Genes and alcoholism: a preliminary report.
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Biomedical subjects
Publications and source records attributed to K Wheeler.
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OBJECTIVE: Assessment of the very long-acting dopamine agonist medication cabergoline in the control of motor fluctuations in Parkinson's disease. DESIGN: Open-label trial (13 weeks). SETTING: Referral centers (Mayo Clinic, Rochester, Minn, and Scottsdale, Ariz). PATIENTS: Volunteer sample of 41 patients with idiopathic Parkinson's disease who were experiencing motor fluctuations while receiving stable doses of carbidopa and levodopa. INTERVENTION: Adjunctive oral cabergoline was incrementally administered once daily with the maintenance dose determined by the clinical response (maximum dose, 5 mg/d). MAIN OUTCOME MEASURES: Standardized serial motor examinations were performed, beginning anywhere from 30 minutes before and continuing to 6 hours after test doses of medications were administered. Scores during adjunctive cabergoline therapy were compared with the prestudy baseline scores during therapy with carbidopa and levodopa without cabergoline. RESULTS: Adjunctive cabergoline therapy significantly improved mean motor scores at the time of each standardized serial examination, from 30 minutes to 6 hours after the administration of test doses of medications. Significant motor score improvement was also measured 24 hours after the last cabergoline dose was administered, suggesting a very long-acting antiparkinsonian effect. Mean dyskinesia scores were slightly but nonsignificantly elevated. Diary card "off-time" was improved by 42%, whereas the levodopa dosage was reduced by 18%. Only three patients dropped out (7% of the total), which contrasts with much higher dropout rates owing to adverse events in previous clinical trials of other antiparkinsonian dopamine agonists. CONCLUSIONS: Cabergoline improved motor control in patients with Parkinson's disease who were experiencing clinical fluctuations. Possible advantages of this medication include an extended clinical response (persisting to 24 hours), tolerability, and ease of use (once per day administration).
OBJECTIVE: This study examined patterns of diagnostic test use for patients with low back pain. Three specific questions were addressed: 1) What tests do physicians recommend for patients with 3 common types of low back pain? 2) Do physicians in various specialties differ in the tests they would order? and 3) How appropriate are physicians' choices of tests, based on current medical knowledge and expert recommendations? METHODS: A stratified national random sample of 2,604 physicians in 8 specialties was mailed questionnaires asking about the tests they would order for hypothetical patients with acute back pain, sciatica, or chronic low back pain. Physicians were also asked which procedures they generally used to evaluate suspected lumbar nerve root compression. These responses were compared with guidelines that have been suggested by the Quebec Task Force on Spinal Disorders, based on comprehensive evaluation of the scientific literature. RESULTS: Approximately 1,100 physicians responded to the survey (43% response rate). Magnetic resonance imaging was the most frequently used procedure for evaluating suspected lumbar nerve root compression, although a majority of neurosurgeons would still use myelography. Neurosurgeons and neurologists were twice as likely as other specialists to order an imaging study for patients with acute nonradiating pain or chronic back pain. Physiatrists and neurologists were more than 3 times as likely as other specialists to order electromyograms for acute back pain with sciatica or chronic back pain. Rheumatologists were almost twice as likely as other specialists to order laboratory tests for both acute and chronic back pain. The reported use of imaging and electrodiagnostic tests was generally premature and more extensive than that recommended by the Quebec Task Force. CONCLUSION: There is little consensus, either within or among specialties, on the use of diagnostic tests for patients with back pain. Thus, the diagnostic evaluation depends heavily on the individual physician and his or her specialty, and not just the patient's symptoms and findings. Furthermore, many physicians may be ordering imaging studies too early and for patients who do not have the appropriate clinical indications. These results suggest a need for additional clinical guidelines as well as better adherence to existing guidelines.
The objective of this study was to establish the validity and reliability of a visual analog scale that rates HIV-related symptom severity and general well-being. Three groups of subjects completed the HIV Assessment Tool (HAT): uninfected subjects (n = 53); people with HIV infection (n = 60), and people with CDC-defined AIDS (n = 43) according to the 1987 criteria. Test-retest reliability was .96 and Cronbach's alpha was .92. Face, content, and construct validity were established. Significant differences were found between healthy subjects and those with HIV or AIDS supporting discriminant validity. Correlation of the Karnofsky performance status with the HAT was significant (r = .51, p < .001) which demonstrated concurrent validity. Factor analysis helped identify general well-being, general symptoms, and HIV-specific symptoms. The instrument can be used to relate HIV symptoms to disease progression, and to evaluate the effectiveness of nursing interventions.
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We herein illustrate an unusual but very helpful maneuver in the localization of parathyroid adenomas that have proven difficult to find at initial surgical exploration. This case also illustrates how metabolically active thyroid tumors can interfere with the localization of parathyroid tumors when using the technetium-thallium subtraction scan technique, and a possible way of overcoming such interference.
Cross-linking of surface Ig (sIg) on resting B cells can generate intracellular signals; however, for T-dependent antigens to promote growth and differentiation additional surface receptors must be engaged. Ligation of CD40 can stimulate B cell proliferation in the presence of interleukin-4. A recently identified counterstructure for CD40 is found on T helper cells and is believed to represent the cognate ligand for B cell activation. This study investigates the role of CD40 as an accessory molecule in sIg-dependent B cell activation. Simultaneous ligation of sIg and CD40 by monoclonal antibodies (mAb) in the presence of mouse L cells which express human Fc gamma receptor type II (Fc gamma RII-L cells) results in potent stimulation of small resting B cells. When CD40 is co-ligated, picomolar concentrations of mouse IgG1 anti-mu, and anti-delta mAb can stimulate B cell proliferation. This requires interaction of the anti-Ig mAb with the Fc gamma RII-L cells: a mouse IgG2a anti-mu mAb which is not recognized by Fc gamma RII, was > or = 1000-fold less effective. These findings suggest a mechanism for B cell activation whereby engagement of T cells via CD40 and its cognate ligand provides potent enhancement of signals delivered through sIg. Based on these observations, models for the activation of B cells by T-dependent antigens are presented.
We administered cabergoline, a potent, once-a-day dopamine against, to 61 patients with advanced Parkinson's disease (PD) and response fluctuations--"wearing-off" and "on-off" phenomena. The patients were on stable doses of levodopa/carbidopa. During the first 5 weeks, patients were randomized to allow equal numbers to end titration at each of five daily doses of cabergoline from 0.5 to 2.5 mg. We evaluated the patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and diaries of motor performance. This part of the study was double-blinded. After 5 weeks, the mean Activities of Daily Living (ADL) score on the UPDRS decreased by 22% (p < 0.0001), the mean Motor Score in the "off" period decreased by 14% (p < 0.0001), and the mean Motor Score in the "on" period decreased by 22% (p < 0.0001). The mean percent "off" time decreased by 9.0%. Twenty-three patients (38%) achieved at least a 25% improvement in the combined ADL and motor examination of the UPDRS. Four patients dropped out because of adverse effects. We treated 37 patients, including some patients who had experienced a transient 25% improvement, for an additional 8 weeks in an open manner until they achieved a 25% improvement or reached a maximum of 5 mg/d. The other patients were continued in a double-blind manner on the dose of cabergoline they had achieved at the end of week 5. At the end of 13 weeks, the group of 37 patients achieved additional significant improvements in mean ADL and mean motor scores in the "on" and "off" periods. The percent time "off" decreased by 31%.(ABSTRACT TRUNCATED AT 250 WORDS)
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Bone marrow transplantation (BMT) has been recommended for children with high-risk acute lymphoblastic leukaemia (ALL) in first remission. The recent MRC UKALL X trial was designed to facilitate a non-randomised comparison between BMT and chemotherapy in children deemed to be at high risk of treatment failure. 198 children aged 1-15 had a presenting leucocyte count of more than 100 x 10(9)/l. All received induction and early intensification therapy. Children with an HLA-compatible sibling donor were eligible for BMT in first remission. All other children received cranial irradiation at 24Gy, late intensification, and two years of continuous treatment. 183 children achieved a stable remission of whom 111 were HLA typed; these tended to be older and to have T-cell ALL. A donor was identified in 41 cases, of whom 34 proceeded to BMT at a median time of 17 weeks; there was no difference in distribution of age, sex, or leucocyte count between the groups receiving BMT and chemotherapy. Comparison of the 144 children who were in remission at 17 weeks and received chemotherapy with the 34 proceeding to BMT showed no significant difference in event-free survival at five years (69% for BMT and 52% for chemotherapy). There were significantly more treatment-related deaths in the marrow transplant group (6 vs 4) and more relapses in the chemotherapy group (59 vs 4). There was no significant difference in event-free survival between children who were HLA typed and had a donor and those without a donor, although there were fewer relapses among the former. BMT can be evaluated in the context of a multicentre trial for paediatric ALL but the number of children with donors is too small to make a significant impact on overall survival. However, marrow transplantation was associated with a much lower relapse rate than that with the UK ALL protocol, and with better definition of higher risk patients BMT may be of benefit in some children with high-risk ALL in first remission.
Previous experiments have demonstrated that consumption of a glucose polymer-electrolyte (GP-E) beverage is superior to water in minimizing exercise-induced decreases in plasma volume (PV). We tested the hypothesis that elevated plasma concentrations of vasopressin and/or aldosterone above that seen with water ingestion may explain this observation. Six trained cyclists performed 115 min of constant-load exercise (approximately 65% of maximal oxygen consumption) on a cycle ergometer on two occasions with 7 days separating experiments. Ambient conditions were maintained relatively constant for both exercise tests (29-30 degrees C; 58-66% relative humidity). During each experiment, subjects consumed 400 ml of one of the following beverages 20 min prior to exercise and 275 ml immediately prior to and every 15 min during exercise: (1) distilled water or (2) GP-E drink contents = 7% carbohydrate (glucose polymers and fructose; 9 mmol.l-1 sodium; 5 mmol.l-1 potassium; osmolality 250 mosmol.l-1). No significant difference (P > 0.05) existed in mean skin temperature, rectal temperature, oxygen consumption, carbon dioxide production or the respiratory exchange ratio between treatments. Further, no significant differences existed in plasma osmolality and plasma concentrations of sodium, potassium, chloride or magnesium between treatments. Plasma volume was better maintained (P < 0.05) in the GP-E trial at 90 and 120 min of exercise when compared to the water treatment. No differences existed in plasma levels of vasopressin or aldosterone between treatments at any measurement period. Further, the correlation coefficients between plasma concentrations of vasopressin and aldosterone and change in PV during exercise were 0.42 (P < 0.05) and 0.16 (P > 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
An increasing number of nurses have become psychoanalysts in the past few years. The author discusses the process of psychoanalysis and issues related to this expanded role for nurses from her own personal experience in analytic training.
This study compared the efficacy of a 7% glucose polymer beverage containing electrolytes (GP) versus a nonnutrient, nonelectrolyte placebo (P) in maintaining blood homeostasis during recovery from football and determined whether consumption of the GP beverage improved anaerobic performance immediately after football competition when compared with the placebo. Forty-four high school football players participated in a 50-play scrimmage designed to simulate game conditions. At each of six periods before and during the scrimmage, players consumed 170 ml of the GP or P beverage. Eight maximal-effort 40-yd sprints (40-sec rest intervals) were performed before and after the scrimmage to assess the decrement in anaerobic performance from the scrimmage. Venous blood samples were drawn before and after the scrimmage and analyzed. The pre- to postscrimmage differences in mean and peak sprint velocities did not differ between treatments, nor did body weight and plasma. In contrast, the percent decrease in plasma volume was significantly greater in the P group. Postscrimmage increases in glucose and insulin were greater in the GP group. These data suggest that CHO-electrolyte drinks do not prevent a decline in anaerobic performance when compared to water, but a CHO-electrolyte drink is more effective in maintaining PV than water during recovery from anaerobic exercise.
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The purpose of these experiments was to examine the influence of various fluid replacement drinks on exercise-induced disturbances in homeostasis during heavy exercise. Nine trained cyclists performed constant load exercise on a cycle ergometer to fatigue on three occasions with 1-week separating experiments. The work rate was set initially at approximately 85% of VO2max (range 82-88%) with fatigue being defined as a 10% decline in power output below the initial value. During each experiment subjects consumed one of the following three beverages prior to and every 15 min during exercise: (1) non-electrolyte placebo (NEP; 31 mosmol.kg-1); (2) glucose polymer drink containing electrolytes (GP; 7% CHO, 231 mosmol.kg-1), and (3) electrolyte placebo drink without carbohydrate (EP; 48 mosmol.kg-1). Both the GP and EP beverage contained sodium citrate/citric acid (C) as a flavoring agent while C was not contained in the NEP drink. Although seven of nine subjects worked longer during the GP and EP treatment when compared with the NEP trial, the difference was not significant (P greater than 0.05). No differences (P greater than 0.05) existed between the GP and EP treatments in performance time. Exercise changes in rectal temperature, heart rate, delta % plasma volume and plasma concentrations of total protein, free fatty acids, glucose, lactate, potassium, chloride, calcium, and sodium did not differ (P greater than 0.05) between trials.(ABSTRACT TRUNCATED AT 250 WORDS)
Fifteen children with mediastinal non-Hodgkin's lymphoma were treated with MRC UKALL X, the current national protocol for acute lymphoblastic leukaemia. The treatment was well tolerated, and in a minimum follow up period of 46 months the event free survival of 93% was significantly better than that in a group of historical controls treated with intermittent chemotherapy regimens whose survival was only 57%. We conclude that intensive induction and consolidation treatment, with continued oral drugs, provides an effective approach to the management of mediastinal non-Hodgkin's lymphoma.
Twenty-three complex femoral fractures were treated with interlocking nails. After fracture healing, knee function was analyzed, including alignment, quadriceps and hamstring strength, thigh atrophy, and range of motion (ROM). Similar to previous studies in the preinterlocking nail era, knee function was impaired in comparison with the contralateral limb. Seventy-three percent of patients had decreased quadriceps strength, and 60% had decreased hamstring strength. Sixty-five percent had thigh atrophy. The ROM and alignment were satisfactory. Despite the advantages of early ROM with femoral fractures treated with interlocking nails, knee function is often unsatisfactory once fracture union has occurred. Therefore, a formal knee rehabilitation program is recommended to achieve an optimal result.