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Biomedical subjects

N A Saunders

Publications and source records attributed to N A Saunders.

At least 55 records · Page 3Linked to original sources
PubMed1997

Comparison of effects of sustained isocapnic hypoxia on ventilation in men and women.

Sleep-related respiratory disturbances are more common in men than in premenopausal women. This might, in part, be due to different susceptibilities to the respiratory depressant effects of hypoxia. Therefore, we compared ventilation during 10 min of baseline room-air breathing and 20-min sustained isocapnic hypoxia (fractional inspired O2 = 11%, arterial saturation of O2 approximately 80%) followed by 10 min of breathing 100% O2 in 10 normal men and in 10 women in the follicular phase of the menstrual cycle. Control measurements were made during two transitions from room air (10 min) to 100% O2 (10 min) and averaged. Inspired minute ventilation (VI) after 2 min of hypoxia was the same in men and women [131 +/- 6.1% baseline for men, 136 +/- 7.7% baseline for women; not significant (NS)] and declined to the same level after 20 min (115 +/- 5.0% baseline for men, 116 +/- 6.6% baseline for women; NS) associated with a similar decline in inspiratory time and tidal volume. Breathing frequency did not change. VI decreased transiently during subsequent 100% O2 breathing in both men and women, associated with reduced frequency and duty cycle and increased expiratory time. The fall in VI was significantly greater than that observed during control hyperoxia experiments in men but not in women. We conclude that ventilatory responses to sustained isocapnic hypoxia do not differ between awake healthy men and women in the follicular phase of their menstrual cycle. However, after termination of isocapnic hypoxia, men appear to depress their ventilation to a greater degree than women.

Adult↗
PubMed1996

Emerging issues in sleep-disordered breathing.

Community studies of problems with breathing during sleep suggest that sleep-disordered breathing is a better general term than sleep apnoea. Male sex, increasing age and increasing neck size are the main factors differentiating people with from those without sleep-disordered breathing. The contribution of sleep-disordered breathing to morbidity has not been established. Future research should address the possible cardiovascular associations of sleep-disordered breathing, its impact on sleepiness in the community, and the cost-effectiveness of treatment.

Australia↗
PubMed1996

WHO-sponsored international collaborative study to evaluate methods for subtyping Listeria monocytogenes: restriction fragment length polymorphism (RFLP) analysis using ribotyping and Southern hybridization with two probes derived from L. monocytogenes chromosome.

Seven laboratories participated in a WHO-sponsored international collaborative study, to evaluate methods for subtyping Listeria monocytogenes, by performing restriction fragment length polymorph sm (RFLP) analysis-based subtyping of an international study set of 80 strains of L. monocytogenes that included 22 epidemiologically related groups. The RFLP analysis was done by Southern hybridization with one of two types of probes found in multiple copies on the chromosome of L. monocytogenes. Six laboratories performed ribotyping. These laboratories used EcoRI enzyme to restrict the L. monocytogenes DNA and ribosomal RNA or DNA as the probe for Southern hybridizations. The seventh laboratory used Ncil to restrict the DNA, and two probes, one randomly cloned and the other containing repeat sequences cloned from L. monocytogenes DNA. The overall discriminating power of ribotyping, as estimated by calculation of Simpson's index of diversity, ranged from 0.83 to 0.88 for the six laboratories. The discriminating power of the combination of two probes used by Laboratory 7 was 0.91. Ribotyping and the cloned probes used by Laboratory 7 discriminated poorly between serotype 4b strains. Neither method identified three atypical strains (identified by other subtyping methods) included in three apparently epidemiologically related groups. Ribotyping did not discriminate between strains of serotypes 4b and 4b(X) in one epidemiologically related group of strains; one cloned probe used by Laboratory 7 discriminated between these strains. Intra-laboratory reproducibilities for the seven laboratories ranged from 80.0 to 100%. as determined by their abilities to correctly identify 11 pairs of duplicate strains included in the study set. Inter-laboratory reproducibilities were generally very good considering that no attempt was made to standardize protocols used by the participants.

Bacterial Typing Techniques↗
PubMed1996

Virulence regulon polymorphism in group A streptococci revealed by long PCR and implications for epidemiological and evolutionary studies.

A method based on long PCR amplification and restriction endonuclease analysis of the virulence regulon was developed for a rapid (2 days), simple differentiation of group A streptococci. The PCR product size varied from 12.3 kb for serotypes M1 (NCTC 8198) and M12 (NCTC 10085) to 7.8 kb for serotype M6 (NCTC 8302). The fragment patterns formed on HaeIII digestion of the products were unique and this allowed the differentiation of each of the M-type strains (M1, M3, M4, M5, M6, M11, M12, M28, M76 and M78) studied. Contemporary M1 isolates all gave the same fragment pattern but differed from the prototype strain (NCTC 8198) in not having a 1.25-kb fragment. Isolates of serotypes M1 and M3 each had similar patterns, an indication of their clonality and global dispersion. In contrast, more than one restriction fragment length polymorphism (RFLP) pattern was detected among clinical isolates of serotypes M5, M6, M12, M4, M(R)28 and M78. Two strains that were M-protein non-typable by serological means were provisionally classified as M6 by comparisons of HaeIII long PCR fragment patterns.

Biological Evolution↗
PubMed1996

Development of a simplified polymerase chain reaction-enzyme immunoassay for the detection of Chlamydia pneumoniae.

The 16S rRNA genes of two Chlamydia pneumoniae and two C. psittaci strains of different serovars were sequenced then compared to previously reported Chlamydia 16S rRNA gene sequences. Chlamydia pneumoniae-specific regions were identified and specific primers for nested PCR were synthesized. Nested PCR reactions were performed, in a single tube, by varying the annealing temperature of the amplification cycles. The initial thermal cycles were selected to allow annealing and extension of only the outer primer pair, whilst in later cycles a temperature that allowed inner primer annealing was employed. The inner primers were labelled, one with biotin and the other with fluorescein and consequently the dual labelled amplicon could be immobilized onto antibiotin-coated microtitre plates and detected colorimetrically via an antifluorescein-enzyme conjugate. The assay was found to be sensitive and specific. No cross reactions were observed with C. trachomatis, C. psittaci or other common respiratory pathogens.

Chlamydophila pneumoniae↗
PubMed1996

Heminested inverse PCR for IS6110 fingerprinting of Mycobacterium tuberculosis strains.

A heminested inverse PCR (HIP) for the amplification of sequences flanking the Mycobacterium tuberculosis insertion sequence IS6110 has been developed. The method depends upon primers that anneal to IS6110 at sites between its 5' end and the closest BsrFI site. The accuracy of HIP was demonstrated by the amplification of sequences within plasmid constructs carrying one or two copies of the insertion sequence IS986 in different orientations. The identities of the amplicons produced from strains carrying a single copy of IS6110 were verified by nucleotide sequencing. Analyses of 204 M. tuberculosis strains including those involved in outbreaks showed that IS6110 HIP is highly discriminatory and reproducible. HIP fingerprinting of these 204 strains generated 136 distinct types, and its discriminatory power was equivalent to that of standard restriction fragment length polymorphism analysis. The method is therefore of value for the rapid fingerprinting of M. tuberculosis strains for epidemiological purposes.

Base Sequence↗
PubMed1996

Effects of sustained and repetitive isocapnic hypoxia on ventilation and genioglossal and diaphragmatic EMGs.

We compared the effects of sustained isocapnic hypoxia (SIH; 20 min) and repetitive isocapnic hypoxia (RIH; 10 2-min episodes) on ventilation (VI), genioglossal (EMGgg) and diaphragmatic electromyographic (EMGdi) activities, and supraglottic airway resistance in 11 normal supine male subjects (36.6 +/- 2.2 yr) during wakefulness. Seven of the subjects had control measurements on a separate day. Desaturation was similar (arterial O2 saturation 80-84%) in the SIH and RIH protocols. SIH and RIH caused a biphasic ventilatory response: early augmentation of VI (169.5 +/- 6.9 and 168.9 +/- 4.3% of baseline, respectively; not significant) followed by a significant roll-off (VI after 20 min of cumulative hypoxia 153 +/- 4.0 and 150.8 +/- 10.2% respectively; not significant). Moving-time-average EMGdi signals (peak inspiratory and phasic) demonstrated a similar biphasic response in the two protocols. Mean EMGgg responses, however, differed. During SIH, peak inspiratory EMGgg increased early and remained elevated. Phasic and tonic EMGgg signals showed a similar trend. During RIH, early augmentation of peak inspiratory and phasic EMGgg signals was followed by a marked roll-off in activity such that by the 10th hypoxic episode neither value increased above baseline. In the 2-min periods between hypoxic episodes, there was a progressive suppression of peak inspiratory and phasic EMGgg values below baseline. Supraglottic airway resistance did not change significantly during either SIH or RIH. VI and phasic EMGs did not change during control experiments. We conclude that in awake normal male subjects SIH and RIH cause similar biphasic responses in VI and EMGdi activity. Phasic EMGgg activity responses differ between SIH and RIH: EMGgg remains augmented during SIH, whereas during RIH early augmentation is followed by marked suppression.

Adult↗
PubMed1995

State of the art: typing Mycobacterium tuberculosis.

After years of decline, infections due to Mycobacterium tuberculosis appear to be increasing in the developed world. This has led to a search for improved methods of typing strains in order to answer new questions concerning the epidemiology of tuberculosis. Owing to the phenotypic and genotypic homogeneity of the species, classical fingerprinting methods, including phage typing, serotyping and multilocus enzyme electrophoresis, have proven ineffective. However, new methods based on the analysis of repetitive DNA sequences have been introduced and are now being used to elucidate the emerging pattern of disease.

Bacterial Typing Techniques↗
PubMed1995

Four-year follow-up of mortality and sleep-related respiratory disturbance in non-demented seniors.

To ascertain whether sleep-disordered breathing (SDB) in the elderly is associated with increased mortality, a prospective cohort study with 4-year follow-up was conducted at a retirement village complex in Sydney, Australia. The subjects were 163 non-demented retirement village residents. Logistic regression was used to assess SDB and co-morbidity as independent predictors of mortality. Respiratory disturbance index (RDI) was measured in the home; those subjects with RDIs > or = 15 were classified as having SDB. Co-morbidity was measured by an index of Burden of Illness based on the medical history obtained at baseline. At 4 years, 27% (4/15) of those subjects with RDIs > or = 15 and 22% (33/148) of those with RDIs < 15 were dead. RDI had an odds ratio (OR) of 1.00 (95% CI: 0.96, 1.04). Burden of Illness had an OR of 1.90 (95% CI: 1.34, 2.71). Adjustment for age and sex did not alter these findings. Significant predictors of mortality from the illness measure were a history of hypertension, Parkinson's disease and other severe illnesses (usually cancer). RDI was not a predictor of mortality in this population of non-demented seniors, where the prevalence of high levels of RDI was low.

Age Factors↗
PubMed1995

Proposals to unify the genera Grahamella and Bartonella, with descriptions of Bartonella talpae comb. nov., Bartonella peromysci comb. nov., and three new species, Bartonella grahamii sp. nov., Bartonella taylorii sp. nov., and Bartonella doshiae sp. nov.

Polyphasic methods were used to examine the taxonomic positions of three newly identified Grahamella species. A comparison of the 16S rRNA gene sequences of these organisms with the sequences available for other bacteria revealed that these three species form a tight monophyletic cluster with members of the genus Bartonella. This cluster is only remotely related to other members of the order Rickettsiales. Determinations of the levels of DNA relatedness between Grahamella species and Bartonella species (by using a modified hydroxyapatite method) revealed that all of the species belonging to these two genera are distinct but closely related. On the basis of these data and the results of guanine-plus-cytosine content and phenotypic characterization studies, we propose that the genera Grahamella and Bartonella should be unified and that the latter name should be retained. Bartonella talpae and Bartonella peromysci, new combinations for former Grahamella species, are created, and the following three new Bartonella species are described: Bartonella grahamii, Bartonella taylorii, and Bartonella doshiae. A taxonomic analysis of Grahamella species complete the study of all members of the family Bartonellaceae, and the results of this study support the proposal that the family should be transferred out of the order Rickettsiales.

Alphaproteobacteria↗
PubMed1995

Development and implementation of an innovative intern training programme.

The quality of medical education during internship is a cause for concern. This paper describes a structured educational programme for interns that was based around learning modules, clinical attachments and bedside teaching. The programme was incorporated into the term rotation of interns within an Area Health Service, and evaluated. Learning modules were timetabled by a Programme Coordinator and interns were reminded to attend. Clinical attachments were organized by the interns from a list of willing supervisors. Attendance at timetabled learning modules averaged 67%, which was greater than the 27% attendance at clinical attachments. Both sessions received high ratings for quality and clinical relevance. This structured education programme was based upon adult learning methods and was both feasible and well received by interns. Intern training programmes need to be programmed into the working week to ensure attendance, and modified following evaluation by interns. Such programmes should be considered by all hospitals to which interns are allocated.

Australia↗
PubMed1995

Intergenic 16S rRNA gene (rDNA)-23S rDNA sequence length polymorphisms in members of the family Legionellaceae.

A method based on PCR amplification of the 16S rRNA gene (rDNA)-23S rDNA intergenic regions was developed for the identification of species within the family Legionellaceae. The sizes of the PCR products varied from 1,353 to 350 bp. Strains of Legionella pneumophila were characterized as having products of approximately 900 and 530 bp, and L. birminghamensis had products of 1,390, 960, and 380 bp. Of the 38 species of legionellae examined, only 7 were indistinguishable (L. erythra from L. rubrilucens, L. anisa or L. cherrii from L. tucsonensis, and L. quateirensis from L. shakespearei). Two environmental isolates were identified as L. pneumophila. Strain LLAP-3, which was a symbiont of amoebae, could not be associated with any Legionella sp. studied.

Bacterial Typing Techniques↗
PubMed1995

A community study of snoring and sleep-disordered breathing. Symptoms.

Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random sample of the community. The sample was biased in favor of men, snorers, and subjects with subjective sleep complaints. They answered a questionnaire and were monitored in their homes for sleep-disordered breathing (SDB). This report concerns the presence of symptoms associated with the obstructive sleep apnea (OSA) syndrome in the subjects with SDB detected in this community sample. Most of the symptoms commonly recognized as occurring in OSA were associated with SDB in our sample: snoring that disturbed the sleep of other persons, reports of apnea, reports of gasping or choking sounds during sleep, and finding the bedclothes in disarray in the mornings had significant univariate associations with SDB. Nocturnal choking and morning headache were negatively associated with SDB. Excessive daytime somnolence (EDS) was reported by 41% of those with SDB, but it was also reported by 37% of snorers without SDB and by 37% of nonsnorers. We conclude that the symptoms seen in clinic patients with OSA also occur in subjects with SDB who have not presented for medical attention. Enumeration of these symptoms by questionnaire, however, is a poor test for OSA in the community. EDS was reported by a higher than expected proportion of subjects not affected by SDB, suggesting that causes of self-reported EDS other than SDB may be common.

Accidents, Traffic↗
PubMed1995

A community study of snoring and sleep-disordered breathing. Prevalence.

We conducted a study of the prevalence of sleep-disordered breathing in subjects derived from a random sample of the population. A total of 2,202 subjects 35 to 69 yr of age were approached. Four hundred forty-one answered a questionnaire concerning their sleep symptoms, general health, and habits such as alcohol consumption, and they were monitored for sleep-disordered breathing (SDB). The sample was biased in favor of snorers and those with other subjective sleep complaints. Fifty-six percent of the subjects were men. Of the 441 subjects 79 (17.9%) had SDB (more than 15 episodes of apnea or hypopnea per hour: respiratory distress index [RDI] > or = 15), 289 were snorers but had RDI < 15, and 73 were nonsnorers. The prevalence of SDB in this sample was therefore at least 3.6% (79 of 2,204). The minimum prevalence in men was 5.7%, and in women it was 1.2%. Logistic regression identified only male sex as an independent predictor of snoring without SDB (adjusted odds ratio [OR], 3.24; 95% CI, 1.33 to 7.82), body mass index (adjusted OR for an increase of 5 kg/m2, 0.95; 95% CI, 0.85 to 1.05), and alcohol consumption (adjusted OR for an increase of 10 g/day, 1.05; 95% CI, 0.84 to 1.37) were not significant predictors of snoring. The independent predictors of SDB among snorers were age (adjusted OR for an increase of 5 yr, 1.26; 95% CI, 1.08 to 1.47) and neck circumference (adjusted OR for an increase of 2 cm, 1.53; 95% CI, 1.16 to 2.00).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A community study of snoring and sleep-disordered breathing. Health outcomes.

Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random sample of the community. They answered a questionnaire and were monitored in their homes for sleep-disordered breathing (SDB). This report concerns the association between observed SDB and arterial hypertension and vascular disease. Hypertension was defined as self-report of a diagnosis of hypertension made by a physician, current treatment for hypertension, or a systolic pressure greater than 150 mm Hg or a diastolic pressure greater than 90 mm Hg. Coronary artery disease was defined by self-report of angina or myocardial infarction of "heart attack." There were few cases of stroke or claudication, and a category of "occlusive vascular disease" was defined by self-report of coronary artery disease or of "blocked arteries" or stroke. Subjects were classified as snorers (n = 289) or nonsnorers (n = 73) by self-report of regular snoring, and as having SDB (n = 79) if more than 15 abnormal respiratory events were recorded per hour of recording. There were significant increases in the prevalence of hypertension, coronary artery disease, and occlusive vascular disease from nonsnorers (26, 7, and 10%, respectively) through snorers (39, 12, and 17%) to subjects with SDB (57, 20, and 28%). The crude odds ratio for SDB versus nonsnorers was 3.8 (95% CI, 1.9 to 7.5) for hypertension, 3.5 (1.2 to 10.0) for coronary artery disease, and 3.7 (1.5 to 9.1) for occlusive vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Control of growth regulatory and differentiation-specific genes in human epidermal keratinocytes by interferon gamma. Antagonism by retinoic acid and transforming growth factor beta 1.

Interferon gamma (IFN-gamma) is a potent inducer of squamous differentiation in normal human epidermal keratinocytes. This induction is characterized by a > or = 95% decrease in the mRNA level of two growth regulatory genes, cdc2 and E2F-1, and a 7-15-fold increase in the expression of two squamous cell-specific genes, transglutaminase type I and cornifin. In contrast to the decrease in cdc2 and E2F-1 expression, the increase in transglutaminase type I and cornifin mRNAs by IFN-gamma occurs after a lagtime of more than 12 h. These results are consistent with the hypothesis that in normal human epidermal keratinocyte cells irreversible growth arrest precedes the expression of the squamous-differentiated phenotype. The action of IFN-gamma on the expression of squamous cell-specific genes is antagonized by retinoic acid and transforming growth factor beta 1. Both factors are potent suppressors of the induction of transglutaminase type I and cornifin; however, they do not prevent the commitment to irreversible growth arrest. Several squamous cell carcinoma cell lines do not show a detectable decrease in cdc2 or increase in transglutaminase type I mRNA levels after IFN-gamma treatment and appear to be altered in their control of squamous differentiation.

CDC2 Protein Kinase↗
PubMed1994

Differential responsiveness of human bronchial epithelial cells, lung carcinoma cells, and bronchial fibroblasts to interferon-gamma in vitro.

The present study examines interferon-gamma (IFN gamma)-induced changes in the expression of immunomodulatory genes, proliferation-associated genes, and squamous-specific genes in primary cultures of human bronchial epithelial cells and fibroblasts. IFN gamma induced the expression of guanylate binding protein (GBP or p67) and the MHC class II antigen, HLADR alpha, in both epithelial cells and fibroblasts. In contrast, the expression of complement component C3 was induced in bronchial epithelial cells but not in fibroblasts. Similarly, IFN gamma induced growth arrest (EC50 approximately 50 U/ml) only in bronchial epithelial cells. This growth arrest was accompanied by a down-regulation of cdc2, E2F-1, and p53 mRNA levels and was associated with expression of the squamous-specific marker genes, transglutaminase type I and cornifin. These findings are consistent with IFN gamma inducing squamous differentiation in bronchial epithelial cells. In contrast, several lung carcinoma cell lines did not respond to IFN gamma with respect to the down-regulation of proliferation-associated genes or the induction of squamous-specific genes. However, GBP expression was induced in all the cell lines in response to IFN gamma. The present study demonstrates that cultured human bronchial epithelial cells are sensitive to the immunomodulatory, growth-inhibitory, and differentiation-inducing properties of IFN gamma. In contrast, several lung carcinoma cell lines are insensitive to the growth-inhibitory and differentiation-inducing actions of IFN gamma, suggesting they may have acquired defects in certain IFN gamma signaling pathways. Although the growth of human bronchial fibroblasts is not altered, expression of certain immunomodulatory genes is induced by IFN gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗