Search PubMed⌕ Search

Biomedical subjects

E Levin

Publications and source records attributed to E Levin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects on mouse uterus of three antitumoral drugs acting upon estrogen and progesterone receptors directly and through other transduction pathways.

Three antitumoral drugs, tamoxifen (Tam), medroxyprogesterone acetate (MPA), and 8-Cl-cyclic AMP (8Cl), were administered separately and in combination to normal adult mice in order to record their effects on uterus weight, on estrous cycle, and on two estrogen receptor (ER) and progesterone receptor (PgR) parameters, namely content and nucleo-cytoplasm distribution. Tam decreased uterus weight (49%) and total ER content (118+/-6 vs 328+/-20 fmol/mg protein in controls) but increased total PgR (1183+/-230 vs 743+/-52 fmol/mg protein in controls) and nuclear retention of ER and PgR. MPA down-regulated PgR content and increased uterus weight (36%), but failed to modify ER and PgR nuclear retention. The only parameter changed by 8Cl was nucleo-cytoplasm PgR distribution. Tam + MPA association produced the same results as Tam alone for ER and PgR nuclear retention, but receptor content was not significantly different from that of controls. Both drugs, administered separately, had opposite effects on PgR content; when both were acting concurrently, an algebraic addition of effects was observed, as if both transcription circuits were triggered independently. Remaining Tam effects, not modified by a combination with MPA, indicated the predominance of Tam on the corresponding parameters. When Tam and 8Cl were administered together, 8Cl counteracted the effect of Tam only on PgR content. When associated with MPA, 8Cl changed the effects of MPA on ER and PgR nuclear retention, whereas on receptor content, only that of ER was increased (502+/-47 vs 328+/-20 fmol/mg protein in controls). These crossed effects indicate that interrelations between different transduction pathways can affect certain functional circuits while sparing others. The possibility of acting pharmacologically upon different transcription pathways represents a novel approach to modify drug effects directed to specific transduction targets through cross-talk between their components.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Care homes. Home truths.

Proposed joint inspectorates of care homes open the way for health input into residential care. An investigation into quality-of-care measures concluded that health professionals should be included in inspectorate teams, particularly in view of the increasing dependency of residents. No association was shown between cost and quality, but higher costs were associated with short-term car provision. When costing residential care, the impact on community and primary healthcare services may need to be taken into account.

Aged↗
PubMed1998

An experimental model of diabetes and cancer in rats.

The aim of this study was to develop an experimental model for the study of cancer associated with diabetes. For diabetes induction, Sprague-Dawley rats were given streptozotocin (STZ, 90 mg/kg body weight (BW), by intraperitoneal injection on the second day of life. For mammary tumour induction, rats were injected with 50 mg/kg BW of N-nitroso-N-methylurea (NMU) at 50, 80 and 110 days old. The neoplastic process and the effect of tamoxifen treatment was examined in non-diabetic and diabetic rats. The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02). A more benign histological pattern for tumours in diabetic animals was observed. Mammary tumours in diabetic rats grew more slowly than in controls. Tamoxifen (1 mg/kg/day) treated diabetic rats showed tumour regression in 67% of NMU-induced mammary tumours versus 53% in controls (NS). Our results show that tumour progression seems to be affected by diabetes in this experimental model. We suggest this is the result of changes to insulin-like growth factors and their receptors, which occur in diabetics, and our future research will examine this hypothesis.

Animals↗
PubMed1998

The Awareness Questionnaire: factor structure and internal consistency.

Patients with traumatic brain injuries often show impaired awareness of their impairments. This impaired awareness can decrease motivation for treatment and limit eventual functional outcome. The importance of this phenomenon has led to the development of multiple techniques and scales for measuring impaired awareness. The present paper briefly reviews the various methods of operationalizing impaired awareness and describes a new scale (the Awareness Questionnaire) designed to incorporate all these methods. Findings of previous studies supporting the validity of the Awareness Questionnaire are presented. The present investigation examined the factor structure and internal consistency of the Awareness Questionnaire with samples of 126 traumatic brain injury survivors and 75 family members/significant others. Principal components factor analysis with varimax rotation indicated three factors: cognitive, behavioural/affective, and motor/sensory. Investigation of internal consistency (Cronbach Coefficient Alpha) in both the patient and family sample yielded satisfactory results. These findings are supportive of continued use and investigation of the Awareness Questionnaire.

Activities of Daily Living↗
PubMed1998

Impaired awareness and employment outcome after traumatic brain injury.

Inaccurate self-awareness is a common finding after traumatic brain injury. Such impaired awareness has been hypothesized to limit patients' eventual functional outcomes by decreasing motivation for treatment and resulting in selection of inappropriate long-term goals. Previous investigations of the association between impaired awareness and employment outcome have produced inconsistent results. The present article reviews these studies and presents the results of our new investigation of this issue. In addition, we studied the comparability of two methods of measuring impaired awareness. Results provided strong support for a positive relationship between accurate self-awareness and favorable employment outcome at follow-up.

Adolescent↗
PubMed1998

Characteristics of impaired awareness after traumatic brain injury.

Impaired awareness of the effects of brain injury is a commonly observed and poorly understood finding in traumatic brain injury survivors. Nonetheless, impaired awareness has been identified as a major factor in determining outcome for traumatic brain injury survivors. Review of previous studies of impaired awareness in this patient population revealed a number of preliminary findings regarding the nature of this phenomenon. The present paper presents the results of 2 new studies with a total of 111 traumatic brain injury patients conducted to bring further clarity to this area. Findings confirmed and extended many results of previous investigations. Specific findings included patient overestimation of functioning as compared to family member ratings, patient report of greater physical than nonphysical impairment, greater patient-family agreement on specific ratings of patient functioning than on general ratings, greater agreement of family and clinician ratings of patient functioning with each other than with patient self-ratings, and partial disagreement of different methods of measuring impaired awareness.

Activities of Daily Living↗
PubMed1998

Vascular approach to gastroduodenal ulceration: new studies with endothelins and VEGF.

Endothelins (ET) and VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) are products mainly of endothelial cells, which are also regulated via autocrine and paracrine pathways by these peptides. As a follow-up to our focus on vascular factors in ulcer pathogenesis and healing, we review here our recent studies with ET-1 and VEGF/VPF in animal models and human subjects. Our new results demonstrated a rapid and time-dependent release of ET-1 into the systemic circulation after intragastric administration of ethanol or HCI in rats, and ethanol in humans. The ET-1 release preceded the development of hemorrhagic erosions in both species and might be used as a diagnostic tool to noninvasively quantify acute gastric mucosal lesions. The development of solitary duodenal ulcers in the rat was preceded only by an organ- (involving only the duodenum and not the stomach) and molecule-specific (induced only by cysteamine and not by the nonulcerogenic analog ethanolamine) rapid local release of ET-1. The severity of cysteamine-induced duodenal ulcers was dose-dependently decreased by pretreatment with ET-1 antibodies or antagonist bosentan. A single intragastric dose of VEGF/VPF resulted in gastroprotection against ethanol, while daily intragastric treatment with the peptide for three weeks stimulated angiogenesis in the base of cysteamine-induced duodenal ulcers and accelerated ulcer healing. Thus, modulation of vascular factors seems to be sufficient for both acute gastroprotection and chronic duodenal ulcer healing.

Animals↗
PubMed1997

Evaluation of a displacement assay with tamoxifen as prognostic indicator in breast-cancer patients with estrogen-receptor-positive tumors.

A displacement assay with tamoxifen, based on the relative binding affinity of tamoxifen and estradiol for the estrogen receptor (ER), was proposed in 1990 as prognostic indicator for breast-cancer patients. Validation of its predictive results in relation to the outcome of 73 patients with ER+ tumors is analyzed. ER, progesterone receptor (PgR) determinations and other conventional prognostic factors in relation to the displacement assay, were considered. Displacement assay results allowed ER+ tumors to be grouped as displaceable (D) or weakly displaceable (WD), with the implication that D tumors should respond better to tamoxifen (Tam) administration. Survival and disease-free interval curves showed highly significant differences between patients with ER+ D and ER+ WD tumors. For survival, including all tumor stages, 73.9% of patients were alive at 9 years after surgery in the group with D tumors and 37.0% in the group with WD tumors (p < 0.005); relative contribution of the different stages is analyzed. Addition of axillary-node number increased the prognostic significance of displacement categories for survival and disease-free interval. PgR determination as another ER functional expression failed to show significant differences for survival and disease-free interval between ER+ PgR+ and ER+ PgR- tumors. Thus, results from the displacement assay and from PgR determinations reflect 2 independent ER functional expressions. Displacement assay data appear as reliable prognostic indicators of breast-cancer outcome, and contribute to more appropriate treatment decisions in this pathology.

Antineoplastic Agents, Hormonal↗
PubMed1997

Ultrasonographic guidance for needle biopsy of breast lesions.

The use of imaging-guided needle biopsies of the breast to establish the histology of lesions has become an important tool in the clinical management of breast pathology. Avoiding excision of benign lesions and allowing definitive surgery of malignant lesions to be planned from the outset are to the benefit of the patient and also decrease the cost of breast health care. The use of ultrasonographic guidance for such procedures provides a safe and effective real time technique to sample tissue while the patient lies in a comfortable supine position. The operator who has a good understanding of the procedure will be able to obtain reliable specimens efficiently and consistently.

Biopsy, Needle↗
PubMed1997

[New concepts on hormone dependence in breast cancer].

The type of hormone dependence in mammary neoplasias is usually defined by the presence or absence of estrogen and progesterone receptors. At present, new advances in the knowledge related to the functionality of these receptors are changing our previous concepts. Estrogen receptors classified as negative by biochemical or immunocytochemical methods because of deletions or mutations in their ligand-binding domain, are still able to regulate the expression of genes related to cellular proliferation. Receptors defined as positive, may present other defective domains with disappearance or distortion of their transcriptional function. As a result, regulation of the cellular proliferative process is distorted and the tumoral growth seems autonomous, as if the receptors were absent. The modular organization of the receptor molecule allows a relative functional independence of the constitutive domains. Functional assays to evaluate receptor behavior under different experimental or clinical situations are necessary. A displacement assay with tamoxifen, for studying the relative binding affinity of tamoxifen and estradiol for the estrogen receptor contributes to a more appropriate use of this antiestrogen in mammary oncology. Conformational changes and mutations in one or several of these genomic molecules may after the transcriptional message with repercussion on cellular proliferation. In this way, antiprogestinic agents can show progestin agonistic effects when combined with cAMP analogues; on the other hand, opposite effects on cellular growth by cAMP analogues can be observed according to the type of hormone dependency (autonomous or dependent) of the tumors. Modulation of steroid receptor transcriptional activity is also achieved through non-transcriptional proteins associated to the receptor molecule. These proteins are then potential targets for the pharmacological regulation of the transcription message. Resistance to antihormone treatments in breast cancer is a dominant feature in the evolution of this malignancy. It cannot be attributed to the presence or absence of steroid receptors when only defined by their quantitative variations.

Antineoplastic Agents, Hormonal↗
PubMed1996

Receptors characterization of intraperitoneally N-nitroso-N-methylurea-induced mammary tumors in rats.

Mammary adenocarcinomas induces in female Sprague-Dawley rats by three intraperitoneal injections of N-nitroso-N-methylurea were studied in order to characterize their estrogen (ER), progesterone (PgR), prolactin (PRLR) and epidermal growth factor (EGFR) receptors. All samples evaluated showed the presence of ER and PgR in the cytosol fraction and PRLR amd EGFR in the membrane fraction. Q (fmol/mg) and K(d) (nM) values were as follows: ER, 56 +/- 11 and 0.5 +/- 0.1; PgR, 109 +/- 25 and 2.2 +/- 0.5 and PRLR, 335 +/- 75 and 0.5 +/- 0.2, respectively. In all tumors studied, two specific sites were found for EGFR, one with Q(1) = 22 +/- 9 and K(d1) = 0.6 +/- 0.3, and the other with Q(2) = 125 +/- 33 and K(d2) = 2.1 +/- 0.5. Receptor content was found to be independent of tumor histopathological variety. Displacement index (DI) with estradiol and tamoxifen of [I(3)H]E2-ER binding showed great heterogeneity, with values ranging from 0.01 to1.54. No correlation between ER content and DI values was found. Antiestrogenic binding sites were not found in the microsomal fraction of ten mammary tumors examined. Proliferation of this experimental mammary tumor may be regulated by a complex interaction of steroid and polypeptide hormones, as well as growth factors.

Animals↗
PubMed1996

Effect of tamoxifen on intraperitoneal N-nitroso-N-methylurea induced tumors.

The effect of tamoxifen (TAM) was evaluated on a mammary tumor model induced in Sprague-Dawley rats by intraperitoneal administration of three N-nitroso-N-methylurea (NMU) doses. Animals received TAM (1 mg/kg per day) from 10 days before the first NMU dose up to 140 days later. Thereafter, treatment was discontinued and the observation period was extended 60 days longer. Mean overall latency period, tumor number per rat and tumor incidence were recorded. Significant differences between treated and control batches were observed in tumor number per rat (1.8 +/- 1.1 versus 5.2 +/- 1.6; P < 0.05) and in tumor incidence (50% versus 100%; P < 0.05), respectively. No significant difference in latency period between both batches was recorded. All lesions induced in the control batch were malignant, whereas only 45% of those induced in TAM-treated animals were malignant and the remaining 55% were preneoplastic. At 60 days after treatment discontinuance, tumor incidence increased to 90% and also tumor number per rat increased to 4.6 +/- 1.5. TAM effect was also evaluated in rats with NMU-induced tumors by treatment with 1 mg/kg per day during 60 days starting when tumors reached a 1.5-cm diameter. Regression to less than 80% of initial size in 49% of the tumors was observed, while in ovariectomized rats, 33% of tumors regressed. Estrogen receptor content, ER (fmol/mg protein) and Kd (nM) in control tumors were: 56 +/- 10 and 0.5 +/- 0.1. In tumors of TAM-treated animals, ER was less than 5 fmol/mg protein. Findings demonstrate that TAM significantly decreased the appearance of tumors induced in rats by i.p. injection of NMU and when TAM treatment was initiated after tumor induction, some tumors failed to respond to hormonal manipulation. Differential tumor growth response after TAM or oophorectomy in each tumor indicates that in the same rat it is possible to distinguish hormone-dependent and hormone-autonomous tumor populations. Hormonal regulation of tumor growth can be under intrinsic control, regardless of the hormonal status of the whole organism.

Animals↗
PubMed1995

Acute and long-term beta-adrenergic blockade for patients with neurocardiogenic syncope.

OBJECTIVES: This study was designed to prospectively evaluate the long-term outcome of drug therapy guided by head-up tilt testing for the management of unexplained syncope and near syncope. BACKGROUND: Head-up tilt testing is used to evaluate patients with unexplained syncope. The validity of acute drug testing and the efficacy of long-term oral therapy for prevention of recurrent syncope have not been investigated in large patient groups. METHODS: We studied 296 consecutive patients with unexplained syncope or near syncope who underwent 80 degrees head-up tilt testing with and without isoproterenol challenge. The efficacy of intravenous and oral beta-blocker therapy was evaluated by repeat testing. Patients with both positive and negative responses to therapy were followed up for rates of recurrence of syncope. RESULTS: A total of 193 patients (65%) had a positive tilt test response; 89% of these 193 required isoproterenol challenge to elicit this response. Patients with a positive tilt test result had lower values for heart rate at rest (mean +/- SD 69 +/- 13 vs. 74 +/- 14 beats/min, p = 0.046) and systolic blood pressure (137 +/- 28 vs. 145 +/- 30 mm Hg, p = 0.0018) at baseline than did the patients with a negative tilt test result. Intravenous propranolol blocked the positive response in 163 (90%) of 181 patients retested. Oral beta-blockers were effective by tilt test criteria in 118 (94%) of 125 patients; 12 (10%) had recurrent clinical symptoms while taking beta-blockers. Eight (42%) of 19 patients who had a negative tilt test response during beta-blocker therapy had recurrent symptoms when they stopped therapy. Three (23%) of 13 patients receiving empiric beta-blocker therapy had recurrent symptoms. The follow-up period for the patients with a positive tilt test result was 28 +/- 11 months (range 5 to 48). CONCLUSIONS: Intravenous propranolol is effective in preventing neurocardiogenic syncope diagnosed during head-up tilt testing and predicts the response to oral beta-blocker therapy. Oral beta-blocker therapy prevents recurrent syncope in the majority of patients. Recurrence of syncope is lowest when efficacy of oral beta-blocker therapy is confirmed by repeat head-up tilt testing.

Administration, Oral↗
PubMed1995

Opposite effect of a cAMP analogue on tumoral growth related to hormone dependence of a murine mammary tumor.

Interactions among transcription factors are one of the mechanisms that regulate gene expression. Through protein-protein associations different signaling pathways become connected and the message triggered by each of the molecules involved can modify other related routes. In a murine mammary tumor induced by medroxyprogesterone acetate (MPA), further treatment with this agent showed a different response on tumor growth. In one group of tumors, growth rate was increased (hormone dependent, HD), whereas in the other group the progestin agent failed to modify the rate of tumor development (hormone autonomous, HA). Progesterone receptors (PgR) and estrogen receptors (ER) were expressed in both groups. Administration of 8-CI-cAMP, a cAMP analogue, stimulated tumor growth in the HD subline and inhibited growth in the HA subline. Simultaneous administration of 8-CI-cAMP and MPA resulted in suppression of inhibitory 8-CI-cAMP action in the HA tumor subline attributable to changes in molecular configuration of protagonic members of each signaling pathway, whereas in the HD subline growth was additive as if each of the pathways were acting separately. MPA induced down regulation of PgR in both tumor sublines and up regulation of ER in the C4-HD subline. The effect of 8-CI-cAMP alone or associated with MPA was more complex and variations in PgR and ER content by themselves are insufficient to explain changes in tumoral growth. A model consistent with our experimental findings is presented.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients.

OBJECTIVE: To assess a bedside technique for diagnosing osteomyelitis. DESIGN: We prospectively assessed infected pedal ulcers for detectable bone by probing with a sterile, blunt, stainless steel probe. We then examined the relationship between detection of bone and the presence or absence of osteomyelitis that was defined histopathologically and/or clinically. SETTING: A tertiary care center. PATIENTS: Seventy-five hospitalized diabetic patients with a total of 76 infected foot ulcers were studied. RESULTS: Osteomyelitis was diagnosed in 50 instances (66%) and was excluded in 26 instances. Bone was detected by probing in 33 of 50 ulcers with contiguous osteomyelitis; in contrast, bone was probed in only four of 26 ulcers without contiguous osteomyelitis (P < .001). Bone detected on probing was visible in only three instances. Palpating bone on probing the pedal ulcer had a sensitivity of 66% for osteomyelitis, a specificity of 85%, a positive predictive value of 89%, and a negative predictive value of 56%. CONCLUSIONS: Palpation of bone in the depths of infected pedal ulcers in patients with diabetes is strongly correlated with the presence of underlying osteomyelitis. If bone is palpated on probing, specialized roentgenographic and radionuclide tests to diagnose osteomyelitis are unnecessary. Probing for bone should be included in the initial assessment of all diabetic patients with infected pedal ulcers.

Aged↗