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Biomedical subjects

S Mandel

Publications and source records attributed to S Mandel.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cardiac output and stroke volume changes with endurance training: the HERITAGE Family Study.

PURPOSE: The purpose of this study was to determine the magnitude of changes in cardiac output (Qc), stroke volume (SV), and arterial-mixed venous oxygen difference (a-vO2 diff) during submaximal exercise following a 20-wk endurance training program, with the primary focus on identifying differences in response by race, sex, and age. METHODS: The participants in this study (N = 631) were healthy and previously sedentary men (N = 277) and women (N = 354) of varying age (17-65 yr) and race (blacks, N = 217; whites, N = 414) who had completed the HERITAGE Family Study protocol. After baseline measurements, participants trained on cycle ergometers 3 d x wk(-1) for a total of 60 exercise sessions starting at the HR associated with 55% of maximal oxygen uptake (VO2max) for 30 min/session and building to the HR associated with 75% of VO2max for 50 min/session, which was maintained during the last 6 wk. HR, Qc (CO2 rebreathing), and SV (Qc/HR) were determined in duplicate at 50 W and at 60% of VO2max on two different days both before and after training. RESULTS: After training, there were significant decreases in HR and Qc, and significant increases in SV and a-vO2 diff at 50 W (except for no change in a-vO2 diff in black men). The changes in HR differed by sex and age, and the changes in SV, Qc, and a-vO2 diff differed by race. Qc decreased by 0.6 L x min(-1) at 50 W for the total sample, consistent with the decrease in VO2 at this power output. At 60% of VO2max HR decreased, and SV, Q, and a-VO2 diff increased. There were small differences in response by sex (HR and SV), race (HR), and age (HR and Qc). CONCLUSION: It is concluded that the cardiovascular systems of men and women, blacks and whites, and younger and older subjects are not limited in their ability to adapt to endurance training.

Adolescent↗
PubMed2001

Heart rate and blood pressure changes with endurance training: the HERITAGE Family Study.

PURPOSE: The purpose of this study was to determine the magnitude of change in resting and exercise heart rate (HR) and blood pressure (BP), by race, sex, and age, after a 20-wk endurance training program in 507 healthy and previously sedentary subjects from the HERITAGE Family Study. METHODS: After baseline measurements, subjects exercised on cycle ergometers 3 d x wk(-1) for a total of 60 exercise sessions starting at 55% of VO2max for 30 min x session(-1) and building to 75% of VO2max for 50 min x session(-1) for the last 6 wk. HR and BP at rest and during exercise (50 W, 60% of VO2max maximal exercise) were each determined in duplicate on two different days both before and after training (resting values at 24-h and 72-h posttraining). RESULTS: After the period of training, there was a small decrease in resting HR (-2.7 to -4.6 beats x min(-1) across groups at 72-h posttraining), and small changes (i.e., < 3 mm Hg) in resting systolic (SBP), diastolic (DBP), and calculated mean BP (MBP), which varied by race, sex, and age. During exercise at the same absolute work rate (50 W), HR, SBP, DBP, and MBP were all significantly reduced, with greater reductions in HR in women compared with men, and greater reductions in BP in blacks and older subjects compared with whites and younger subjects, respectively. At the same relative work rate (60% VO2max), HR, DBP, and MBP were reduced, but SBP remained unchanged. Blacks had a greater reduction in DBP, but whites had a greater reduction in HR. Finally, at maximal exercise, there was a small decrease in HR, with men and whites decreasing more than women and blacks; an 8 mm Hg increase in SBP, with men increasing more than women; a 4 mm Hg decrease in DBP, with blacks decreasing more than whites; and no change in MBP. CONCLUSION: In conclusion, the reductions in resting HR and BP with training were generally small, but the reductions during exercise were substantial and clinically important, with the older and the black populations experiencing greater reductions.

Adolescent↗
PubMed2001

Combined tall cell carcinoma and Hürthle cell carcinoma (collision tumor) of the thyroid.

Tall cell carcinoma and Hürthle cell carcinoma are 2 aggressive forms of differentiated follicular-derived thyroid carcinomas. We present a case where these malignant tumors of thyroid coexisted. The tumor originated in the thyroid as a mixed tumor and metastasized as a tall cell tumor to the lymph nodes and as a Hürthle cell carcinoma to lungs. The coexistence of these tumor types is rare and sheds light on the histogenesis of Hürthle cell tumors and the metastatic behavior of combined tumors.

Adenocarcinoma↗
PubMed2000

Thyroid nodules with FNA cytology suspicious for follicular variant of papillary thyroid carcinoma: follow-up and management.

Thyroid nodules diagnosed as follicular neoplasm on fine-needle aspiration biopsy (FNAB) may represent hyperplastic/adenomatous nodules, follicular adenoma or carcinoma, and follicular variants of papillary thyroid carcinoma (FVPTC) on histologic follow-up. In our laboratory, we attempted to identify a subset of cases which showed cellular specimens with focal features (nuclear chromatin clearing, membrane thickening, and rare grooves) suspicious for the follicular variant of papillary thyroid carcinoma. These cases are reported as follicular-derived neoplasms with nuclear features suspicious for FVPTC to distinguish them from those diagnosed as follicular neoplasm. This study documents our experience with 52 cases so diagnosed and followed prospectively with histologic follow-up. A neoplastic nodule was confirmed in 45/52 cases (86%), of which 40 were malignant (77%). FVPTC was identified in 35/52 cases (67%). Four cases were usual papillary carcinoma, 3 were follicular adenoma, 2 were Hürthle-cell adenoma, and 1 was insular carcinoma. In 7 cases, the subsequent histologic findings were nonneoplastic (5 hyperplastic nodules and 2 colloid nodules). Our prospective study shows that in cellular smears from thyroid nodules, a careful search for the nuclear features of papillary carcinoma should be performed, and it is appropriate to diagnose cases as suspicious for FVPTC if the nuclear features of papillary carcinoma are focal. The surgical management of this group may include an intraoperative confirmation of cytologic diagnosis by scrape preparation and/or frozen section in order to avoid a second surgical intervention for completion thyroidectomy.

Adenocarcinoma↗
PubMed2000

Ultrasound-guided fine-needle aspiration biopsy of the thyroid: role of on-site assessment and multiple cytologic preparations.

Several studies have shown that ultrasound guidance can serve as a valuable aid in improving the diagnostic yield of fine-needle aspiration (FNA) biopsy of thyroid nodules. In this study, we evaluated the combined impact of ultrasound-guidance, rapid on-site evaluation of FNA specimens, and different cytologic preparations (fresh and alcohol-fixed smears, Millipore filter) and staining methods (Diff-Quik and Papanicolaou stains) on the diagnostic yield of thyroid FNA. Ultrasound-guided FNA was performed on 282 patients (313 cases) between November 1997 and April 1999. The diagnostic categories included: benign (198 cases, 63.2%); indeterminate (42 cases, 13.4%); suspicious for follicular variant of papillary carcinoma (26 cases, 8.3%), malignant (32 cases, 10.1%); and nondiagnostic (15 cases, 5%). The nondiagnostic cases also included 6 cystic lesions without any solid component and 3 thyroid-bed aspirations. After excluding these, the nondiagnostic rate was only 2%. Histological follow-up was available in 77 (77/313) cases. The concordance rate between cytological and histological diagnosis was 100% in malignant, 67% in suspicious, and 56% in indeterminate cases. All cases with histologic follow-up were selected to evaluate the independent diagnostic efficacy of each aforementioned cytologic staining method. A definite diagnosis could be made solely on the basis of air-dried, Diff-Quik-stained preparations in 50 (65%), alcohol-fixed, Papanicolaou stained smears in 68 (88%), and Millipore filter preparations in 70 (91%) cases. We conclude that ultrasound-guided FNA combined with on-site evaluation and different cytologic preparations can significantly improve the diagnostic accuracy of thyroid FNA specimens.

Adenoma↗
PubMed2000

Iron chelating, antioxidant and cytoprotective properties of dopamine receptor agonist; apomorphine.

There have been many attempts to discover neuroprotective drugs for the treatment of Parkinson's disease (PD). Many of these compounds either do not cross the blood brain barrier or are not very effective in the 6-hydroxydopamine or MPTP (N-methyl-4-phenyl-1,2,3,6-terahydropyridine) models of PD. We have examined several compounds including dopamine receptor agonist bromocritine, lisuride, pergolide and R-apomorphine for their neuroprotective action against the above neurotoxins in PC12 and dopamine neuroblastoma cell lines in culture and in vivo. R-apomorphine exhibited relatively potent neuroprotective action in vitro, cell culture and in vivo as a radical scavenger and iron chelator, because of its catechol structure. The recent clinical trials with apomorphine, where parkinsonian subjects can be weaned off L-dopa would suggest that this drug either exerts a neuroprotective action or that continuous sustained stimulation of dopamine receptor may be responsible for its unusual pharmacological activity. Apomorphine has a far more broad neuroprotective activity in the various models as compared with 1-selegiline and may therefore be an ideal drug to study neuroprotection in parkinsonian subjects with the use of PET or SPECT.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

cDNA microarray to study gene expression of dopaminergic neurodegeneration and neuroprotection in MPTP and 6-hydroxydopamine models: implications for idiopathic Parkinson's disease.

cDNA microarray membranes comprising 1,200 different gene fragments have been employed to identify gene expression profile in MPTP-induced nigro striatal dopamine neurodegeneration and its protection with Rapomorphine. Both MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and R-apomorphine (R-APO) induced alterations in specific patterns of gene expression. MPTP altered the expression of 49 different genes involved in oxidative stress (oxidative stress-induced protein A 170, cytochrome P450 1A1 and Osp94), inflammation (cytotoxic cytokines, eg: IL-1, IL-6, TNF-alpha), protective cytokines (IL-10), glutamate receptors (NMDA but not AMPA receptors), neurotrophic factors (GDNF, EGF), nitric oxide synthase and transferrin receptor, as determined by microarray membrane hybridization. Furthermore, an additional cascade of further, yet undefined events, also occurred (cell cycle regulators and signal transduction factors), that might act in parallel to oxidative stress (OS) and inflammation, to converge eventually into a common pathway leading to neurodegeneration. R-APO, previously shown by us to protect against MPTP neurotoxicity, prevented the over expression of several genes known to participate in cell death. cDNA microarrays will provide new prospects to study and identify various mechanism of neurodegeneration and neuroprotection not feasible with conventional biochemical procedures, as well as new prospects to develop effective neuroprotective drugs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

MPTP and 6-hydroxydopamine-induced neurodegeneration as models for Parkinson's disease: neuroprotective strategies.

The etiology of Parkinson's disease is not known. Nevertheless, a significant body of biochemical data from human brain autopsy studies and from animal models points to an ongoing process of oxidative stress in the substantia nigra, which could initiate dopaminergic neurodegeneration. It is not known whether oxidative stress is a primary or secondary event. Oxidative stress, as induced by the neurotoxins 6-hydroxydopamine and MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), has been used in animal models to investigate the process of neurodegeneration to facilitate the development of antioxidant, neuroprotective drugs. It is apparent in these animal models that radical scavengers, iron chelators, dopamine agonists, nitric oxide synthase inhibitors and certain calcium channel antagonists provide neuroprotection against such toxins if given prior to the insult. Furthermore, recent work from human and animal studies has provided evidence of an inflammatory process. This expresses itself as proliferation of activated microglia in the substantia nigra, activation and translocation of transcription factors and neurotrophic factor (NF), kappa-beta and elevation of cytotoxic cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. Both radical scavengers and iron chelators prevent lipopolysaccharide (LPS) and iron-induced activation of NF kappa-beta. If an inflammatory response is involved in Parkinson's disease, it would be logical to consider antioxidants and the newly developed, non-steroidal, anti-inflammatory drugs such as cyclo-oxygenase (COX2) inhibitors as a form of treatment. However, to date there has been little or no success in the clinical treatment of neurodegenerative diseases (for example, Parkinson's disease, ischaemia etc.) where neurons die, while in animal models the same drugs provide neuroprotection. This may indicate that either the animal models employed do not reflect the events in neurodegenerative diseases, or that because neuronal death involves a cascade of events, a single neuroprotective drug is not effective. Thus, consideration should be given to multi-neuroprotective drug therapy in Parkinson's disease, similar to the approach taken in AIDS and cancer therapy.

Animals↗
PubMed2000

Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study.

We studied the effects of 20 weeks of supervised cycle-ergometer exercise on plasma lipids in 675 healthy, sedentary, normolipidemic white and black men and women aged 17 to 65 years, participating in the HERITAGE Family Study. Fasting plasma lipids were assessed twice at baseline and 24 and 72 hours after the last exercise session and adjusted for plasma volume changes. No significant differences from the mean baseline levels were observed for total, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B (Apo B). A significant reduction (P < .01) from baseline levels in plasma total and VLDL triglycerides was observed only in the 24-hour posttraining specimens, reflecting a response to the last bout of exercise. High-density lipoprotein (HDL) cholesterol increased 3.6% for the combined group, primarily due to an increase in HDL2, with an associated increase in Apo A-1 (P < .001). No significant differences were noted in the HDL response by sex, race, or age. An inverse correlation (r = -.241) was observed between the increase in HDL cholesterol and change in body fat only in men, and the increase in HDL cholesterol was unrelated to the change in maximal oxygen uptake (VO2max).

Adolescent↗
PubMed2000

Neuroprotective strategies in Parkinson's disease using the models of 6-hydroxydopamine and MPTP.

The etiology of Parkinson's disease is not known. Nevertheless a significant body of biochemical data from human brain autopsy studies and those from animal models point to an on going process of oxidative stress in the substantia nigra which could initiate dopaminergic neurodegeneration. It is not known whether oxidative stress is a primary or secondary event. Nevertheless, oxidative stress as induced by neurotoxins 6-hydroxydopamine and MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) has been used in animal models to investigate the process of neurodegeneration with intend to develop antioxidant neuroprotective drugs. It is apparent that in these animal models radical scavengers, iron chelators, dopamine agonists, nitric oxide synthase inhibitors and certain calcium channel antagonists do induce neuroprotection against such toxins if given prior to the insult. Furthermore, recent work from human and animal studies has provided also evidence for an inflammatory process. This expresses itself by proliferation of activated microglia in the substantia nigra, activation and translocation of transcription factors, NF kappa-beta and elevation of cytotoxic cytokines TNF alpha, IL1-beta, and IL6. Both radical scavengers and iron chelators prevent LPS (lipopolysaccharide) and iron induced activation of NF kappa-B. If an inflammatory response is involved in Parkinson's disease it would be logical to consider antioxidants and the newly developed non-steroid anti-inflammatory drugs such as COX2 (cyclo-oxygenase) inhibitors as a form of treatment. However to date there has been little or no success in the clinical treatment of neurodegenerative diseases per se (Parkinson's disease, ischemia etc.), where neurons die, while in animal models the same drugs produce neuroprotection. This may indicate that either the animal models employed are not reflective of the events in neurodegenerative diseases or that because neuronal death involves a cascade of events, a single neuroprotective drug would not be effective. Thus, consideration should be given to multi-neuroprotective drug therapy in Parkinson's disease, similar to the approach taken in AIDS and cancer therapy.

Animals↗
PubMed2000

An interactive CD-ROM for nutrition screening and counseling.

OBJECTIVES: The goal of this project was to develop an interactive CD-ROM for nutrition screening and counseling, designed to produce dietary behavior change in fat and fruit and vegetable intake. METHODS: The design was based on principles of relevance to the learner, readiness for change, feedback, individualization, facilitation of skills, and goal setting. It was tested in community settings such as libraries, senior centers, and Women, Infants, and Children clinics. RESULTS: Nearly 80% of the respondents (n = 284), including numerous low-income persons, reported learning something new about nutrition and health or their own dietary habits. More than 50% of those recontacted 2 to 4 weeks later had put some of their dietary goals into practice. CONCLUSIONS: This program is useful for dietary screening, feedback, skill building, and motivation in settings in which in-person counseling by nutrition professionals is not feasible.

Adult↗
PubMed2000

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: mimic of Hodgkin disease in nodal metastases.

We present the clinical and pathologic findings of a case of sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid in a 39-year-old woman. This particular case is notable because it initially presented as a cervical lymph node metastasis, and the initial clinical and histologic impression was Hodgkin disease, nodular sclerosis type. Sclerosing mucoepidermoid carcinoma with eosinophilia is a differentiated malignant neoplasm of the thyroid that can be confused with anaplastic carcinoma, medullary carcinoma, squamous cell carcinoma, or, as in this case, Hodgkin disease. A correct diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia involves awareness of this entity and appropriate immunohistochemical analysis. In this article, we briefly review the literature and stress the histologic and cytologic findings characteristic of sclerosing mucoepidermoid with eosinophilia of the thyroid.

Adult↗
PubMed1999

Apomorphine protects against MPTP-induced neurotoxicity in mice.

R-apomorphine is a potent radical scavenger and iron chelator. The neuroprotective property of R-apomorphine, a dopamine D1-D2 receptor agonist, has been studied in the MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. Pretreatment with 5-10 mg/kg R-apomorphine administered subcutaneously in C57BL mice protects against MPTP (24 mg/kg administered intraperitoneally) induced loss of nigrostriatal dopamine neurons as indicated by striatal dopamine content, tyrosine hydroxylase content, and tyrosine hydroxylase activity. In vitro, R-apomorphine inhibited mice striatal MAO-A and MAO-B activities with IC50 values of 93 microM and 241 microM. It is suggested that the neuroprotective effect of R-apomorphine against MPTP neurotoxicity derives from its radical scavenging and MAO inhibitory actions and not from its agonistic activity because the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species-induced oxidative stress.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

Potent neuroprotective and antioxidant activity of apomorphine in MPTP and 6-hydroxydopamine induced neurotoxicity.

Apomorphine is a potent radical scavenger and iron chelator. In vitro apomorphine acts as a potent iron chelator and radical scavenger with IC50 of 0.3 microM for iron (2.5 microM) induced lipid peroxidation in rat brain mitochondrial preparation, and it inhibits mice striatal MAO-A and MAO-B activities with IC50 values of 93 microM and 241 microM. Apomorphine (1-10 microM) protects rat pheochromocytoma (PC12) cells from 6-hydroxydopamine (150 microM) and H2O2 (0.6 mM) induced cytotoxicity and cell death. The neuroprotective property of (R)-apomorphine, a dopamine D1-D2 receptor agonist, has been studied in the MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. (R)-apomorphine (5-10 mg/kg, s.c.) pretreatment in C57BL mice, protects against MPTP (24 mg/kg, i.p.) induced loss of nigro-striatal dopamine neurons, as indicated by striatal dopamine content, tyrosine hydroxylase content and tyrosine hydroxylase activity. It is suggested that the neuroprotective effect of (R)-apomorphine against MPTP neurotoxicity derives from its radical scavenging and MAO inhibitory actions and not from its agonistic activity, since the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species induced-oxidative stress.

Animals↗
PubMed1999

Alterations in body weight and composition consequent to 20 wk of endurance training: the HERITAGE Family Study.

BACKGROUND: Obesity is a major public health problem in the United States. The role of physical activity and formal exercise in controlling body weight has not been clearly determined. OBJECTIVE: This study determined the magnitude of change in body weight and composition across sex, race, and age in response to 20 wk of endurance training. DESIGN: Men and women (n = 557) of various ages (16-65 y) and 2 races (black and white) exercised on cycle ergometers 3 d/wk for a total of 60 exercise sessions starting at 55% of maximal oxygen consumption (VO(2)max) for 30 min/session and building to 75% of VO(2)max for 50 min/session, where it was maintained during the last 6 wk. Skinfold-thickness measurements, circumferences, body composition (by hydrostatic weighing), and body fat distribution (by computed tomography scan at L4-L5 and the waist-hip ratio) were determined before and after training. RESULTS: All skinfold-thickness and circumference measures, waist-hip ratio, body mass index, total body mass, fat mass, percentage body fat, and computed tomography scan measures of total, subcutaneous, and visceral abdominal fat decreased with training, whereas total body density and fat-free mass increased. These changes were significant, but small. There were several differences in training response by sex and race, but not by age. CONCLUSIONS: A short-term exercise intervention can induce favorable changes in body composition, but the magnitude of these changes is of limited biological significance. Increasing physical activity likely has a major effect on body-composition and fat distribution characteristics only when it is of a greater magnitude and sustained for much longer periods

Adolescent↗
PubMed1999

The pivotal role of iron in NF-kappa B activation and nigrostriatal dopaminergic neurodegeneration. Prospects for neuroprotection in Parkinson's disease with iron chelators.

R-Apomorphine (APO) the catechol-derived dopamine D1-D2 receptor agonist has been shown to be highly potent iron chelator and radical scavenger and inhibitor of membrane lipid peroxidation in vitro, in vivo and in cell culture employing PC12 cells. Its potency has been compared to the prototype iron chelator desferrioxamine (desferal), dopamine, nifedipine and dopamine D2 receptor agonists, bromocriptine, lisuride, pergolide and pramipexole. APO also inhibits brain and mitochondrial protein oxidation. In vivo APO protects against MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)- induced striatal dopaminergic neurodegeneration in C57 black mice with as low as 5 mg/kg. APO is a reversible competitive inhibitor of monoamine oxidase (MAO) A and B with IC50 values of 93 and 214 uM, respectively. The iron chelating and radical scavenging actions of desferal and APO explains their ability to inhibit iron and 6-hydroxydopamine (6-OHDA)-induced neurodegeneration and activation of redox-sensitive transcription factor NF-kappa B and the subsequent transactivation of promoters of genes involved in inflammatory cytokines. Iron is thought to play a pivotal role in neurodegeneration, and APO may be an ideal drug to investigate neuroprotection in Parkinson's disease where iron and oxidative stress have been implicated in the pathogenesis of nigrostriatal dopamine neuron degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗