Sensory dynamic orthoses in mild to moderate upper limb tremor in multiple sclerosis: a mixed methods feasibility study.

OBJECTIVE: To explore the feasibility of conducting a Phase III randomized controlled trial evaluating sensory dynamic orthoses for upper limb tremor in multiple sclerosis. DESIGN: Mixed methods: double blind randomized placebo controlled pilot study and semi-structured interviews. SETTING: Rehabilitation centre. SUBJECTS: A total of 21 people with multiple sclerosis with upper limb tremor. INTERVENTIONS: Participants received a sensory dynamic orthosis sleeve or a non-compressive sleeve (placebo) that they wore eight hours a day, for nine weeks. MAIN MEASURES: Outcomes were completed at baseline and nine weeks. The primary outcome measure was the Fahn-Tolosa-Marin (FAHN) Tremor Rating Scale. Secondary outcome measures included the: Action Research Arm Test, Canadian Occupational Performance Measure, Psychological Impact of Assistive Device Scale and the Nine-hole Peg Test. RESULTS: Both sleeves were acceptable, although achieving a good fit was an issue. There were no significant between-group differences for the primary outcome measure. The median ± interquartile range change scores were 0.5 ±6.5 and 2 ±8 for the placebo and treatment group, respectively. The median ± interquartile range Canadian Occupational Performance Measure (performance subscale) demonstrated significant improvements ( p = 0.01) for the placebo group (1.1 ±1.65) compared with the treatment group (0 ±1.2). There was no between-group differences in the satisfaction subscale. The primary outcome measure was sensitive to detect change; however the Action Research Arm Test was not responsive in this study population. CONCLUSION: Undertaking an randomized controlled trial would be feasible and a minimum of 200 participants would be needed for a fully powered, definitive randomized controlled trial.

Pretest variables that improve the predictive value of exercise testing in women.

AIM: Graded exercise testing (GXT) is used in coronary artery disease (CAD) prevention and rehabilitation programs. In women, this test has a decreased accuracy and predictive value but there are few studies that examine the predictors of a verified positive test. The aim of this study was to determine those pretest variables that might enhance the predictive value of the GXT in women clients. METHODS: Medical records of 1761 patients referred for GXT's over a 5 yr period of time were screened. Demographic, medical, and exercise test variables were analyzed. The GXT's of 403 women were available for inclusion and they were stratified into 3 groups: positive responders that were subsequently shown to have CAD (N.=28 verified positive [VP]), positive responders that were not shown to have CAD (N.=84 non-verified positive [NVP]) and negative GXT responders (N.=291). Both univariate and a multivariate step-wise regression statistics were performed on this data. RESULTS: Pretest variables that differentiated between VP and NVP groups are: (an older age=65.8 vs. 60.2 yrs. P<0.05; a greater BMI=30.8 vs. 28.8 kg/m2; diabetes status or an elevated fasting glucose =107.4 vs. 95.2 mg/dL P<0.05; and the use of some cardiovascular medications. Our subsequent linear regression analysis emphasized that HDL cholesterol and beta blocker usage were the most predictive of a positive exercise test in this cohort. CONCLUSION: The American Heart Association recommends GXT's in women with an intermediate pretest probability of CAD. But there are only two clinical variables available prior to testing to make this probability decision: age and quality of chest pain. This study outlined that other pre-exercise test variables such as: BMI, blood chemistry (glucose and lipoprotein levels) and the use of cardiovascular medications are useful in clinical decision making. These pre-exercise test variables improved the predictive value of the GXT's in our sample.

Shame, guilt, and communication in lung cancer patients and their partners.

Lung cancer patients report the highest distress levels of all cancer groups. In addition to poor prognosis, the self-blame and stigma associated with smoking might partially account for that distress and prevent patients from requesting help and communicating with their partners. The present study used innovative methods to investigate potential links of shame and guilt in lung cancer recovery with distress and marital adjustment. A specific emphasis was an examination of the impact of shame on partner communication. Lung cancer patients (n = 8) and their partners (n = 8) completed questionnaires and interviews that were videotaped. We report descriptive statistics and Spearman correlations between shame and guilt, relationship talk, marital satisfaction, distress, and smoking status. We coded the interviews for nonverbal expressions of shame. Greater self-reported shame was associated with decreased relationship-talk frequency and marital satisfaction, and with increased depression and smoking behaviour. Nonverbal shame behaviour also correlated with higher depression and increased smoking behaviour. Guilt results were more mixed. More recent smoking behaviour also correlated with higher depression. At a time when lung cancer patients often do not request help for distress, possibly because of shame, our preliminary study suggests that shame can also disrupt important partner relationships and might prevent patients from disclosing to physicians their need for psychosocial intervention and might increase their social isolation. Even if patients cannot verbally disclose their distress, nonverbal cues could potentially give clinicians an opportunity to intervene.

Granular cell leiomyoma of the oral cavity.

Granular cytoplasmic change is a reported but uncommon finding in leiomyoma. Leiomyoma in the oral cavity is also uncommon, and granular cell change in oral leiomyomas, to the best of our knowledge, has not been previously reported in the English literature. Two cases of oral leiomyomas with significant granular cell change are presented. These tumors may be confused with the more common granular cell tumor, however, routine histology and immunohistochemistry aided in establishing the diagnosis. Ultrastructural studies were done for one case. Both tumors were immunoreactive for muscle markers, namely, smooth muscle actin and desmin. One of the tumors (case 2) reacted postiviely for HHF-35 and alpha-1 antitrypsin. The tumors were unreactive for S-100 protein, pancytokeratin, myoglobin, and factor VIII related antigen (case 2).

High levels of untreated distress and fatigue in cancer patients.

The purpose of the study was to assess a large representative sample of cancer patients on distress levels, common psychosocial problems, and awareness and use of psychosocial support services. A total of 3095 patients were assessed over a 4-week period with the Brief Symptom Inventory-18 (BSI-18), a common problems checklist, and on awareness and use of psychosocial resources. Full data was available on 2776 patients. On average, patients were 60 years old, Caucasian (78.3%), and middle class. Approximately, half were attending for follow-up care. Types of cancer varied, with the largest groups being breast (23.5%), prostate (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of all patients met criteria for general distress in the clinical range. A higher proportion of men met case criteria for somatisation, and more women for depression. There were no gender differences in anxiety or overall distress severity. Minority patients were more likely to be distressed, as were those with lower income, cancers other than prostate, and those currently on active treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer patients were the most distressed. Almost half of all patients who met distress criteria had not sought professional psychosocial support nor did they intend to in the future. In conclusion, distress is very common in cancer patients across diagnoses and across the disease trajectory. Many patients who report high levels of distress are not taking advantage of available supportive resources. Barriers to such use, and factors predicting distress and use of psychosocial care, require further exploration.

Cardiopulmonary evaluation of the use of medetomidine hydrochloride in cats.

OBJECTIVE: To evaluate the cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine hydrochloride in clinically normal cats. ANIMALS: 7 clinically normal cats. PROCEDURE: Cats were anesthetized with isoflurane, and thermodilution catheters were placed for measurement of central venous, pulmonary, and pulmonary capillary wedge pressures and for determination of cardiac output. The dorsal pedal artery was catheterized for measurement of arterial blood pressures and blood gas tensions. Baseline variables were recorded, and medetomidine (20 microg/kg of body weight, IM) was administered. Hemodynamic measurements were repeated 15 and 30 minutes after medetomidine administration. RESULTS: Heart rate, cardiac index, stroke index, rate-pressure product, and right and left ventricular stroke work index significantly decreased from baseline after medetomidine administration, whereas systemic vascular resistance and central venous pressure increased. However, systolic, mean, and diastolic arterial pressures as well as arterial pH, and oxygen and carbon dioxide tensions were not significantly different from baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: When administered alone to clinically normal cats, medetomidine (20 microg/kg, IM) induced a significant decrease in cardiac output, stroke volume, and heart rate. Arterial blood pressures did not increase, which may reflect a predominant central alpha2-adrenergic effect over peripheral vascular effects.

Gender differences in leucine, but not lysine, kinetics.

There is a controversy in the literature as to the effects of gender on leucine kinetics. Two research groups found that men oxidize more leucine during exercise, whereas another group showed no gender effects. The purpose of our study was to examine the effects of gender on leucine and, for comparison purposes, lysine kinetics. Our subjects (n = 14) were seven matched pairs of men and women selected for their exercise habits and age. After 1 wk of a standardized diet, they exercised at 50% of maximal O(2) uptake for 1 h. There was an effect of exercise in both genders: an increased leucine oxidation and an attenuation in nonoxidative leucine disposal compared with rest (P < 0.05). Furthermore, our study confirms that there are gender differences in leucine, but not lysine, kinetics. Men had a higher rate of leucine oxidation and a lower rate of nonoxidative leucine disposal during exercise (P < 0.05). For women, a larger proportion of their exercise energy needs came from fat; for men, a greater fraction came from carbohydrate (P < 0.05). We conclude that female exercisers rely to a greater extent on fat as an energy source, thereby using less carbohydrate, amino acid, and protein as a fuel source.

Relationship between leucine oxidation and oxygen consumption during steady-state exercise.

PURPOSE: The purpose of this study was to assess the relationship between whole-body leucine oxidation and oxygen consumption during steady-state exercise. Our hypothesis was that leucine oxidation will be responsive to increased whole-body energy needs. METHODS: Sixteen healthy individuals (7 women and 9 men) were infused with a stable isotope of leucine and, for comparison purposes, lysine during 60 min of moderate-intensity exercise. RESULTS: Leucine oxidation was increased (P < 0.05) and nonoxidative leucine disposal was decreased (P < 0.05), whereas leucine and lysine rate of appearance remained unchanged (P = NS) during exercise. Linear regression analysis indicated a modest relationship between leucine oxidation and steady-state oxygen consumption (R = 0.69; P < 0.003) during steady-state exercise. The coefficient of determination (R(2) = 0.49) indicates that approximately half of the variance in whole-body leucine oxidation during exercise can be explained by whole-body oxygen consumption. CONCLUSION: In a statistically appropriate sample size of humans whose dietary intake was controlled, the whole-body rate of leucine oxidation during exercise was only partially influenced by energy demands.

Physiology of pain.

The substantial increase in our collective knowledge of pain physiology and pharmacology over the past decade has had a significant effect on the practice of clinical veterinary medicine. An overview of the basic anatomical and physiologic components of nociceptive processing is presented, as well as a discussion of the sensitizing events that occur within the nervous system in acute and chronic pathologic pain states. The unique features of visceral and neuropathic pain are also outlined. With the goal of improving the success of our therapeutic interventions, the final section is devoted to the various classes of analgesic drugs and techniques, and how they are best incorporated into pain management strategies.

Adjunctive analgesic therapy.

Adjuvant analgesics are drugs that have weak or nonexistent analgesic action when administered alone but can enhance analgesic actions when coadministered with known analgesic agents. Such agents are often administered in cases of refractory pain. For some chronic pain syndromes, however, they may constitute a first-line approach. Because pain is such an individual experience, analgesic regimens may require several drugs at varying dosages to confer a comfortable state. Adjunctive therapies such as the tricyclic antidepressants, anticonvulsants, N-methyl-D-aspartic acid receptor antagonists and low-dose intravenous local anesthetics, to name a few, have proved to be efficacious in relieving certain types of pain, especially neuropathic and cancer pain. Their use in animals is increasing, with anecdotal reports of some success.

The major components of human energy balance during chronic beta-adrenergic blockade.

PURPOSE: The authors compare the major components of energy balance--dietary food intake, resting metabolic rate, and physical energy expenditure--in patients receiving beta-blocking medications and healthy controls. METHODS: The authors recruited subjects who were receiving beta-blocking agents (n = 22) from local hospitals and clinics. Twenty-two healthy controls were matched to each patient based on age, weight, and gender. Resting metabolic rates were determined using indirect calorimetry. Three-day dietary intakes and physical activity assessments were analyzed. RESULTS: There were no between-group differences in calories ingested or self-reported physical activity patterns. However, resting metabolic rates were lower in the beta-blocked subjects (beta-blocked = 1,541 +/- 464 kcals/day; controls = 1,817 +/- 426 kcals/day; P < 0.05). CONCLUSIONS: beta-adrenergic blockade causes a reduction in resting metabolic rate. Therefore, beta-blocked individuals should increase physical activity, decrease dietary intake, or both to maintain daily energy balance and prevent weight gain that accompanies a reduction in metabolic rate.

Setting up a pain management programme. The Ayrshire experience.

A controlled trial of an outpatient cognitive behavioural pain management programme for sufferers of non-cancer chronic pain is described. A multidisciplinary team set up a programme of ten half day sessions for groups of ten to fourteen patients aiming to improve activity levels and control over pain; to reduce maladaptive pain behaviours and drug intake; to mitigate negative mood; to modify unhelpful beliefs and to maintain treatment gains by operant and cognitive methods. Self report questionnaires were employed before and six weeks, six months and one year after the programme. Fifty-eight patients entered the study group and 39 patients completed the programme and initial follow up with further attrition in long term follow up. There were no changes in the waiting list control group of twelve subjects but the study group made significant short and long term improvements in pain severity, activity levels, mood, coping and experienced fewer catastrophizing thoughts.

Diet restriction and age alters skeletal muscle capillarity in B6C3F1 mice.

The effects of 40% diet restriction on skeletal muscle fiber area, capillary density (CD) and capillary to fiber ratio (C/F) were compared in 12, 24 and 30-month-old female B6C3F1 female hybrid mice. We hypothesized that diet restriction (DR) would retard the aging effects observed in skeletal muscle, in particular DR would pose opposite effects on skeletal muscle capillarity and fiber area. Samples were prepared for light microscopic examination by standard methods and for morphometric analysis using NIH-image software. There was a significant effect of age on muscle fiber area (p<0.05). The age-associated decrease in fiber area between 12 and 30 months of age was greater (p<0.05) in the ad libitum (AL) (37.7%) animals as compared to the diet restricted (DR) mice (29.2%). Diet had a significant effect on CD (p<0.05) and C/F (p<0.05). This finding suggests that the lower capillarity in the older DR mice may have been due to their larger muscle fibers. The results of this study support the contention that diet restriction delays the progression of age-associated muscle atrophy.

Comparison of leucine kinetics in endurance-trained and sedentary humans.

Whole body leucine kinetics was compared in endurance-trained athletes and sedentary controls matched for age, gender, and body weight. Kinetic studies were performed during 3 h of rest, 1 h of exercise (50% maximal oxygen consumption), and 2 h of recovery. When leucine kinetics were expressed both per unit of body weight and per unit of fat-free mass, both groups demonstrated an increase in leucine oxidation during exercise (P < 0.01). Trained athletes had a greater leucine rate of appearance during exercise and recovery compared with their sedentary counterparts (P < 0.05) and an increased leucine oxidation at all times on the basis of body weight (P < 0.05). However, all of these between-group differences were eliminated when leucine kinetics were corrected for fat-free tissue mass. Therefore, correction of leucine kinetics for fat-free mass may be important when cross-sectional investigations on humans are performed. Furthermore, leucine oxidation, when expressed relative to whole-body oxygen consumption during exercise, was similar between groups. It is concluded that there was no difference between endurance-trained and sedentary humans in whole body leucine kinetics during rest, exercise, or recovery when expressed per unit of fat-free tissue mass.

Paternal uniparental disomy of chromosome 6 and transient neonatal diabetes mellitus.

Transient neonatal diabetes mellitus occurs in growth-retarded infants, has an incidence of 1 in 400000 live births and has been associated with both paternal uniparental disomy of chromosome 6 and paternal duplications of 6q. We analysed samples from our cohort of patients with transient neonatal diabetes mellitus for uniparental disomy of chromosome 6 using polymorphic microsatellite repeat analysis. We report here the fifth case of paternal uniparental disomy of chromosome 6 associated with classic transient neonatal diabetes mellitus and estimate that uniparental disomy of chromosome 6 accounts for approximately one fifth of cases of transient neonatal diabetes mellitus.

Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy.

OBJECTIVE: To use information collected by the Confidential Enquiry into Stillbirths and Deaths in Infancy to help obstetric, midwifery and paediatric practice in the management of shoulder dystocia. DESIGN: Review of casenotes by a multidisciplinary focus group. SAMPLE: All 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy from England, Wales and Northern Ireland in 1994 and 1995, where stillbirth or neonatal death was attributed to shoulder dystocia. MAIN OUTCOME MEASURES: Case notes were reviewed with respect to a range of perinatal variables. Comparisons were made with normative data from other studies when appropriate. RESULTS: Maternal obesity and big babies were over-represented in pregnancies complicated by fatal shoulder dystocia. Fetal compromise was recorded in 26% of labours. The median time interval between delivery of the head and the rest of the body was only five minutes. The lead professional at the time the head was delivered was a midwife in 65% of cases. Middle grade or senior obstetric staff were supervising 47% of cases by the time the body was delivered. CONCLUSIONS: Antenatal prediction of shoulder dystocia is imprecise, and the majority of deliveries are attended by midwives. A relatively brief delay in delivery of the shoulders may be associated with a fatal outcome.

Beta 1-adrenoreceptors regulate resting metabolic rate.

This was a randomized, cross-over experiment designed to determine which beta-adrenergic receptors, beta 1, beta 2, or both, regulate metabolic rate in humans. All subjects (3 women, 4 men) were administered a 7-d therapeutic dose of a selective beta 1-antagonist (atenolol 50 mg BID), a combined beta 1, beta 2-antagonist (propranolol 80 mg BID), and a placebo control (BID). Indirect calorimetry was determined before and after 1 h of submaximal exercise. Exercise was performed at 50% of the trial specific VO2peak because maximal exercise was significantly decreased in the presence of the nonselective beta 1, beta 2-antagonist (VO2peak placebo: 44.90 +/- 4.40 mL.kg-1.min-1 vs beta 1, beta 2-antagonism: 39.20 +/- 3.00 mL.kg-1.min-1; P < 0.05). Both the beta 1 and the combined beta 1, beta 2-adrenoreceptor antagonists reduced resting oxygen consumption to a similar extent (0.247 +/- 0.007 L.min-1 placebo, vs 0.218 +/- 0.007 L.min-1 beta 1-antagonism, vs 0.226 +/- 0.007 L.min-1 beta 1, beta 2-antagonism; P < 0.05). However, the 30-min and 60-min excess post-exercise oxygen consumption (mean EPOC) remained unchanged. It is concluded that the beta 1-receptors are regulating the effects of the sympathetic nervous system on resting but not exercise recovery metabolic rate. These metabolic side effects may suggest that changes need to be made in the nutritional requirements of patients using beta-adrenergic antagonists.