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S Goldman

Publications and source records attributed to S Goldman.

At least 73 records · Page 4Linked to original sources
PubMed2000

Fate of 2-deoxy-2-[18F]fluoro-D-glucose in control and diabetic rats.

Recent experiments conducted in vitro have documented a marked difference in the time course for D-[U-14C]glucose net uptake by pieces of pancreatic tissue versus isolated pancreatic islets. The present study aimed, therefore, at assessing whether the endocrine pancreas contributes to a detectable extent to the overall net uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) by the pancreatic gland. For this purpose, the radioactive content of the pancreas was compared to that of plasma, erythrocytes, liver, brain, hypophysis and parotid gland 3 min, 15 min and 240 min after the intravenous injection of FDG to both control rats and animals injected with streptozotocin and later treated with insulin or not. In the control rats, the radioactive content (cpm/mg wet wt.) of erythrocytes was always lower than that of liver. In other organs, it displayed the following hierarchy pancreas < parotid < hypophysis < brain, the absolute values being either lower (3 min) or much higher (240 min) than in liver. In the diabetic rats, whether treated with insulin or not, the radioactive content of erythrocytes, pancreas, brain, hypophysis and parotid gland, relative to the paired value found in liver, was equal or lower than that of control rats when the animals were hyperglycemic and equal or higher than that of control rats when the animals became hypoglycemic as the result of intensive insulin treatment. Even only 3 min after the injection of FDG, and despite persistent hyperglycemia in the streptozotocin-injected and insulin-treated rats, the pancreas/ liver paired ratio in radioactive content failed to be significantly lower in the diabetic animals than in control rats. These findings indicate that 2-deoxy-2-[18F]fluoro-D-glucose is not a suitable tool to detect any preferential labelling of insulin-producing cells, relative to acinar cells, at least when considering only the total radioactive content of the pancreatic gland.

Animals↗
PubMed2000

Fate of 2-deoxy-2-[18F]fluoro-D-glucose in hyperglycemic rats.

Sustained hyperglycemia allows the preferential labelling of pancreatic glycogen by D-[U-14C]glucose in control rats, as compared to animals previously injected with streptozotocin (STZ rats). The major aim of the present study was to investigate whether a sizeable difference between control and STZ rats could also be observed in terms of the radioactive content of the pancreatic gland 8 h after the intravenous injection of 2-deoxy-2-[18F]fluoro-D-glucose, both types of animals being examined at the same level of hyperglycemia. Although the radioactive content of muscle, liver and kidney was lower in STZ rats than in control animals, such a difference failed to achieve statistical significance in brain, hypophysis, pancreas and parotid gland. It is proposed, therefore, that 11C-labelled D-glucose, rather than 2-deoxy-2-[18F]fluoro-D-glucose should be used in the perspective of the non-invasive imaging of the endocrine pancreas.

Animals↗
PubMed1999

Radiation therapy for consolidation of metastatic or recurrent sarcomas in children treated with intensive chemotherapy and stem cell rescue. A feasibility study.

PURPOSE: To assess the role of consolidative radiation therapy (CRT) in conjunction with myeloablative therapy with or without total body irradiation (TBI) in children and young adults with metastatic or recurrent sarcoma. METHODS AND MATERIALS: Twenty-one pediatric sarcoma patients with metastatic (10) or recurrent (11) disease were entered on a prospective feasibility study of intensive myeloablative therapy with or without TBI. Median patient age was 17.8 years (range, 9.4-24.7 years). Primary histologies included Ewing's (12), PNET (3), and other soft tissue sarcomas (6). Twenty patients received induction chemotherapy. Myeloablative therapy consisted of TBI in 11 patients with either high dose melphalan/etoposide (9) or high dose cytoxan/thiotepa (2). TBI consisted of 12 Gy in 2 Gy fractions delivered twice daily over 3 days. Ten patients received high dose chemotherapy alone, either with thiotepa/carboplatinum/etoposide (8) or cytoxan/carboplatinum (2). Myeloablative therapy was followed by autologous stem cell rescue (ASCR) 24 to 48 hours after completing chemotherapy. Fourteen patients (67%) received CRT either prior to (5) or following (9) myeloablative therapy. Median CRT dose was 37.2 Gy (range, 20-60). Fifty-one disease sites were present prior to myeloablative therapy. Twelve (24%) were bulky (> 8 cm) and 18 (35%) underwent surgical debulking. The median follow-up of surviving patients was 15 months (range, 8-20) with 25% of patients having been followed for more than 20 months. RESULTS: The 3-year actuarial disease-free (DFS) and overall survival (OS) rates for the entire group were 36% and 27%, respectively. Following myeloablative treatment, responses were: 11 complete, 6 partial, 1 stable, and 3 progressive disease. Sixteen patients (71%) have relapsed. The most common site of relapse was the lung (13). Of the 51 disease sites present prior to myeloablative therapy, 36 sites (71%) were amenable to CRT. Nonamenable sites were: multiple lung metastases (13) and bone marrow (2). Twenty-six amenable sites (51%) received CRT either prior to (14) or following (12) ASCR. Amenable sites treated with CRT had a better 3-year actuarial local control (80 vs 37%) (p = 0.0065) than amenable sites not treated with CRT. Factors associated with improved disease-free survival (DFS) in univariate analysis were induction chemotherapy response (p = 0.002) and extent of surgical resection (p = 0.045). There was a trend toward improved DFS on univariate analysis with the use of TBI as part of myeloablative therapy (p = 0.07). The one factor associated with improved OS on univariate analysis was induction chemotherapy response (p = 0.007). Multivariate analysis revealed that induction chemotherapy response is the only factor that remains significant for DFS (p = 0.032) as well as for OS (p = 0.017). Patients with complete response to induction therapy had 40% probability of survival versus all other patients who had 10% survival (p = 0.05). CONCLUSION: Consolidative radiotherapy is feasible in primary metastatic or recurrent pediatric sarcoma patients treated with myeloablative therapy with or without TBI. CRT to sites amenable to irradiation provided an improved 3-year actuarial local control than that seen in sites amenable to CRT that did not undergo radiotherapy. There was a trend for improved DFS with the use of TBI. Improved DFS and OS can be predicted by response to induction therapy. This intensive regimen may improve the cure rate of advanced pediatric sarcomas in select patients.

Adolescent↗
PubMed1999

Brain glucose metabolism in eating disorders assessed by positron emission tomography.

OBJECTIVE: As anorectic and bulimic patients present similar clinical and neurobiological symptoms, the purpose of this study was to compare brain glucose metabolism at rest in these patients. METHODS: Positron emission tomography with (18-F)-fluorodeoxyglucose was used to evaluate cerebral glucose metabolism (CMRglu) in 10 normal-weight bulimic women, in 10 underweight anorectic patients, and in 10 age- and sex-matched healthy volunteers. RESULTS: Absolute global cortical glucose activity was significantly lower in anorectic patients compared with bulimic and control subjects. Anorectic patients compared with normal control subjects also showed higher relative CMRglu in the inferior frontal cortex and in the basal ganglia, and putamen and caudate relative hypermetabolism when compared with bulimic patients. Thus, both eating disorder groups differed from control subjects in low relative parietal values of glucose. DISCUSSION: While absolute global metabolism seems to be related to weight loss, we can hypothesize either a common parietal cortex dysfunction in eating disorders or a particular sensitivity of this cortex to consequences of eating disturbances.

Adolescent↗
PubMed1999

Glucocorticoids-potent modulators of astrocytic calcium signaling.

Glucocorticoids are the first line of choice in the treatment of cerebral edema associated with brain tumors. High-dose glucocorticoids reduce the extent of edema within hours, often relieving critical increases in intracranial pressure, but the mechanisms by which glucocorticoids modulate brain water content are not well-understood. A possible target of action may be glucocorticoid receptor-expressing astrocytes, which are the primary regulators of interstitial ion homeostasis in brain. In this study, we demonstrate that two glucocorticoids, methylprednisolone and dexamethasone, potentiate astrocytic signaling, via long-range calcium waves. Glucocorticoid treatment increased both resting cytosolic calcium (Ca2+i) level and the extent and amplitude of Ca2+ wave propagation two-fold, compared to matched controls. RU-486, a potent steroid receptor antagonist, inhibited the effects of methylprednisolone. The glucocorticoid-associated potentiation of Ca2+ signaling may result from upregulation of the cellular ability to mobilize Ca2+ and release ATP, because both agonist-induced Ca2+i increments (via ATP and bradykinin) and ATP release were proportionally enhanced by glucocorticoids. In contrast, neither gap junction expression (as manifested connexin 43 immunoreactivity) nor functional coupling was significantly affected by methylprednisolone. Confocal microscopy revealed both the expression of glucocorticoid receptors and nuclear translocation of these receptors when exposed to methylprednisolone. We postulate that the edemolytic effects of glucocorticoids may result from enhanced astrocytic calcium signaling.

Adenosine Triphosphate↗
PubMed1999

Overexpression of endothelium nitric oxide synthase reverses the diminished vasorelaxation in the hindlimb vasculature in ischemic heart failure in vivo.

After myocardial infarction (MI), nitric oxide (NO)-mediated vasorelaxation is attenuated in both conduit and resistance arteries. To determine if the attenuated vasorelaxation after MI is due to downregulation of eNOS protein, pharmacological, immunoblotting, and gene transfer of eNOS were performed in rats 3 weeks after MI. Gene transfer was accomplished using a "first-generation" serotype 5, replication-deficient, adenoviral vector (1.2 x 10(9) pfus) containing eNOS cDNA in the hindlimb vasculature for 30 min. Five days after infection, overexpression of eNOS protein was confirmed by immunohistochemical staining and immunoblotting. Recombinant gene expression was localized primarily to the vascular endothelial cells. After MI, eNOS protein level decreased (3.3 +/- 0.9 vs 2.1 +/- 0.8 intensity units/microg protein, n=6, P<0.05); after gene transfer it increased (P<0.05) two-fold to 4.3 +/- 1.2 intensity units/microg protein, n=5. There were no changes in hemodynamics in MI rats transfected with eNOS. Acetylcholine (ACh)-stimulated vasorelaxation was decreased (P<0.05) by 30% after MI and was restored to normal with eNOS transfection. Addition of 100 microm NG-nitro-L-arginine methyl ester (L-NAME) abolished the difference between sham, MI, and MI transfected rats. L-arginine (1 mm) restored the ACh-response in MI-transfected rats toward control, but it did not eliminate the difference between MI and sham rats. We conclude that the attenuated endothelial NO-mediated vasorelaxation in the hindlimb after MI is due to a downregulation of eNOS protein and overexpression of eNOS transgene restores normal endothelial NO-mediated vasorelaxation.

Acetylcholine↗
PubMed1999

Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET.

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [18F]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients.

Adult↗
PubMed1999

Pergolide potentiates L-DOPA-induced dopamine release in rat striatum after lesioning with 6-hydroxydopamine.

We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) receptor agonist on biotransformation of exogenous L-DOPA in hemi-Parkinsonian rats. DA and metabolites were assayed by microbore liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 67% and 87% decrease in striatal EC levels of DA in intact and denervated striatum respectively. In intact striatum but not in denervated striatum, pergolide decreased EC levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (53% and 42% decrease, respectively). L-DOPA (100 mg/kg, i.p.) produced significant increase in EC levels of DA, DOPAC and HVA in intact and denervated striatum with and without local perfusion of 10(-4) M pergolide. In denervated striatum, L-DOPA-induced DA increase was significantly higher in rats with pergolide. Our results suggest that, in an animal model of Parkinson's disease, pergolide in association with L-DOPA favors the restoration of striatal EC DA levels.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction.

OBJECTIVES: To examine the relative roles of eNOS and iNOS (endothelial and inducible nitric oxide synthases) on basal and beta-adrenergic receptor (beta-AR)-stimulated arterial hemodynamic responses after myocardial infarction (MI). METHODS: Left ventricular (LV) pressures and steady-state and pulsatile arterial hemodynamics were measured at baseline, and after acute NOS inhibition with either NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) or iNOS inhibition with aminoguanidine (AG, 75 mg/kg) in sham-operated and MI Sprague-Dawley rats. RESULTS: In sham rats, L-NAME decreased (P < 0.05) peak positive LV dP/dt and aortic blood velocity by 19% and 53%, respectively, and increased (P < 0.05) mean arterial pressure (MAP); systemic vascular resistance, and LV end-diastolic pressure (EDP) by 20, 189 and 89%, respectively. The frequency-dependent components of hemodynamics including aortic input impedance modulus, characteristic impedance, and phase shift were increased (P < 0.05) with L-NAME, while pulsatile power was decreased (P < 0.05). AG increased (P < 0.05) aortic input impedance modulus and characteristic impedance but had no effect on any other hemodynamic variable. In MI rats, L-NAME decreased (P < 0.05) LV dP/dt and aortic blood velocity by 22 and 55%, respectively, and increased (P < 0.05) SVR by 108%. There was no effect of L-NAME on MAP or LV EDP in MI rats. After MI, AG increased (P < 0.05) heart rate and LV dP/dt but had no effect on other LV or pulsatile hemodynamic variables. Compared to sham rats, heart rate, LV dP/dt, and blood velocity-isoproterenol dose responses were shifted downward (P < 0.05), while SVR-isoproterenol dose response was shifted upward (P < 0.05) in MI rats. In sham rats, L-NAME potentiated (P < 0.05, at > 10(-2) micrograms/kg) the isoproterenol-induced increase in LV dP/dt and aortic blood velocity, and potentiated (P < 0.05) the isoproterenol-induced decline in SVR. As expected, AG had no effects on isoproterenol-stimulated hemodynamics in sham rats. After MI, there was no effect of L-NAME or AG on isoproterenol-stimulated hemodynamics. CONCLUSIONS: (1) Circulatory and cardiac responses to inhibition of NO by L-NAME suggest that eNOS, but not iNOS, is the principal regulator of integrated arterial hemodynamic function in rats. (2) Both basal and beta-AR-stimulated NO regulation of hemodynamic are attenuated after MI. (3) The attenuation of arterial hemodynamic effects after isoproterenol is mediated, in part, by alterations in the beta-AR-activation of eNOS system after MI.

Adrenergic beta-Agonists↗
PubMed1999

Prophylactic coronary artery revascularization for elective vascular surgery: study design. Veterans Affairs Cooperative Study Group on Coronary Artery Revascularization Prophylaxis for Elective Vascular Surgery.

This article describes the design of an ongoing randomized trial intended to test whether patients who require elective vascular surgery would benefit from preoperative coronary artery revascularization prior to the vascular procedure. The primary objective is to determine whether coronary artery revascularization reduces long-term mortality (mean 3.5 years) in patients undergoing vascular surgery. The study design calls for 620 patients to be randomized and followed for a mean of 3.5 years following vascular surgery. Secondary endpoints include measures of quality of life and cost-effectiveness. Patients with coronary artery disease in need of an elective vascular operation are considered candidates for the study. Anatomic exclusion criteria include ejection fraction <20%, severe aortic stenosis (valve area <1.0 cm2), left main stenosis > or =50%, nonobstructive coronary artery disease (stenosis <70%), and coronary arteries that are not amenable to revascularization. Prior to the vascular surgery, the trial randomizes eligible patients to coronary artery revascularization (either bypass surgery or angioplasty) versus medical therapy. The trial stratifies the randomization by hospital and type of vascular surgery (intraabdominal versus infrainguinal) because of differences in long-term prognosis in those patients. A 1-year feasibility trial involving five Veterans Affairs (VA) medical centers of variable vascular surgical loads has been completed. The results showed that over 90% of expected patients could be randomized. As a result, a larger VA Cooperative Study involving 18 centers will begin recruitment of patients. The findings should help determine the best strategy for managing patients with coronary artery disease in need of elective vascular surgery.

Algorithms↗
PubMed1999

Influence of baseline lipids on effectiveness of pravastatin in the CARE Trial. Cholesterol And Recurrent Events.

OBJECTIVES: We sought to assess the influence of baseline lipid levels on coronary event rates and the effectiveness of pravastatin therapy in the Cholesterol And Recurrent Events (CARE) study. BACKGROUND: The CARE study cohort provided a relatively unique opportunity to examine the relation between lipid levels and clinical events in a post-myocardial infarction (MI) population with relatively low cholesterol and low density lipoprotein (LDL) cholesterol values. METHODS: There were 4,159 patients with a previous infarct and a total cholesterol level <240 mg/dl, LDL cholesterol level 115 to 174 mg/dl and triglyceride level <350 mg/dl randomly allocated to placebo (n=2,078) or pravastatin 40 mg/day (n=2,081). Time to either coronary death or nonfatal MI (primary end point) or to the secondary end point, which included undergoing a coronary revascularization procedure, was determined as a function of baseline lipids (total, LDL, high density lipoprotein [HDL] cholesterol and triglyceride levels). RESULTS: Quartile analysis indicated important effects for LDL cholesterol, in which a higher LDL was associated with greater cardiac event rates (in the placebo group, every 25-mg/dl increment in LDL was associated with a 28% increased risk [5% to 56%, p=0.015]) in the primary event. The differential event rates with respect to baseline LDL cholesterol for placebo and pravastatin groups reduced the difference in clinical outcomes at lower LDL cholesterol levels. In both the placebo and pravastatin groups, an inverse relation between baseline HDL cholesterol and cardiac events was observed (10 mg/dl lower baseline HDL cholesterol level was associated with a 10% [0% to 19%, p=0.046] increase in coronary death or nonfatal MI). CONCLUSIONS: Within the LDL cholesterol levels in CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in the placebo group as well as the clinical effectiveness of pravastatin therapy.

Adult↗
PubMed1999

Mitogen-activated protein kinase in human eggs.

Mitogen-activated protein (MAP) kinase in human eggs has been investigated by using immunoblotting with both anti-Active MAPK and anti-ERK2 antibodies. The results showed that the main form of MAP kinase was p42ERK2. It was in a dephosphorylated form in oocytes at the germinal vesicle stage, but fully phosphorylated in unfertilised mature eggs. MAP kinase phosphorylation was significantly decreased when pronuclei were formed after intracytoplasmic sperm injection. Neither MAP kinase expression nor activity was detected in morphologically degenerated eggs. Although MAP kinase still existed in early embryos arrested at the 8-cell or morula stages, little, if any, activity could be detected. These data suggest that MAP kinase may play an important role in the cell cycle regulation of human eggs, as in other mammalian species.

Adult↗
PubMed1999

Carboplatin therapy for optic pathway tumors in children with neurofibromatosis type-1.

Symptomatic optic pathway tumors (OPT) occur in 7% of children with neurofibromatosis type-1 (NF-1). Although tumor progression following diagnosis is unusual in such children, specific therapy may be necessary for patients with either severe or progressive disease. We reviewed the records of 9 children (6 girls, 3 boys) with NF-1 associated OPT who were treated with the second generation platinum compound carboplatin. Carboplatin was given at a dose of 560 mg/mm2 every 4 weeks for a mean of 15 cycles. The mean age at presentation of the OPT was 3.4 years. Eight children had abnormal ophthalmologic examinations at the time of diagnosis. Only 4 patients had documented evidence of progressive disease prior to the institution of therapy. No patient had evidence of progressive disease following therapy. Four patients had radiologic evidence of tumor shrinkage and 2 patients had definite improvement in vision. There was only minimal toxicity. In conclusion, carboplatin is a safe and effective treatment for OPT in children with NF-1. However, as disease stabilization of NF-1 associated OPT often occurs following clinical presentation, the clinician should document tumor progression or visual deterioration prior to the institution of therapy.

Antineoplastic Agents↗
PubMed1999

Immunological reconstitution and correlation of circulating serum inflammatory mediators/cytokines with the incidence of acute graft-versus-host disease during the first 100 days following unrelated umbilical cord blood transplantation.

We investigated early immunological reconstitution and the production of circulating inflammatory mediators and their relationship to aGVHD in children during the first 100 days following unrelated UCBT. Nine patients had an underlying malignant disease (ALL, ANLL), and two, non-malignant diseases (SAA, ALD). The median age was 10 years (range: 1.25-21). Seven of 11 patients were alive by day 100, two died from regimen-related toxicity, and two died from severe aGVHD (grade >/=III). Myeloid engraftment (ANC >/=500/mm3 x 2 days) occurred at a median of 24 days (range: 14-55), while platelet engraftment (platelet count >/=20 000/mm3 untransfused x 7 days) was delayed and occurred at a median of 52 days (range: 33-95). The mean cell dose of CD34+ cells was 3.3 +/- 3.51 x 10(5)/kg, and of CD34+/CD41+ cells was 3.94 +/- 3.99 x 10(4)/kg. Acute GVHD (grade II-IV) developed in seven patients (77%), and severe aGVHD (grade III-IV) developed in five patients (55%). Serum levels of IL-2Ralpha, IL-2, IL-4, IL-7, IL-12, and IFNgamma were not significantly different between patients with grades 0-I aGVHD and patients with grades II-IV aGVHD. Evaluation of immunological reconstitution on day 90 post UCBT demonstrated an early recovery of the absolute numbers of B cells (CD19+) and NK cells (CD3-/CD56+). Immunoglobulin levels for IgG, IgM and IgA remained normal throughout the study period. PMN functional studies demonstrated normal superoxide generation, bacterial killing (BK), and chemotaxis (CTX). However, both helper (CD3+/CD4+) and suppressor (CD3+/CD8+) T cell subsets remained low during the first 100 days post UCBT with mean +/- s.e.m. values of 120 +/- 29/mm3 and 10 +/- 50/mm3, respectively (normal = 900-2860/mm3 (CD3/CD4), normal = 630-1910/mm3 (CD3/CD8)). Mitogen response studies showed low blastogenesis to PHA and PWM, with a mean c.p.m. +/- s.e.m. value of 1.7 +/- 0.67 x 10(4) for PHA (NL >/= 75 x 10(3)) and 8.42 +/- 4.1 x 10(3) for PWM (NL >/=25 x 10(3)). In conclusion, serum levels of inflammatory mediators were not predictive nor did they correlate with the severity of aGVHD. Recovery of NK cells, B cells, and PMN functions occurred within the first 90 days post transplant. However, T cell subsets, CD3+/CD4+ and CD3+/CD8+, and T cell functional activity remained significantly decreased and may account for the high incidence of infectious morbidity seen during this immediate post UCBT period.

Acute Disease↗
PubMed1999

Thyroid hormone and thyroid hormone analogues in the treatment of heart failure.

The thyroid hormone analogue DITPA is a promising potential new treatment for heart failure. Although the mechanism of action is incompletely determined, it is clear that DITPA improves systolic as well as diastolic function. It is also clear that the effects of DITPA are intrinsic to the muscle and not the result of changes in the structure or geometry of the left ventricle. On the basis of these experimental studies, we applied to the USA Food and Drug Administration for an Investigational New Drug application to study the use of DITPA in patients. These studies are currently in progress. While we await the outcome of these clinical trials, it is important to emphasize that even if the end-point is not a new drug to treat heart failure, our investigations are based on a systematic evaluation integrating biochemistry and physiology. We believe that this is the way to approach the problem of developmental pharmacology.

Animals↗
PubMed1999

Effects of AT1 receptor blockade after myocardial infarct on myocardial fibrosis, stiffness, and contractility.

Angiotensin II type 1 (AT1) receptor blockade attenuates myocardial fibrosis after myocardial infarction (MI). However, whether inhibition of fibrosis by AT1 receptor blockade influences myocardial stiffness and contractility is unknown. We measured left ventricular (LV) hemodynamics, papillary muscle function, and myocardial stiffness and fibrosis in rats randomized to losartan or placebo 1 day after MI and treated subsequently for 8 wk. Losartan decreased LV and right ventricular weights as well as mean aortic and LV systolic pressures in sham and MI rats. LV end-diastolic pressure increased after MI and was decreased with losartan. Maximal developed tension and peak rate of tension rise and decline were decreased in MI vs. sham rats. Interstitial fibrosis developed after MI and was prevented in losartan-treated MI rats. The development of abnormal myocardial stiffness after MI was prevented by losartan. After MI, AT1 receptor blockade prevents an abnormal increase in myocardial collagen content. This effect was associated with a normalization of passive myocardial stiffness.

Angiotensin Receptor Antagonists↗
PubMed1999

Depression and anxiety symptoms in women at high risk for breast cancer: pilot study of a group intervention.

OBJECTIVE: The psycho-oncology literature to date contains only one outcome study based on a group model for high-risk relatives of breast cancer patients. The authors set out to study the effects of group intervention in high-risk relatives of breast cancer patients. METHOD: Thirty-three high-risk relatives of breast cancer patients participated in a six-session, 12-hour group intervention model that consisted of educational and psychosocial components. RESULTS: There was a significant reduction of depression symptoms as reported on the Center for Epidemiologic Studies Depression Scale. Similarly, there was a significant reduction of anxiety symptoms as reported on the State-Trait Anxiety Inventory state scale. CONCLUSIONS: In this pilot study, the investigators found the group intervention model effective at reducing symptoms of depression and reactive (not chronic) anxiety.

Adaptation, Psychological↗