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Biomedical subjects

R S Wilson

Publications and source records attributed to R S Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1988

New intrathecal drugs in Alzheimer's disease and psychometric testing.

Bethanechol chloride, a muscarinic agonist, was administered intrathecally to a sample of AD patients in double-blind crossover and open escalating-dose trials. There was a modest amelioration of disturbed behavior at a moderately high dose level, but no improvement in memory or cognition was seen at any dose. At the highest dose, cognition deteriorated. These findings, in conjunction with the results of the multicenter trial described by Harbaugh, suggest that the clinical efficacy of bethanechol in AD is limited. The disappointing results of trials with varied cholinomimetic therapies suggest that more than one biochemical abnormality is responsible for the AD dementia. The neuropeptide, somatostatin, is also reduced in AD, and the level of reduction is correlated with the degree of dementia. Manipulation of this transmitter, alone or in conjunction with acetylcholine, would appear to be a next logical step in the development of an effective neurotransmitter replacement therapy for AD. Implanted drug pumps will be needed for such clinical trials. The naturally occurring somatostatin-14 is not suitable because of its short half life. Sandostatin, an analog, is chemically stable and not metabolized by brain tissue. It does not cross the blood-brain barrier so that intrathecal administration is necessary. Pharmacological research in AD is complicated by a variety of psychometric problems including the criterion-related and construct validity of the outcome measures. Patients differ in their tolerance of various therapeutic agents and in the extent of the neurochemical pathology. It is critically important, therefore, to evaluate individual, as well as group, responses to treatment. The telephone log method may provide a useful way of generating enough observations for single subject analyses without overburdening the patient with repeated testing.

Activities of Daily Living↗
PubMed1988

Intraventricular bethanechol infusion for Alzheimer's disease: results of double-blind and escalating-dose trials.

Ten patients with biopsy-proven Alzheimer's disease (AD) received low-dose (0.35 mg/d) intraventricular bethanechol, a muscarinic agonist, and saline placebo in a 24-week double-blind crossover design. Eight of these ten patients later participated in an open escalating-dose (to 1.75 mg/d) trial of bethanechol. Patients' drug responses were assessed by neuropsychological examination and informant measures of activities of daily living, mood disturbance, and abnormal behavior. Bethanechol appears to have a narrow therapeutic window for positive effects; low doses did not reliably alter patient functioning, moderately increased doses appeared to have a palliative effect on patient mood and behavior, and the highest dose was detrimental to patient functioning. Bethanechol does not appear to ameliorate the dementia of AD, but may exert a mildly positive effect on patient behavior and mood.

Aged↗
PubMed1988

Relationship of aluminum to neurocognitive dysfunction in chronic dialysis patients.

Aluminum has been proposed as the causative agent in dialysis encephalopathy syndrome. We prospectively assessed whether other, less severe, neuropsychologic abnormalities were also associated with aluminum. A total of 16 patients receiving chronic dialytic therapy were studied. The deferoxamine infusion test (DIT) was used to assess total body aluminum burden. Neurologic function was evaluated by quantitative measures of asterixis, myoclonus, motor strength, and sensation. Cognitive function was assessed by measures of dementia, memory, language, and depression. There were four patients with a positive DIT (greater than 125 micrograms/L increment in serum aluminum) that was associated with an increase in the number of neurologic abnormalities observed, as well as an increase in severity of myoclonus, asterixis, and lower extremity weakness. Patients with a positive DIT also showed significant impairment in memory; however, no differences were noted on tests of dementia, depression, or language. There was no significant correlation between sex, age, presence of diabetes, mode of dialysis, years of chronic renal failure, years of dialysis or years of aluminum ingestion and any neurologic or neurobehavioral measurement, serum aluminum level, or DIT. These changes may represent early aluminum-associated neurologic dysfunction.

Adult↗
PubMed1987

Clonidine and Gilles de la Tourette's syndrome: double-blind study using objective rating methods.

Clonidine has been suggested to be effective in Gilles de la Tourette's syndrome (GTS), but no double-blind study has ever evaluated its effects using objective measures. Thirty patients with GTS completed a 6-month placebo-controlled crossover study of the effectiveness of clonidine. Videotapes were obtained at each 3-week visit and were evaluated randomly at the end of the study for distribution, frequency, and severity of motor and vocal tics. Quantifiable psychometric examinations were performed as well. The use of clonidine did not significantly (p less than 0.05) reduce motor tics, vocalizations, or behavior. The effect of a low dose (0.0075 mg/kg/day) was no different from that of a high dose (0.015 mg/kg/day); children's responses were no different from adults'; and those also receiving neuroleptic agents showed the same lack of efficacy as seen in patients on no other medication. Dosing schedule did not affect the objective ratings; scores from clonidine given twice a day were equivalent to those for three times a day.

Adolescent↗
PubMed1987

A new method for representing mental growth.

A new method is described for plotting the growth in mental development from birth to adolescence. Using data from a large sample of twins followed since birth, a dimension of mental growth was constructed by arraying all tests in order of difficulty, then computing the average gain from age to age. The gain was expressed in standard-deviation units, which reflected the upward shift in the score distribution from time X to time X + 1. When cumulated over ages, the scores generated a mental growth curve for the sample as a whole, as well as for each case individually. The curves displayed a very rapid gain in mental growth over the first 24 months of life, with the complexity of mental functions advancing by nearly 20 standard deviations from birth to two years. Thereafter the gain progressively tapered off until reaching a final increment of 0.5 SD gain between 15 years and adulthood. At this point, the terminal level of mental growth reached an average value of 31 SD units, with a spread of individual differences equal to +/- 3 SD units. The scores at each age represented a combination of base level plus gain from the preceding age, and during infancy the gain scores were large in relation to base. At later ages, however, the gain scores were comparatively small, both in absolute terms and in relation to base. These characteristics help explain the typical low-order correlations obtained among mental test scores during infancy, vs the progressively larger correlations obtained at later ages.

Adolescent↗
PubMed1987

Memory failure in Huntington's disease.

Patients with Huntington's disease (HD) were compared to normal controls of equivalent age and verbal intelligence on a set of verbal learning tasks. Although the HD patients showed the expected deficit in secondary (long-term) memory, their performance was otherwise comparable to that of the control groups. Primary (short-term) memory was normal, there was normal sensitivity to proactive interference, and the patients showed an advantage, albeit reduced, in recall of related compared to unrelated word lists. The findings suggest that mnemonic input is encoded semantically in HD though less efficiently than in unafflicted individuals, and that difficulty accessing information in semantic (knowledge-based) memory may be partially responsible for the memory disorder of HD.

Adolescent↗
PubMed1987

Cortical biopsy results in Alzheimer's disease: correlation with cognitive deficits.

Neuropsychologic and pathologic data are presented for a group of 11 patients with a clinical diagnosis of probable Alzheimer's disease (AD) according to recently proposed criteria. In all cases, the diagnosis was verified by cortical biopsy. In addition, increased cortical plaque counts were associated with greater deficits in language production and comprehension and poorer performance on an index of global mental status. These results suggest that a clinical diagnosis of AD is very accurate when patient selection is restricted to typical cases and that language deficits may provide a useful indicator of severity of disease in AD patients.

Aged↗
PubMed1987

A rating scale for Gilles de la Tourette's syndrome: description, reliability, and validity data.

We developed a rating scale for tic disorders that uses only objective criteria and accommodates the variety of tic manifestations. Using short videotaped recordings with the examiner out of the taping room, we measured five tic variables: number of body areas affected, frequency of motor tics and vocalizations, and severity of motor tics and vocalizations. The rating scale fulfilled tests for inter-rater reliability and temporal stability, and correlated well with scales used to assess global changes over prolonged periods. It objectively detected improvement in tics with neuroleptics, the one pharmacotherapy accepted to abate tics in most patients.

Clonidine↗
PubMed1986

Pain in Parkinson's disease.

We studied the prevalence and character of pain in Parkinson's disease (PD) and its association with motor fluctuations. Of 95 outpatients, 46% experienced pain they attributed to PD. Patients with pain were younger but no more disabled on objective motor scores than patients without pain. Musculoskeletal, dystonic, and joint pains were most frequent. Painful episodes, especially musculoskeletal cramps, usually occurred when parkinsonian disability was maximal.

Age Factors↗
PubMed1986

A model of deposition and embolization of proteins and platelets on biomaterial surfaces.

A theoretical model for the deposition and detachment of protein and platelets on biomaterial surfaces is presented here. This work is an extension of the model previously reported. Two mechanisms of protein and platelet removal are assumed: A characteristic time elapses before adsorbed protein detaches from the surface, carrying away platelets and protein which have deposited on top of it; and thrombi that attain a critical size are subject to hydrodynamic forces which embolize them from the surface. A theoretical distribution of thrombus sizes is assumed. Analysis of the effects of varying model parameters on predicted protein and platelet deposition reveals that the addition of the embolization process does not change the overall structure of the deposition profiles, but does significantly affect the finer details.

Adsorption↗
PubMed1986

Changes in salbutamol concentration in the reservoir solution of a jet nebulizer.

An increase in concentration of salt in the reservoir solution of jet nebulizers driven by dry compressed gas has been observed but changes in salbutamol concentration have not been investigated; therefore: Concentration changes were observed following 10 minutes nebulization for two driving sources and starting volumes. Using an electric compressor, the time courses of changes in drug concentration and output were observed for a 5 mg dose of salbutamol in 2 and 4 ml starting volumes. Changes in drug concentration were smaller for a 4 ml starting volume and for compressor driven nebulizers. Salbutamol concentration increased with the length of nebulization and the rate of increase was inversely related to starting volume. There was poor agreement between fluid and drug output for the 2 ml starting volume and drug output did not increase significantly when nebulization exceeded 4 minutes. For the 4 ml fill there was closer agreement between fluid and drug output and drug output exceeded that for the 2 ml fill after 10 minutes. In conclusion, fluid output alone is an inadequate measure of drug output and changes in drug concentration cannot be overlooked when assessing nebulizers for nebulizer therapy.

Aerosols↗
PubMed1986

Cognitive assessment in Alzheimer's disease: cross-sectional and longitudinal perspectives.

This paper describes select results of a longitudinal study of 62 mild to moderate Alzheimer's disease (AD) patients, in comparison to 60 age-matched healthy controls. Initial neurologic, radiologic, psychiatric, laboratory and cognitive examinations, required two full days, followed by one-day examinations at annual intervals. Of the total original sample, 31 AD patients and 39 controls could actually be followed for three annual examinations. Cognitive examination data confirmed cross-sectional (group discriminative) validity of memory and language measures, and showed the expected longitudinal deterioration in the AD sample, with controls maintaining consistent performance over the three years. However, those measures showing largest group differences at initial examination were not the best for tracking patient deterioration over time. Implications of these results for the selection of cognitive assessment measures are discussed.

Alzheimer Disease↗
PubMed1986

Interpretation of pulmonary artery wedge pressure and pullback blood gas determinations during positive end-expiratory pressure ventilation and after exclusion of the bronchial circulation in the dog.

Left atrial pressure (LAP) and pulmonary artery wedge pressure (PWP) were measured at different heights during graded increases in positive end-expiratory pressure (PEEP). Six healthy anesthetized dogs were placed in lateral decubitus positions with a balloon-tipped pulmonary artery catheter inserted in each lung. PWP in the gravitationally superior lung overestimated LAP at 15 and at 20 cm H2O PEEP (p less than 0.05). PWP in the dependent lung was virtually identical to LAP at all degrees of PEEP. Wedge blood could be aspirated through the distal lumen of the pulmonary artery catheters during balloon inflation at all degrees of PEEP except for 3 attempts. PCO2 in wedge blood in both the nondependent and dependent lungs at all degrees of PEEP was consistently lower than PCO2 in arterial blood (p less than 0.05). Wedge blood was arterialized, i.e., oxygen saturation greater than 95%, in all but 4 specimens. Surgical elimination of the bronchial artery supply to the lung in 3 dogs did not affect PWP or blood gas measurements. We conclude that in this animal model: (1) the tip of a pulmonary artery catheter must be below the level of the left atrium, Zone III location, to accurately reflect LAP at high degrees of PEEP; (2) arterialization of wedge blood samples does not guarantee that PWP reflects LAP; (3) bronchial artery blood supply does not affect PWP or wedge blood gas measurements, even at high degrees of PEEP.

Animals↗