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Biomedical subjects

R H Brown

Publications and source records attributed to R H Brown.

At least 19 recordsLinked to original sources
PubMed1992

Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.

Paramyotonia congenita (PMC), a dominant disorder featuring cold-induced myotonia (muscle stiffness), has recently been genetically linked to a candidate gene, the skeletal muscle sodium channel gene SCN4A. We have now established that SCN4A is the disease gene in PMC by identifying two different single-base coding sequence alterations in PMC families. Both mutations affect highly conserved residues in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Abnormal function of this cytoplasmic loop therefore appears to produce the Na+ current abnormality and the unique temperature-sensitive clinical phenotype in this disorder.

Amino Acid Sequence↗
PubMed1992

Effect of angular traction on the performance of modern vacuum extractors.

OBJECTIVE: Our objective was to describe the effect of off-axis traction on the performance of modern vacuum extractors. STUDY DESIGN: Eight vacuum extractors were examined in the laboratory with a force indicator and fetal cephalic model. Devices evaluated included the 6 cm Malmstrom, Mity-Vac, M-Type, O'Neil, Posterior, Silc, Tender-Touch, and silicone elastomer. Maximal tractive force (pop-off) was measured for each device at 10-degrees increments from the vertical. RESULTS: Multivariate regression analysis described the best model as follows: Maximal tractive force = Constant + Angle + Vacuum (p < 0.05). The partial regression coefficients for angle were negative in all devices except the Posterior cup. At increasing angles of off-axis traction, maximal tractive force decreased in the following order: Silc, silicone elastomer, Tender-Touch, M-Type, Mity-Vac, O'Neill, Malmstrom, and Posterior. CONCLUSIONS: Application of oblique traction resulted in a linear decline in maximal tractive force. An understanding of in vitro performance may allow tailoring of cup selection to the clinical situation.

Evaluation Studies as Topic↗
PubMed1992

Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.

Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability.

Adult↗
PubMed1992

Arterial delivery of myoblasts to skeletal muscle.

One of the major limitations of myoblast implantation as a therapy for muscular disease is that multiple injections by intramuscular implantation may be required for widespread delivery of cells. Also, some sites (eg, the diaphragm) are relatively inaccessible to injection. As an alternative, we have undertaken intra-arterial administration of myoblasts. For these experiments, we used donor cell myoblasts from the immortal L6 cell line labeled with lacZ via the beta-gal-at-gal retrovirus. In our model, target rat skeletal muscle (tibialis anterior [TA]) was injured using 0.5 ml of 0.5% bupivacaine and 15 IU of hyaluronidase; saline was injected into the contralateral side as a control. We infused 3 x 10(6) lacZ-positive cells into the abdominal aorta of previously injured, immunosuppressed (cyclosporine A) rats. At 7, 14, and 28 days, TA, liver, heart, lung, and spleen were examined for lacZ staining. In both the injured and control muscles, a few differentiated, lacZ-positive muscle cells were present, both singly and in groups, at each time point. These studies demonstrate that genetically labeled, transformed myoblasts may migrate from the arterial circulation to muscle and fuse there to form differentiated muscle cells. It is conceivable that intra-arterial delivery of myoblasts may have a role in the therapy of selected diseases of skeletal muscle.

Animals↗
PubMed1992

Differential glucocorticoid effects on the fusion of Duchenne/Becker and control muscle cultures: pharmacologic detection of accelerated aging in dystrophic muscle.

We report that the glucocorticoid methylprednisolone (Mepd) enhanced myogenesis in normal primary human muscle cultures, but inhibited myogenesis of most Duchenne/Becker muscle cultures. A decline in the magnitude of myogenic stimulation of Mepd correlated with age in a random group of control patients, including some with neurologic diseases other than Duchenne/Becker dystrophy. A case of Duchenne muscular dystrophy from an exceptionally young patient yielded a muscle culture that was myogenically stimulated by Mepd. These results suggest that continuous cycles of degeneration and regeneration of dystrophic muscle in vivo may result in a change of the glucocorticoid response of the muscle progenitor cells. The glucocorticoid effects suggest caution in the long-term clinical use of these agents for muscle disease such as Duchenne muscular dystrophy.

Adolescent↗
PubMed1992

Inequities in oral health: implications for the delivery of care and health promotion.

This paper has summarised data showing that inequities in oral health and the receipt of oral health care exist in New Zealand. We submit that these inequities, and the consequences of oral ill-health, are of such seriousness that they cannot be ignored. Overcoming barriers to oral ill health and barriers to dental care will be a complex task. Although much can be done by the dental providers and their organisations, there is need for oral ill health to be viewed within the overall context of inequity and disadvantage within society.

Adolescent↗
PubMed1992

Dentures, prosthetic treatment needs, and mucosal health in an institutionalised elderly population.

A survey of 359 elderly residents of rest homes and geriatric hospitals in the Manawatu and Horowhenua regions showed that 80.5 percent were fully edentulous. Full upper and lower dentures were worn by 64 percent of the total sample, and 31 percent of the dentate group wore one or more partial dentures. Prosthetic treatment needs were dominated by full dentures: 18 percent of upper dentures and 26 percent of lower dentures were considered to need replacement. A further 24 percent of full lower dentures required relining. Only 7 percent of the dentures were named. One third of the subjects had mucosal lesions, the most common lesions being angular cheilitis (present in 18 percent of subjects), traumatic ulcers (14 percent), atrophic glossitis (12 percent), and leukoplakia (present in 8 percent of subjects). No malignant lesions were found.

Aged↗
PubMed1991

A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis.

HYPERKALAEMIC periodic paralysis (HYPP) is an autosomal dominant disease that results in episodic electrical inexcitability and paralysis of skeletal muscle. Electrophysiological data indicate that tetrodotoxin-sensitive sodium channels from muscle cells of HYPP-affected individuals show abnormal inactivation. Genetic analysis of nine HYPP families has shown tight linkage between the adult skeletal muscle sodium channel alpha-subunit gene on chromosome 17q and the disease (lod score, z = 24; recombination frequency 0 = 0), strongly suggesting that mutations of the alpha-subunit gene cause HYPP. We sequenced the alpha-subunit coding region isolated from muscle biopsies from affected (familial HYPP) and control individuals by cross-species polymerase chain reaction-mediated complementary DNA cloning. We have identified an A----G substitution in the patient's messenger RNA that causes a Met----Val change in a highly conserved region of the alpha-subunit, predicted to be in a transmembrane domain. This same change was found in a sporadic case of HYPP as a new mutation. We have therefore discovered a voltage-gated channel mutation responsible for a human genetic disease.

Amino Acid Sequence↗
PubMed1991

Telemeterized in vivo hip joint force data: a report on two patients after total hip surgery.

Two telemeterized femoral components were implanted in two patients as part of normal total hip replacement procedures. The two components were instrumented to measure the three force components directed along: (a) the neck axis, (b) transverse to the neck axis and in the plane of the prosthesis, and (c) transverse to the neck axis and perpendicular to the plane of the prosthesis. Data were collected at multiple sessions during the early postoperative period for a number of standard activities, including gait, stair climbing, rising from a chair, single leg stance, double leg stance, ipsilateral and contralateral straight leg lifts while supine, ipsilateral flexion and extension while standing, and ipsilateral abduction while standing and lying on the contralateral side. These data are summarized and compared with the published results from analytic studies and with the results from previous studies using instrumented femoral components. Peak loads for gait during the period of study were roughly 2.7 body weights (BW) when the patients walked at their normal pace. Contact forces at the hip during stationary single leg stance approximated the peak loads during gait with values ranging from 2.1 to 2.8 BW. The highest forces recorded reached values approaching 5.5 BW and occurred during periods of instability while the patient engaged in stationary single leg stance. Our in vivo data indicate that forces generated during the above activities increase in magnitude quite rapidly during the early postoperative period and that during this period the patients have the ability to perform the activities of daily living without generating the high amplitude joint contact forces suggested by the results of dynamic studies. Joint contact forces during gait were found to depend on speed, but the high absolute magnitudes predicted by model studies were not supported by the in vivo data.

Aged↗
PubMed1991

Methylprednisolone increases dystrophin levels by inhibiting myotube death during myogenesis of normal human muscle in vitro.

The glucocorticoid methylprednisolone (Mepd) increased dystrophin and myosin heavy chain levels in differentiated cultures of cloned human myoblasts. Mepd increased the number of myotubes per area by preventing myotube death and detachment during myogenesis in vitro. Myotube death was the result of an endogenous process initiated early during myoblast fusion. It occurred between days 4 and 5 of differentiation (3 days after its initiation) and was inhibited by cycloheximide, indicating that a programmed death mechanism may be involved. Inhibition of myotube death accounted for the increased levels of muscle-specific proteins; the amount of dystrophin per myonucleus was the same with or without Mepd treatment. These effects of glucocorticoids on primary muscle cultures may bear on the recent observation that prednisone transiently enhances muscle function in Duchenne muscular dystrophy.

Adult↗
PubMed1991

Differential effect of glucocorticoids on pulmonary responses and eosinophils.

The persistent airway hyperresponsiveness of Basenji-Greyhound (BG) dogs to 10% citric acid (CA) is abolished by chronic administration of methylprednisolone (MP) and is accompanied by the disappearance of eosinophils from the bronchoalveolar lavage (BAL) fluid. To determine whether the disappearance of eosinophils from BAL fluid was temporally related to the loss of airway responsiveness to CA, we investigated the time course of the reduction in airway responsiveness to CA and correlated it with changes in cell profiles in BAL fluid in a group of BG dogs treated with MP for 1 to 7 days. Six dogs in separate studies were pretreated with MP (2 mg/kg/day) subcutaneously for either 1, 3 or 7 days. Each dog served as its own control for each set of studies. Under thiopental anesthesia, lung resistance (RL) was calculated from transpulmonary pressure and flow measurements prior to and 5 minutes following the completion of a 10% CA aerosol. BAL was performed on a separate occasion with the animals pretreated with MP for either 1, 7, 10 or 14 days. Baseline RL was not significantly different in each control and treatment group. The pulmonary response to CA challenge was diminished following 1, 3 and 7 days of MP pretreatment. Although eosinophils disappeared from the peripheral blood following 1 day of MP treatment, eosinophils in BAL did not begin decreasing until 10 days of MP pretreatment. This temporal dissociation between CA hyperresponsiveness and eosinophils in the BAL fluid suggests that epithelial damage by toxic products of eosinophils in the airway lumen does not play a direct role in citric acid induced airway hyperresponsiveness in BG dogs.

Aerosols↗
PubMed1991

A sodium channel defect in hyperkalemic periodic paralysis: potassium-induced failure of inactivation.

Hyperkalemic periodic analysis (HPP) is an autosomal dominant disorder characterized by episodic weakness lasting minutes to days in association with a mild elevation in serum K+. In vitro measurements of whole-cell currents in HPP muscle have demonstrated a persistent, tetrodotoxin-sensitive Na+ current, and we have recently shown by linkage analysis that the Na+ channel alpha subunit gene may contain the HPP mutation. In this study, we have made patch-clamp recordings from cultured HPP myotubes and found a defect in the normal voltage-dependent inactivation of Na+ channels. Moderate elevation of extracellular K+ favors an aberrant gating mode in a small fraction of the channels that is characterized by persistent reopenings and prolonged dwell times in the open state. The Na+ current, through noninactivating channels, may cause the skeletal muscle weakness in HPP by depolarizing the cell, thereby inactivating normal Na+ channels, which are then unable to generate an action potential. Thus the dominant expression of HPP is manifest by inactivation of the wild-type Na+ channel through the influence of the mutant gene product on membrane voltage.

Electrophysiology↗
PubMed1991

Assessment of pulmonary airway reactivity with high-resolution CT.

The evaluation of airway reactivity plays a central role in the diagnosis of bronchial hyperreactivity and asthma. The authors used high-resolution computed tomography (HRCT) to assess airway reactivity and compared the results with simultaneously performed measurements of airway pressure (Paw). Ten anesthetized and ventilated dogs were studied in a control state, after saline aerosol application, and after histamine aerosol challenge. In each condition, Paw was determined and HRCT was performed at functional residual capacity. On the HRCT scans, the cross-sectional areas of airway lumina were measured by using a computer edging process. After histamine challenge, HRCT demonstrated a decrease in airway areas of 43% +/- 2% (mean +/- standard error) from baseline (control) and Paw increased 99% +/- 18%. Surprisingly, saline aerosol challenge also resulted in a significant decrease in airway areas (26% +/- 3%) from control, while Paw measurements did not change significantly. Airway reactivity varied between dogs and within dogs. The authors conclude that HRCT can depict the site and degree of airway reactions and thus represents a new tool to assess airway reactivity in vivo.

Animals↗
PubMed1991

In vivo measurements of airway reactivity using high-resolution computed tomography.

Changes in airway resistance are reported to account for only a portion of changes in total lung resistance. The fraction of total lung resistance caused by airway resistance is difficult to quantify in vivo. High-resolution computed tomography (HRCT) has potential application for directly measuring changes in airway size in vivo. In the present investigation, we studied five anesthetized mongrel dogs using HRCT to locate and measure changes in airway area after aerosol histamine challenge in the absence and presence of deep inspiration. We also related changes in total lung resistance to changes in airway area. We found that in all dogs after histamine aerosol challenge, airway area decreased (range, 23 +/- 7 to 67 +/- 5%, mean +/- SEM), and total lung resistance increased (range, 191 to 378%). After deep inspiration (equal to three times tidal volume), four of the five dogs showed further significant decreases in airway area (range, 13 +/- 6 to 71 +/- 8%), whereas all five dogs showed decreases in RL (range, 3 to 35%). The fact that preconstricted airways constricted further after deep inspiration while the measured RL decreased suggests that RL may not always be a reliable indicator of changes in the size of conducting airways larger than 1 mm.

Airway Resistance↗