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Biomedical subjects

G Mikhail

Publications and source records attributed to G Mikhail.

At least 19 recordsLinked to original sources

Plasma catecholamines, pharmacotherapy and mood of subjects with cardiovascular disorder.

This study investigated whether drug therapy explains why the concentration of arterial plasma catecholamines in patients who have received an orthotopic heart transplant (OHT) or coronary bypass and graft (CABG) is greater than in those with heart failure (HF). The results suggest that the differences in plasma catecholamine concentrations in these groups of patients could not be attributed to administration of any of the drugs studied here. An additional finding is that the use of aspirin is associated with a higher concentration of plasma noradrenaline, but not adrenaline. Patients who were taking aspirin also had a more positive mood, as rated by the Profile of Mood States; this was mainly because they had a lower fatigue score than did patients who were not taking this drug. In contrast, several agents (warfarin, Ca2+-channel blockers and 'mixed cardiac' drugs), which had no effects on catecholamine overspill, were linked with negative mood; this was expressed consistently as a higher tension score. These findings suggest that drugs which are administered for their effects in the periphery could also influence patients' psychological status. With the possible exception of aspirin, this does not involve changes in spillover of catecholamines in the periphery.

Adult↗

Role of vasoactive mediators in primary and secondary pulmonary hypertension.

The role of vasoactive mediators, such as endothelin-1, nitric oxide, prostacyclin, and thromboxane, in pulmonary hypertension remains undefined. This study investigated the circulating levels and transpulmonary gradients of these vasoactive mediators in patients with primary and secondary pulmonary hypertension to define whether there is increased production or decreased clearance of these substances in the lung vasculature.

Adult↗

High expression of endothelial nitric oxide synthase in plexiform lesions of pulmonary hypertension.

The pathogenesis of pulmonary hypertension (PH) remains poorly understood. Vasoconstriction, although likely to be a major factor in the disease, varies between patients and studies of a variety of vasoactive substances have sometimes yielded conflicting results. Amongst these substances, alteration of the nitric oxide (NO) system has been cited as a possible pathogenic factor but both reduction and elevation of the expression of endothelial NO-synthase (eNOS) have been reported in pulmonary vessels. The present study has used immunocytochemistry with well-characterized antibodies to eNOS to investigate its expression in lung tissue taken at transplantation from 44 patients with PH (22 primary, 22 secondary) and 12 non-hypertensive controls. Semi-quantitative assessment showed that although the levels of eNOS expression in pulmonary vessels were variable within both hypertensives and controls, a statistically significant (P < 0.01) reduction of immunoreactivity was found in small arterioles from hypertensives compared with controls. In contrast, consistently strong expression of eNOS was seen in the endothelium of plexiform lesions in both the primary and the secondary PH patients. Although a decrease in the NO system of patients with PH has been reported, these findings show a distinct regional distribution of the enzyme with particularly high levels in plexiform lesions, a previously unreported observation, and offer a new perspective on the disease and on the evaluation of possible novel therapeutic approaches.

Adolescent↗

Psychological adjustment after cardiac transplantation.

Psychosocial function improves after cardiac transplantation but the extent of improvement is not established. Neither are the factors established that account for variability in function between patients following successful transplantation. We therefore compared illness-related dysfunction in patients following orthotopic cardiac transplantation (OCT) with that in angina-free patients following coronary artery bypass graft (CABG) and stable patients in heart failure awaiting transplantation (HF). We also measured two factors that might contribute to variation in function: emotional distress and concern with physical symptoms. Psychosocial function was as good in OCT as in CABG patients and, in both, was better than in HF patients. Differences in emotional distress and in physical symptoms showed a similar pattern and contributed to, but did not completely account for, differences in function. Concern with physical symptoms contributed to variability in functional impairment in HF but not CABG patients; transplantation strengthened this relationship. The results show that successful cardiac transplantation enhances psychosocial function to a level comparable with that after CABG, and suggest targets for psychological or educational intervention to improve quality of life after transplantation in patients whose recovery is inhibited by concern about physical symptoms.

Adaptation, Psychological↗

Medium term results of lung transplantation for end stage pulmonary sarcoidosis.

BACKGROUND: Lung transplantation is an accepted therapeutic option for patients with end stage pulmonary sarcoidosis. However, the medium term outcome of transplantation in this patient group is unknown. METHODS: This study was performed to evaluate our experience with lung transplantation for end stage pulmonary sarcoidosis. Between July 1988 and July 1997 12 patients (nine men) underwent lung transplantation for sarcoidosis at our institution. Ten underwent single lung transplantation and two double lung transplantation. RESULTS: Survival at three and five years was 70% and 56%, respectively. Three patients developed obliterative bronchiolitis at six, 18, and 45 months. One died at the time of retransplantation. Sarcoid granulomas have recurred in the donor organ in three patients. In one the development of granulomas has been associated with clinical deterioration, necessitating retransplantation. Mean (SD) forced expiratory volumes in one second at three and five years were 1.37 (0.67) 1 and 1.34 (0.13) 1, respectively. CONCLUSIONS: Lung transplantation is a viable option for patients with end stage pulmonary sarcoidosis. The medium term results are comparable with patients undergoing lung transplantation for other indications. Despite histological recurrence of sarcoidosis, the risk of clinically important recurrence is low.

Adult↗

Psychological stress does not affect plasma catecholamines in subjects with cardiovascular disorder.

Whereas the effects of cardiac transplantation on the catecholamine response to physical exercise have been studied previously, the impact on psychological stress is unknown. Here, the arterial catecholamine response to the Stroop test of patients with an orthotopic heart transplant (OHT) was compared with that in subjects who had received a coronary artery bypass graft (CABG) or who were in heart failure and destined for a heart transplant (HF). Subjects were tested whilst sitting and their usual drug therapy was maintained. The Stroop test increased subjects' subjective tension but did not affect arterial concentrations of adrenaline or noradrenaline in any group of subjects. Also, the concentration of both catecholamines was significantly higher in OHT and CABG subjects than in the HF group, but their relative concentration was unaffected by cardiovascular status or stress. It is concluded that the absolute concentrations of arterial catecholamines, but not their relative concentrations, depend on clinical status. Moreover, under these test conditions, subjects with a history of cardiovascular disorder do not show the normal catecholamine response to psychological stress.

Adolescent↗

An evaluation of nebulized prostacyclin in patients with primary and secondary pulmonary hypertension.

AIMS: To investigate the response to inhaled prostacyclin in patients with primary and secondary pulmonary hypertension and to compare its effects to those of intravenous prostacyclin and inhaled nitric oxide. METHODS AND RESULTS: Twelve patients with pulmonary hypertension (seven primary and five secondary) were studied. All patients had a pulmonary artery balloon flotation catheter inserted into the proximal pulmonary artery and radial arterial line. Prostacyclin was nebulized with 81.min-1 of oxygen and administered in doses increasing from 15 to 50 ng.kg-1.min-1 via a facemask. Eight of these patients also received intravenous prostacyclin in doses of 1 to 5 ng.kg-1.min-1 and nitric oxide in doses of 10 to 100 ppm via a facemask. Haemodynamic measurements were taken during each treatment. In the 12 patients, nebulized prostacyclin produced a significant reduction in mean pulmonary artery pressure from 56 +/- 5 to 45 +/- 4 mmHg (P = 0.0001). The pulmonary vascular resistance decreased by 38% from 964 +/- 169 to 595 +/- 116 dyne.s-1.cm-5 (P = 0.0001). Direct comparison with inhaled nitric oxide and intravenous prostacyclin in eight patients demonstrated that nebulized prostacyclin produced a greater fall in mean pulmonary artery pressure than the other two agents without any significant effect on systemic arterial pressure. CONCLUSION: Nebulized prostacyclin appears to be more effective at reducing pulmonary artery pressure in patients with pulmonary hypertension when compared to intravenous prostacyclin and inhaled nitric oxide. This could have important clinical implications for the management of patients with pulmonary hypertensions.

Administration, Inhalation↗

Imaging of pregnancy-related complications.

Thirty-six cases of pregnancy-related complications were studied with plain radiography, ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging alone or in combination. Among the complications diagnosed with these various techniques were venous thromboembolic disorders, deep vein thrombosis, ovarian vein thrombosis, endometritis and pyometra, HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelet counts), hepatic hematoma and rupture, fatty liver, uterine rupture, various hematomas and a foreign body, tubo-ovarian abscess, cerebral venous thrombosis, cerebral ischemia, and cerebral edema. Prompt detection and appropriate management of many of these complications could result in decreased maternal and fetal mortality and morbidity. Although US should be considered first because it can be performed bedside, does not require use of ionizing radiation, and is cost-effective, CT is superior in demonstrating the extent of the abnormality and MR imaging is best for detection of neurologic complications of pregnancy. The radiologist should select the best available method and tailor the examination according to the presumptive clinical diagnosis and the individual problem to be solved.

Adult↗

Clomiphene and tamoxifen inhibit progesterone synthesis in granulosa cells: comparison with estradiol.

The actions of clomiphene, tamoxifen, and 17 beta-estradiol were studied in an isolated avian granulosa cell system during short term incubations. A dose-dependent inhibition of ovine LH-enhanced progesterone production was observed for all three compounds, with an IC50 of 3 X 10(-6) M and maximal inhibition (95%) at 5 X 10(-5) M. A similar inhibition was found when cells were stimulated by either 8-bromo-cAMP or forskolin. Neither clomiphene nor tamoxifen had an inhibitory effect on the conversion of pregnenolone to progesterone, a step that was blocked by 17 beta-estradiol and isoxazole , a known inhibitor of 3 beta-hydroxysteroid dehydrogenase. On the other hand, cells exposed to clomiphene failed to use [6-3H]25-hydroxycholesterol, while estradiol significantly increased the conversion of labeled substrate to pregnenolone at the expense of progesterone (30% vs. 7% of the total radioactivity). By comparison, in control cells, progesterone represented the major metabolite with 36% of the total radioactivity; pregnenolone had only 2.8%. The results demonstrate that these triphenylethylene compounds, which are used clinically as antiestrogens, inhibit steroidogenesis at a step before pregnenolone formation, probably at the site of the cholesterol side-chain cleavage enzyme complex, while 17 beta-estradiol inhibits 3 beta-hydroxysteroid dehydrogenase.

1-Methyl-3-isobutylxanthine↗

The prostanoid content in peritoneal fluid and plasma of women with endometriosis.

Peritoneal fluid and plasma collected at laparoscopy in women with and without endometriosis were evaluated for prostanoid content. 6-Keto-prostaglandin F1 alpha (6-keto-F1 alpha), thromboxane B2 (TxB2), 15-keto- 13, 14-dihydroprostaglandin F2 alpha (PGFM), prostaglandin F (PGF) and prostaglandin E (PGE) were assayed in peritoneal fluid, with 6-keto-F1 alpha, TxB2, and PGFM being studied in plasma. The concentrations of these prostanoids in women with endometriosis were not significantly different from the concentrations in the disease-free group, nor was a significant difference seen in any of the prostanoids studied in relationship to the severity of the endometriosis. The results suggest that routine study of prostanoid levels in patients with endometriosis may not be of a diagnostic or prognostic value.

Ascitic Fluid↗

Estrogen-androgen balance in anovulation.

The balance of estradiol (E2) and testosterone (T) in 15 anovulatory patients was evaluated by measuring the daily plasma concentration of E2 and T, and their free and protein-bound fractions for a 3- to 4-week period. Similar daily plasma E2 and T data were obtained from five normal ovulatory cycles as a control group. The daily concentration of the free, non-testosterone-estradiol-binding globulin (TeBG)-bound (index), and total E2 fluctuated in a wider range than that of the T in the ovulatory as well as in the anovulatory cycles. The percentage of free (%F) and TeBG-bound (%TeBG) fractions of both E2 and T were relatively constant. The concentration of the free, index, and total E2 and T showed a parallel pattern even in anovulatory cycles. An increased %F fraction associated with a decreased %TeBG fraction of E2 and T was observed in anovulatory patients who were hypo- or normoestrogenic; however, an opposite shifting of these two fractions was observed in anovulatory patients who were severely hypoestrogenic. In a hyperestrogen-normoandrogenic state, there was a significant increase in the binding of E2 and T. The daily binding capacity of plasma TeBG revealed a greater fluctuation than the binding fractions, and it decreased in anovulatory patients, especially in the hyperandrogenic state. E2:T ratio of concentration showed a curve-linear relationship to %F, %TeBG, and binding capacity of sex steroids.

Anovulation↗

Plasma hormones in DES-exposed females.

Random blood samples were obtained from 114 women with history of diethylstilbestrol (DES) exposure in utero and were analyzed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone (E1), estradiol (E2), androstenedione (A), testosterone (T), and progesterone (P) by respective radioimmunoassays. Colposcopic examinations of the lower genital tract and biopsies of suspicious areas of vaginal mucosa were performed in every patient. The mean age of these patients was 21.6 +/- 0.3 years (mean +/- SE) and mean age of menarche was 12.6 +/- 1.0 years. The incidence of irregular menses was 16.7%. A positive colposcopic finding was observed in 73.7% of all patients, 69.5% of patients with regular menses, and 94.7% of patients with irregular menses. Histologically confirmed vaginal adenosis was found in 43% of all patients, 46.3% of patients with regular menses, and 42.1% of patients with irregular menses. No significant differences were observed between DES-exposed versus unexposed females with regular menses in all hormones except testosterone. An elevated testosterone level was noted in postovulatory and perimenstrual phases of DES-exposed females. Elevated testosterone was also observed in DES-exposed females with irregular menses. Cross-analysis of hormone levels among the patients with lower genital tract pathology failed to show any statistical differences.

Adolescent↗

Free and protein-bound steroids in amniotic fluid of midpregnancy.

Ninety-seven amniotic fluid (AF) specimens, 67 with male fetuses and 30 with female fetuses, were obtained by amniocentesis at 14 to 18 weeks of gestation for analysis of free and protein-bound estrone (E1), estradiol (E2), androstenedione (A), testosterone (T), and progesterone (P). Ten maternal plasma (MP) samples of comparable gestational age were analyzed for the same free and protein-bound steroids. Significantly lower total E1, E2, A, and T, but not P, levels were found in AF when compared to MP. The percentage of free steroids was higher in AF than in MP, while the percentage of specific protein-bound steroids was lower in the AF than in MP. Free (unbound) steroid levels of E1 and P were higher in AF than in MP, whereas levels of E2 were lower in AF than in MP. The free A and T levels in MP were lower than in AF with male fetuses, yet higher than in AF with female fetuses. Possible biologic activity of steroids in this fluid may depend on the dynamic balance between the free, the specific protein-bound, and the nonspecific protein-bound steroids.

Adult↗

Daily plasma prolactin in various gynecologic endocrinopathies.

Daily plasma prolactin levels were measured in women with various gynecologic endocrinopathies in order to compare mean levels and variations over the sampling interval with prolactin levels in women with normal ovulatory cycles. The normal-cycle mean prolactin level was 14.7 ng/ml +/- 1.4 (SE). Levels greater than 42 ng/ml, 2 SD above the mean, were considered abnormal. Patients with endocrinopathies were classified as "normoprolactinemic" if the mean prolactin level was less than 42 ng/ml and less than 12% of the daily values peaked to greater than 42 ng/ml. An "intermediate" group was defined in which the mean prolactin level was less than 42 ng/ml but more than 12% of daily values peaked to greater than 42 ng/ml. Those patients whose mean prolactin levels were greater than 42 ng/ml were considered "hyperprolactinemic". Significant differences were noted when mean prolactin levels were compared with normal-cycle levels in 16 or 18 women with various gynecologic endocrinopathies. The need for repeated prolactin sampling in certain clinical situations, as well as the possibility that a "critical" prolactin level is necessary for normal ovarian function, is discussed.

Anovulation↗

Plasma hormone profile in anovulation.

Daily plasma hormones, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, androstenedione, and testosterone (T), were measured in 16 anovulatory patients for a span of 3 to 4 weeks. The clinical diagnoses in this group of patients included the following: anovulation-eumenorrhea (n = 5), anovulation-polymenorrhea (n = 1), anovulation-oligomenorrhea (n = 3), congenital adrenal hyperplasia (n = 1), polycystic ovarian disease (n = 4), severe hypothalamic amenorrhea (n = 1), and postpartum amenorrhea-galactorrhea (n = 1). Follicular activity was evident in polymenorrheic and oligomenorrheic patients, and menstruation occurred in these patients following estrogen withdrawal. No follicular maturation was noted in the group of patients with anovulation-eumenorrhea, and menstruation in these patients was considered breakthrough bleeding. Low FSH levels were observed in anovulatory patients with eumenorrhea, polymenorrhea, and oligomenorrhea. Significantly high LH values were noted in both classic and non-classic polycystic ovarian disease. Extremely low E1 and E2 levels were found in patients with severe hypothalamic amenorrhea and postpartum amenorrhea-galactorrhea. Slightly elevated progesterone levels were observed in polymenorrheic and oligomenorrheic patients prior to menstruation; this was frequently associated with an LH surge or elevation. Elevated T levels were consistently associated with hirsutism but not with obesity.

Adolescent↗