and DHT inhibited platelet-derived growth factor (PDGF)-or insulin-like growth factor (IGF-1)-induced DNA synthesis (-50% to 80%), whereas PDGF- or IGF-1-dependent DNA synthesis in E304 cells was further increased by E2. The antiestrogens tamoxifen and raloxifene mimicked the effects of E2 on DNA synthesis in both VSMCs and E304 cells. However, when coincubated with a stimulatory concentration of E2 (0.3 nmol/L), tamoxifen and raloxifene blocked E2-induced [3H]thymidine incorporation in E304 cells but not in VSMCs. Finally, the androgen antagonist flutamide inhibited the biphasic effects of DHT on VSMCs and blocked the increase in DNA elicited by DHT in E304 cells. The results suggest complex, dose-dependent, and cell-specific interactions of estrogens, androgens, and their respective antagonists in the control of cellular proliferation in the vascular wall. Gonadal steroid-dependent inhibition of VSMC proliferation and stimulation of endothelial replication may contribute to vascular protection and remodeling responses to vascular injury.

Analysis of Variance↗

The Escherichia coli histone-like protein HU affects DNA initiation, chromosome partitioning via MukB, and cell division via MinCDE.

Escherichia coli hupA hupB double mutants, lacking both subunits (HU1 and HU2) of the histone-like protein HU, accumulate secondary mutations. In some genetic backgrounds, these include mutations in the minCDE operon, inactivating this system of septation control and resulting in the formation of minicells. In the course of the characterization of hupA hupB mutants, we observed that the simultaneous absence of the HU2 subunit and the MukB protein, implicated in chromosome partitioning, is lethal for the bacteria; the integrity of either HU or MukB thus seems to be essential for bacterial growth. The HU protein has been shown to be involved in DNA replication in vitro; we show here that its inactivation in the hupA hupB double mutant disturbs the synchrony of replication initiation in vivo, as evaluated by flow cytometry. Our results suggest that global nucleoid structure, determined in part by the histone-like protein HU, plays a role in DNA replication initiation, in proper chromosome partitioning directed by the MukFEB proteins, and in correct septum placement directed by the MinCDE proteins.

Adenosine Triphosphatases↗

Role of the lipoxygenase pathway in angiotensin II-induced vasoconstriction in the human placenta.

We have previously shown that the vasopressor effect of angiotensin II (Ang II) is inhibited by lipoxygenase (LO) blockers. To elucidate the specific mechanism involved, we studied the relationship between the contractile effect of Ang II and LO products in a human placental preparation. In perfused placental cotyledons, Ang II (boluses of 1 to 10 microg) increased perfusion pressure and 12-hydroxyeicosatetraenoic acid (12-HETE) release. The LO blockers phenidone and n-propyl gallate reduced the maximal Ang II-induced increment in pressure from 26+/-3 to 16+/-3 and 18+/-4 mm Hg, respectively (P<.05 for both). Ang II alone (10 microg) increased 12-HETE release from 8.9+/-3.6 to 37.6+/-0.4 ng/min, and this rise was entirely blocked by both phenidone and n-propyl gallate. Pressure increase generated by an increase in flow rate had no effect on 12-HETE formation. In deendothelialized umbilical artery segments, Ang II (10(-7) mol/L) increased 12-HETE formation by 47+/-5% (n=20). In cultured umbilical artery smooth muscle cells, Ang II increased 12-HETE formation from 48.1+/-7.2 to 75.1+/-15.3 ng/mg protein, and this effect was also blocked by the specific LO inhibitor baicalein (10(-6) mol/L). These results provide evidence that the vasopressor effect of Ang II is functionally coupled to 12-LO activation, which apparently takes place in arterial smooth muscle cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Erectile dysfunction in hypertensive subjects. Assessment of potential determinants.

Hypertension is often cited as a risk factor for erectile dysfunction. To clarify the relation between hypertension and erectile dysfunction, we evaluated 32 consecutive hypertensive and 78 normotensive impotent men with respect to multiple potential determinants and parameters of erectile function, including medical and sexual history, depression, hormonal profile, penile nocturnal tumescence, penile vascular supply, and pudendal nerve conduction. The hypertensive men were older, had higher body mass index, and used more medications than the normotensive men. The groups were not different with respect to the prevalence of smoking and peripheral vascular disease, but the hypertensive men had a marginally higher rate of ischemic heart disease (P = .06). The prevalence of depression, abnormal nocturnal penile tumescence, anomalous pudendal nerve conduction, and impairment in arterial supply as determined by penile brachial index were similar in the two groups. Testosterone and bioavailable testosterone levels were lower in the hypertensive men. After stratification by age and body mass index, hypertensive men younger than 50 years with body mass index less than 30 kg/m2 had significantly lower testosterone levels (12.0 +/- 1.7 versus 21.3 +/- 1.4 nmol/L, P < .02) but not bioavailable testosterone levels (3.9 +/- 0.7 versus 6.4 +/- 0.7 nmol/L, P < .17) than the corresponding normotensive group. Prolactin, follicle-stimulating hormone, and luteinizing hormone levels of the two groups were not significantly different. Contrary to common belief and with the exception of lower circulating testosterone levels, the overall analysis showed little difference between hypertensive and normotensive men with respect to a wide range of classic determinants of erectile function. Direct study of the local vascular erectile apparatus appears necessary for further elucidation of the mechanisms underlying erectile dysfunction in hypertensive men.

Adult↗

The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases.

The role of the low dose (1 microgram) ACTH stimulation test in the evaluation of patients with pituitary diseases was systematically assessed by relating its results to those obtained on gold standard tests of hypothalamo-pituitary-adrenal (HPA) reserve, such as insulin-induced hypoglycemia or a metyrapone challenge. Ten patients with pituitary diseases (8 men and 2 women) and proven impairment of HPA function and 9 patients (5 men and 4 women) with similar pituitary pathologies but preserved HPA function were studied (pituitary controls). A group of 7 normal volunteers (3 men and 4 women) served as normal controls. None of the subjects was taking glucocorticoids on a chronic basis or had been taking any recently. All subjects underwent ACTH tests at 0800 h with 3 different levels of stimulation (1, 5, and 250 micrograms), and serum cortisol was assayed 0, 30, and 60 min after injection. A pass result was defined as a peak cortisol value of 497 nmol/L or more. Basal cortisol values were indistinguishable among the groups. Pituitary controls did not differ from normal controls for any of the challenges. In healthy controls, peak cortisol levels attained with the low dose stimulation were clearly lower than with the standard dose (670 +/- 39 vs. 919 +/- 50 nmol/L; P = 0.002). However, every normal control passed the low dose stimulation, whereas none of the patients with impaired HPA function did (P = 0.00005). Although the cortisol values achieved on the standard (250 micrograms) dose by the subjects with impaired HPA function were significantly lower than those in normal controls (P < 0.005), they were generally normal in absolute terms. Indeed, using the peak value criterion, 7 of these 10 patients would have qualified as pass on the 5-micrograms challenge, and 9 of 10 would have passed the 250-micrograms test. Thus, the low dose ACTH test appears to perform better than the standard pharmacological test. As we have shown that this test correlates well with reference tests of HPA function, it is suggested that it should replace the standard ACTH test in the diagnosis of secondary adrenal insufficiency.

Adrenocorticotropic Hormone↗

Minor depression and functional impairment.

OBJECTIVE: To describe a method of assessing minor depression and its effects on functional status, medical co-morbidity, seasonality, and demographic variables. DESIGN: A survey administered to a nonrandom sample of 302 patients. SETTING: A university-based family practice outpatient center. PATIENTS: Patients who were seen for routine ambulatory care were asked to complete the Inventory to Diagnose Depression scale and a modified version of the Dartmouth COOP Functional Assessment Charts, including a measure of seasonality. MAIN OUTCOME MEASURES: Six categories of functional impairment were examined across two categories of depression (major and minor) and the nondepressed. Major depression is defined strictly by criteria in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Minor depression is defined as depressed mood or anhedonia and one other of the nine depression symptoms. RESULTS: Forty-seven patients (15.6%) had minor depression. Using chi 2 analysis, significant differences were found among the three levels of depression for each functional status category. Logistic regression analysis showed patients with minor depression to have greater odds of more impairment in feelings (odds ratio [OR], 4.01; 95% confidence interval [CI], 1.75 to 9.19), pain (OR, 2.58; 95% CI, 1.18 to 5.63), and social activities (OR, 2.48; 95% CI, 1.19 to 5.17) compared with the nondepressed patient. The cluster of impairment distinguishing minor from major depression differed somewhat, with more impairment in daily activities (OR, 19.6; 95% CI, 3.45 to 112.00) and feelings (OR, 24.4; 95% CI, 1.78 to 333.00) and greater lung disease (OR, 13.7; 95% CI, 2.19 to 80.00) and seasonality (OR, 5.9; 95% CI, 1.10 to 32.1 for highest seasonality) in patients with major depression. CONCLUSIONS: There appears to be significant functional disability associated with the presence of minor depression. Seasonality was also present in those with minor depression, although it was of greater importance among those with major depression. Despite lack of national consensus on the definition of minor depression, limitations owing to sampling method, and statistical modeling, there is evidence that patients with minor depression reveal a different constellation of impairment than do those with major depressive disorder.

Activities of Daily Living↗

Effect of 5-alpha-reductase inhibition on sex-hormone-binding globulin in elderly men.

In this study we examined the possibility that chronic reduction in serum dihydrotestosterone (DHT) attained by pharmacologic inhibition of 5 alpha-reductase modulates serum sex-hormone-binding globulin (SHBG) levels in elderly men. Twenty-one men, ages 58-79 years (mean 66) with benign prostatic hypertrophy were treated with the 5 alpha-reductase inhibitor finasteride (5 mg daily) for 12 months. Serum DHT declined by 80% (p < 0.001) and total testosterone rose by 14% (p < 0.05). Serum SHBG concentration remained unchanged (44.1 +/- 4.5 vs 45.2 +/- 5.7 nmol/l for pre- and post-therapy levels, respectively). Thus, the conversion of testosterone to DHT is not required to maintain the androgenic effect on serum SHBG concentration in elderly men.

Aged↗

Morality and AIDS.

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Acquired Immunodeficiency Syndrome↗

Erythropoietin therapy obviates the need for recurrent transfusions in a patient with severe hemolysis due to prosthetic valves.

Erythropoietin has been proved extremely effective in ameliorating the anemia of chronic renal failure and is currently under intensive investigation. We describe a patient with severe anemia and secondary hemochromatosis due to prosthetic valves, who has been successfully treated with erythropoietin. During 12 months' follow-up, an acceptable hemoglobin level was maintained without any need for blood transfusions; in addition, there was evidence indicating regression of hemochromatosis. This patient illustrates that erythropoietin therapy might prove beneficial for similar cases.

Anemia, Hemolytic↗

[Sedural toxicity].

Phenazopyridine (Sedural) is widely used in the treatment of dysuria. It is considered a benign drug and most physicians are unaware of its potential toxicity. A 24-year-old woman who developed methemoglobinemia, acute renal failure and hemolytic anemia following a single 1 g dose of the drug is presented.

Acute Kidney Injury↗

Three years of a required geriatrics module for third-year medical students.

The Parker Jewish Geriatric Institute, a teaching nursing home at which an accredited internal medicine geriatrics fellowship is based, co-developed with the Department of Family Practice of the medical school at the State University of New York at Stony Brook a mandatory geriatrics module for third-year medical students. The module's implementation over a three-year period (1985-1987) with 278 medical students is described. The authors conclude that if time and effort are given to the development of a geriatrics curriculum, and if appropriate instructors are chosen, then learning geriatrics in long-term-care settings can be as rewarding and exciting an experience for medical students as their experiences in other clinical settings, even when that learning is required.

Adult↗