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Biomedical subjects

A Ramirez

Publications and source records attributed to A Ramirez.

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

Transvaginal sonography, saline contrast sonohysterography and hysteroscopy for the investigation of women with postmenopausal bleeding and endometrium > 5 mm.

OBJECTIVES: To determine the ability of transvaginal ultrasound, with or without saline infusion, to detect focally growing lesions in the uterine cavity in women with postmenopausal bleeding and endometrium > 5 mm, and to determine the accuracy of conventional ultrasound, saline contrast sonohysterography and diagnostic hysteroscopy under general anesthesia to diagnose endometrial polyps, submucous myomas and uterine malignancy. DESIGN: In a prospective study, 105 women with postmenopausal bleeding and endometrium > 5 mm underwent conventional ultrasound examination and saline contrast sonohysterography. Diagnostic and operative hysteroscopy under general anesthesia was then performed. The presence of focally growing lesions and the type of lesion (endometrial polyp, submucous myoma, malignancy or unclear focal lesion) were noted at ultrasound examination and at hysteroscopy. RESULTS: There was almost perfect agreement (96%) between saline contrast sonohysterography and hysteroscopy in the diagnosis of focally growing lesions. Saline contrast sonohysterography and hysteroscopy both had a sensitivity of approximately 80% with regard to diagnosing endometrial polyps (false-positive rates of 24% and 6%, respectively), whereas conventional ultrasound missed half of the polyps (sensitivity, 49%; false-positive rate, 19%). Hysteroscopy was superior to both saline contrast sonohysterography and conventional ultrasound with regard to discriminating between benign and malignant lesions (sensitivity, 84%, 44%, and 60%; false-positive rate, 15%, 6% and 10%, respectively). The risk of malignancy was increased seven-fold (odds ratio, 7.3; 95% confidence interval, 1.9-27.8) in women with distension difficulties at saline contrast sonohysterography, and two thirds of the women with a poorly distensible uterine cavity had a malignant diagnosis. CONCLUSION: Saline contrast sonohysterography is as good as hysteroscopy at detecting focally growing lesions in the uterine cavity in women with postmenopausal bleeding. However, neither hysteroscopy nor saline contrast sonohysterography can reliably discriminate between benign and malignant focal lesions. Distension difficulties at saline contrast sonohysterography should raise a suspicion of malignancy.

Adult↗
PubMed2001

Cigarette smoking behavior among US Latino men and women from different countries of origin.

OBJECTIVES: This study sought to compare smoking behavior among Latino men and women from different countries of origin. METHODS: A telephone-administered survey was conducted in 8 cities with Latino men and women of different national origin living in census tracts with at least 70% Latino individuals. RESULTS: A total of 8882 participants completed the survey; 53% were women. The average age of respondents was 44 years; 63% were foreign-born, and 59% preferred Spanish for the interview. Current smoking was more prevalent among men (25.0%, 95% confidence interval [CI] = 23.7, 26.3) than among women (12.1%, 95% CI = 11.1, 13.0). Smoking rates were not significantly different by national origin among men, but Puerto Rican women had higher rates of smoking than other women. Central American men and women had the lowest smoking rates. Foreign-born respondents were less likely to be smokers (odds ratio [OR] = 0.77, 95% CI = 0.66, 0.90) than US-born respondents, and respondents with 12 years or less of education had an increased odds of smoking (OR = 1.17, 95% CI = 1.01, 1.35). High ac culturation was associated with more smoking in women (OR = 1.12, 95% CI = 1.00-1.25) and less smoking in men (OR = 0.86, 95% CI = 0.78-0.95). Puerto Rican and Cuban respondents were more likely to be current smokers and to smoke more than 20 cigarettes per day. CONCLUSIONS: Older, US-born, and more-educated respondents were less likely to be current smokers. Respondents of Puerto Rican and Cuban origin were more likely to smoke. Acculturation has divergent effects on smoking behavior by sex.

Acculturation↗
PubMed2001

Primary care physician supply and colorectal cancer.

OBJECTIVES: Our goal was to determine if increasing primary care physician supply was associated with lower incidence and mortality rates for colorectal cancer. STUDY DESIGN: We performed an ecologic study of Florida's 67 counties, using data from the state tumor registry and the American Medical Association physician masterfile. POPULATION: Florida residents were included. OUTCOMES MEASURED: We measured age-adjusted colorectal cancer incidence and mortality rates for Florida's 67 counties during the period 1993 to 1995. RESULTS: Increasing primary care physician supply was negatively correlated with both colorectal cancer (CC) incidence (CC = -0.46; P < .0001) and mortality rates (CC = -0.29; P =.02). In linear regression that controlled for other county characteristics, each 1% increase in the proportion of county physicians who were in primary care specialties was associated with a corresponding reduction in colorectal cancer incidence of 0.25 cases per 100,000 (P < .0001) and a reduction in colorectal cancer mortality of 0.08 cases per 100,000 (P =.0008). CONCLUSIONS: Incidence and mortality of colorectal cancer decreased in Florida counties that had an increased supply of primary care physicians. This suggests that a balanced work force may achieve better health outcomes.

Colorectal Neoplasms↗
PubMed2000

Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes.

beta 1 integrins are ubiquitously expressed receptors that mediate cell-cell and cell-extracellular matrix interactions. To analyze the function of beta1 integrin in skin we generated mice with a keratinocyte-restricted deletion of the beta 1 integrin gene using the cre-loxP system. Mutant mice developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression of alpha 6 beta 4 integrin, and the number of hemidesmosomes decreased. Basement membrane components were atypically deposited and, at least in the case of laminin-5, improperly processed, leading to disruption of the basement membrane and blister formation at the dermal-epidermal junction. In contrast, the integrity of the basement membrane surrounding the beta 1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta 1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the maintenance of some, but not all basement membranes, in keratinocyte differentiation and proliferation, and in the formation and/or maintenance of hemidesmosomes.

Animals↗
PubMed2000

Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice.

Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas appeared in mice 6 months or older. Less differentiated tumors, diagnosed as small cell carcinomas, were also observed in two of the older mice. Both lobes of the mouse prostate gland (dorsolateral and ventral) presented preneoplastic and neoplastic changes. The incidence of tumors in mice >/=6 months of age (38 mice total) was 50%. The development of neoplasia in these transgenic mice appeared to follow a stepwise progression through early preneoplastic changes that ultimately culminated in frank neoplasia. These mice offer an animal model for prostate cancer that will allow study of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.

Animals↗
PubMed2000

Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion.

Transgenic mice overexpressing insulin-like growth factor-1 (IGF-1) in the basal layer of skin epidermis were generated using the bovine keratin 5 promoter (BK5). Neonatal transgenic mice were slightly smaller at birth and exhibited early ear unfolding, wrinkled and thickened skin, and slightly enlarged ears compared with nontransgenic littermates. Morphological evaluation of the skin revealed that persistent overexpression of IGF-1 in the basal layer of the epidermis resulted in epidermal hyperplasia, hyperkeratosis, and an increased labeling index that persisted in adult mice. Phenotypic changes observed in skin were associated with transgene expression in the basal layer of the epidermis and activation of the IGF-1 receptor. Squamous papillomas (some of which converted to carcinomas) developed in a significant proportion (approximately 50%) of older BK5.IGF-1 mice. Treatment of BK5.IGF-1 transgenic mice with multiple topical applications of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, in the absence of tumor initiation led to the development of additional skin papillomas. Furthermore, treatment of BK5.IGF-1 transgenic mice with an initiating dose of 7,12-dimethylbenz[a]anthracene only led to the formation of additional papillomas in the absence of promotion. In two-stage carcinogenesis experiments, BK5.IGF-1 transgenic mice developed 7-fold more papillomas than nontransgenic littermates. Phosphatidylinositol-3-kinase and protein kinase B (Akt) activities were elevated (3-4-fold), and mitogen-activated protein kinase activity was elevated approximately 1.7-fold in the epidermis of transgenic mice compared with nontransgenic mice. In addition, UV light-induced epidermal apoptosis was significantly suppressed in BK5.IGF-1 transgenic mice. These data suggest that persistent activation of IGF-1 receptor signaling pathways in basal epithelial cells leads to spontaneous tumor promotion and that up-regulation of both mitogenic and cell survival signaling pathways may play an important role in the action of IGF-1 in this model system.

Animals↗
PubMed2000

Summary measures and statistics in the analysis of quality of life data: an example from an EORTC-NCIC-SAKK locally advanced breast cancer study.

Quality of Life (QL) is now included as an endpoint in many phase III cancer clinical trials. Numerous statistical techniques have been presented in the literature to analyse QL data but there is still no agreement as to what is the optimal approach of analysis. In this paper we, therefore, present and compare various techniques which have all appeared in the literature and which may be globally described as summary measures and summary statistics. These techniques are illustrated using data from an EORTC clinical trial in locally advanced breast cancer (EORTC trial 10921). It is also explained in this paper how and when these techniques may be used in other cancer settings. For EORTC trial 10921, it is shown that by choosing different techniques different conclusions may be drawn concerning the QL outcome. This highlights the importance of choosing an appropriate primary statistical method and for describing it a priori in the protocol and analysis plan. In this paper, we show the importance of performing sensitivity or supportive analysis to support conclusions drawn from the primary analysis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

An evaluation of a cancer counselling service.

The CancerBACUP London Counselling Service offered short-term face-to-face counselling to self-referred cancer patients and their relatives and friends, provided by experienced supervised counsellors working within a humanistic theoretical framework. This study aimed to identify its clients' characteristics, use of the service, extent of perceived benefits and satisfaction with the service. Sociodemographic data were collected in Data Sheets from all 384 clients who booked an appointment over 18 months; they were predominantly female, < 50 years old and from non-manual social classes. Significantly more people in those classes and in the 30-59 age group attended three or more sessions. Three hundred and nine clients who attended at least once were sent an Evaluation Form; 142 responded. The probability of the Evaluation Forms' return was greater for those who had completed more sessions; the great majority of respondents felt that they had benefited, and were satisfied with the service. This study, notwithstanding its limitations, shows that a short course of counselling may be perceived by clients to be helpful; it also raises other issues of value to those involved in cancer services and/or counselling provision.

Adult↗
PubMed1999

Sympathectomy inhibits the vasoactive effects of nicotine in conscious rats.

OBJECTIVE: The mechanisms underlying the pressor response to nicotine are incompletely understood. Although sympatho-adrenergic activation plays a major role, the relative contribution of adrenal vs. neurally released catecholamines and the possible role of non-adrenergic factors (e.g. vasopressin release) is not established. METHODS: We examined the cardiovascular responses to graded i.v. injections of nicotine (1 to 100 micrograms kg-1) in conscious Wistar-Kyoto rats under control conditions and (i) after chemical sympathectomy by 6-hydroxydopamine, which destroys sympathetic endings but spares the adrenal medulla; (ii) after an alpha-adrenergic blockade by phenoxybenzamine; (iii) after a V1 vasopressin receptor blockade by a specific antagonist. RESULTS: In control rats, nicotine caused a dose-dependent tachycardiac and pressor response. Both responses were abolished by sympathectomy, whereas the alpha-blockade left the tachycardiac response unaffected but inhibited the pressor response: the V1 vasopressin receptor blockade had no effect on either the tachycardiac or pressor response. CONCLUSIONS: We conclude that in the conscious rat; (1) the pressor response to nicotine mainly depends on peripheral alpha-adrenergically-mediated vasoconstriction; (2) the vasomotor effect is caused by neural rather than adrenomedullary catecholamine release; (3) the nicotine-induced increase in heart rate (and presumably cardiac output) is per se unable to raise blood pressure, and (4) the nicotine-induced release of vasopressin plays no significant role in the pressor response.

Adrenergic alpha-Antagonists↗
PubMed1999

Short-term pravastatin mediates growth inhibition and apoptosis, independently of Ras, via the signaling proteins p27Kip1 and P13 kinase.

Growth factor-stimulated DNA synthesis in a variety of cell lines has been shown to be decreased after overnight (or longer) treatment with the 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, the statins. Although this anti-mitogenic effect had been presumed to be the result of the impairment of Ras lipidation, a stable modification (T1/2 approximately 20 h), this study provides new data demonstrating that brief (approximately 1 h) pretreatment of rat vascular smooth muscle cells with 100 microM pravastatin before platelet-derived growth factor-BB (PDGF-BB) stimulation results in attenuation of DNA synthesis through a Ras-independent mechanism. PDGF-BB-stimulated PDGF-beta receptor tyrosine phosphorylation, Ras activity, and mitogen-activated protein/extracellular signal-regulated kinase activity are unaffected by from 10 min to 1 h of pravastatin incubation, while Raf activity is markedly increased after 1 h of pravastatin. Phosphatidylinositol-3 kinase activity and phosphorylation of its downstream effector Akt are decreased after 1 h pravastatin incubation. Rho is stabilized by pravastatin, and ADP-ribosylation of Rho by C3 exoenzyme decreases PDGF-stimulated phosphatidylinositol-3 kinase activity, mimicking the effect of pravastatin on this signaling protein. Levels of the cyclin-dependent kinase inhibitor p27Kip1 are increased when cells were preincubated with pravastatin for 1 h and then exposed to PDGF, and apoptosis is induced by pravastatin incubation times as short as 1 to 4 h. Thus, short-term, high-dose pravastatin inhibits vascular smooth muscle cell growth and induces apoptosis independently of Ras, likely by means of the drug's effect on p27Kip1, mediated by Rho and/or phosphatidylinositol-3 kinase. This work demonstrates for the first time that the statins may be therapeutically useful when applied for short periods of time such that potential toxicity of long-term statin use (such as chronic Ras inhibition) may be avoided, suggesting future therapeutic directions for statin research.

Animals↗
PubMed1999

Central benzodiazepine involvement in clonidine cardiovascular actions.

It is well known that the GABAergic and noradrenergic systems play an important role in blood pressure and heart rate regulation. Benzodiazepines and beta-carbolines, respectively, increase or decrease the probability of chloride-channel opening induced by GABA. The aim of this study was to determine, in conscious rats, the interaction existing between the central alpha2-adrenoceptor stimulation induced by clonidine and the facilitation or impairment of benzodiazepine receptor activity through the administration of either diazepam, a benzodiazepine receptor agonist, or methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), an inverse benzodiazepine agonist. Clonidine (5-10 microg, intracerebroventricularly) reduced heart rate and increased mean blood pressure by activation of central alpha2-adrenoceptors. Diazepam (2 mg/kg, intravenously (i.v.)) induced an increase in heart rate, while DMCM (0.3 mg/kg, i.v.) elicited a bradycardic effect. The bradycardic effects induced by both clonidine and DMCM were antagonized by the prior administration of methylatropine (1.5 mg/kg, i.v.). DMCM (0.3 mg/kg, i.v.) prevented the clonidine effects on heart rate and mean blood pressure, while diazepam (2 mg/kg, i.v.) failed to modify these effects. Our results suggest that the bradycardic effects of clonidine are mediated by a vagal stimulation and are related to the activation of a GABAergic pathway.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1998

Effects of pimozide on the psychopathology of delusional disorder.

1. The effects of pimozide on the psychopathology of delusional disorder were studied. 2. After six weeks, pimozide (2-12 mg/day) administration had no effect on the Brief Psychiatric Rating Scale, or in the psychological, social and occupational functioning, as measured by the Global Assessment of Functioning Scale. 3. When the different dimensions of the delusional experience were looked upon, no modifications were observed in any of them after six weeks of pimozide treatment. 4. These data failed to support the therapeutic role of pimozide in the treatment of delusional disorder and may suggest, when compared to other disorders with prominent delusions such as schizophrenia, a different neurobiology for the illness.

Adult↗
PubMed1998

TGF-beta- and angiotensin-II-induced mesangial matrix protein secretion is mediated by protein kinase C.

BACKGROUND: Glomerulonephritis is characterized by the accumulation of extracellular matrix protein within the glomerulus. This process, when allowed to proceed unimpeded, leads to glomerulosclerosis and eventually to cessation of glomerular filtration. There is evidence that protein kinase C (PKC) activation plays an important role in mediating at least some of the effects of TGF-beta in vascular smooth-muscle cells. The current study was undertaken to determine whether PKC activity is required for both TGF-beta and angiotensin II (Ang II) to induce mesangial cell matrix protein secretion. METHODS: PKC was inhibited by two separate methods, and [3H]thymidine incorporation was assessed in both the presence and the absence of PKC inhibition. Conditioned medium from cells stimulated with TGF-beta or Ang II was collected and analysed for secreted matrix proteins and sulphated proteins by SDS-polyacrylamide gel electrophoresis and western blotting. RESULTS: Twenty-four-hour incubation of rat mesangial cells with phorbol-12-myristate-13-acetate (PMA) reduced total PKC activity to basal levels. Both TGF-beta and Ang II were mitogenic in mesangial cells, and chronic PMA pre-incubation inhibited this DNA synthesis. TGF-beta-and Ang-II-induced sulphated protein secretion into conditioned medium was markedly attenuated in PKC-downregulated cells. Secretion of the specific matrix proteins laminin and fibronectin by mesangial cells stimulated with either TGF-beta or Ang II was also diminished in PKC-downregulated cells and in cells pre-incubated with the specific PKC inhibitor, chelerythrine. There was no evidence of generalized cell toxicity or decreased non-specific protein synthesis caused by these PKC inhibitors. CONCLUSIONS: PKC is a key intermediary in the process by which TGF-beta and Ang II cause DNA synthesis and mesangial cell matrix protein production. Thus, PKC inhibitors deserve further study as potential therapeutic agents for a variety of glomerular diseases.

Alkaloids↗
PubMed1998

MEK inhibition augments Raf activity, but has variable effects on mitogenesis, in vascular smooth muscle cells.

Proteins comprising the mitogen-activated protein (MAP) kinase signaling cascade are activated by a variety of growth factors, but the precise role of this series of kinase reactions, especially Raf kinase and MAP kinase kinase (MEK), in vascular smooth muscle (VSM) cell mitogenesis is not known. In this study, a specific and selective inhibitor of MEK, PD-98059, was used to examine the role of MEK in DNA synthesis and Raf-1 activity in VSM cells stimulated with serum as well as with growth factors encompassing both tyrosine kinase and G protein-coupled receptor classes. Although significant increases in DNA synthesis are seen after stimulation of VSM cells with either 10% serum,platelet-derived growth factor (PDGF)-BB, or alpha-thrombin, preincubation of the cells with 50 microM PD-98059 for 1 h inhibits stimulation by PDGF and thrombin, but not by serum. There is a dose-dependent inhibition of the mitogenic effect by PD-98059 in all cases; these results are not affected when PD-98059 is added at times ranging from 4 h before to 2 h after growth factor addition (times at which PD-98059 exerts its inhibitory effect). In the presence of PD-98059, stimulated MAP kinase activity is attenuated when growth factors are added between 10 min and 4 h, times which correspond to both early and sustained phases of MAP kinase activity. In addition, Raf-1 activity is markedly increased by incubation of the cells with PD-98059,despite attenuation of hyperphosphorylation of this kinase. Thus growth factors coupled to both tyrosine kinase and G protein receptors require components of the MAP kinase cascade (MEK and/or MAP kinase) for VSM cell mitogenesis, whereas serum is capable of stimulatory effects in the absence of active MEK and MAP kinase. Furthermore, there exists a functional feedback stimulatory effect of inhibited MEK on its upstream activator Raf-1 in the case of serum as well as growth factors coupled to tyrosine kinase and G protein receptors.

Animals↗
PubMed1998

Nursing case management in the NICU: enhanced coordination for discharge planning.

A primary goal of health care today is finding alternative ways to provide high-quality, cost-effective care. A model of care that addresses these issues is nursing case management. This article describes the development and implementation of nursing case management in a Level III regional center with the primary goal of enhancing coordination for discharge planning. The model involves development of clinical pathways and utilization of nurse practitioners as case managers. Decreased length of stay, charge per case, and readmission rates are demonstrated following implementation of this program.

Case Management↗