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Biomedical subjects

S Lawrence

Publications and source records attributed to S Lawrence.

At least 55 records · Page 3Linked to original sources

Nasal continuous positive airway pressure treatment: current realities and future.

Nasal continuous positive airway pressure (CPAP) is a highly effective treatment for obstructive sleep apnea syndrome. The apnea/hypopnea index (AHI) is reduced 10-fold, but the patient dropout rate is up to 30%, and usage is typically < 5 hours per night. Titration, designed to make the best trade-off between effectiveness and side effects, is expensive. Autotitrating devices make this trade-off on a minute-by-minute basis, potentially reducing mean pressure delivery, reducing side effects, and increasing compliance. The aim of this study was to test the effectiveness of the AutoSet self-adjusting nasal CPAP system (ResMed, Sydney, Australia) in eliminating obstructive events and normalizing the arousal index. Forty-five subjects (41 males and 4 females with AHI) values of > 20/hour were recruited, with written informed consent. Subjects slept for a diagnostic night, followed by a treatment night, in the laboratory, using the AutoSet system with full polysomnographic monitoring of respiratory and sleep variables. Arousals were scored using ASDA criteria. Hypopneas were scored when there was a 50% reduction in ventilation for > 10 seconds, associated with a 4% drop in oxygen saturation. For comparison, the ASDA arousal index in 16 normal subjects (without nasal CPAP) is provided. Results are given as mean +/- standard error of the mean. AHI was reduced from 55 +/- 3 to 1.5 +/- 0.35 events/hour (p < 0.0001). The arousal index was reduced from 65 +/- 3 to 18 +/- 2 events/hour (p < 0.0001), identical to the value in the 16 healthy normal subjects. There was a 158% +/- 21% increase in slow-wave sleep (p = 0.01) and a 186% +/- 27% increase in rapid eye movement sleep (p = 0.013). The AutoSet self-adjusting nasal CPAP system adequately treats obstructive sleep apnea syndrome on the first night under laboratory conditions.

Female↗

Controlled retainer-screw access placement for screw-retained implant prosthesis.

An implant-supported prosthesis is often secured to the underlying gold cylinders by retaining screws. There must be access to these screws from the oral surface of the prosthesis. Conventional preparation of this access is from the oral surface. This approach is difficult because the underlying gold cylinder is obscured. It may be damaged by a rotary cutting instrument as the access is prepared above it, because the cylinder cannot be seen during the preparation. Alternatively, the access hole may be unnecessarily enlarged in an attempt to find the cylinder. This loss of structure may weaken the prosthesis. A new approach, using 18-gauge stainless steel wire as a rotary cutting instrument, permits preparation of the access chamber from the intaglio surface of the prosthesis. This reduces risk of damage to the gold cylinder and is less destructive to the overlying material.

Bone Screws↗

Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness.

To investigate genetic factors in asthma and atopy, we sought allelic associations for 12 markers near candidate loci for serum total, immunoglobulin E (IgE), and bronchial hyperresponsiveness (BHR) to inhaled histamine in 131 families comprising 685 individuals, selected randomly without regard to atopy or asthma. Nonparametric linkage and association analyses were performed with the Nonparametric Analysis of Lineage and Association (NOPAR) program, and parametric analyses were performed with the Complex Inheritance with Diathesis and Severity (COMDS) program on an ordered polychotomy of ranked scores. On chromosome 11q, allele 168 at the D11S527 locus was significantly associated with BHR (p<0.0003) but not with log IgE. At the D11S534 locus, allele 235 was significantly associated with log IgE (p = 0.007) but not with BHR. Both D11S527 and D11S534 were too distant from the gene encoding the high-affinity IgE receptor FcepsilonRIbeta to account for the association. At the interleukin-9 (IL-9) locus, the 118 allele showed significant association with serum total IgE (p<0.003) but not with histamine BHR. Parametric tests are more conservative, perhaps because they demand consistency with mendelian inheritance and tight linkage. These findings provide support for the view that both chromosomes 5 and 11 may contain genes relevant to asthma and atopy, a possible candidate being the interleukin-4 (IL-4) gene cluster. Because these associations are extremes in a large number of tests, they require confirmation in other samples.

Adolescent↗

Evolutionary dynamics of the FMR1 locus.

Rare haplotypes for close flanking markers are associated with increased allele size and frequency of the fragile X mutation. Exceptional founder haplotypes can be identified, but many haplotypes with rare alleles contribute to full mutations. A transition matrix constructed from the data predicts that a population with reduced variability will manifest a slowly increasing frequency of premutations and full mutations, reach a distribution close to the observed one after a few hundred generations, and then slowly be depleted of these alleles. This prediction is opposite to less well supported inference of increasing frequency of progressive amplification, but the data are inadequate to reach any firm conclusions. Factors that may determine the evolution of these systems, but cannot now be evaluated, are discussed.

Biological Evolution↗

An integrated map of chromosome 9.

An integrated map of 211 loci on chromosome 9 is presented for which 198 loci have genetic locations. The results of the analysis indicate very strong interference for the chromosome and positional variations in recombination rates, most extreme in the male map where there is an excess of recombination near the p telomere and a marked suppression of recombination in a large region that includes the centromere.

Chromosome Mapping↗

Exclusion from proximal 11q of a common gene with megaphenic effect on atopy.

We have typed three markers on proximal 11q in 131 random families with three or more children studied for atopy. A summary map that includes the FCER1B candidate was constructed. Using a 2-locus disease model, we performed combined segregation and linkage analysis of three models, none of which suggested linkage. Nine marker loci on other chromosomes were also negative. In the regions swept by these 12 markers we cannot rule out a rare gene, perhaps of large effect, nor a common gene of small effect. However, a common gene of large effect is excluded. These results and alternative strategies are discussed in the perspective of inconsistent evidence for a major atopy gene.

Alleles↗

Attitudes and behaviors of African-American and Mexican-American women delivering newborns in inner-city Los Angeles.

To study some of the factors relating to the care of mothers and newborns in an inner-city hospital, three sources of information were reviewed: an obstetric database including information on prenatal care and perinatal mortality, a database of all admissions to the hospital neonatal intensive care unit over the past 5 years, and a detailed questionnaire concerning attitudes and behaviors of recently delivered women. While analyses from these hospital-based data are not conclusive, the results add evidence for the following propositions: 1) Optimal prenatal care is infrequently obtained by mothers delivering at inner-city hospitals. Lack of prenatal care is clearly associated with increased perinatal mortality. While the need for prenatal care is appreciated by 98% of the mothers in this sample, the most frequent reasons why prenatal care is not obtained earlier or more frequently involve knowledge about and access to prenatal care. 2) Inner-city mothers, in general, manifest attitudes and behaviors that promote the welfare of their pregnancies and newborns. These attitudes and behaviors are in stark contrast to those that are frequently attributed to inner-city women by the media. 3) Acute perinatal medical and nursing care are perceived by many postpartum women as suboptimal, particularly in terms of the lack of respect shown to patients by nurses and doctors. 4) Improved acute obstetric and neonatal care improves perinatal morbidity and mortality of infants delivered at inner-city hospitals.

Adult↗

Effects of oral creatine loading on single and repeated maximal short sprints.

This investigation determined whether oral creatine (Cr) loading could enhance single and repeated short sprint performance. A 1 x 10 s cycle sprint (Study One) and 6 x 6 s (departing every 30 s) repeated cycle sprints (Study two) were the performance tests used. Separate groups of subjects, randomly assigned to either a Cr or placebo (P) group, were used in each study in a double blind design. After performing a familiarization and two baseline tests subjects loaded with 5g of Cr or P four times per day for five days before repeating the tests one and three days post-loading. In Study One (n = 9 in each group), work completed (kJ) at 2, 4, 6, 8 and 10 s and peak power (W) were greater than baseline values in each of the post-loading trials in both the Cr and P groups. There were no between group performance differences. In Study Two (n = 11 in each group) after loading, the Cr group recorded significantly greater scores than the P group in total work (kJ) completed over the 6 sprints, work completed in sprint 1, and peak power (W). Post-exercise blood lactate and pH responses were not different between the Cr and P groups after loading in either study. Although Study One results are equivocal, Study Two results suggest that Cr supplementation can enhance both single (if sprint 1 results are considered in isolation) and repeated short sprint performance.

Administration, Oral↗

Integration of gene maps: chromosome X.

Omitting 1137 loci that are included in the location database but have only cytogenetic assignment, there are 605 loci in the integrated map that synthesizes physical and genetic data and subsumes a composite physical location, cytogenetic and regional assignments, mouse homology, rank, and references. With error filtration and allowance for interference the genetic length is 211 cM, to which the p arm contributes 100 cM. The physical length is 164 Mb, with 62 Mb in the p arm. Current problems in map integration are discussed and some solutions proposed.

Animals↗

Treatment of asymptomatic congenital syphilis: benzathine versus procaine penicillin G therapy.

We compared the efficacy of two treatment regimens for asymptomatic congenital syphilis. Between June 1989 and July 1991, we prospectively and randomly assigned 169 patients to receive either one dose of benzathine penicillin G or procaine penicillin G for 10 days. There were no significant differences between the treatment groups in regard to birth weight, sex, race, gestational age, Apgar scores, infant or maternal rapid plasma reagin (RPR) titers, fluorescent treponemal IgM antibody, or maternal treatment. Patients were examined at 2 to 3, 6, and 12 months after treatment; treatment failure was defined as clinical signs or persistent laboratory evidence of congenital syphilis. Nine patients were removed from the study during the neonatal period, eight were lost to follow-up, and 152 patients were examined 2 to 3 months or more after treatment. Among these 152 patients, none had clinical evidence of congenital syphilis at follow-up, and all the patients tested at 2 to 3 months after treatment (68 in the benzathine penicillin G group and 61 in the procaine penicillin G group) had at least a fourfold decrease in RPR titers. The RPR became nonreactive in all but three of the infants (two in the procaine penicillin G group and one in the benzathine penicillin G group; all three were 2 to 3 months of age when last tested). We conclude that treatment failure did not occur with either regimen and that there was no significant difference in outcome between the two groups.

Female↗

The anaphylaxis hypothesis of sudden infant death syndrome (SIDS): mast cell degranulation in cot death revealed by elevated concentrations of tryptase in serum.

A series of cases of sudden unexpected post-neonatal deaths from two centres in the UK have been investigated for evidence of mast cell activation using the biochemical markers tryptase and 9 alpha,11 beta-PGF2. Tryptase was selected as a possible marker because it is a component of mast cell secretory granules and, unlike histamine, it is not released from basophils. The prostaglandin 9 alpha,11 beta-PGF2 is an initial and pharmacologically active metabolite of PGD2, the major mast cell-derived cyclooxygenase product. This prostaglandin was chosen to serve as a marker of newly generated mediator release. In the study, unexplained infant deaths were associated with a higher concentration of tryptase in serum compared with cases of unexpected, but subsequently explained death. However, 9 alpha,11 beta-PGF2 was found to be an unsuitable post mortem marker in this situation. These results provide direct evidence that mast cell degranulation, possibly as a result of anaphylaxis, may be occurring around the time of death in some cases of cot death.

Anaphylaxis↗

Genetic analysis of atopy and asthma as quantitative traits and ordered polychotomies.

Traits related to atopy and asthma were defined in a random cohort of 131 families with three or more children. Correlation analysis provides no evidence of imprinting, maternal effect, or a major role of environment shared by sibs. Commingling analysis favours more than one distribution, the upper one being common for asthma and very common for atopy. Segregation analysis of rank-transformed variables provides only equivocal evidence of major genes against a polygenic background but suggests that such genes (if present) are individually common and not of large effect. Segregation analysis under a two-locus model gives consistent results with minimal distributional assumptions. To enter combined segregation analysis we favour a restricted model in which the major locus is additive on the liability scale and the pseudopolygenic modifier locus accounts for at least half the genetic variance. Total IgE and bronchial reactivity are proposed for meta-analysis of atopy and asthma respectively. Genetic analysis of complex inheritance is discussed and it is shown that allelic association with random loci is not a feasible approach.

Adolescent↗

Integration of gene maps: chromosome 21.

Physical, cytogenetic, and genetic data including microsatellite markers and a covering sequence-tagged site (STS) map have been entered into a location database and integrated into a summary map that subsumes a composite physical location, sex-specific genetic locations, cytogenetic and regional assignments, mouse homology, rank, and references. With the omission of 52 loci whose location is known only from cytogenetic assignment to an interval greater than 10 megabases, there are 198 loci in the covering STS map and an additional 145 loci. The physical length is consistent with 11 megabases for 21p and 39 megabases for 21q. With error filtration and allowance for high interference, the genetic length in males corresponds to the chiasma map (54.7 centimorgans), and the genetic length in females is 76.5 centimorgans. The relation between map integration and the STS paradigm is illustrated and discussed.

Chromosome Mapping↗