Search PubMed⌕ Search

Biomedical subjects

R M Hays

Publications and source records attributed to R M Hays.

At least 19 recordsLinked to original sources
PubMed2001

Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systematic review.

Management of children with cerebral palsy (CP) is the focus of considerable resources in many countries, so that evaluation of the efficacy for new and established treatments is imperative. Botulinum toxin type A (BTX-A) is a relatively new method of spasticity management in children with cerebral palsy. It has been the focus of extensive research since its application to cerebral palsy 10 years ago. In a systematic review relating to the management of the lower limb in cerebral palsy 156 papers were identified. These were categorized according to Sackett and the World Health Organisation International Classification of Impairments, Disabilities and Handicaps model. We identified 10 randomized trials evaluating the use of BTX-A in the lower limb in children with cerebral palsy in a systematic review. A meta-analysis showed the pooled risk difference between BTX-A and placebo in three trials was 0.25 (95% CI 0.13, 0.37) and 0.23 (95% CI -0.06, 0.53) for two trials of BTX-A and casting using the physicians rating scale. These represent moderate treatment effects that are dosage-dependent. Outcomes were also compared for function in five studies. The type of evidence for BTX-A was graded by each treatment indication and directions for future research were then drawn from the available evidence.

Botulinum Toxins, Type A↗
PubMed2001

Outcome measurement of effectiveness of botulinum toxin type A in children with cerebral palsy: an ICIDH-2 approach.

The ICIDH-2 serves as a useful framework for differentiating measurement by dimensions of the disabling process. Such differentiation is important to achieve more valid measurement of health related outcomes. We have attempted to examine one intervention, treatment with botulinum toxin type A, for one patient population, children with cerebral palsy, and to describe the outcome measures used in the evaluation of that intervention using this evolving classification system. This process supports the concept that measurement of health outcomes should focus on the nature and extent of functional limitations in physical, social and psychological domains. The selection of measurement outcomes must be determined not only by the requirements of the scientific process but also by the needs of the patients who are the intended beneficiaries of the intervention.

Botulinum Toxins, Type A↗
PubMed2001

Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services.

BACKGROUND: Children with complex chronic conditions (CCCs) might benefit from pediatric supportive care services, such as home nursing, palliative care, or hospice, especially those children whose conditions are severe enough to cause death. We do not know, however, the extent of this population or how it is changing over time. OBJECTIVES: To identify trends over the past 2 decades in the pattern of deaths attributable to pediatric CCCs, examining counts and rates of CCC-attributed deaths by cause and age (infancy: <1 year old, childhood: 1-9 years old, adolescence or young adulthood: 10-24 years old) at the time of death, and to determine the average number of children living within the last 6 months of their lives. DESIGN/METHODS: We conducted a retrospective cohort study using national death certificate data and census estimates from the National Center for Health Statistics. Participants included all people 0 to 24 years old in the United States from 1979 to 1997. CCCs comprised a broad array of International Classification of Diseases, Ninth Revision codes for cardiac, malignancy, neuromuscular, respiratory, renal, gastrointestinal, immunodeficiency, metabolic, genetic, and other congenital anomalies. Trends of counts and rates were tested using negative binomial regression. RESULTS: Of the 1.75 million deaths that occurred in 0- to 24-year-olds from 1979 to 1997, 5% were attributed to cancer CCCs, 16% to noncancer CCCs, 43% to injuries, and 37% to all other causes of death. Overall, both counts and rates of CCC-attributed deaths have trended downward, with declines more pronounced and statistically significant for noncancer CCCs among infants and children, and for cancer CCCs among children, adolescents, and young adults. In 1997, deaths attributed to all CCCs accounted for 7242 infant deaths, 2835 childhood deaths, and 5109 adolescent deaths. Again, in 1997, the average numbers of children alive who would die because of a CCC within the ensuing 6-month period were 1097 infants, 1414 children, and 2548 adolescents or young adults. CONCLUSIONS: Population-based planning of pediatric supportive care services should use measures that best inform our need to provide care for time-limited events (perideath or bereavement care) versus care for ongoing needs (home nursing or hospice). Pediatric supportive care services will need to serve patients with a broad range of CCCs from infancy into adulthood.

Adolescent↗
PubMed1998

Selective dorsal rhizotomy: efficacy and safety in an investigator-masked randomized clinical trial.

The objective of this single-center investigator-masked randomized clinical trial was to investigate the efficacy and safety of selective dorsal rhizotomy (SDR) in children with spastic diplegia. Forty-three children with spastic diplegia were randomly assigned on an intention-to-treat basis to receive SDR plus physical therapy (PT), or PT alone. Thirty-eight children completed follow-up through 24 months. Twenty-one children received SDR (SDR+PT group) and 17 received PT (PT Only group). SDR was guided with electrophysiological monitoring and performed by one experienced neurosurgeon. All subjects received equivalent PT. Spasticity was quantified with an electromechanical torque measurement device (spasticity measurement system [SMS]). The Gross Motor Function Measure (GMFM) was used to document changes in functional mobility. Primary outcome measures were collected at baseline, 6, 12, and 24 months by evaluators masked to treatment. At 24 months, the SDR+PT group exceeded the PT Only group in mean reduction of spasticity by SMS measurement (-8.2 versus +5.1 newton meters/radian, P=0.02). The SDR+PT group and the PT Only group demonstrated similar improvements in independent mobility on the GMFM (7.0 versus 7.2 total percent score, P=0.94). Outcomes on secondary variables were consistent with primary outcomes. There were no serious adverse events. We conclude that SDR is safe and reduces spasticity in children with spastic diplegia. SDR plus PT and equivalent PT without SDR result in equal improvements in independent mobility at 24 months. SDR may not be an efficacious treatment for children with mild spastic diplegia.

Adolescent↗
PubMed1998

Electrophysiological monitoring during selective dorsal rhizotomy, and spasticity and GMFM performance.

The relation between abnormal electrophysiological responses to intraoperative stimulation during selective dorsal rhizotomy (SDR) and the degree of spasticity and motor dysfunction was explored in 92 children with spastic cerebral palsy (CP) who underwent SDR at a single center. The proportion of abnormally responding rootlets was compared with the degree of spasticity measured with the modified Ashworth Scale (MAS) and with the spasticity measurement system (SMS) at discrete segmental levels. Motor impairment measured with the Gross Motor Function Measure (GMFM) was also compared with the proportion of abnormally responding dorsal rootlets. A consistent relation between the proportion of abnormally responding rootlets and the degree of spasticity and gross motor abnormality at the corresponding muscles could not be demonstrated. There was also no consistent association between the proportion of rootlets ablated during SDR and the change in spasticity measured with the MAS and SMS, or to the change in motor function as measured with the GMFM. These data suggest that the intraoperative monitoring technique most commonly used for SDR is unlikely to identify accurately those neural elements which contribute to spasticity in children with CP.

Adolescent↗
PubMed1996

Microtubular disruption prolongs the expression of human bilirubin-uridinediphosphoglucuronate-glucuronosyltransferase-1 gene transferred into Gunn rat livers.

DNA delivered to the liver by asialoglycoprotein receptor-mediated endocytosis is degraded in lysosomes within 48 h. To test the hypothesis that microtubular disruption should promote transgene persistence by interrupting endosomal translocation to lysosomes, plasmids containing bacterial chloramphenicol acetyltransferase (pSV2-CAT) or human bilirubin-UDP-glucuronosyltransferase-1 (pSVK3-hBUGT1) genes were complexed with asialoglycoprotein-polylysine conjugates, and 1 mg of the complexed DNA was injected intravenously into bilirubin-UDP-glucuronosyltransferase-deficient Gunn rats. 30 min before DNA injection, one group received 0.75 mg of colchicine/kg of body weight intraperitoneally, which was shown by immunofluorescent confocal microscopy to disrupt the microtubular network. Control rats received normal saline. In colchicine-pretreated rats receiving pSV2-CAT, hepatic chloramphenicol acetyltransferase activity persisted for 9-14 weeks, whereas in the saline-pretreated group the activity was detectable for 48 h only. In colchicine-pretreated Gunn rats receiving pSVK3-hBUGT1, the DNA persisted in liver for 10 weeks, bilirubin glucuronides were excreted in bile, and serum bilirubin levels declined by 25-35% in 2-4 weeks and remained reduced for 8 weeks. Without colchicine pretreatment, the DNA was detectable in liver for 2 days only, and serum bilirubin levels were not reduced. Thus, microtubular disruption provides a noninvasive method for prolonging the effect of liver-targeted gene therapy.

Animals↗
PubMed1996

Cellular and molecular events in the action of antidiuretic hormone.

The urinary concentrating mechanism and the action of antidiuretic hormone (ADH) were subjects of great controversy in the 1950's. Since then, steady progress has been made in our understanding of the cellular action of ADH. We have a good picture of the cyclic process by which vesicles carrying water channels move from cytoplasm to apical membrane, deposit water channels, and are then recovered by endocyosis. There is progress towards a complete description of the structure of the channels themselves. As well, in secretory cells such as the nerve terminal and the chromaffin cell, there are principles of cytoskeletal control and vesicle docking that appear to apply to the nephron.

Animals↗
PubMed1995

Neuromuscular disease: rehabilitation and electrodiagnosis. 2. Nerve disease.

The purpose of this section of the Self-Directed Physiatric Education Program Study Guide on rehabilitation in diseases affecting nerve and muscle is to assist practitioners and trainees in physical medicine and rehabilitation by providing an overview of the evaluation, treatment, and rehabilitative care of patients with inherited and acquired neuropathies. Both diffuse and focal processes are discussed. Current research is briefly reviewed, and the utility and limitations of electrodiagnostic studies are discussed.

Diagnosis, Differential↗
PubMed1995

Neuromuscular disease: rehabilitation and electrodiagnosis. 3. Muscle disease.

The purpose of this section of the Self-Directed Physiatric Education Program Study Guide on rehabilitation in diseases affecting nerve and muscle is to assist practitioners and trainees in physical medicine and rehabilitation by providing practical information about inherited and acquired muscle diseases. It emphasizes clinical management issues and new developments in commonly encountered muscle disorders.

Humans↗
PubMed1995

Vesicle fusion proteins in rat inner medullary collecting duct and amphibian bladder.

The delivery of water channels to the apical membrane in response to antidiuretic hormone (ADH) requires the targeting of channel-containing vesicles to specific sites in the membrane, followed by fusion and exocytosis. A complex array of proteins is now believed to mediate targeting and fusion in eukaryotic cells. They include N-ethylmaleimide-sensitive fusion protein (NSF), soluble NSF attachment proteins (SNAP), and cellubrevin, a vesicle-associated protein present in the nerve terminal. We asked whether these proteins are in epithelial cells of rat inner medullary collecting duct (IMCD) and amphibian bladder. Immunoblots on both tissues showed the presence of NSF and alpha-SNAP. Cellubrevin was present in immunoblots of the IMCD, but not the bladder. Immunogold electron microscopy showed NSF, alpha-SNAP, and cellubrevin in rat IMCD cells, with vesicular labeling. In the bladder, NSF was seen on vesicles and aggrephores. We conclude that components of the vesicle-targeting and fusion systems are present in kidney and amphibian bladder and may mediate a wide variety of fusion events, including those initiated by ADH.

Animals↗
PubMed1995

Water channel-carrying vesicles in the rat IMCD contain cellubrevin.

Antidiuretic hormone (arginine vasopressin) induces a cyclic process of docking, fusion, and endocytosis of water channel-containing vesicles in the collecting duct. There is now evidence that docking and endocytosis are mediated by an array of proteins associated with vesicles and target membranes. In recent studies, we have shown that cellubrevin, a member of the vesicle-associated membrane protein family, as well as other docking proteins, are expressed in the rat inner medullary collecting duct. We now show by immunogold electron microscopy that cellubrevin is present on vesicles containing water channels, that it is associated with both coated and uncoated vesicles, and that it is present on the apical membrane. Cellubrevin, therefore, is in a position to mediate one or more steps in arginine vasopressin-induced water channel cycling.

Animals↗
PubMed1995

Fulminating systemic capillary leak syndrome with lymphocytosis and hypogammaglobulinemia.

We report a case of fulminating systemic capillary leak syndrome which temporarily responded to verapamil, a calcium channel blocker. We noted two features of the disease not previously reported: a rise in lymphocyte count 2-3 days prior to an attack, and hypogammaglobulinemia. These findings are discussed in relation to the possible etiology of this disease.

Agammaglobulinemia↗
PubMed1994

Depolymerization of hepatocellular microtubules after partial hepatectomy.

Asialoglycoproteins (ASG) are internalized by hepatocytes by ASG receptor (ASGR)-mediated endocytosis. We have shown previously that when a plasmid DNA, pAlb(9-12)CAT (expressing chloramphenicol acetyltransferase driven by an albumin promoter enhancer), was complexed with an ASG-polylysine conjugate and injected intravenously in rats, 80% of the DNA was internalized by the liver. In normal recipient rats, over 95% of the internalized DNA was degraded in 4 h; the plasmid was undetectable after 48 h. In contrast, when 66% hepatectomy was performed 20 min after DNA administration, the internalized DNA persisted for several weeks in cytoplasmic vesicles (Chowdhury, N. R., Wu, C. H., Wu, B. Y., Yerneni, P. C., Bommineni, V. R., and Chowdhury, J. R. (1993) J. Biol. Chem. 268, 11265-11271). Since microtubules are required for the translocation of ligand-containing endosomes to lysosomes, the site of ligand degradation, we hypothesized that persistence of the endocytosed DNA might be related to changes in microtubular structure and function. To test this hypothesis, we examined hepatocellular microtubules by immunofluorescence confocal microscopy. Liver from untreated rats or sham-operated controls showed a network of fibrillar microtubules throughout the cytoplasm. The extent of the microtubular network was substantially reduced 3-6 h after 66% hepatectomy. By 24 h, microtubules had regenerated. Intraportal infusion of cycloheximide (250 mg/kg body weight) 15 min before 66% hepatectomy, prevented microtubular disruption, indicating that protein synthesis is required for this process. Immunotransblot analysis showed that hepatic alpha-tubulin concentration remained unchanged through microtubular disassembly and subsequent reassembly, which is consistent with conservation and reutilization of tubulin released by depolymerization of microtubules.

Animals↗
PubMed1994

Pain management for children following selective dorsal rhizotomy.

Selective dorsal rhizotomy (SDR) is a neurosurgical procedure used for treating lower extremity spasticity in patients with cerebral palsy. The purpose of this paper is to present a review of our institution's first three years' experience with postoperative pain and spasticity management in patients who have undergone SDR. The medical records of the 55 patients who had an SDR during the study period were reviewed. The basis of postoperative analgesia was morphine, with the majority of patients receiving continuous morphine infusions (20-40 micrograms.kg-1.hr-1 (n = 49), 60 micrograms.kg-1.hr-1 (n = 1)). Four patients used a patient-controlled delivery system. One patient had successful analgesia with epidural morphine. Ketorolac (1 mg.kg-1 i.v. loading dose followed by 0.5 mg.kg-1 i.v. every six hr for 48 hr) was used as an adjunct to morphine in six patients. For management of postoperative muscle spasm, an intravenous benzodiazepine was used (diazepam 0.1 mg.kg-1 (n = 2), or midazolam infusion 10-30 micrograms.kg-1.hr-1 (n = 51)). All patients were cared for on a ward where nurses were familiar with the use of continuous opioid and benzodiazepine infusions. All patients received continuous cardiorespiratory monitoring as well as frequent nursing assessment. There were no episodes of postoperative apnoea or excessive sedation. We have found the use of continuous infusions of morphine and midazolam, along with adjunct ketorolac, to be effective in treating postoperative pain and muscle spasms following SDR.

Adolescent↗
PubMed1994

The role of selective dorsal rhizotomy in cerebral palsy: critical evaluation of a prospective clinical series.

This is a prospective observational study of a consecutive series of 34 children with spastic cerebral palsy treated at a single center. 10 had spastic quadriplegia and 24 had spastic diplegia. All were followed for at least one year. After selective dorsal rhizotomy (SDR), all children received one month of physical therapy at the center and were prescribed a program of physical therapy in their community. The children were assessed before and one year after SDR and physical therapy, using the Ashworth Scale, deep tendon reflex response, range of motion and the Gross Motor Function Measure. The results show that there is often a decrease in lower-extremity spasticity and functional improvement after SDR with physical therapy, but that there is considerable variability in outcome. Randomized prospective clinical trials with masked objective outcome measures are needed to determine the efficacy of SDR.

Cerebral Palsy↗