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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

Using administrative data to compare the relative effectiveness of amlodipine vs nifedipine CC.

OBJECTIVE: To describe an approach for using claims data to compare the effectiveness of 2 similar drugs used for similar indications within a health maintenance organization. STUDY DESIGN: A database study comparing the effectiveness of amlodipine and nifedipine CC in the initial treatment of hypertension. PATIENTS AND METHODS: The claims records of Pennsylvania Medicaid patients between 18 and 64 years of age with continuous eligibility in 1994 were studied. Pharmacy, hospital, and outpatient claims data were merged, and adult patients receiving the target drugs for the specified indication were identified. The effectiveness of the 2 agents used were compared based on the concept that a change in dispensed medication suggested either an adverse event or lack of effectiveness. Adherence rates, adverse events, and pharmacy and nonpharmacy costs associated with the 2 agents were also compared. RESULTS: Patients receiving amlodipine and nifedipine CC as initial treatment for hypertension had similar demographic characteristics and numbers of comorbid conditions. More patients started on nifedipine CC switched to another calcium channel blocker (15.8% for nifedipine CC vs 10.3% for amlodipine). More patients started on amlodipine switched to another class of antihypertensive agent (13.2% for amlodipine vs 7.3% for nifedipine CC). Patients in both groups received adjunctive antihypertensive drugs at a similar frequency (35% for nifedipine CC vs 42%, for amlodipine). Rates of adherence were similar. In adherent patients, there was no difference in rates of reported adverse events. The nonpharmacy costs were similar between groups. Patients in the amlodipine group also had a trend toward higher overall pharmacy charges (all medications) and higher charges for antihypertensive medications other than the study drugs ($302 vs $188, P = .054). CONCLUSIONS: Claims data are often the best available evidence for comparing the effectiveness of pharmaceuticals in real clinical practice. While these comparisons have inherent limitations, the accuracy of the assessment can be maximized by limiting the assessment to agents with the same specific indications. Other important elements include comparison of crossover rates to other pharmaceuticals in the same class; rates of addition of other pharmaceuticals in the same class, adherence, adverse events, and overall healthcare charges.

Adult↗
PubMed1998

Macrophage and microglial responses to cytokines in vitro: phagocytic activity, proteolytic enzyme release, and free radical production.

Certain cytokines are believed to play a key role in the development of autoimmune demyelinating diseases. Little is known, however, about the effects of these cytokines in the regulation of the key event in myelin destruction, the phagocytosis of myelin by phagocytic cells. We investigated the effects of certain cytokines and growth factors on cultured peritoneal macrophages and microglia in respect to their various functions, phagocytosis, secreted proteolytic activity, and oxidative activity. Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccharide (LPS), all proinflammatory factors, actually decreased (IFN-gamma and LPS), or had no effect (TNF-alpha) on myelin phagocytosis by macrophages, but substantially increased phagocytic activity by microglia. Surprisingly, interleukins 4 and 10 (IL-4 and IL-10), considered to be downregulating cytokines, increased phagocytic activity by macrophages, while with microglia, IL-4 had no effect, but IL-10 almost doubled myelin phagocytosis. Transforming growth factor-beta (TGF-beta) had no significant effect on either cell. These cytokines did not affect proteolytic secretion in microglia, while IFN-gamma and LPS induced a doubling of the secreted proteases. This proteolytic activity was almost completely suppressed by calpain inhibitors, although some gelatinase appeared to be present. Microglia exerted much more oxidative activity on the membranes than macrophages, and granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 1beta (IL-1beta) significantly increased microglial oxidative activity. The pattern of responses of macrophages and microglia to the cytokine types indicate that in cytokine-driven autoimmune demyelinating disease, microglia may be the more aggressive cell in causing tissue injury by phagocytosis and oxidative injury, while infiltrating macrophages may produce most of the proteolytic activity thought to contribute to myelin destruction.

Animals↗
PubMed1998

Expression of beta-endorphin and its receptors in the spinal cord of obese-diabetic ob/ob mice.

Immunocytochemistry was used to demonstrate the presence of beta-endorphin, and quantitative autoradiography with [125I]beta-endorphin was used to study beta-endorphin binding sites, in spinal cord of lean and obese diabetic ob/ob mice. The proportion of beta-endorphin-positive neurones was approximately 6-fold higher in the ventral horn, and 2-fold higher in the dorsal horn of ob/ob mice than in lean controls. The maximum density of beta-endorphin binding sites was significantly higher in the dorsal horn and intermediate zone of ob/ob mice. The Kd value for the binding was similar in the ventral horn and intermediate zone in lean and ob/ob mice, but slightly lower in the dorsal horn of ob/ob mice. The findings indicate upregulation of both beta-endorphin and its receptors in spinal neurones of ob/ob mice.

Animals↗
PubMed1998

Evidence for two populations of N-methyl-D-aspartate receptors in neonatal rat spinal cord. The effect of peripheral nerve axotomy.

Quantitative autoradiography was used to characterise the binding of the N-methyl-D-aspartate (NMDA) receptor antagonist [3H]dizocilpine maleate (MK801) in the white matter and dorsal, intermediate and ventral subregions of the grey matter in the lumbar spinal cord of neonatal rats. The effect on the binding of unilateral sciatic nerve section on the day of birth was examined. In unoperated animals the Bmax and Kd of the binding had decreased in all subregions by two weeks, when the values were similar to those in the adult. After axotomy the Bmax values declined during the first 14 days in all subregions although the density appeared higher in the grey matter in the ventral horn compared to sham operated control. In the axotomised animals, the Kd values for the white matter and ventral horn grey matter had declined by two weeks but in the dorsal and intermediate subregions of the grey matter the values remained elevated. The results are consistent with the presence of two populations of NMDA receptor at birth. In the normal animals the lower affinity receptor disappears in all subregions, but after axotomy it is retained in the dorsal and intermediate subregions for at least 2 weeks.

Animals↗
PubMed1998

Expression of nitric oxide synthase in the spinal cord in amyotrophic lateral sclerosis.

The expression of nitric oxide synthase was studied in human postmortem cervical spinal cord from four individuals with amyotrophic lateral sclerosis (ALS) and four individuals who had died from non-neurological causes. A novel autoradiographic method employing [3H]nitro-L-arginine, a potent inhibitor of the enzyme, as the binding ligand, was used. The expression was quantified in four discrete subregions of the grey matter, and in the dorsal and ventral white matter. The maximum density of binding in the superficial dorsal, deeper dorsal horn, and intermediate subregions of the grey matter was similar in ALS and control tissue, but it was higher in the ALS tissue, in the ventral horn, and in the dorsal and ventral white matter, compared to the corresponding regions in the control tissue. Saturation analysis of the binding indicated a single population of high affinity binding sites in all subregions in the control tissue. However, in the ALS tissue, in all subregions, the presence of two populations of binding sites with different ligand binding affinities were indicated. It is possible therefore that the expression of an inducible isotype of nitric oxide synthase may contribute to the neuropathic changes seen in ALS.

Aged↗
PubMed1998

Lateral ventricular injections of the NK3 agonist senktide affect salt taste-elicited responses.

Central injections of the selective tachykinin NK3 receptor agonist senktide (SENK) suppresses salt appetite. Also, following SENK, intraoral infusions of hypertonic NaCl elicit fewer ingestive taste reactivity responses and more aversive responses than following intraventricular injections of isotonic saline. This pattern of taste reactivity results suggest that SENK affects the oral stimulating properties of salt taste. Before accepting this interpretation, however, alternative explanations need to be examined. The following experiments evaluated whether the effects of intraventricular SENK injection on taste reactivity could be due to: 1) a general oral motor impairment that reduces ingestive responding to tastes (Experiment 1) or; 2) SENK having aversive consequences (Experiment 2). In Experiment 1, the effects of intraventricular injections of SENK (200 ng) on taste reactivity responses to 0.5 M NaCl and 0.1 M sucrose were measured in sodium deficient rats. Intraoral infusions of 0.5 M NaCl elicited fewer ingestive taste reactivity responses following SENK than injections of isotonic saline in sodium deficient rats. Sucrose continued to elicit the same high number of ingestive taste reactivity responses following intraventricular injections of isotonic saline and SENK. Thus, SENK did not cause a general decrease in ingestive responding. A conditioned taste aversion test was employed in Experiment 2 to determine if SENK had aversive consequences. Rats were given 30 min access to alanine (0.3 M) and were then administered either lithium chloride (LiCl) or intraventricular injections of SENK (200 ng) on three consecutive days. Rats avoided alanine that was paired with LiCl, but those rats that had alanine paired with SENK showed no avoidance of the taste even after three pairings. These results replicate findings that intraventricular injections of the NK3 agonist SENK decreases the palatability of NaCl (as measured by taste reactivity) and suggest that its effect on NaCl-elicited taste reactivity is not due to the treatment causing a motor impairment or malaise.

Animals↗
PubMed1998

Field sweep broadline NMR spectroscopy.

A novel NMR spectrometer is described that is uniquely versatile in its ability to accurately record broad lines by sweeping the superconducting magnetic field and to perform standard high resolution solid state NMR experiments. Broadline observation is illustrated by 27Al spectra from static samples. Such an instrument opens up many nuclei for serious study by NMR in the solid state for the first time.

Fourier Analysis↗
PubMed1998

Effects of phorbol myristate acetate (PMA) on functions of macrophages and microglia in vitro.

Peripheral macrophages infiltrating the central nervous system and resident microglia phagocytize myelin in cell-mediated demyelinating diseases, including experimental autoimmune encephalomyelitis and multiple sclerosis. A cascade of cytokines is believed to modulate the immunological sequence of events occurring in these conditions, and several of these mediate their effects through the protein kinase C pathway. Therefore, we compared the effects of phorbol myristate acetate (PMA), an activator of protein kinase C, on various functions of cultured macrophages and microglia. PMA at moderate concentrations induced apoptosis in macrophages, and this process appeared to be increased in the presence of myelin. In contrast, microglia were activated by PMA, and greatly increased their phagocytosis of myelin. Control macrophages released a considerable amount of proteolytic activity into the medium, as measured by the breakdown of myelin basic protein, and in the process of undergoing apoptosis from PMA-treatment, even higher amounts were released. The enzyme activity in control macrophage medium was inhibited mainly by PMSF and calpain inhibitors, while that from PMA-treated macrophages was inhibited by calpain inhibitors only. An ICE inhibitor was ineffective in inhibiting activity in medium from PMA-treated cells undergoing apoptosis. Medium from microglia contained very little proteolytic activity, and this was not increased by PMA. Cultured macrophages showed little evidence of oxygen free radical release as measured by the TBARS procedure, and PMA had no effect. Microglia, on the other hand, produced higher levels of reactive oxygen species, with a further increase of 18% by PMA. Thus major functions of these phagocytic cells appear to be modulated by the protein kinase C pathway, although the two cell types show very different responses to an activator of this signal.

Animals↗
PubMed1998

Vascular endothelial cadherin is expressed by perineurial cells of peripheral nerve.

AIMS: To study the distribution of vascular endothelial (VE) cadherin in peripheral nerves. METHODS AND RESULTS: Using two monoclonal antibodies that detect VE-cadherin (TEA1.31 and 7B4) an immunohistochemical study of VE-cadherin expression in five common peroneal nerve biopsies and five skin specimens containing small peripheal nerves was performed. VE-cadherin was consistently expressed by the perineurium of nerves but not by other nerve elements such as Schwann cells or axons. CONCLUSION: This report indicates that VE-cadherin is not. as was previously thought, a specific marker of endothelial cells and further defines the phenotype of the perineurial cell. The established role of VE-cadherin in controlling the permeability of vascular endothelium suggests that this molecule may have a similar role in the perineurium. VE-cadherin may therefore be important in the maintenance of the blood-nerve barrier, the peripheral nerve equivalent of the blood-brain barrier.

Antibodies, Monoclonal↗
PubMed1998

Epithelioid sarcoma: presence of vascular-endothelial cadherin and lack of epithelial cadherin.

AIMS: To evaluate the pattern of cadherin expression in epithelioid sarcoma. METHODS AND RESULTS: Seven epithelioid sarcomas were immunostained by a polyclonal antibody that detects all cadherin subtypes and by monoclonal antibodies that detect epithelial cadherin (E-cadherin) and vascular-endothelial cadherin (VE cadherin). In addition, the tumours were immunostained for a variety of epithelial (cytokeratin, EMA, AUA1) and endothelial (Factor VIII-related antigen, CD34, CD31) markers. Tumours cells of all seven epithelioid sarcomas expressed cadherins. Surprisingly, E-cadherin was not detected in any of the sarcomas. VE-cadherin was detected in five of seven cases. All seven tumours expressed cytokeratins and EMA but none expressed AUA1. CD34 was detected in six of seven cases and CD31 was detected in a single case. No case expressed Factor VIII-related antigen. CONCLUSIONS: Most epithelioid sarcomas strongly express cadherins, a feature which may contribute to their epithelioid appearance. The absence of detectable E-cadherin suggests that epithelial differentiation in these tumours is, at most, incomplete. The expression of VE-cadherin by the majority of cases, in the absence of E-cadherin, is consistent with an element of mesenchymal differentiation, possibly endothelial or perineurial. The additional presence of other markers such as CD34 and CD31 in some cases favours endothelial differentiation.

Adult↗
PubMed1998

Facing death: donor and recipient responses to the gift of life.

Bone marrow transplantation is an increasingly preferred method of treatment for patients with aplastic anemia, some forms of leukemia, and certain tumors, such as lymphoma and breast cancer. When the patient's only alternative is death, psychosocial and cultural aspects of the relationship between the donor and the recipient become of paramount importance. In relation to organ transplantation, the gift has a special emotional meaning because it signifies life and creates a spiritual bond between the donor and the recipient. The article explores the theme of gift exchange and its psychosocial implications in bone marrow transplant donors and recipients. The impact of the relationship of the donor to the recipient is of particular interest because a live donor is indicated for all bone marrow transplants. The influence of cultural and religious attitudes also is investigated.

Adult↗
PubMed1998

Intravascular synovial sarcoma.

A case of intravascular biphasic synovial sarcoma arising from the wall of the left femoral vein in a 34 year old woman is described. This is the third case of an intravascular synovial sarcoma known to be reported in the medical literature. The two previous cases arose from the left femoral vein and inferior vena cava in women of 34 and 31 years old, respectively. A characteristic clinical pattern appears to be emerging--that is, location in large veins of the lower extremity and trunk in young adult females. Synovial sarcoma must be considered in the differential diagnosis of intravascular "tumours".

Adult↗
PubMed1998

Differential recovery of acetylcholinesterase in guinea pig muscle and brain regions after soman treatment.

1. In brain areas of untreated guinea-pigs the highest activity of acetylcholinesterase was seen in the striatum and cerebellum, followed by the midbrain, medulla-pons and cortex, and the lowest in the hippocampus. The activity in diaphragm was seven-fold lower than in the hippocampus. 2. At 1 h after soman (27 micrograms/kg) administration the activity of the enzyme was dramatically reduced in all tissues studied. In muscle the three major molecular forms (A12, G4 and G1) showed a similar degree of inhibition and a similar rate of recovery and the activity had returned to normal by 7 days. 3. In the brain soman inhibited the G4 form more than the G1 form. The hippocampus, cortex and midbrain showed the greatest reductions in enzyme activity. At 7 days the activity in the cortex, medulla pons and striatum had recovered but in the hippocampus, midbrain and cerebellum it was still inhibited. 4. Thus the effects of soman administration varied in severity and time course in the different tissues studied. However the enzyme activity was still reduced in all tissues at 24 h when the overt signs of poisoning had disappeared.

Acetylcholinesterase↗
PubMed1998

Perceptions of caring. Comparison of antepartum and postpartum patients.

An exploratory, comparative survey design was used to describe and compare similarities and differences in perception of caring behaviors between hospitalized antepartum and short-stay postpartum patients. Forty-two patients completed the 63-item Caring Behavior Assessment instrument (CBA). The scale, based on Watson's theory of caring, contains seven categories. There were no statistically significant differences in age, education, gravida, or para between the two groups. Significantly more women in the postpartum group were married. There were no statistically significant differences or correlations in the total CBA scores and the demographic variables. No statistically significant differences in total CBA scores were found between antepartum participants and postpartum participants. These findings corroborate the results of "caring" studies in other patient populations, that satisfying basic needs--that is, evidence of technical knowledge and skills--is more important to patients than meeting higher order needs.

Adult↗
PubMed1998

Thyroarytenoid muscle activity associated with hypophonia in Parkinson disease and aging.

OBJECTIVE: To compare electromyographic (EMG) amplitudes of the thyroarytenoid (TA) muscle in young and older individuals and individuals with idiopathic PD (IPD) under conditions of known vocal loudness (sound pressure level). BACKGROUND: Voice disorders frequently accompany aging and IPD, but it is unclear how laryngeal muscle physiology is affected by these processes and how changes in laryngeal muscle activity result in characteristic changes of the voice. METHODS: Absolute and relative (to maximum) EMG amplitudes of the TA muscle were compared during speech and nonspeech tasks. Corresponding sound pressure level (SPL) measures were obtained for the speech tasks. RESULTS: Absolute TA amplitudes were consistently the highest in the young individuals, lowest in the individuals with IPD, and intermediate in the older individuals. Relative TA amplitudes were generally the highest for the young individuals, lowest for the older individuals, and intermediate for the individuals with IPD. SPL findings showed the older individuals and individuals with IPD produced most of the speech tasks with comparable SPLs, and these levels were consistently lower than those of the young individuals. CONCLUSIONS: Reduced levels of TA muscle activity may contribute to the characteristic hypophonic voice disorders that frequently accompany IPD and aging.

Adult↗
PubMed1998

Monitoring working memory load during computer-based tasks with EEG pattern recognition methods.

We assessed working memory load during computer use with neural network pattern recognition applied to EEG spectral features. Eight participants performed high-, moderate-, and low-load working memory tasks. Frontal theta EEG activity increased and alpha activity decreased with increasing load. These changes probably reflect task difficulty-related increases in mental effort and the proportion of cortical resources allocated to task performance. In network analyses, test data segments from high and low load levels were discriminated with better than 95% accuracy. More than 80% of test data segments associated with a moderate load could be discriminated from high- or low-load data segments. Statistically significant classification was also achieved when applying networks trained with data from one day to data from another day, when applying networks trained with data from one task to data from another task, and when applying networks trained with data from a group of participants to data from new participants. These results support the feasibility of using EEG-based methods for monitoring cognitive load during human-computer interaction.

Adult↗