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Biomedical subjects

S Meltzer

Publications and source records attributed to S Meltzer.

At least 19 recordsLinked to original sources
PubMed2006

GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?

OBJECTIVE: The aim of the study was to evaluate the influence of type of GnRH-analog used during controlled ovarian hyperstimulation (COH) on the outcome of in vitro fertilization (IVF) cycles. PATIENTS AND METHODS: All consecutive women aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004 were enrolled in the study. Only patients undergoing up to their third IVF cycle attempt were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred, and clinical pregnancy rate were compared between women given GnRH-agonist or GnRH-antagonist during COH. RESULTS: Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the agonist group and 261 in the antagonist group. A clinical pregnancy was achieved in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66 patients in the antagonist grup (pregnancy rate 25.3%); this difference was statistically significant (p < 0.01). The agonist group also used significantly more gonadotropin ampoules, required longer stimulation, and had higher estradiol levels on the day of human chorionic gonadotropin administration. CONCLUSION: The midluteal long GhRH-agonist suppressive protocol should be the protocol of choice in young patients in their first three IVF cycle attempts.

Adult↗
PubMed2001

Proton pump inhibitors reduce cell cycle abnormalities in Barrett's esophagus.

Neoplastic progression in Barrett's esophagus is a multi-step process in which the metaplastic columnar epithelium sequentially evolves through a metaplasia-dysplasia-carcinoma sequence. The expression and DNA copy number of key cell cycle regulatory genes in paired normal and Barrett's esophagus samples was evaluated. Protein levels were evaluated in 60 formalin-fixed, paraffin-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mucosal samples expressed the p27(kip1) protein, but did not display appreciable nuclear staining for p16(kip4), p21(cip1) or cyclins D1 and E. Barrett's metaplastic specimens displayed increased expression levels of p16(kip4) (74%), p21(cip1) (89%) and cyclins D1 (43%) and E (37%). p27 protein was absent in three cases. There was a significant correlation between the expression of p16(kip4) and cyclin E, and p21(cip1) and p27(kip4) with cyclin D1. DNA analysis did not reveal any amplification or deletion of these genes. Acid suppression, however, was associated with significantly lower expression levels of key cell cycle proteins. Increased expression of key cell cycle regulatory genes appears to occur early in the neoplastic progression associated with Barrett's esophagus. Treatment with proton pump inhibitors appears to alter this increased expression.

Adult↗
PubMed2000

Manipulation of gold nanoparticles in liquid environments using scanning force microscopy

Precise and controlled manipulation of individual gold nanoparticles (deposited on a Si/SiO2 surface) in liquid environments using the tip of a scanning force microscope is reported for the first time. Experiments were performed in deionized water and in ethanol as a prototype for an organic solvent. Analysis of the amplitude signal of the cantilever before and during manipulation reveals that the particles are pushed across the surface, similar to the manipulation of nanoparticles in air.

Journal Article↗
PubMed2000

Optimizing insulin delivery: assessment of three strategies in intensive diabetes management.

OBJECTIVE: To compare three intensive management strategies with respect to metabolic control (glycated haemoglobin, preprandial blood glucose, lipid profile, body weight, hypoglycaemic episodes) and psycho-social adaptation (quality of life, self-efficacy, stress and perceived complexity). RESEARCH DESIGN AND METHODS: Fifteen adults with type 1 diabetes completed this 1-year, randomized, prospective, cross-over study. The three treatment strategies were categorized according to flexibility with insulin self-adjustments as follows: Simplified (SIMP) = meal plan based on food exchanges with no self-adjustments of insulin for food, exercise and stress; Qualitative (QUAL) = meal plan based on food exchanges with qualitative adjustment of insulin for food, exercise and stress; Quantitative (QUANT) = meal plan using carbohydrate counting with quantitative adjustment of insulin for food and qualitative adjustment for exercise and stress. All three strategies allowed for adjustments of insulin for preprandial blood glucose and the option of adjusting diet for exercise. All subjects followed each strategy for 3.5 months. Subjects kept detailed log sheets where they recorded preprandial blood glucose, insulin dosages, food intake, activity and stress level at least four times/day. The psycho-social aspects were determined with validated questionnaires that were completed before and after each strategy. RESULTS: There were no statistically significant differences in metabolic control, quality of life and self-efficacy between the three strategies. The mean (+/- s.e.) for HbA1 levels (normal < 8.5%) were: Baseline: 10.9+/-0.06 and End of SIMP = 9.7+/-0.03; QUAL = 9.5+/-0.04; QUANT = 10.2+/-0.04. Body weight and serum lipid levels did not change significantly. The frequency of severe hypoglycaemic episodes for the entire study was 20 episodes/100 patient-years. Perceived complexity of treatment strategy increased (p < 0.0001) from SIMP to QUANT (least to most flexible). Although the majority of subjects (n = 11) were following a strategy similar to SIMP prior to entering the study, 12 subjects chose to continue with QUAL, three with QUANT and none with SIMP at the end of the study. CONCLUSIONS: These results indicate that a strategy that allows for flexibility of self-adjustments of insulin and is not very complex (such as QUAL) may be the strategy of choice for intensive management programmes.

Adult↗
PubMed1999

Identifying the null subject: evidence from event-related brain potentials.

Event-related brain potentials (ERPs) were recorded during spoken language comprehension to study the on-line effects of gender agreement violations in controlled infinitival complements. Spanish sentences were constructed in which the complement clause contained a predicate adjective marked for syntactic gender. By manipulating the gender of the antecedent (i.e., the controller) of the implicit subject while holding constant the gender of the adjective, pairs of grammatical and ungrammatical sentences were created. The detection of such a gender agreement violation would indicate that the parser had established the coreference relation between the null subject and its antecedent. The results showed a complex biphasic ERP (i.e., an early negativity with prominence at anterior and central sites, followed by a centroparietal positivity) in the violating condition as compared to the non-violating conditions. The brain reacts to NP-adjective gender agreement violations within a few hundred milliseconds of their occurrence. The data imply that the parser has properly coindexed the null subject of an infinitive clause with its antecedent.

Adult↗
PubMed1999

Viagra for temporary erectile dysfunction during treatments with assisted reproductive technologies.

During treatments with assisted reproductive technologies (ART), some men may have difficulties in producing spermatozoa on demand at the time of insemination, either for intrauterine insemination (IUI) or for in-vitro fertilization (IVF). This situation imposes tremendous stress on the couple and may cause cancellation of the treatment. Here we describe, for the first time, the use of sildenafil citrate (ViagraTM) for temporary erectile dysfunction in couples undergoing ART. The first case was a man who could not produce spermatozoa for the first IVF treatment after an exhausting trial for 12 h, despite the fact that he never had problems in providing sperm samples during previous IUI cycles. Using Viagra enabled him to provide spermatozoa, but the delay in oocyte insemination resulted in no embryonic development. This prompted us to be more alert to this option and to suggest the use of Viagra to men who had a history of erectile dysfunction during previous ART cycles. In these cases, the use of Viagra was planned in advance and it successfully solved any unpredictable erectile dysfunction on the day of insemination. Such cases emphasize the need to think in advance of this potential use of Viagra during ART.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

The preclinical pharmacological profile of the potent and selective leukotriene B4 antagonist CP-195543.

CP-195543 [(+)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid] is a structurally novel, selective and potent leukotriene B4 (LTB4) receptor antagonist. In vitro CP-195543 inhibited [3H]LTB4 binding to high-affinity LTB4 receptors on human neutrophils (HN) and murine spleen membranes with IC50 values of 6.8 nM (Ki = 4.9 nM) and 37.0 nM (Ki = 26.9 nM), respectively. CP-195543 inhibited human and mouse neutrophil chemotaxis mediated by LTB4 with IC50 values of 2.4 nM and 7.5 nM, respectively. Evidence of noncompetitive antagonist effects on the HN high-affinity LTB4 receptor was obtained by Scatchard analysis of [3H]LTB4 binding to and chemotaxis of HN to LTB4. Scatchard analyses of [3H]LTB4 binding to low-affinity receptors on HN indicated that CP-195543 acted as a competitive antagonist at this receptor, and inhibition of LTB4-mediated CD11b up-regulation on HN was inhibited competitively by CP-195543 (pA2 = 7.66). In whole blood, CP-195543 also blocked CD11b up-regulation on HN (pA2 = 7.12) and murine neutrophils (pA2 = 7.06) with a similar potency. LTB4-mediated CD11b up-regulation on human monocytes and eosinophils in whole blood were inhibited by CP-195543 with IC50 values of 270 nM and 420 nM, respectively. CP-195543 at 10 microM failed to inhibit HN chemotaxis and CD11b up-regulation mediated through alternative (i.e., complement fragment 5a, interleukin-8, platelet-activating factor) G-protein-coupled chemotactic factor receptors. In vivo, after oral administration, CP-195543 blocked LTB4-mediated neutrophil infiltration in guinea pig and murine skin with ED50 values of 0.1 mg/kg and 2.8 mg/kg p.o., respectively. When administered in osmotic pumps, CP-195543 reduced the clinical symptoms and attendant weight loss in an IL-1-exacerbated murine model of collagen-induced arthritis with half-maximal effects associated with plasma drug levels of 0.4 to 0.5 microg/ml. Collectively these data provide evidence of the in vitro potency and in vivo efficacy of a novel LTB4 antagonist and support its clinical evaluation in a variety of inflammatory diseases in man.

Animals↗
PubMed1998

1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association.

OBJECTIVE: To revise and expand the 1992 edition of the clinical practice guidelines for the management of diabetes in Canada incorporating recent advances in diagnosis and outpatient management of diabetes mellitus and to identify and assess the evidence supporting these recommendations. OPTIONS: All aspects of ambulatory diabetes care, including organization, responsibilities, classification, diagnosis, management of metabolic disorders, and methods for screening, prevention and treatment of complications in all forms of diabetes were reviewed, revised as required and expressed as a set of recommendations. OUTCOMES: Reclassification of types of diabetes based on pathogenesis; increased sensitivity of diagnostic criteria; recommendations for screening for diabetes; improved delivery of care; recommendations for tighter metabolic control; and optimal methods for screening, prevention and treatment of complications of diabetes. EVIDENCE: All recommendations were developed using a justifiable and reproducible process involving an explicit method for the citation and evaluation of the supporting evidence. VALUES: All recommendations were reviewed by an expert committee that included people with diabetes, family physicians, dietitians, nurses, diabetologists, as well as other subspecialists and methodologists from across Canada. BENEFITS, HARM AND COSTS: More aggressive screening strategies and more sensitive testing and diagnostic procedures will allow earlier detection and management of diabetes. Cost-effectiveness analyses suggest that this will lead to savings in health care costs relating to diabetes care by reducing the incidence of complications of diabetes. Similarly, tighter metabolic control in most people with diabetes, through intensive diabetes management, seeks to reduce the incidence of complications and, hence, their associated social and economic burdens. RECOMMENDATIONS: This document contains numerous detailed recommendations pertaining to all aspects of ambulatory diabetes care, ranging from service delivery to prevention and treatment of diabetes-related complications. The terms "insulin-dependent diabetes mellitus" and "non-insulin-dependent diabetes mellitus" should be replaced by the terms "type 1" and "type 2" diabetes. Testing for diabetes using fasting plasma glucose (FPG) level should be performed every 3 years in those over 45 years of age. More frequent or earlier testing should be considered for people with additional specific risk factors for diabetes. The FPG level at which diabetes is diagnosed should be reduced from 7.8 to 7.0 mmol/L to improve the sensitivity of the main diagnostic criterion and reduce the number of missed diagnoses. Depending on the type of diabetes and the therapy required to achieve euglycemia, people with diabetes should generally strive for close metabolic control to achieve optimal glucose levels. This entails receiving appropriate diabetes education through a diabetes health care team, diligent self-monitoring of blood glucose, attention to lifestyle and adjustments in diet and physical activity, and the appropriate and stepwise use of oral agents and insulin therapies needed to maintain glycemic control. Also highlighted is the need for appropriate surveillance programs for complications and management options. VALIDATION: All recommendations were graded according to the strength of the evidence and consensus of all relevant stakeholders. Collateral efforts of the American Diabetes Association and the World Health Organization and the input of international experts were also considered throughout the revision process.

Canada↗
PubMed1992

Effect of hyperprolactinemia on the androgen response to an oral glucose load.

OBJECTIVE: To investigate the effect of hyperprolactinemia on the androgen response to an oral glucose load in patients with normal and abnormal carbohydrate metabolism. DESIGN: Sixty-three women underwent a 75-g oral glucose tolerance test (OGTT) at approximately 6 weeks' postpartum. SETTING: University hospital setting. PATIENTS: Patients with a previous history of gestational diabetes. MAIN OUTCOME MEASURE: Adrenal and ovarian androgen response to oral glucose load. RESULTS: Results were stratified by the result of the OGTT (patients with impaired glucose tolerance or diabetes as a single group and patients with a normal OGTT as a separate group) and prolactin (PRL) level. All androgens decreased significantly over the 2-hour test in all groups except dehydroepiandrosterone sulfate (DHEAS) in the patients with both elevated PRL and abnormal glucose tolerance. CONCLUSION: Hyperprolactinemia and insulin resistance may act synergistically in the adrenal to alter DHEAS suppression and may result in chronically elevated circulating DHEAS levels.

Adult↗
PubMed1990

Acute effects of exercise on food intake in obese and nonobese women.

The animal model of exercise-induced anorexia was employed in humans to develop a laboratory paradigm for studying the acute effect of exercise on food intake. Each of nine obese and nine nonobese women exercised either strenuously (90 W) or moderately (30 W) on a cycle ergometer for 40 min or rested in the laboratory on each of 3 nonconsecutive days. Intake of a liquefied test meal (1.04 kcal/g) eaten 15 min after exercise was significantly less after the strenuous (620 g) than after the moderate (754 g) exercise in the nonobese women but was no different after the two conditions (532 g after strenuous, 581 g after moderate) in the obese women. Heart rate and energy expenditure were increased in proportion to the exercise by the same amount in both groups. The results demonstrate for the first time that food intake is reduced immediately after strenuous exercise in nonobese women, as it is in animals, and validate the feasibility of this laboratory paradigm.

Adult↗
PubMed1989

Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma.

Airway inflammation with neutrophil infiltration may play a role in airway hyperreactivity. Neutrophils may exert their effects through the generation of superoxide O2- anion and other oxygen-derived free radicals. O2- generation by neutrophils has been demonstrated to be modulated by adenosine at physiologic concentrations. Therefore, we have investigated the function of peripheral blood neutrophils with respect to O2- anion generation and its regulation by adenosine in both subjects with asthma and normal subjects and also the relationship between O2- anion generation and airway hyperresponsiveness in subjects with asthma. Purified neutrophils were obtained from eight subjects with stable asthma and seven normal control subjects not taking chronic medications. O2- anion generation in subjects with asthma was significantly higher compared with that of normal subjects after stimulation with either N-formyl-methionyl-leucyl-phenylalanine (mean, 14.8 nmol/10(6) cells for subjects with asthma versus mean, 9.6 nmol/10(6) cells for normal subjects; p less than 0.01) or phorbol myristate acetate (mean, 13.6 nmol/10(6) cells versus mean, 8.1 nmol/10(6) cells; p less than 0.05). Adenosine inhibited N-formyl-methionyl-leucyl-phenylalanine-stimulated O2- anion generation in a dose-related fashion in subjects with asthma and normal subjects to a similar degree. Adenosine had no effect on O2- anion generation after phorbol myristate acetate stimulation. These results indicate that neutrophils from subjects with asthma produce more O2- anion when they are stimulated than do neutrophils from normal subjects and that this difference is not due to adenosine modulation. In subjects with asthma, O2- anion generation correlated with the degree of airway hyperresponsiveness to inhaled methacholine.

Adenosine↗
PubMed1988

The definition of mitochondrial H+ ATPase assembly defects in mit- mutants of Saccharomyces cerevisiae with a monoclonal antibody to the enzyme complex as an assembly probe.

mit- mutants with genetically defined mutations in the mitochondrial structural genes of the H+-ATPase membrane subunits 6, 8 and 9 were analysed to determine the H+-ATPase assembly defects that resulted as a consequence of the mutations. These include mutants which do not synthesize one of the membrane subunits and mutants which can synthesize these subunits, but in an altered form. Protein subunits which can still be assembled to the defective H+-ATPase in these mutants were determined by immunoprecipitation using a monoclonal antibody to the beta-subunit of the enzyme complex. The results suggest that the assembly pathway of the mitochondrially synthesized H+-ATPase subunits involves the sequential addition of subunits 9, 8 and 6 to a membrane-bound F1-sector. In addition to subunits of the F0- and F1-sectors, two other polypeptides (Mr = 18,000 and Mr = 25,000) are associated with the yeast H+-ATPase. These polypeptides were not observed in the immunoprecipitates obtained from mutants in which the F0-sector is not properly assembled.

Antibodies, Fungal↗
PubMed1988

Assembly of functional proton-translocating ATPase complex in yeast mitochondria with cytoplasmically synthesized subunit 8, a polypeptide normally encoded within the organelle.

A mitochondrial gene from Saccharomyces cerevisiae encoding a hydrophobic membrane protein, subunit 8 of the F0/F1-type mitochondrial ATPase complex, has been functionally replaced by an artificial nuclear gene specifying an imported version of this protein. The experiments reported here utilized a multicopy expression vector (pLF1) that replicates in the nucleus of yeast cells and that carries an inserted DNA segment, specifying a precursor protein (N9/Y8) consisting of subunit 8 fused to an N-terminal cleavable transit peptide (the leader sequence from Neurospora crassa ATPase subunit 9). The successful incorporation of the imported subunit 8 into functional ATPase complexes after transformation with pLF1 expressing N9/Y8 was indicated by the efficient genetic complementation of respiratory growth defects of aap1 mit- mutants, which lack endogenous subunit 8. The reconstitution of ATPase function was confirmed by biochemical assays of ATPase performance in mitochondria and by immunochemical analyses that demonstrated the assembly of the cytoplasmically synthesized subunit 8 into the ATPase complex. Reconstitution of ATPase function required the cytoplasmically synthesized subunit to have a transit peptide. The strategy for importation and reconstitution developed for subunit 8 leads to a systematic approach to the directed manipulation of mitochondrially encoded membrane-associated proteins that has general implications for exploring membrane biogenesis mechanistically and evolutionarily.

Fungal Proteins↗
PubMed1987

Specificity of proto-oncogene amplification in human malignant diseases.

DNAs from 253 fresh human tumors of 38 different types were hybridized with 17 different oncogene probes. The analysis demonstrated unique associations between amplification of specific oncogenes and specific types of tumors. In a large number of cases it was determined that amplified oncogenes occurred in 10 to 20% of tumors with the following specific associations: c-myc in adenocarcinomas, squamous carcinomas and sarcomas but not hematologic malignancies; c-erbB2 in adenocarcinomas, particularly breast cancers; c-erbB1 in squamous carcinomas; N-myc in neuroblastomas. A small number of cases suggested other specific associations: amplified c-myb in breast cancers; amplified c-ras-Ha and c-ras-Ki in ovarian carcinomas. In addition, there was a correlation between amplification of c-myc and the clinical stage of adenocarcinomas, and amplification of c-erbB2 and the clinical stage and lymph node involvement of breast cancers.

Carcinoma↗