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Biomedical subjects

M C Smith

Publications and source records attributed to M C Smith.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cognitive speed in nondemented Parkinson's disease.

Studies of speed of cognitive processing in Parkinson's disease (PD) have yielded mixed results. This may relate in part to a differential effect on cognitive speed by the type of information to be processed. In the present study, we compared medication fasted, nondemented individuals with mild idiopathic PD (N = 26) with age-matched controls (N = 12) on a test requiring easy and hard same-different discriminations for verbal, quantitative, and spatial information, as well as on a traditional memory scanning paradigm. A voice-activated relay rather than a key press was used to eliminate the need for limb and finger movements. Simple reaction time and movement time were also measured in a task requiring subjects to move a hand held stylus to a designated target. The PD group performed as fast as the control group across all tasks except movement time. Thus, in our paradigm, the presence of PD alone does not predict cognitive slowing in the presence of motor slowing.

Aged↗
PubMed1998

Quality of life assessment by community pharmacists: an exploratory study.

Implicit in the evolving role of pharmacy is that its practitioners embrace the concept of quality of life (QoL). In recent years there has been an increased interest in incorporating health-related quality of life (HRQoL) measures into clinical practice, primarily focusing on the physician as the user of this information. Pharmacists may be able to use these instruments in their practices to provide better pharmaceutical care. To explore the feasibility of such an undertaking, questionnaires were mailed to a national sample of community pharmacies. In addition to the questionnaire, the respondents were provided with examples of two instruments: the Duke Health Profile and the QOLIE-10. A definition of HRQoL was provided to the respondents. After two mailings and a reminder postcard, a usable response rate of 27.2% was achieved. The results revealed that over 80% of the respondents currently discuss HRQoL issues with their patients. In addition, 66% reported that they attempt to assess the HRQoL of their patients, albeit usually on a subjective, informal basis. After viewing examples of HRQoL instruments, over three-quarters of the respondents reported a willingness to use HRQoL assessment tools in their practices. However, only 53.7% of the respondents were familiar with the concept of HRQoL. Less than 5% reported familiarity with formal instruments. The self-reported knowledge of pharmacists concerning HRQoL was low and the respondents recognized a significant gap between their current knowledge and the level of knowledge needed to assess the HRQoL of their patients formally. The results suggest a possible role for the pharmacist in HRQoL assessment. However, the use of HRQoL instruments in community pharmacies will require further training and education on the part of pharmacists concerning the concept of HRQoL, the issues involved in its measurement and how they can use HRQoL information in their practices. In addition, a number of unanswered questions must be addressed through the research process in order for HRQoL questionnaires to become clinical tools in the practice of pharmacy.

Adult↗
PubMed1998

Influence of early post partum ovulation on the re-establishment of pregnancy in multiparous and primiparous dairy cattle.

To investigate the influence of early ovulation after calving on subsequent fertility, milk progesterone concentrations were monitored twice weekly in multiparous (n = 87) and primiparous (n = 60) Holstein/Friesian dairy cattle. Luteal activity before 21 days post partum was defined as 'early'. In multiparous cows, calving-to-conception interval (CCI) was longer, services per cow were more numerous and conception rate to all inseminations was lower with early luteal activity (n = 41, 16.8 +/- 0.39 days post partum) than with later luteal activity (n = 46, 37.8 +/- 2.09 days post partum); multiparous cows with early luteal activity required more exogenous fertility treatments and were more likely to fail to conceive by 100 days post partum. In contrast, in primiparous cows, no significant relationships were detected between early (n = 32) or later (n = 28) luteal activity and the CCI, number of services per cow or conception rates to all inseminations. However, primiparous cows that ovulated before 21 days post partum had fewer normal progesterone profiles. Early ovulation after calving was associated with reduced pregnancy rates and prolonged CCIs in multiparous but not in primiparous dairy cows.

Animals↗
PubMed1998

Multiple subpial transection in patients with extratemporal epilepsy.

Multiple subpial transection (MST) was developed to permit the treatment of partial epilepsies that reside in or encroach on eloquent cortex (language and sensorimotor cortex). It was conceived after the discoveries of the columnar organization of neocortex and that expression and spread of seizures utilize the transverse fiber network. Although the technique is simple in principle, it takes a skilled and practiced hand to avoid damage to the neocortical columns and vascular supply. The efficacy in controlling seizures with MST in extratemporal epilepsy is similar to that of resective surgery. Activities of daily living are not adversely impacted by MST. MST is a viable alternative to resection in extratemporal epilepsy.

Activities of Daily Living↗
PubMed1998

The effects of acquisition cost and budget-based compensation on the attitudes of pharmacy directors toward the adoption of a cost-effective new drug.

To test the effect of differences in acquisition cost and budget-based monetary compensation systems on the intent to support the adoption of a cost-effective new drug, over 350 hospital pharmacy directors were asked to indicate their intentions as to the adoption of a cost-effective new thrombolytic agent, presented at 3 different prices. Although the economic savings for the hypothetical product were constant across all price points tested, respondents exposed to the highest price were more likely to resist the adoption of the new agent than those exposed to lower prices (p < 0.001). Respondents whose compensation was contingent on their control of the drug budget indicated a higher likelihood to resist the adoption of the new agent than did those whose salary was not so determined. These findings indicate that significant hurdles, psychological and organisational, still exist for the acceptance and use of pharmacoeconomic information in the hospital setting.

Decision Making↗
PubMed1997

Distorted visual feedback effects on drawing in Parkinson's disease.

We investigated the effects of distorted visual feedback on the drawing performance of a group with Parkinson's disease (PD) and a control group. Twenty older healthy adults and 20 PD patients copied figures onto a digitizer tablet with a pen under normal and distorted visual feedback conditions. PD patients were less able than controls to adjust the size of their drawing to compensate for distortions in visual feedback. The effect was particularly pronounced when patients were required to draw smaller than normal. Nevertheless, with practice. PD patients showed a similar degree of improvement in size as controls, although they did not match the control group's level of performance. Overall, these findings support the notion that PD may have specific difficulty adjusting to a change in gain (or discrepancy) between visual and kinesthetic feedback when they must alter the size of their drawing. These findings point to the putative role of the basal ganglia in adjusting for the intermodal discrepancy between sensory feedback, and re-scaling the size of movements.

Aged↗
PubMed1997

Detection of specific human immunodeficiency virus type 1 Tat-TAR complexes in the presence of mild denaturing conditions.

Gene expression from the human immunodeficiency virus 1 (HIV-1) is greatly enhanced by binding of the virally encoded Tat protein to a 59-base RNA stem-loop structure, the Transactivation Responsive Element (TAR), located at the 5'-termini of all viral transcripts. This interaction was investigated in vitro using 32P-labelled TAR and highly purified Tat in which cysteine residues were blocked by sulpitolysis (S-Tat). It is shown that specific complex formation between S-Tat and TAR can occur in the presence of urea, with urea concentrations between 5 and 6 M causing an approximately two-fold increase in the level of binding. Two conditions favoring RNA secondary structure, low temperature (0 degree C) and the presence of divalent cations (Mg2+), diminished the level of specific binding. These observations suggest that the presence of mild denaturants promoted macromolecular refolding or rearrangement in a manner that increased the number of molecules available for binding, and present a general method for studying protein/RNA interactions where analysis has been obstructed by improper protein or RNA conformation.

Base Sequence↗
PubMed1997

Cationic liposome-mediated uptake of human immunodeficiency virus type 1 Tat protein into cells.

The human immunodeficiency virus type 1 (HIV-1) Tat protein strongly transactivates gene expression from the viral long terminal repeat (LTR) and is required for virus efficient replication. Previous studies have shown that cells scrape-loaded in the presence of purified recombinant Tat can absorb the protein in a receptor-independent fashion. Using recombinant Tat in which cysteine residues were blocked by sulfitolysis to prevent disulfide aggregation (S-Tat) we were unable to observe this phenomenon, possibly because of improper protein folding. In this study we report that the block to cellular uptake could be overcome by mixing S-Tat with a cationic liposome, Lipofectin. When mixed with Lipofectin, S-Tat effected a specific, concentration-dependent transactivation of HIV-1 LTR-directed reporter gene activity in Hela Cells. Cellular uptake was confirmed by Western blot analysis with an anti-Tat antibody. The method described utilizes cells plated in a 96-well format, requires only nanogram quantities of S-Tat protein and is much less labor-intensive than assays involving scrape-loading, making it suitable for use as a high-throughput screen for detecting Tat inhibitors. The method may have applications for the analysis of other recombinant proteins that require uptake into intact cells for determination of functionality and presents a general technique for introducing exogenous proteins into cells.

Blotting, Western↗
PubMed1997

Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: a report from the African American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators.

African Americans have excess hypertension and end-stage renal disease presumed due to hypertension compared to Caucasians. The AASK was designed to examine the impact of antihypertensive therapies and two levels of blood pressure control on the rate of decline of GFR in African Americans with presumed hypertensive renal disease. During the pilot phase of the trial, eligible participants were requested to undergo renal biopsy to assess the underlying lesions in this population. Eighty-eight hypertensive (diastolic BP > 95 mm Hg) non-diabetic African American patients between the ages of 18 to 70 years, with GFR between 25 to 70 ml/min/1.73 m2 and without marked proteinuria were assessed for possible renal biopsy. Forty-three patients did not undergo renal biopsy due to refusal or contraindications. Adequate renal biopsies were obtained in 39 of the remaining 46 patients. Biopsy findings were analyzed and then compared to clinical parameters. The 39 patients studied, 29 men and 10 women, were on average 53.0 +/- 11.0 years old, and had a MAP of 109 +/- 15 mm Hg and GFR 51.7 +/- 13.6 ml/min/1.73 m2 (not significantly different from nonbiopsied patients). Thirty-eight of these 39 biopsies showed arteriosclerosis and/or arteriolosclerosis, severity on average 1.5 +/- 0.9 and 1.5 +/- 0.8, respectively on a 0 to 3+ scale. Interstitial fibrosis was moderate, 1.3 +/- 0.9 (0 to 3+ scale). Segmental glomerulosclerosis was present in five biopsies, and in one patient, biopsy and clinical findings were consistent with idiopathic focal segmental glomerulosclerosis. Additional lesions included mesangiopathic glomerulonephritis in one patient, basement membrane thickening suggestive of diabetic nephropathy in one, and cholesterol emboli in two cases. Arteriolar and arterial sclerosis were tightly linked, and correlated with interstitial fibrosis and the reciprocal of serum creatinine. Global glomerulosclerosis was extensive, involving on average 43 +/- 26% of glomeruli. The extent of this lesion did not correlate with degree of arteriolar or arterial thickening, but did correlate with systolic blood pressure (P = 0.0174), the reciprocal of serum creatinine (P = 0.0009), serum cholesterol (P = 0.0129) and interstitial fibrosis (P < 0.0001). These data underscore that renal biopsies in non-diabetic hypertensive African-Americans with mild to moderate renal insufficiency in the absence of marked proteinuria are overwhelmingly likely to show renal vascular lesions consistent with the clinical diagnosis of hypertensive nephrosclerosis.

Adult↗
PubMed1997

Histoplasmosis and kidney disease in patients with AIDS.

Renal disease in patients infected with human immunodeficiency virus (HIV) often presents with significant proteinuria and progressive renal failure; focal glomerulosclerosis is the most common renal pathology identified. To our knowledge, we report the first case of nephrotic-range proteinuria and preserved renal function in an HIV-infected patient in association with disseminated histoplasmosis. The initial level of proteinuria was 12.5 g/24 h. The patient developed a concomitant lesion on his neck, which was biopsied and identified as Histoplasma capsulatum by fungal stains and culture. The serum CF titer of antibody against yeast antigens of H. capsulatum was 1:8. The level of serum albumin decreased to 2.0 g/dL, and the level of serum cholesterol increased to 284 mg/dL. Immunohistochemical staining of renal biopsy tissue demonstrated immune complexes within the mesangium; H. capsulatum antigen was also demonstrated in the mesangium. Therapy with oral itraconazole resulted in marked clinical improvement. The findings in this case emphasize the need to rule out treatable causes of the nephrotic syndrome in AIDS, especially in cases of immune-complex glomerulonephritis.

AIDS-Related Opportunistic Infections↗
PubMed1997

Adult age-group differences in recall for the literal and interpretive meanings of narrative text.

This study examined age differences in recall for the literal and interpretive meanings of narrative text. Following presentation of one of two stories rich in both literal and interpretive content, younger (mean age = 19.2 years) and older (mean age = 72.2 years) adults were asked to retell and to interpret the story. Response task order was counterbalanced across participants. When asked to retell a story as close to the original as possible, the younger adults recalled more of the literal propositional content than did the older adults in the retell-first, although not in the interpret-first, condition. In addition, both older and younger adults recalled more of the main ideas (gist) relative to the details. When asked to interpret the same story, more older than younger adults produced deep and synthetic representations of the story's interpretive meanings. In addition, there was a clear preference among the older age group for deep-synthetic responding. Although more younger than older adults produced analytic interpretations, within the younger group there was no clear preference for either an analytic or a deep-synthetic style.

Adolescent↗
PubMed1997

Oncogenic mutations in ras create HLA-A2.1 binding peptides but affect their extracellular antigen processing.

Point mutations in oncogene products such as ras may create neoantigenic determinants recognizable by T lymphocytes as tumor antigens, that could be marshalled to eliminate a tumor by inducing specific cytotoxic T lymphocytes (CTL) with an appropriate vaccine. Peptide-pulsed dendritic cells are a promising new approach to cancer vaccines. For such an approach to work, the determinant must be appropriately processed to the right size fragment and be presented by an appropriate HLA molecule. We have investigated both of these issues for a series of ras codon 12 and 13 point mutations that contain sequences predicted to bind to HLA-A2.1, the most common class I HLA molecule. We find that not only do the different mutations affect binding to HLA-A2.1, but also they affect extracellular antigen processing in two ways: by influencing the trimming of flanking residues from the longer sequence and by influencing the susceptibility of the optimal decamer to further proteolytic degradation. The influence of internal residues on cleavage of flanking residues downstream demonstrates the importance of distant interactions between separated amino acid side chains and/or conformational effects in determining antigen processing. These results may be important in designing an effective vaccine to induce mutant ras-specific tumor immunity.

Antigen Presentation↗
PubMed1997

Sleep disturbances in Parkinson's disease patients and spouses.

OBJECTIVES: The prevalence of self-rated sleep disturbance in patients with Parkinson's disease (PD) and their spouses was compared with healthy controls, and the association of sleep disturbance with demographic, psychological, and disease variables was assessed. DESIGN: The sleep ratings from three groups, PD patients, their spouses, and healthy controls, were compared using analyses of variance. Stepwise regressions were used to predict sleep disturbance for each group and gender. SETTING: Participants completed questionnaires as part of a nationwide survey in Germany. PARTICIPANTS: Participants included 153 PD-spouse pairs and a group of 103 healthy controls. MEASUREMENTS: Zung Self-Rating Depression Scale and self-ratings of sleep disturbance, stress level, and disease symptoms (for PD patients). RESULTS: Sleep disturbances were significantly higher in women than in men in all groups. For PD patients, sleep disturbance occurred frequently in 25% of male and 41% of female participants and was best predicted by the patient's depression rating. For spouses, frequent sleep disturbance was reported by 27% of male and 48% of females and was likewise predicted by the spouse's own rating of depression. A second, relatively less common type of sleep disturbance was also reported by spouses. This disturbance was associated with waking during the night to help the patient and was best predicted by patient factors. CONCLUSION: Improvement of sleep quality of caregivers may be an important component of treatment to reduce distress caused by PD.

Aged↗
PubMed1997

Investigation of a listeriosis epizootic in sheep in New York state.

OBJECTIVE: To investigate potential sources of an epizootic of listerial encephalitis, using molecular diagnostic and typing methods. SAMPLE POPULATION: A flock of about 655 sheep. PROCEDURE: An epizootiologic investigation was performed. Clinical, feed, and environmental samples were tested for Listeria monocytogenes, using polymerase chain reaction and culture methods; recovered isolates were "fingerprinted," using an automated ribotyping system. RESULTS: Listeria monocytogenes was recovered from brain specimens of 7 sheep with clinical signs of listerial encephalitis. All clinical isolates had fingerprints identical to those of isolates from farm equipment used to transport silage. Corn silage, which was not fed to the sheep, also contained L monocytogenes of the same pattern type as defined by ribotyping. Listeria monocytogenes was not isolated from the stored haylage designated for feeding the sheep (the cut-off point for isolation being < 10(2) colony-forming units/g). CONCLUSIONS: Corn silage was implicated as the source of a listeriosis epizootic. It appears to have cross-contaminated the haylage destined for the sheep during handling with a front-end loader. Suspension of silage feeding coincided with cessation of listeriosis cases. CLINICAL RELEVANCE: Use of advanced molecular techniques can help to identify the sources and restrict the scope of an epizootic. In epizootics, a single L monocytogenes strain can lead to infection of multiple animals, with rapid progression of the disease.

Animals↗