Neuroendocrine mechanisms underlying sensory integration of social signals.

Individuals integrate information about their environment into adaptive behavioural responses, yet how different sensory modalities contribute to these decisions and where in the brain this integration occurs is not well understood. We presented male cichlid fish (Astatotilapia burtoni) with sensory information in three social contexts: intruder challenge, reproductive opportunity and a socially neutral situation. We then measured behavioural and hormonal responses along with induction of the immediate early gene c-Fos in candidate forebrain regions. In the intruder challenge context, males were exposed to either a visual stimulus of a dominant male, the putative male pheromone androstenedione, or both. We found that, compared to the neutral context, a visual stimulus was necessary and sufficient for an aggressive response, whereas both chemical and visual stimuli were needed for an androgen response. In the reproductive opportunity context, males were exposed to either a visual stimulus of a receptive female, a progesterone metabolite (female pheromone) only, or both. We further found that the visual stimulus is necessary and sufficient for an androgen response in the reproductive opportunity context. In the brain, we observed c-Fos induction in response to a visual challenge stimulus specifically in dopaminergic neurones of area Vc (the central region of the ventral telencephalon), a putative striatal homologue, whereas presentation of a chemical stimulus did not induce c-Fos induction in the intruder challenge context. Our results suggest that different sensory cues are processed in a social context-specific manner as part of adaptive decision-making processes.

Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of autonomic and urologic disorders and low back and head pain. METHODS: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and the selected indications. Authors reviewed, abstracted, and classified articles based on the quality of the study (Class I-IV). Conclusions and recommendations were developed based on the highest level of evidence and put into current clinical context. RESULTS: The highest quality literature available for the respective indications was as follows: axillary hyperhidrosis (two Class I studies); palmar hyperhidrosis (two Class II studies); drooling (four Class II studies); gustatory sweating (five Class III studies); neurogenic detrusor overactivity (two Class I studies); sphincter detrusor dyssynergia in spinal cord injury (two Class II studies); chronic low back pain (one Class II study); episodic migraine (two Class I and two Class II studies); chronic daily headache (four Class II studies); and chronic tension-type headache (two Class I studies). RECOMMENDATIONS: Botulinum neurotoxin (BoNT) should be offered as a treatment option for the treatment of axillary hyperhidrosis and detrusor overactivity (Level A), should be considered for palmar hyperhidrosis, drooling, and detrusor sphincter dyssynergia after spinal cord injury (Level B), and may be considered for gustatory sweating and low back pain (Level C). BoNT is probably ineffective in episodic migraine and chronic tension-type headache (Level B). There is presently no consistent or strong evidence to permit drawing conclusions on the efficacy of BoNT in chronic daily headache (mainly transformed migraine) (Level U). While clinicians' practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data.

Intrathecal baclofen in the treatment of spasticity.

Spasticity is a disorder of the sensorimotor system resulting in velocity-dependent increased muscle tone and tendon reflexes. Intrathecal baclofen is currently the most effective means of treating diffuse abnormal spasticity of both cerebral and spinal origin in the adult and pediatric patient. Careful patient assessment, selection and continued therapies are essential to a successful intrathecal baclofen management program. Once a patient receives a baclofen pump, close monitoring is needed for dose adjustment and pump problems. Baclofen overdose and withdrawal by either system failure or human error can cause significant side effects and be life threatening. Excellent understanding of the baclofen delivery system, programming and dose effects are needed to evaluate any patient complaints. Future uses of intrathecal pump therapy includes use of other intrathecal drugs besides baclofen (or in combination with baclofen) and the effects of placing the catheter tip at various spinal levels. At the University of Minnesota, Sister Kenny Institute and Gillette Children's Specialty Healthcare our experience has shown excellent results with this form of therapy over the last 12-16 years.

Geographic differences in event rates by model for end-stage liver disease score.

The ability of the model for end-stage liver disease (MELD) score to accurately predict death among liver transplant candidates allows for evaluation of geographic differences in transplant access for patients with similar death risk. Adjusted models of time to transplant and death for adult liver transplant candidates listed between 2002 and 2003 were developed to test for differences in MELD score among Organ Procurement and Transplantation Network (OPTN) regions and Donation Service Areas (DSA). The average MELD and relative risk (RR) of death varied somewhat by region (from 0.82 to 1.28), with only two regions having significant differences in RRs. Greater variability existed in adjusted transplant rates by region; 7 of 11 regions differed significantly from the national average. Simulation results indicate that an allocation system providing regional priority to candidates at MELD scores > or = 15 would increase the median MELD score at transplant and reduce the total number of deaths across DSA quintiles. Simulation results also indicate that increasing priority to higher MELD candidates would reduce the percentage variation among DSAs of transplants to patients with MELD scores > or = 15. The variation decrease was due to increasing the MELD score at time of transplantation in the DSAs with the lowest MELD scores at transplant.

Long term effects of intra-articular botulinum toxin A for refractory joint pain.

UNLABELLED: The purpose of this case series review is to describe our 12 month clinical experience with intra-articular injections of Botulinum toxin Type A (BoNT/A) for refractory joint pain. Eleven patients with chronic arthritis who had failed treatment with oral and/or intra-articular medications and were not surgical candidates were referred to us for management of moderate to severe refractory joint pain in 15 joints. The use of BoNT/A to treat joint pain is a non-FDA approved "off label" treatment with potential side effects. After a detailed explanation of the joint injection procedure, signed informed consent was obtained for the procedure. Fifteen joints were injected with BoNT/A (Allergan, Inc): six lower extremity joints (3 knees, 3 ankles) with 25-50 units and nine shoulders with 50-100 units. Patients were followed for one year or longer. Maximum relief of pain was measured by comparing baseline pain on a numeric rating scale (0-10) to pain at the time of maximum relief (paired t-test). Maximum improvement in function was assessed using paired t-tests for improvement in active flexion and abduction for the shoulder joint, and by the time to perform sit to stand ten times (the timed stands test, TST) for the lower extremity joints. RESULTS: Two patients were female and nine were male, aged 42-82 years. Five had osteoarthritis (OA), five had rheumatoid arthritis (RA) and one had psoriatic arthritis. All patients were on analgesic and/or anti-inflammatory medications and all joints had previous intra-articular steroid or viscosupplement injections with inadequate or unsatisfactory benefit. A clinically and statistically significant improvement was noted after IA-BoNT/A injections. The mean maximum decrease in lower extremity joint pain was 55% (p =0.02) and the 36% (p =0.044) improvement in the Timed Stands Test was noted at four to ten weeks after injection. There was a 71% mean maximum reduction in shoulder pain severity from 8.2 +/- 1.1 to 2.4 +/- 1.9 (p <0.001). Active range of motion increased 67% in flexion (from 67.8 +/- 27.6 to 113.3 +/- 46.6 degrees, p =0.001) and 42% in abduction (from 50 +/- 18.5 degrees to 71.1 +/- 23.1 degrees p =0.01). No immediate or delayed adverse effects related to BoNT/A were noted after the injection. Duration of pain relief was variable and ranged from 3 to 12 months. Five joints were re-injected with IA-Bont/A and had a similar decrease in joint pain that lasted 3 to 12 months. CONCLUSIONS: This is the first report of the long term effects of intra-articular BoNT/A injections to treat chronic joint pain and the efficacy of repeated injections. Although this study was small, and uncontrolled the results suggest that IA-BoNT/A injections are an effective and safe treatment for chronic joint pain disorders.

Characteristics associated with liver graft failure: the concept of a donor risk index.

Transplant physicians and candidates have become increasingly aware that donor characteristics significantly impact liver transplantation outcomes. Although the qualitative effect of individual donor variables are understood, the quantitative risk associated with combinations of characteristics are unclear. Using national data from 1998 to 2002, we developed a quantitative donor risk index. Cox regression models identified seven donor characteristics that independently predicted significantly increased risk of graft failure. Donor age over 40 years (and particularly over 60 years), donation after cardiac death (DCD), and split/partial grafts were strongly associated with graft failure, while African-American race, less height, cerebrovascular accident and 'other' causes of brain death were more modestly but still significantly associated with graft failure. Grafts with an increased donor risk index have been preferentially transplanted into older candidates (>50 years of age) with moderate disease severity (nonstatus 1 with lower model for end-stage liver disease (MELD) scores) and without hepatitis C. Quantitative assessment of the risk of donor liver graft failure using a donor risk index is useful to inform the process of organ acceptance.

Clenbuterol in the prevention of muscle atrophy: a study of hindlimb-unweighted rats.

OBJECTIVE: To determine whether the administration of clenbuterol, a beta2-adrenergic agonist, prevents loss of muscle mass during a period of imposed inactivity. DESIGN: Randomized trial. SETTING: Basic laboratory research. ANIMALS: Thirty Fischer 344 Brown Norway F1 Hybrid rats, 12 and 30 months of age. INTERVENTIONS: The rats were randomly assigned to a control group, or to 1 of 2 experimental groups: hindlimb unweighted for 2 weeks (HU-2), or hindlimb unweighted with daily injections of clenbuterol for 2 weeks (HU-2Cl). MAIN OUTCOME MEASURES: Muscle mass weighed in milligrams and single fiber cross-sectional area histochemically evaluated. RESULTS: In both age groups, the HU-2 animals had greater muscle atrophy (decrease in muscle mass) in the soleus muscle than the extensor digitorum longus (EDL) muscle. In the HU-2Cl groups, the decline in muscle mass of both the soleus and EDL muscles was attenuated by about 4% to 20%. In the HU-2 group, single fiber cross-sectional area decreased for both fiber types (type I, 20%-40%; type II, 37%-50%) in both age groups. Clenbuterol retarded the inactivity-induced decline in single fiber cross-sectional area by 12% to 50%. In the EDL muscles of the HU-2Cl group, we found hypertrophy in both fiber types in the 30-month-old animals and in type I fibers in the 12-month-old animals. CONCLUSIONS: Clenbuterol attenuated the decrease in muscle mass and single fiber cross-sectional area in both age groups. By preventing the loss of muscle mass, clenbuterol administered early in rehabilitation may benefit severely debilitated patients imposed by inactivity. The attenuated muscle atrophy found with clenbuterol in the present study provides cellular evidence for the reported change in muscle strength after its administration after knee surgery. Thus, the administration of clenbuterol may lead to a more rapid rate of rehabilitation.

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.

Doxorubicin chemomyectomy as a treatment for cervical dystonia: histological assessment after direct injection into the sternocleidomastoid muscle.

The sternocleidomastoid muscle (SCM) is one of the major muscles involved in producing abnormal head position in cervical dystonia patients. This study tested whether doxorubicin chemomyectomy, direct injection of doxorubicin into the SCM to permanently remove muscle fibers, has the potential to be a nonsurgical, permanent treatment for cervical dystonia. The right SCM of rabbits was injected with either 1 or 2 mg doxorubicin. Animals were sacrificed 1-2 months postinjection. The SCM was prepared for histological examination of muscle fiber loss and fiber type composition. In all cases, direct injection of doxorubicin resulted in significant decreases in total muscle cross-sectional areas ranging from 75% up to 98%. Individual myofiber cross-sectional areas were smaller than normal after 2 mg doxorubicin treatment, but similar to normal fiber size after 1 mg doxorubicin. There were increased numbers of myofibers that expressed slow and neonatal myosin heavy chain isoforms in these remaining muscle fibers compared to the untreated SCM on the contralateral side. Developmental myosin heavy chain (MHC) was also present in 53% of the remaining myofibers of the treated muscles. The fiber type composition of muscles contralateral to the doxorubicin injections was compared to the fiber type composition of SCM from normal, untreated controls; no difference was seen in the proportions of fast, slow, and neonatal MHC fiber types in these SCM muscles. In summary, the direct injection of doxorubicin into the SCM resulted in significant muscle loss. This supports the use of doxorubicin chemomyectomy as a potential permanent, nonsurgical treatment for cervical dystonia.

Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia.

We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested.

Long-term survival after surgical revascularization for atherosclerotic renal artery disease.

PURPOSE: We analyzed the long-term clinical outcome and survival after surgical revascularization for atherosclerotic renal artery stenosis. MATERIALS AND METHODS: The study group comprised 222 patients who underwent surgical revascularization for atherosclerotic renal artery stenosis between 1974 and 1987. The indications for performing surgical revascularization were treatment of hypertension in 60 patients, preservation of renal function in 12, and control of hypertension and preservation of renal function in 148. Postoperative blood pressure, renal function and survival data were analyzed during a mean followup of 7.4 years. RESULTS: There were 5 operative deaths (2.2%) and postoperative thrombosis or stenosis of the repaired renal artery occurred in 16 patients (7.3%). Long-term cure or improvement of renovascular hypertension was achieved in 72.4% of patients. Preoperative renal function correlated significantly with a favorable blood pressure response to surgical revascularization (p = 0.013). Long-term improvement or stabilization of renal function was achieved in 71.3% of patients. Preoperative renal function (p = 0.034) and bilateral atherosclerotic renal artery stenosis (p = 0.04) correlated significantly with a favorable renal function result after surgical revascularization. Actuarial 5 and 10-year survivals for the entire series from the time of surgical revascularization were 81 and 53%, respectively. The expected 5 and 10-year survivals for a comparable healthy population are 89 and 77%, respectively. Using a multivariate analysis, factors correlating with diminished long-term survival were age older than 60 years (p = 0.002), coronary artery disease (p = 0.031), and previous vascular operations (p = 0.001). CONCLUSIONS: These data support the long-term therapeutic efficacy of surgical revascularization in patients with atherosclerotic renal artery stenosis. The merits of newer forms of therapy, such as percutaneous transluminal angioplasty and endovascular stenting, must ultimately be weighed against these results.

A surface swab method for culturing Foley catheters assays the pericatheter (urethral) but not the urine (luminal) microbial population.

Assessment of the urethral flora in patients with indwelling bladder catheters is problematic in the presence of urinary tract infection (UTI). A new surface swab method that samples the external catheter surface without interference from contaminated luminal contents is described. In vitro, recovery of adherent bacteria from the external catheter surface by the surface swab method was proportional to the bacterial density as measured by a comparison scrape method. In a prospective longitudinal assessment of three chronically catheterized subjects with polymicrobial catheter-associated UTI, a conventional roll plate catheter culture method suggested substantial overlap between the urethral and urine microbial populations, possibly a result of contamination of catheter cultures by infected urine. In contrast, the surface swab method revealed little overlap between these floras, evidence suggesting a predominantly luminal (rather than meatal) route of UTI acquisition. The new surface swab method should prove useful in future studies of the pathogenesis and prevention of catheter-associated UTI.

Central nervous system ischemia after varicella infection and desmopressin therapy for enuresis.

A 7-year-old boy had a left-sided cerebrovascular accident 48 hours after beginning intranasal desmopressin acetate (DDAVP) therapy for persistent secondary nocturnal enuresis and approximately 2 weeks after varicella infection. A possible connection between desmopressin therapy or varicella infection (or both) and the patients neurologic symptoms is discussed, as is the relationship of desmopressin with hypercoagulability, Suggestions for patient/parent education, medical history taking, and patient surveillance are offered to prescribing physicians.

Quantitative measurement of cervical range of motion in patients with torticollis treated with botulinum A toxin.

Improvement in cervical range of motion in patients with spasmodic torticollis by botulinum A toxin injection is difficult to objectively measure. Recently, a three-dimensional cervical range of motion system (EMROM) that measures primary as well as secondary cervical angles has been developed. This system uses an electromagnetic tracking system for data collection and a personal computer for analysis and graphic display of the data. We have tested the EMROM system and, from our results, believe that it can be used clinically to objectively and accurately measure cervical range of motion in patients who have spasmodic torticollis and who receive botulinum toxin injections.

[An economic comparison between digital luminescence radiography and conventional film processing in intensive care medicine]. / Wirtschaftlichkeitsvergleich zwischen Digitaler Lumineszenzradiographie und konventioneller Filmverarbeitung in der Intensivmedizin.

The costs of a conventional film-screen radiography daylight-system and storage-phosphor computed radiography (Fuji AC-1) are compared. In 1990, 3841 radiologic procedures (mostly portable chest X-rays) were performed in 3474 patients of a surgical intensive care unit. With conventional film-screen radiography 6.8% retakes were necessary for diagnostic or technical reasons. Comparing the fixed and variable costs of both systems conventional film-screen radiography was more economic under the given conditions of the test. It is concluded that computed radiography in intensive care patients has definite advantages in terms of image quality and reproducibility, however, in order to compete successfully in the economic turf CR has to be implemented in a picture archiving and communication system (PACS).

A functional electric stimulation system using an electrode garment.

A functional electric stimulation system for standing and ambulating that uses a commercially available electrode garment has been developed. The garment allows electrodes to be applied rapidly and securely. Two channels of a four-channel stimulator are used to stimulate the quadriceps muscles and permit the user to stand. The other two channels are used to stimulate the peroneal nerve, which causes a flexor withdrawal reflex and permits stepping. The user controls stepping by hand-held switches. The system provides a means for standing, exercising, and limited ambulation.

Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a double-blind study.

The ability of botulinum A toxin to denervate and relax a spastic external urethral sphincter was evaluated in a double-blind study involving five men with high spinal cord injuries and detrusor-sphincter dyssynergia. The sphincter was injected with either a low dose of botulinum A toxin or normal saline once per week for three weeks. Electromyography of the external urethral sphincter indicated denervation in the three patients who received toxin injections. The urethral pressure profile decreased an average of 25cm of water, postvoiding residual volume of urine decreased an average of 125cc, and bladder pressure during voiding decreased to an average of 30cm of water. Bulbosphincteric reflexes were more difficult to obtain, and they showed a decreased amplitude with normal latency. In the two patients who received normal saline injections, parameters were unchanged from baseline values until subsequent injection with botulinum A toxin once per week for three weeks when their responses were similar to those of the other three patients. Mild generalized weakness lasting two to three weeks was noted by three patients after initial toxin injections. The duration of the toxin's effect averaged two months. The results suggest that botulinum A toxin, an inhibitor of acetylcholine release at the neuromuscular junction, may be useful in the treatment of detrusor-sphincter dyssynergia.

Augmentation enterocystoplasty for the management of voiding dysfunction in spinal cord injury patients.

A total of 12 spinal cord injury adults underwent augmentation enterocystoplasty for treatment of a high pressure neurogenic bladder. These patients suffered from urinary incontinence, recurrent urinary tract infection, upper tract deterioration and severe autonomic dysreflexia. A sigmoid colon segment fashioned into a cup-patch was used in 11 patients and detubularized cecum was used in 1. The artificial urinary sphincter was implanted in 3 patients at augmentation enterocystoplasty and in 1 after enterocystoplasty. After a mean followup of 15 months all patients were continent on clean intermittent self-catheterization, the upper tract had remained stable or had improved and the symptoms of autonomic dysreflexia had disappeared. A third of the patients are on maintenance antibiotic therapy to control bacteriuria.

Pediatric rehabilitation. 6. Musculoskeletal and soft tissue disorders.

This self-directed learning module highlights advances in evaluation and treatment of congenital and acquired musculoskeletal disorders in the child. It is a section of the chapter on pediatric rehabilitation for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. This section contains information on alterations of limb structure and gait, scoliosis, torticollis, sports injuries and overuse syndromes, and unexplained pain in children.

Pediatric rehabilitation. 1. General principles and special considerations.

This self-directed learning module addresses core concepts in the assessment of any child with disability, including physical growth and development, evolution of reflexes, and cognitive and personality development. It is a section of the chapter on pediatric rehabilitation for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. The rehabilitation perspective is emphasized, especially as it changes to accommodate the developing child, with a focus on specific chronic disorders such as respiratory disease, congenital heart disease, and malignancy. These types of disorders serve as a model for the management of problems that require special medical, rehabilitative, and psychosocial consideration.