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Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 73 records · Page 4Linked to original sources
PubMed1999

Evaluating the impact of hospitalists.

The hospital-based generalist physician is a recent organizational innovation in health care in the United States. Does the hospitalist model provide improved health care? The answer to this question lies in a rigorous evaluation of the hospitalist system in the clinical setting. This paper describes key outcomes that need to be assessed and methodologic issues that need to be addressed when conducting and interpreting the results of evaluations of the hospitalist model. To provide evidence about the value of the hospitalist model, quality of care should be evaluated through the measurement of both processes and outcomes. The clinical processes assessed may include diagnostic tests and treatments that are causally linked with outcomes. A variety of outcomes can be measured, such as death, clinical or physiologic status, physical function, and psychological well-being. The analysis of resource use data can aid in an assessment of the relative costs and effectiveness of clinical services. An evaluation of the hospitalist model requires an adequate research design, which should include a precise definition of the model being studied, the selection of an appropriate comparison group, the collection of clinical and demographic information on patients, the specification of both process and outcome measures, and the use of statistical techniques that are appropriate to the questions being asked and the data being collected. The design must distinguish between outcomes attributable to the introduction of hospitalists and those attributable to other changes in medical treatments and the organization of care.

Forecasting↗
PubMed1999

ACEA-1328, a NMDA receptor/glycine site antagonist, acutely potentiates antinociception and chronically attenuates tolerance induced by morphine.

The effect of ACEA-1328, a competitive and systemically bioavailable NMDA receptor/glycine site antagonist, was studied on morphine-induced antinociception and tolerance in CD-1 mice using the tail flick test. To study the effect of acute administration of ACEA-1328 on morphine-induced antinociception, mice were injected with either ACEA-1328 (1, 5, and 10 mg kg(-1)) or Bis-Tris (0.2 m) immediately followed by an injection of morphine and tested for antinociception 30 min later. ACEA-1328 significantly increased the antinociceptive potency of morphine. To study the effect of chronic administration of ACEA-1328 on morphine-induced antinociception and tolerance, mice were treated, either once per day for 9 days or twice daily for 4 days, with ACEA-1328 or with the vehicle. Mice were then, within 1 min, injected daily with either morphine or saline. On the day of the test, mice were injected with only morphine and tested for antinociception 30 min later. In comparison to the acute effect of ACEA-1328, chronic treatment with the NMDA receptor/glycine site antagonist did not affect the antinociceptive potency of morphine. Chronic treatment with morphine, by both methods, produced a significant degree of tolerance. Concurrent administration of ACEA-1328 with the opioid analgesic completely blocked morphine tolerance. Our results demonstrate that acute, but not chronic, treatment with ACEA-1328 increased the antinociceptive potency of morphine. Furthermore, co-administration of the NMDA receptor antagonist with morphine abolished the development of tolerance. Overall, the data support a growing body of evidence showing that activation of the NMDA receptor plays a functional role in opioid-induced antinociception and tolerance.

Analgesics, Opioid↗
PubMed1999

Different tachykinin receptors mediate chloride secretion in the distal colon through activation of submucosal neurones.

We investigated the role of tachykinin receptor subtypes on secretory responses in the guinea-pig distal colon using Ussing chamber experiments and intracellular recordings from submucosal neurones. Choline acetyltransferase (ChAT) and vasoactive intestinal polypeptide (VIP) were demonstrated in submucosal neurones by immunohistochemistry. In Ussing chamber experiments substance P (SP), the NK1-receptor agonist [SAR9,Met(O2)11]-SP and the NK-3-receptor agonist (MePhe7)-NKB increased dose-dependently short-circuit currents. The NK-2-receptor agonist (betaAla8)-NKA(4-10) had no effect. Responses to 1-100 nM SP, [(SAR9,Met(O2)11]-SP and (MePhe7)-NKB were tetrodotoxin-sensitive but hexamethonium-insensitive. While (MePhe7)-NKB-responses were atropine-sensitive at all concentrations, the atropine sensitivity of the secretory responses to SP and [SAR9,Met(O2)11]-SP dramatically decreased with increasing concentrations. [SAR9,Met(O2)11]-SP and (MePhe7)-NKB effects were blocked by the selective NK-I and NK-3 antagonists CP-99,994-1 (1 microM) and SR 142801 (1 microM), respectively. Combination of both antagonists blocked the SP-response. SR 142801 also suppressed the response to [SAR9,Met(O2)11]-SP. Desensitization with [SAR9,Met(O2)11]-SP significantly decreased (MePhe7)-NKB-responses but not vice versa. In intracellular recordings 90% of submucosal neurones were activated by both ISAR9,Met(O2)11]-SP and (MePhe7)-NKB as indicated by membrane depolarisation and enhanced spike discharge. These effects were tetrodotoxin-resistant and potentiated by atropine. NK-1-and NK-3-mediated responses occurred equally in ChAT-positive and in VIP-positive neurones. The results suggest the importance of NK-1- and NK-3-receptors on cholinergic and non-cholinergic submucosal neurones for secretory processes in the guinea-pig distal colon.

Action Potentials↗
PubMed1999

Peptides and polypeptides as modulators of the immune response: thymopentin--an example with unknown mode of action.

Peptides and polypeptides play a critical role in the immune system and are therefore predestined as a source for new approaches in immunotherapy. For example, antigenic peptides which can trigger a specific immunological response have been successfully used for vaccination. In contrast, cytokines have to be considered as rather non-specific immunomodulators. In addition, certain peptides with unknown mode of action have shown promising immunomodulating properties. An example is the pentapeptide thymopentin (TP5), which represents the active sequence of the originally described thymopoietin (TP). TP was recently identified as a fragment of the thymopoietins (TMPOs), a family of nuclear proteins. In vitro assays showed that TP5 affects the function of T cells and monocytes measured by enhanced cGMP level and the triggering of cellular signalling, respectively. In vivo studies demonstrated the capability of TP5 to improve an imbalanced immune system. TP5 exhibited important clinical features and further investigations on its mode of action are necessary to rationally create TP5 peptide analogs or peptidomimetics.

Adjuvants, Immunologic↗
PubMed1999

Relationships between aggressive behavior in cognitively impaired nursing home residents and use of restraints, psychoactive drugs, and secured units.

This study examined relationships between aggressive behavior in cognitively impaired nursing home residents and physical restraints, psychoactive drugs, and placement on a secured unit. Data were obtained from 116 residents who were consistently aggressive as measured by the Ryden Aggression Scale 2. Subjects averaged 9.5 aggressive behaviors per day. Forty-seven percent of subjects were restrained, and 62% were regularly receiving psychoactive drugs. Use of restraints, antipsychotics, and placement on a secured unit were all significantly related to increased physical aggression scores. Four variables accounted for 23% of the variance in physical aggression scores: location on a secured unit, not receiving an antidepressant, being restrained, and number of psychotropic and/or anxiolytic medications administered. Significantly lower physical aggression scores were noted for subjects receiving antidepressants.

Aged↗
PubMed1999

Silver and thallium(I) complexation with dibenzo-16-crown-4.

Dibenzo-16-crown-4 (1) indicates high silver and thallium(I) ion selectivity over sodium, potassium, and rubidium ion evaluated from the solvent extraction of metal picrates, while its cation-binding ability is lower than those of dibenzo-18-crown-6 (2) and dibenzo-22-crown-6 (3). Taking account of the highest thallium(I) ion selectivity for 1 obtained from extraction experiments, PVC membrane thallium(I)-selective electrodes based on 1 are prepared. The electrode shows the best potentiometric selectivity coefficients for thallium(I) over potassium and rubidium than those of 2 and 3, and commercially available bis(crown ether)s (4).

Crown Ethers↗
PubMed1999

Extraesophageal autonomic dysfunction in patients with achalasia.

A disagreement exists as to whether extraintestinal parasympathetic autonomic function is altered in patients with esophageal achalasia. Therefore, we assessed autonomic dysfunction in esophageal achalasia and considered the most relevant parameters of parasympathetic autonomic function in these patients. In a prospective study, heart rate variation and pupillary function were investigated in 15 patients with achalasia of the esophagus and in 15 controls by application of a battery of standardized autonomic function tests. Significant differences between patients and controls were detected for various parameters of heart rate variation and pupillometry. When compared to values obtained from large groups of healthy subjects, none of the controls but 11 patients had at least one abnormal parameter of parasympathetic autonomic function. It is suggested that in esophageal achalasia parasympathetic dysfunction that extends beyond the gastrointestinal tract can be frequently detected. This finding supports the view of a generalized alteration of the autonomic nervous system in achalasia.

Adult↗
PubMed1999

The half-life of human procathepsin S.

Two processes, synthesis and degradation, contribute to the intracellular concentration of a protein. As most malignant tumors or tumor cell lines show elevated levels of proteinases, we studied the half-life of a cysteine proteinase, procathepsin S, in order to determine whether tumor cells can regulate their cathepsin concentration via changing the degradation rate of the enzyme. The following procathepsin S species were examined: wild-type procathepsin S in macrophages, recombinant procathepsin S in human embryonic kidney cells (HEK 293 cells), recombinant nonglycosylated procathepsin S in HEK 293 cells, wild-type procathepsin S in the established nonsmall cell lung carcinoma cell line 97TM1. The half-lives of both wild-type procathepsins S expressed in macrophages and in HEK 293 cells were 1 h, whereas that of procathepsin S in the tumor cell line was 2 h. Nonglycosylated procathepsin S was not processed. The degradation of mature cathepsin S proceeded with a half-life of 16-18 h. All cell lines studied secreted substantial amounts of procathepsin S into the culture medium. No further maturation of secreted procathepsin S has been observed in the culture medium. We suggest a disturbed sorting mechanism in tumor cells.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Composition of enteral diets and meals providing optimal absorption rates of nutrients in mini pigs.

BACKGROUND: Commercial enteral diets differ widely in nutrient composition. It is unknown whether the nutrient composition of the diets influences intestinal absorption. OBJECTIVE: The objective of this study was to investigate the effects of different enteral diets providing 60% of energy as carbohydrate, protein, or fat or 33.3% of energy from each nutrient on intestinal absorption in mini pigs. DESIGN: Kinetics of nutrient absorption were determined by perfusing a 150-cm jejunal segment. The kinetics of absorption were used to determine optimal relations between the absorption and recovery of each nutrient. From these data, the optimal nutrient composition of the diets providing complete absorption of the macronutrients in the shortest intestinal length was evaluated. Absorption of nutrients was further determined after oral administration of 4 corresponding meals. RESULTS: With all enteral diets, the absorption of nutrients displayed saturation kinetics. Absorption rates of carbohydrate were significantly larger than those of fat and protein. Consequently, the amounts of nutrients remaining unabsorbed per unit length of jejunum differed among the macronutrients. After administration of various test meals, the length of the small intestine required for complete absorption of the nutrients depended on the composition of the meals. The shortest intestinal length for complete absorption was needed for a diet providing 48% of energy as carbohydrate, 23% as protein, and 29% as fat. This composition closely matched the nutritional requirements. CONCLUSION: The nutrient composition of diets can optimize intestinal absorption. This may be especially important in patients with malabsorption or short-bowel syndrome.

Animals↗
PubMed1999

The sodium concentration of enteral diets does not influence absorption of nutrients but induces intestinal secretion of water in miniature pigs.

Contradictory opinions exist as to whether the sodium concentration of enteral diets influences absorption of macronutrients and transepithelial movement of sodium and water. Therefore, we investigated the effects of various sodium concentrations of enteral diets on absorption of macronutrients and on net fluxes of sodium and water. In unanesthetized miniature pigs, a 150-cm jejunal segment was perfused with an oligopeptide (Peptisorb), an oligomeric and a polymeric diet. The polymeric diet was supplemented with pancreatic enzymes. The sodium concentrations varied between 30 and 150 mmol/L. The energy density was 3.4 MJ/L. The sodium concentration of the diets did not influence absorption of macronutrients and of total energy. However, increasing sodium concentrations of the diets were associated with increasing osmolality of the solutions, resulting in a linear increase in net secretion of water and flow rate of chyme. With all diets and sodium concentrations net secretion of sodium occurred. The sodium secretion was independent of the initial sodium concentration of the diets. It was linearly correlated with net flux of water and was largest in miniature pigs infused with the oligomeric diet. The sodium concentration of the jejunal effluent did not correspond to the initial sodium concentration of the diets. The present results indicate that enteral feeding of diets with high energy density inevitably increases net secretion of water and sodium as sodium concentration increases. Therefore, the sodium concentration of diets should be as low as possible to meet only the minimal daily requirement of sodium. Low sodium concentrations of diets have no negative effects on absorption of macronutrients.

Animals↗
PubMed1999

Effectiveness of behavioral therapy to treat incontinence in homebound older adults.

OBJECTIVES: To examine the (1) short-term effectiveness of behavioral therapies in homebound older adults and (2) characteristics of responders and nonresponders to the therapies. DESIGN: Prospective, controlled clinical trial with cross-over design. SETTING: Adults aged 60 and older with urinary incontinence and who met Health Care Financing Administration criteria for being homebound were referred to the study by homecare nurses from two large Medicare-approved home health agencies in a large metropolitan county in southwestern Pennsylvania. MEASURES: Structured continence and medical history, OARS Physical and Instrumental Activities of Daily Living scales, Folstein Mini-Mental State Examination Score, Clock Drawing Test, Geriatric Depression Scale, Performance-Based Toileting Assessment, bladder diaries, and physical examination. RESULTS: One hundred five subjects were randomized to biofeedback-assisted pelvic floor muscle training (53 to the treatment group and 52 to the control groups). Control subjects with complete pre- and post-control data (n = 45) experienced a median 6.4% reduction in urinary accidents in contrast to a median 75.0% reduction in subjects with complete pre- and post-treatment data (n = 48, P < .001). Following the control phase, subjects crossed over to the treatment protocol. Eighty-five subjects completed treatment, achieving a median 73.9% reduction in UI. Exercise adherence was the most consistent predictor of responsiveness to the behavioral therapy. CONCLUSIONS: Clinically significant reductions in urinary incontinence are achievable with behavioral therapies in many cognitively intact homebound older adults despite high levels of co-morbidity and functional impairment.

Aged↗
PubMed1999

Raf-1 causes growth suppression and alteration of neuroendocrine markers in DMS53 human small-cell lung cancer cells.

Ras mutations are common in lung adenocarcinomas and squamous-cell cancers, which are non-small-cell lung cancers (NSCLCs). However, small-cell lung cancers (SCLCs) rarely have ras mutations, suggesting that ras activation may not confer a growth advantage in these cells. In one SCLC cell line DMS53, activated ras expression induced increased neuroendocrine differentiation and decreased cell proliferation. We show here that DMS53 cells undergo differentiation and G1-specific growth arrest in response to ras/raf/ mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) pathway activation. To assess the consequences of activating the raf/MEK/MAPK pathway downstream of ras, we transfected a DMS53 cell line with DeltaRaf-1:ER, an activatable form of c-raf-1. DeltaRaf-1:ER activation suppressed cell proliferation and cloning on soft agar by 90% without evidence of apoptosis. Cell cycle analysis showed a reduced proportion of cells in S phase, and was associated with induction of the cyclin-dependent kinase (cdk) inhibitor p16(INK4). Expression of the cell cycle-specific proteins pRb, Rb2/p130, p107, cyclin A, cdc-2, and E2F-1 was decreased after DeltaRaf-1:ER activation in DMS53 cells. The activity cdk4 and cdk2 was also reduced, as consistent with cell cycle arrest in cells with activated DeltaRaf-1:ER cells. In addition, DeltaRaf-1:ER reduced the expression of neuroendocrine markers, gastrin releasing peptide, and ret gene in DMS53:DeltaRaf-1:ER cells. These results provide further evidence that activation of the raf/MEK/ MAPK signaling pathway, which is associated with transformation in many circumstances, can reduce the growth of SCLC cells, and suggest that activation of this pathway might be clinically efficacious in some settings.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Germination and growth responses of hybridizing Carpobrotus species (Aizoaceae) from coastal California to soil salinity.

Germination, growth, and physiological responses of hybridizing Carpobrotus from coastal California to soil salinity were studied. Hybrids are presumably the result of hybridization and introgression between the exotic Carpobrotus edulis, a succulent perennial invading coastal habitats, and the native or long-naturalized C. chilensis. Germination responses were investigated at 0, 10, 20, and 50% seawater. Seedling growth and physiology were compared by irrigating seedlings with solutions of the same seawater concentrations and in low and high nutrients. Germination was inhibited in the presence of salt, but recovered after transferring the seeds to fresh water. Seeds exposed to salt had higher final germination rates than control. Growth of Carpobrotus was slightly enhanced by low seawater concentrations but reduced at high salinity at both nutrient regimes. Leaf cell sap osmolarity increased with increasing soil salinity, and taxa did not differ significantly in this physiological adjustment. Leaf carbon isotope ratios (∂(13)C) ranged from -28 to -22‰ and became less negative at higher salinities, indicating an improved water use efficiency in the seedlings at high salt concentrations. In addition, ∂(13)C values were generally less negative at high than at low nutrients. Differences among taxa were generally small. The results show that salinity affects both establishment and growth of hybridizing Carpobrotus. The overall weak species differences in salt tolerance indicate that the exotic C. edulis can occupy the same sites as C. chilensis in terms of salinity. The similarity of hybrids in their response to salinity suggests that they may contribute to the invasion by Carpobrotus.

Journal Article↗
PubMed1999

Lymphatic vessels of the human heart: precollectors and collecting vessels. A morpho-structural study.

Only topographic and distributional data are available on the lymphatic outflow vessels of the human heart. Here we describe their structural and ultrastructural features. Fragments of the atria, ventricles and fat surrounding the major coronary branches were obtained from hearts of dilated cardiomyopathy patients. Serial semithin sections were observed under light microscopy and used for tridimensional reconstructions. Ultrathin sections were observed by transmission electron microscopy. Precollectors, the initial lymphatic outflow routes of the heart, are small valved vessels with irregular, discontinuous musculature. They originate in the subepicardial region from a network of epicardial, and from scattered myocardial absorbing lymphatic vessels and drain into the collecting vessels accompanying the major coronary branches. Collecting vessels are larger but structurally similar to precollectors. Wall musculature is independent of the size of the vessel. Their ultrastructure is the same as that of precollectors. Endothelial cells have many Weibel-Palade bodies, cytoplasmic filaments and focal adhesions. The basement membrane is discontinuous and anchoring filaments are frequent and conspicuous. The subendothelial layer contains much elastin. Human heart collecting vessels and precollectors may only be distinguished by their size. The scarcity of musculature suggests that lymph progression in this district is mainly ensured by cardiac revolutions. Their ultrastructural features are determined by adaptation to dynamic forces. The architecture of these vessels (random, disorderly, discontinuous, lacking any exact plan) and their large variations in caliber are in line with the ontogenetic hypothesis that peripheral lymphatic vessels originate from the coalescence of mesenchymal lacunae.

Cardiomyopathy, Dilated↗
PubMed1998

Structure-activity relationships for a series of bis(phenylalkyl)amines: potent subtype-selective inhibitors of N-methyl-D-aspartate receptors.

A series of bis(phenylalkyl)amines, structural analogues of ifenprodil and nylidrin, were synthesized and tested for antagonism of N-methyl-D-aspartate (NMDA) receptors. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The bis(phenylalkyl)amines were selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, the most potent of these, N-[2-(4-hydroxyphenyl)ethyl]-5-phenylpentylamine hydrochloride (20), has an IC50 value of 8 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. The structure-activity relationship of the bis(phenylalkyl)amine series indicates that the piperidine ring and alkyl chain substitutions common to NR2B-selective antagonists such as ifenprodil, CP 101,606, and Ro 25-6981 are not necessary to generate potent and selective ligands. The primary determinants of potency are the phenolic OH group, acting as a hydrogen bond donor, the distance between the two rings, and an electrostatic interaction between the receptor and the basic nitrogen atom. This study provides a framework for designing structurally novel NR2B-selective antagonists which may be useful for treatment of a variety of neurological disorders.

Animals↗
PubMed1998

Synthesis of 7,8-(methylenedioxy)-1-phenyl-3,5-dihydro-4H-2, 3-benzodiazepin-4-ones as novel and potent noncompetitive AMPA receptor antagonists.

A group of 7,8-(methylenedioxy)-1-phenyl-3,5-dihydro-4H-2, 3-benzodiazepin-4-ones was synthesized and assayed for antagonism of rat brain alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors expressed in Xenopus oocytes. The benzodiazepinones inhibited AMPA-activated membrane current responses in a manner consistent with noncompetitive, allosteric inhibition of the receptor-channel complex. The most potent compound in the series was 1-(4-aminophenyl)-7,8-(methylenedioxy)-3,5-dihydro-4H-2, 3-benzodiazepin-4-one (6), which had an IC50 of 2.7 microM. For comparison, the reference compound GYKI 52466 (2) had an IC50 of 6.9 microM. Compound 6 also had potent anticonvulsant activity in a mouse maximum electroshock-induced seizure (MES) assay: the ED50 was 2.8 mg/kg iv, whereas the ED50 for GYKI 52466 was 4.6 mg/kg iv. In contrast to a previous report, the 7,8-dimethoxy analogue of 6 was a low-potency AMPA antagonist (IC50 >100 microM) and weak anticonvulsant (ED50 >10 mg/kg iv). The benzodiazepinones described herein are potent noncompetitive AMPA receptor antagonists that could have therapeutic potential as anticonvulsants and neuroprotectants.

Allosteric Regulation↗