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Biomedical subjects

J Walsh

Publications and source records attributed to J Walsh.

At least 127 records · Page 7Linked to original sources
PubMed1995

Predicting outcomes in thoracic outlet syndrome.

OBJECTIVE: To test the hypothesis that somatosensory evoked potentials (SEP) and results of arterial photoplethysmography (PPG) predict outcome after surgery for thoracic outlet syndrome. DESIGN: A retrospective case series which correlated surgical outcome with preoperative SEP and PPG results using Fisher's exact test. PPG results were considered abnormal when there was complete loss of arterial pulsation, and SEP results when amplitudes were reduced and latencies delayed. SETTING: Royal Prince Alfred Hospital, between March 1984 and February 1992. PATIENTS: Forty-six consecutive patients with clinically diagnosed thoracic outlet syndrome were admitted for surgery; sixteen underwent bilateral operations (total of 63 limbs). INTERVENTIONS: After SEP and PPG tests, all patients underwent thoracic outlet decompressive surgery--excision of the first rib, of the cervical rib (where present), and of other congenital anomalies associated with thoracic outlet syndrome--by the axillary approach. MAIN OUTCOME MEASURES: Surgical outcome was graded as good when symptoms improved and the patient returned to work or pre-illness activities. It was graded as poor when symptoms remained unchanged or worsened, or when there was continued inability to work or engage in usual activities. RESULTS: The follow-up period ranged from 1.9-9.8 years (mean, 5.7 years). Significantly more limbs with abnormal SEP or PPG results had a good outcome (49 of 53 limbs; 93%) than limbs with normal SEP and PPG results (six of 10 limbs; 60%) (P = 0.02). CONCLUSIONS: Abnormal SEP and PPG results correlated with a better postsurgical outcome. These tests may therefore aid in determining prognosis of surgery for thoracic outlet syndrome.

Adolescent↗
PubMed1995

Defective myosin VIIA gene responsible for Usher syndrome type 1B.

Usher syndrome represents the association of a hearing impairment with retinitis pigmentosa and is the most frequent cause of deaf-blindness in humans. It is inherited as an autosomal recessive trait which is clinically and genetically heterogeneous. Some patients show abnormal organization of microtubules in the axoneme of their photoreceptors cells (connecting cilium), nasal ciliar cells and sperm cells, as well as widespread degeneration of the organ of Corti. Usher syndrome type 1 (USH1) is characterized by a profound congenital sensorineural hearing loss, constant vestibular dysfunction and prepubertal onset of retinitis pigmentosa. Of three different genes responsible for USH1. USH1B maps to 11q13.5 (ref. 10) and accounts for about 75% of USH1 patients. The mouse deafness shaker-1 (sh1) mutation has been localized to the homologous murine region. Taking into account the cytoskeletal abnormalities in USH patients, the identification of a gene encoding an unconventional myosin as a candidate for shaker-1 (ref. 14) led us to consider the human homologue as a good candidate for the gene that is defective in USH1B. Here we present evidence that a gene encoding myosin VIIA is responsible for USH1B. Two different premature stop codons, a six-base-pair deletion and two different missense mutations were detected in five unrelated families. In one of these families, the mutations were identified in both alleles. These mutations, which are located at the amino-terminal end of the motor domain of the protein, are likely to result in the absence of a functional protein. Thus USH1B appears as a primary cytoskeletal protein defect. These results implicate the genes encoding other unconventional myosins and their interacting proteins as candidates for other genetic forms of Usher syndrome.

Adult↗
PubMed1995

A type VII myosin encoded by the mouse deafness gene shaker-1.

Genetic deafness is common, affecting about 1 in 2,000 births. Many of these show primary abnormalities of the sensory neuroepithelia of the inner ear, as do several hearing-impaired mouse mutants, suggesting that genes involved in sensory transduction could be affected. Here we report the identification of one such gene, the mouse shaker-1 (sh1) gene. Shaker-1 homozygotes show hyperactivity, head-tossing and circling due to vestibular dysfunction, together with typical neuroepithelial-type cochlear defects involving dysfunction and progressive degeneration of the organ of Corti. The sh1 gene encodes an unconventional myosin molecule of the type VII family. Three mutations are described, two mis-sense mutations and a splice acceptor site mutation, all in the region encoding the myosin head. The myosin type VII molecule encoded by sh1 is the first molecule to be identified that is known, by virtue of its mutations, to be involved in auditory transduction.

Amino Acid Sequence↗
PubMed1995

Somatostatin inhibits B-cell secretion via a subtype-2 somatostatin receptor in the isolated perfused human pancreas.

Recently five somatostatin receptor subtypes (SSTR) have been cloned, allowing the development of highly specific selective agonists for these SSTR. The present study was undertaken to determine which SSTR is responsible for the inhibitory effect of somatostatin on islet hormone secretion. Single-pass perfusion of four agonists was performed in pancreata obtained from four cadaveric organ donors using a modified Krebs-media with 3.9 mM glucose. Sequential 10-min specific receptor agonist infusions (5 ng/ml) of DC32-87 (SSTR2), DC25-12 (SSTR3), DC32-97 (SSTR3), or DC32-92 (SSTR5) were performed in random order separated by 10-min basal periods. Infusion of SSTR2 agonist into the isolated perfused human pancreas resulted in a significant inhibition of insulin and C-peptide secretion (insulin = -1468 +/- 480 pM, P < 0.05, and C-peptide = -2328 +/- 437 pM, P < 0.05) but not islet amyloid polypeptide or somatostatin. These results suggest that the inhibitory effect of somatostatin on B-cell secretion is mediated through the subtype-2 receptor within the human islet.

Adolescent↗
PubMed1995

The influence of somatostatin on glucagon and pancreatic polypeptide secretion in the isolated perfused human pancreas.

The current study was undertaken to determine whether intraislet somatostatin regulates glucagon or pancreatic polypeptide (PP) secretion in the human pancreas. A high-affinity, high-specificity monoclonal somatostatin antibody (CURE.S6) was used to immunoneutralize somatostatin in the isolated, perfused human pancreas. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs media with either 3.9 or 12.9 mM glucose. Sequential test periods separated by basal periods were performed with infusion of either exogenous somatostatin-14 (SS-14), CURE.S6, or a combined infusion. Infusion of SS-14 did not significantly alter glucagon or PP secretion during low-glucose or high-glucose perfusion. Immunoneutralization of intraislet somatostatin with CURE.S6 resulted in a significant increase of glucagon secretion under low-glucose conditions (delta X = 15 +/- 3 pM) (p < 0.05), but did not significantly effect glucagon secretion under high-glucose conditions (delta X = -2 +/- 3 pM) (p = NS). PP secretion remained unchanged during CURE.S6 infusion. Combined infusion of SS-14 and CURE.S6 did not significantly alter glucagon or PP secretion. The data suggest that intraislet somatostatin may have an inhibitory role in the regulation of glucagon secretion during low-glucose conditions and that intraislet somatostatin does not regulate PP secretion in the isolated, perfused human pancreas.

Adolescent↗
PubMed1995

Diaphragm and accessory respiratory muscle stimulation using intramuscular electrodes.

We tested the hypothesis that electrical stimulation of respiratory muscles can be obtained from intramuscular electrodes. In acute anesthetized dogs, suture-type intramuscular electrodes were placed in each hemidiaphragm and needle electrodes were placed in various intercostal regions of the thorax. During a hyperventilation induced period of apnea a 2-second stimulation was applied to the diaphragm or to the thoracic electrodes, followed by a combined thoracic-diaphragm stimulation period. Thoracic expansion and tidal volumes were measured as indices of inspiratory effort. We found that diaphragm stimulation produced tidal volumes between 104% and 180% of spontaneous breathing. Electrodes in the upper thorax produced chest expansion and when combined with diaphragm stimulation increased tidal volumes (p < .05). We conclude that intramuscular electrodes represent a feasible method for long-term electrogenic ventilation. Also, thoracic support for diaphragm pacing in quadriplegics could produce a more effective long-term system that is less prone to fatigue and failure.

Animals↗
PubMed1995

Programmed cell death of retinal ganglion cells during experimental glaucoma.

The death of retinal ganglion cells during glaucoma is thought to result from damage to their axons as they exit the eye through the lamina cribrosa. In this study, intraocular pressure in the rat was increased to twice the normal average by cauterizing two limbal-derived veins. To investigate whether retinal ganglion cells in the glaucomatous eye follow an apoptotic type of death, DNA breaks in nuclei were labeled in situ, using a method that specifically incorporates biotinylated deoxynucleotides by exogenous terminal deoxynucleotidyl transferase to the 3'-OH ends of DNA. The active nature of the death mechanism was demonstrated by the reduction in numbers of biotin-labeled nuclei after administration of the protein synthesis inhibitor, cycloheximide. Our results suggest that retinal ganglion cells of the adult rat die through apoptosis when the intraocular pressure is markedly increased. This raises new possibilities in the treatment of glaucomatous damage to the retina, by the potential interruptibility of a program for neuronal death.

Animals↗
PubMed1995

Music therapy following suctioning: four case studies.

This descriptive study evaluates and compares the effectiveness of music, presented both aurally and vibrotactilely, in reducing agitation and physiological instability following a stress-producing intervention (suctioning) in infants with bronchopulmonary dysplasia. Heart rate, oxygen saturation levels, level of arousal, stressful facial expressions, and autonomic indicators were recorded for each of four preterm infants. All infants experienced a reduction in the level of arousal during the taped music intervention when compared with the control condition. Three infants spent an increased amount of time in a quiet alert state and had improved oxygen saturation levels during the vibrotactile intervention. All infants spent more time sleeping during the taped music condition than without music or with the vibrotactile intervention. Results suggest that music is effective in reducing stress-related behaviors for some infants.

Arousal↗
PubMed1994

Immunogold localization of the 43-kDa dystroglycan at the plasma membrane in control and dystrophic human muscle.

Immunofluorescence and immunogold labelling were used to localise the 43-kDa dystrophin-associated glycoprotein (43DAG) of the dystrophin-glycoprotein complex in control and Duchenne muscular dystrophy (DMD) biopsies. In control muscle 43DAG was localised by immunofluorescence to the periphery of the fibre and, by immunogold, was further delimited to the plasma membrane. The labelling was indistinguishable from that previously reported for the dystrophin C terminus. Moreover, the distance separating adjacent 43DAG labelling sites (120 nm mode) closely matched that separating dystrophin C-terminal sites. This is strong evidence supporting Ervasti & Campbell's model in which the DAG complex is bound close to the C terminus of dystrophin and in which the DAG complexes are separated by approximately the length of the dystrophin rod. In DMD, where there is a 80-90% reduction in the glycoprotein complex, a faint or locally patchy distribution of 43DAG was seen by immunofluorescence. Measurement of nearest-neighbour distances after immunogold labelling showed that in DMD the 43DAG was more dispersed, which is further evidence that dystrophin is normally involved in anchoring the DAGs in the plasma membrane. This is significant because the potential success of dystrophin gene therapy could depend not only on restoring dystrophin but also on restoring the lost DAGs.

Cell Membrane↗
PubMed1994

Use of the Fab fragment for immunoneutralization of somatostatin in the isolated perfused human pancreas.

The role of the somatostatin-secreting D cell in the islet remains controversial. The present study was undertaken to determine whether infusion of the Fab fragment of a highly sensitive somatostatin monoclonal antibody into the isolated, perfused human pancreas would influence insulin secretion. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs-media with 3.9 mM glucose. Sequential test periods separated by basal periods were performed with either somatostatin monoclonal antibody Fab fragment (SFab), somatostatin-14 (SS-14), or a combined infusion. Immunoneutralization of intraislet somatostatin with SFab resulted in a significant increase in both immunoreactive insulin (IRI) (1,122 +/- 497 pM) (p < 0.05) and immunoreactive C-peptide (IRC-P) secretion (146 +/- 53 pM) (p < 0.05). Infusion of SS-14 resulted in inhibition of both IRI secretion (-3,372 +/- 1,360 pM) (p < 0.05) and IRC-P secretion (-708 +/- 220 pM) (p < 0.05). Combined infusion of SFab and SS-14 reversed the inhibitory effect of exogenous SS-14 on IRI and IRC-P secretion. The data suggest that intraislet somatostatin has an inhibitory role in the regulation of B-cell secretion in the human islet and demonstrates that the Fab fragment of the somatostatin monoclonal antibody is an effective tool for immunoneutralization studies in the human pancreas. In addition, immunostaining of the donor pancreata demonstrated the presence of somatostatin-immunoreactive endocrine cells interspersed throughout the islet core and mantle. The demonstrated proximity of somatostatin-immunoreactive endocrine cells to B cells lends anatomic support to the concept that intraislet somatostatin influences insulin secretion in the human islet.

Adult↗
PubMed1994

The response of cultured bone cells to resorbable polyglycolic acid and silicone membranes for use in orbital floor fracture repair.

Two membranes intended for use in repairing fractures of the orbital floor--reinforced silicone and biodegradable polyglycolic acid (PGA)--were evaluated in vitro using a rat bone cell culture model. After two weeks in culture, cells had colonised the surface of both materials. Bone cells penetrated the weave of the PGA membrane after three weeks in culture, forming a calcified collagenous bone-like tissue within the weave of the PGA at the same time as there was evidence of resorption of the PGA. In contrast, cells could easily be dislodged from the surface of the reinforced silicone membrane and there was less evidence of mineralised extra cellular matrix production. The production of a bone-like tissue within the weave of the PGA membrane supported previous reports of osteoconductive activity of this material.

Animals↗
PubMed1994

Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study.

OBJECTIVES: To evaluate the outcome in patients with severe adult respiratory distress syndrome (ARDS) managed with limitation of peak inspiratory pressure to 30 to 40 cm H2O, low tidal volumes (4 to 7 mL/kg), spontaneous breathing using synchronized intermittent mandatory ventilation from the start of ventilation, and permissive hypercapnia without the use of bicarbonate to buffer acidosis. Also, to compare hospital mortality rate with that predicted by the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system and the "ventilator score." SETTING: A ten-bed general intensive care unit in a university hospital. DESIGN: Prospective, descriptive study. PATIENTS: Fifty-three patients with severe ARDS having a lung injury score of > or = 2.5. INTERVENTIONS: Data recording. RESULTS: The hospital mortality rate was significantly lower than that predicted by the APACHE II scores (26.4% vs. 53.3%, p = .004), even after correcting the latter for the effect of hypercapnic acidosis (26.4% vs. 51.1%, p = .008). The mortality rate increased with increasing number of organ failures, but was only 43% in patients with > or = 4 organ failures, 20.5% with < or = 3 organ failures, and 6.6% with only respiratory failure. The mean maximum PaCO2 was 66.5 torr (range 38 to 158 torr [8.87 kPa, range 5.07 to 21.07]), and the mean arterial pH at the same time was 7.23 (range 6.79 to 7.45). There was no correlation between the maximum PaCO2 or the corresponding pH and the total respiratory rate at the same time. No pneumothoraces developed during mechanical ventilation. CONCLUSIONS: These results lend further support to the hypothesis that limitation of peak inspiratory pressure and reduction of regional lung overdistention by the use of low tidal volumes with permissive hypercapnia may reduce ventilator-induced lung injury and improve outcome in severe ARDS. This hypothesis is supported by a large body of experimental evidence, which also suggests that ventilator-induced lung injury may result in the release of inflammatory mediators, and thus may have the potential to augment the development of multiple organ dysfunction. However, the hypothesis requires testing in a randomized trial as acute hypercapnia could potentially have some adverse as well as beneficial effects.

APACHE↗
PubMed1994

Regulatory role of intraislet somatostatin on insulin secretion in the isolated perfused human pancreas.

This study was undertaken to determine whether intraislet somatostatin inhibits insulin secretion in the human islet. A high-affinity monoclonal somatostatin antibody was used to immunoneutralize somatostatin in the isolated, perfused human pancreas. Single pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs medium with either 3.9 or 12.9 mM glucose. Sequential test periods separated by basal periods were performed with either somatostatin-14 (SS-14), somatostatin monoclonal antibody (CURE.S6), or a combined infusion. Infusion of SS-14 resulted in inhibition of insulin secretion under both low glucose (delta X = -712 +/- 212 pM) (p < 0.05) and high glucose (delta X = -21,913 +/- 10,003 pM) (p = 0.06) conditions. Immunoneutralization of intraislet somatostatin with CURE.S6 resulted in a significant increase in insulin secretion under both low glucose (454 +/- 162 pM) (p < 0.05) and high glucose (2,177 +/- 829 pM) (p < 0.05) conditions. Combined infusion of SS-14 and CURE.S6 resulted in a reversal of the inhibitory effect of exogenous SS-14. The data suggest that intraislet somatostatin has an inhibitory role in the regulation of insulin secretion in the human islet.

Adolescent↗
PubMed1994

Cognitive factors affecting abstinence among adolescent polysubstance abusers.

To examine cognitive variables in the maintenance of abstinence among polysubstance-abusing adolescents, analyses of data from 86 adolescents (31 current users, 24 relapsers, and 31 abstainers) were done. Significant differences among these groups were found on a number of cognitive measures. Adolescents successful in maintaining abstinence possessed greater strategic knowledge and greater strategy-related self-efficacy. Further, adolescents who remained abstinent experienced greater reduction in their perceived risk of relapse when exposed to high-risk situations and experienced a corresponding increase in general expectation of enduring abstinence. An exploratory path analysis yielded some unexpected multivariate relationships. In particular, adolescents' knowledge of coping skills and strategy-related self-efficacy did not affect directly their expectations for continued abstinence. Instead, knowledge of coping skill and skill-related confidence appeared to function primarily to free the adolescent from perceptions of risk for relapse and only indirectly to enhance expectations of lasting sobriety.

Adolescent↗