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Biomedical subjects

A Clerk

Publications and source records attributed to A Clerk.

66 records · Page 4Linked to original sources
PubMed1993

A cause of excessive daytime sleepiness. The upper airway resistance syndrome.

Subjects with isolated complaints of chronic daytime sleepiness are usually classified as "idiopathic hypersomniacs" and treated symptomatically. A group of these subjects was investigated during nocturnal sleep and daytime naps. In a subgroup of them, sleep was fragmented by very short alpha EEG arousals throughout the sleeping period. These short arousals are usually ignored in sleep analyses, but their impact is significant (in the 15 subjects identified with the syndrome, the mean sleep latency in multiple sleep latency tests was 5.1 +/- 1 min). These arousals are directly related to an abnormal increase in respiratory efforts during sleep (the mean peak inspiratory esophageal pressure measured in our subjects in the respiratory cycle just preceding a transient arousal was -33 +/- 7 cm H2O). Typically, an arousal occurs within one to three breaths of flow limitation associated with abrupt but limited reduction in tidal volume (ie, abnormal increase in upper airway resistance during sleep). The arousal restores normal breathing. Snoring was noted in association with these transient arousals in 10 of the 15 subjects; however, snoring was neither sufficient nor necessary for the identification of the clinical syndrome. Both sexes were equally represented in the affected group. All studied subjects had upper airway anatomy that was mildly abnormal. Nasal continuous positive airway pressure, used as an experimental tool, eliminated the daytime sleepiness (multiple sleep latency mean score = 13.5 min), the transient arousals (mean alpha EEG arousal index decreased from 31.3 +/- 12.4 to 8 +/- 2 per hour of sleep), and the abnormal upper airway resistance. Chronic daytime sleepiness is a major cause of social, economic, and medical impairment. Recognition of this syndrome and its cause is important, as specific treatments can be developed to eliminate the problem.

Adult↗
PubMed1993

Cardiac failure and benzodiazepines.

Nine patients with stable cardiac failure and mean left ventricular ejection fraction of 30% were investigated. All had previously been prescribed a benzodiazepine hypnotic by their home physicians, but the medication had been discontinued for at least 1 month. Subjects were monitored under three conditions: 1) without any sleeping medication, 2) during nasal CPAP administration and 3) at two points during a month-long administration of the benzodiazepine that had initially been prescribed to them. Overall, the benzodiazepine hypnotic improved the sleep fragmentation noted in these patients by decreasing the arousal index from a mean of 18 +/- 6 per hour at baseline to a mean of 9 +/- 6.5 per hour after one month of benzodiazepine therapy. Total nocturnal sleep time was consequently improved [baseline mean nocturnal total sleep time: 313 +/- 27.3 minutes; benzodiazepine mean nocturnal total sleep time: 350 +/- 17.3 minutes (p < 0.0003)], as was sleep efficiency. However, the benzodiazepine hypnotic had no significant effect on central hypopneas or apneas [baseline mean respiratory disturbance index (RDI): 20.5 +/- 5.85 events/hour; mean RDI after 1 month of drug intake: 21.3 +/- 2.5 events/hour]. Nasal CPAP was also ineffective on the disordered breathing. In this group of subjects, respiration was even significantly worsened with nasal CPAP compared to baseline, as indicated by RDI (p < 0.0001), lowest SaO2 (p < 0.0001) and total nocturnal sleep time (p < 0.0001) measurements.

Benzodiazepines↗
PubMed1993

Dystrophin-related protein, utrophin, in normal and dystrophic human fetal skeletal muscle.

Dystrophin is the product of the Duchenne muscular dystrophy (DMD) gene. Dystrophin-related protein (utrophin), an autosomal homologue of dystrophin, was studied in skeletal muscle from normal fetuses aged 9-26 weeks and one stillbirth of 41 weeks' gestation, and compared with low- and high-risk DMD fetuses aged 9-20 weeks. Utrophin was present at the sarcolemma from before 9 weeks' gestation, although there was variability in intensity both within and between myotubes. Sarcolemmal immunolabelling became more uniform, and levels of utrophin increased to a maximum at approximately 17-18 weeks. Levels then declined, until by 26 weeks sarcolemmal labelling was negligible and levels were similar to adult control muscle. By 41 weeks there was virtually no sarcolemmal labelling, although immunolabelling of capillaries was bright. Similar results were obtained with normal and DMD fetal muscle. Utrophin is therefore expressed in the presence and absence of dystrophin and down-regulated before birth in normal fetal muscle fibres. Samples were not available to determine whether or when, utrophin levels decline in DMD fetal muscle. On Western blots, utrophin was shown to have a smaller relative molecular mass than adult dystrophin, but similar to the fetal isoform. Blood vessels were brightly immunolabelled at all ages, although utrophin immunolabelling of peripheral nerves increased with gestational age.

Antibodies, Monoclonal↗
PubMed1992

Dystrophin immunoreactivity in normal and Duchenne human fetal neurons in culture.

Dystrophin, the protein product defective in Duchenne muscular dystrophy (DMD), is present in all types of muscle and in the brain. The function of the protein is unknown and its role in the brain is unclear, although 30% of DMD patients show nonprogressive mental retardation. We have therefore studied the localisation of dystrophin in cultures of normal and DMD human fetal neurons using antibodies raised to different regions of the protein. Dystrophin immunoreactivity was demonstrated in the soma and axon hillock of normal neurons and appeared to be associated with the inner part of the cell membrane, although some intracellular staining was also observed. Positive dystrophin staining was present only in cells with fully developed neuronal features, although not all the neurons were positive. Glial cells were always negative for the antigen. Immunostaining with antibodies to the brain spectrins indicate that the dystrophin antibodies did not crossreact with these proteins. The possibility of cross-reactivity with other proteins is discussed. Studies of cells cultured from a DMD fetus also showed specific dystrophin immunostaining in neurons, although the muscle was generally negative for dystrophin. However, the localisation of dystrophin immunostaining and that of the brain spectrins and neurofilaments appeared abnormal, as did the overall morphology of the cells. This suggests that dystrophin may play a role during brain development and dystrophin deficiency results in abnormal neuronal features. This would be consistent with the nonprogressive nature of the mental retardation observed in DMD patients.

Blotting, Western↗
PubMed1992

Characterisation of dystrophin in fetuses at risk for Duchenne muscular dystrophy.

Dystrophin, the product of the Duchenne muscular dystrophy (DMD) gene, was studied in muscle from 16 human fetuses at risk for the disease. Eleven high risk (greater than 95% probability) and 5 low-risk (less than 25% probability) fetuses were studied with antibodies raised to different regions of the protein. All low-risk fetuses showed a similar pattern to that of normal fetuses of a comparable age: using Western blot analysis, a protein was detected of similar size and abundance to that of normal fetuses (i.e. smaller molecular weight than that of adult muscle); immunocytochemistry showed uniform sarcolemmal staining in fetuses older than 18 weeks gestation and differential staining of myotubes at different stages of development (distinguished by size) in younger fetuses (less than 15 weeks gestation). In contrast, Western blot analysis of high-risk fetuses detected low levels of dystrophin in 4 cases; 7 fetuses had no detectable protein. Immunocytochemistry with some dystrophin antibodies showed weak staining of the sarcolemma and around central nuclei in younger fetuses; in older fetuses there was little sarcolemmal staining with any antibody other than occasional positive fibres. These results indicate that careful study of dystrophin in fetuses at risk for DMD can be used to establish the clinical phenotype and provide additional information for future family counselling.

Blotting, Western↗
PubMed1992

Gender differences in sleep architecture in sleep apnoea syndrome.

This study compared sleep architecture in women and men with sleep apnoea syndrome. Women (n = 126) had longer sleep latencies, greater amounts of slow wave sleep, and fewer awakenings during the night than men (n = 181), despite no differences in age, RDI (Respiratory Disturbance Index) or oxygen saturation. In a subgroup of men and women treated with nasal CPAP, gender differences generally persisted. There was no difference in the complaint of daytime sleepiness between the groups, but the women reported more fatigue during the day than the men, as well as complaining about more sleep disturbance at night. We interpret these differences in terms of known gender differences in sleep architecture and sleep complaints.

Journal Article↗
PubMed1992

Characterisation of dystrophin during development of human skeletal muscle.

Dystrophin, the 427 x 10(3) Mr product of the Duchenne muscular dystrophy (DMD) gene, was studied in human foetal skeletal muscle from 9 to 26 weeks of gestation. Dystrophin could be detected from at least 9 weeks of gestation at the sarcolemmal membrane of most myotubes, though there was differential staining with antibodies raised to various regions of the protein. Dystrophin immunostaining increased and became more uniform with age and by 26 weeks of gestation there was intense sarcolemmal staining of all myotubes. On a Western blot, a doublet of smaller relative molecular mass than that seen in adult tissue was detected in all foetuses studied. There was a gradual increase in abundance of the upper band from 9 to 26 weeks, and the lower band, although present in low amounts in young foetuses, increased significantly between 20 and 26 weeks of gestation. These data indicate that there are several specific isoforms of dystrophin present in developing skeletal muscle, though the role of these is unknown.

Blotting, Western↗
PubMed1992

From obstructive sleep apnea syndrome to upper airway resistance syndrome: consistency of daytime sleepiness.

Some patients with excessive daytime sleepiness who do not present the features of obstructive sleep apnea syndrome (OSAS) present a sleep fragmentation due to transient alpha EEG arousals lasting between three and 14 seconds. These transient EEG arousals are related to an abnormal amount of breathing effort, indicated by peak inspiratory esophageal pressure (Pes) nadir. In the studied population, these increased efforts were associated with snoring. Usage of nasal CPAP, titrated on Pes nadir values, for several weeks eliminated subjective daytime sleepiness and improved Multiple Sleep Latency Test scores from baseline evaluations. Patients suspected of CNS hypersomnia should be asked about continuous snoring, and their clinical evaluation should include a good review of maxillo-mandibular and upper airway anatomy.

Airway Obstruction↗
PubMed1991

Characterisation of dystrophin in carriers of Duchenne muscular dystrophy.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, was studied in needle biopsy samples taken from the quadriceps muscle of 15 asymptomatic carriers of DMD (13 adults and 2 young girls) and one symptomatic adult carrier. Antibodies to N- and C-terminal regions of dystrophin were used for both Western blot analysis and immunocytochemistry and a monoclonal antibody to beta-spectrin used to assess membrane integrity. All asymptomatic adult carriers showed some abnormality in dystrophin immunostaining but very few negative fibres were present. A clear mosaic of dystrophin positive and negative fibres was seen only in the adult symptomatic carrier and the two young girls. On a Western blot, all carriers studied had dystrophin of normal molecular weight, but most had reduced abundance. In adult carriers, the amount of dystrophin relative to normal controls varied, but it was unrelated to age, serum creatine kinase (CK) levels or to the degree of pathology. Carriers with normal CK showed abnormalities in dystrophin expression. The dystrophin immunoblotting profile of the 2 young girls was very similar to that of their mothers, but the mosaic pattern of immunostaining was not apparent in the older carriers. In conclusion, dystrophin immunostaining and Western blot analysis of biopsy samples from asymptomatic carriers is often abnormal and they may be useful additional aids for establishing carrier status, particularly in younger girls.

Adult↗
PubMed1991

Dystrophin abnormalities in polymyositis and dermatomyositis.

The expression of dystrophin in muscle biopsies from nine cases of polymyositis, ten cases of juvenile dermatomyositis and three adults with dermatomyositis was studied by Western blot analysis and immunocytochemistry. Five antibodies corresponding to different N- and C-terminal regions of the dystrophin gene were used. Sixteen of the 22 cases (73%) showed an abnormality in the expression of dystrophin on Western blot analysis, either with a reduced molecular weight protein or a reduced amount. Immunostaining was abnormal in 11 out of 19 cases (58%) and showed varying degrees of discontinuity or loss of sarcolemmal staining. Immunolabelling of these areas with antibodies to beta-spectrin was normal implying that the changes were not caused by a loss of the sarcolemma. These results show that secondary changes in the expression of dystrophin can occur in the absence of an abnormality in the corresponding gene and that dystrophin cannot be used in isolation as a diagnostic marker for muscular dystrophy.

Adolescent↗