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Biomedical subjects

S J O'Brien

Publications and source records attributed to S J O'Brien.

At least 55 records · Page 3Linked to original sources

Do CuSums have a role in routine communicable disease surveillance?

The swift identification of outbreaks of infection is essential for effective control in the population. One of the functions of surveillance is to detect outbreaks but it could be argued that this is one of the weaker aspects of routine surveillance at present. This paper describes a technique which might meet this surveillance need. The CuSum technique allows rapid measurement of change from expected values based on historical data. It is very simple and seems to be a highly sensitive technique which can signal the need for further scrutiny of the data and/or for public health action, long before a change in incidence is apparent from raw data. This is particularly true for low-incidence infections where large functions can make interpretation difficult. CuSums represent a potentially useful adjunct to other surveillance methods in infection control.

Communicable Disease Control

Comparative genomics: lessons from cats.

The genomics era, spear headed by dazzling technological developments in human and mouse gene mapping, has additionally provoked extensive comparative gene mapping projects for domestic species of several vertebrate orders. As the human genome project promises a one dimensional string of 100,000 genes and sequences, comparative mapping will extend that inference to a second dimension representing index species of the 20 living mammalian orders and to a third dimension by phylogenetic description of the genomes of mammal ancestors. We review here the remarkable extent of genome homology conservation among mammals illustrated by technology applications in the feline genome project.

Animals

The adduction distraction maneuver.

The adduction distraction maneuver is presented as an adjunct to the surgeon's technical skills to assist with the initial introduction of the shoulder arthroscope. Both novice and experienced arthroscopists can experience difficulty establishing access to the glenohumeral joint. Often this results in articular cartilage or soft tissue damage. The adduction distraction maneuver when used in the "beach chair" seated position for shoulder arthroscopy can facilitate posterior portal placement and minimize iatrogenic trauma.

Arthroscopy

Conservation genetics of the koala (Phascolarctos cinereus): low mitochondrial DNA variation amongst southern Australian populations.

Koala (Phascolarctos cinereus) populations in southern Australia have a history of bottlenecks-earlier this century the species became extinct in South Australia, and almost so in Victoria. Subsequently large numbers of animals from island populations (founded from very few animals) have been translocated back to mainland sites and to other islands in the region. As part of a larger study of the genetic structure of koala populations in southern Australia, we have undertaken a survey of mitochondrial DNA restriction fragment length polymorphism (mtDNA-RFLP) variability. Genomic DNA from 91 koalas from five populations was examined using 23 restriction enzymes, and mtDNA fragments were detected using a domestic cat full-length mtDNA clone. Only one of the enzymes, TaqI, revealed polymorphism-a relatively low amount of variation compared with other mammals, although low mtDNA-RFLP variation has also been reported in Queensland koalas. French Island and populations established predominantly from French Island immigrant koalas, either directly or via other island populations, were indistinguishable by haplotype frequencies. The mtDNA data are thus consistent with the interpretation that the koala translocation programme has homogenized gene frequencies amongst those populations involved. South Gippsland is not recorded as having received translocated koalas directly, and has significantly different mtDNA-RFLP haplotype frequencies from all other populations examined. The fact that this distinction was not previously observed in nuclear gene frequencies may reflect predominantly male-mediated dispersal in koalas.

Animals

Methicillin-resistant Staphylococcus aureus (MRSA) in nursing homes in a major UK city: an anonymized point prevalence survey.

An anonymized point-prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) carriage was conducted amongst a stratified random sample of nursing home residents in Birmingham, UK, during 1994. Microbiological sampling from noses, fingers and the environment was undertaken. Information about potential risk factors for the acquisition of MRSA was gathered. MRSA was isolated from cultures of the nose or fingers of 33 of the 191 residents who took part in the study (17%) but only 1 of the 33 positive residents had a clinical infection. Although just 10 of the 87 environmental samples were MRSA positive, there was some environmental contamination in most homes. Risk factors for MRSA carriage were hospital admission within the last year (relative prevalence 2.09, 95% CI 1.13-3.88; P < 0.05) and surgical procedures within the last year (relative prevalence 4.02, 95% CI 2.18-7.43; P = 0.002). Phage-typing of the strains revealed similarities with those circulating in Birmingham hospitals. These findings suggest that the prevalence of MRSA in nursing homes in Birmingham was high, and that the strains may have originated in hospitals.

Bacteriophage Typing

Comparative anchor tagged sequences (CATS) for integrative mapping of mammalian genomes.

Precise comparisons of mammalian gene maps require common anchor loci as landmarks for conserved chromosomal segments. Using a computer script that automates DNA sequence database alignments, we designed 410 evolutionarily conserved primer pair sequences which are specific for anchor locus gene amplification from any mammalian species' DNA. Primer pairs were designed to span introns for polymorphism ascertainment, and to include sufficient exonic sequence (25-400 bp) to allow for gene identification. A total of 318 primer pairs were optimized for domestic cats, and 86% of the sequenced feline PCR products showed homology to the gene of primer origin. A screen of 20 mammals from 11 orders revealed that 35-52% of the 318 primers yielded a single PCR product without further optimization suggesting that nearly 75% can be optimized for any eutherian mammal.

Animals

Novel alleles of the chemokine-receptor gene CCR5.

The CCR5 gene encodes a cell-surface chemokine-receptor molecule that serves as a coreceptor for macrophage-tropic strains of HIV-1. Mutations in this gene may alter expression or function of the protein product, thereby altering chemokine binding/signaling or HIV-1 infection of cells that normally express CCR5 protein. Indeed, homozygotes for a 32-bp deletion allele of CCR5 (CCR5-delta 32), which causes a frameshift at amino acid 185, are relatively resistant to HIV-1 infection. Here we report the identification of 16 additional mutations in the coding region of the CCR5 gene, all but 3 of which are codon altering or "nonsynonymous." Most mutations were rare (found only once or twice in the sample); five were detected exclusively among African Americans, whereas eight were observed only in Caucasians. The mutations included 11 codon-altering nonsynonymous variants, one trinucleotide deletion, one chain-termination mutant, and three synonymous mutations. The high predominance of codon-altering alleles among CCR5 mutants (14/17 [81%], including CCR5-delta 32) is consistent with an adaptive accumulation of function-altering alleles for this gene, perhaps as a consequence of historic selective pressures.

Alleles

Rates of nuclear and cytoplasmic mitochondrial DNA sequence divergence in mammals.

Differential rates of nucleotide substitution among different gene segments and between distinct evolutionary lineages is well documented among mitochondrial genes and is likely a consequence of locus-specific selective constraints that delimit mutational divergence over evolutionary time. We compared sequence variation of 18 homologous loci (15 coding genes and 3 parts of the control region) among 10 mammalian mitochondrial DNA genomes which allowed us to describe different mitochondrial evolutionary patterns and to produce an estimation of the relative order of gene divergence. The relative rates of divergence of mitochondrial DNA genes in the family Felidae were estimated by comparing their divergence from homologous counterpart genes included in nuclear mitochondrial DNA (Numt, pronounced "new might"), a genomic fossil that represents an ancient transfer of 7.9 kb of mitochondrial DNA to the nuclear genome of an ancestral species of the domestic cat (Felis catus). Phylogenetic analyses of mitochondrial (mtDNA) sequences with multiple outgroup species were conducted to date the ancestral node common to the Numt and the cytoplasmic (Cymt) mtDNA genes and to calibrate the rate of sequence divergence of mitochondrial genes relative to nuclear homologous counterparts. By setting the fastest substitution rate as strictly mutational, an empirical "selective retardation index" is computed to quantify the sum of all constraints, selective and otherwise, that limit sequence divergence of mitochondrial gene sequences over time.

Animals

Evolutionary analysis of the 5'-terminal region of hepatitis G virus isolated from different regions in China.

We have determined the nucleotide sequence of the 5'-terminal region of the hepatitis G virus (HGV) genome in 11 hepatitis patients from three cities in China. Phylogenetic analyses revealed that the Chinese isolates were genetically distinct from previously described West African isolates (type 1) and American, European and East African isolates (type 2), with a mean sequence divergence of approximately 10%. The mean divergence between isolates from Lanzhou, in the northwest of China, and those from Shanghai and Nanjing, on the east coast of China, was 5% (range 3-7%). The isolates from Shanghai and Nanjing were closely related to a common strain in Japan, while some of those from Lanzhou were closely related to a southeast Asian type 3 isolate. Thus, the Chinese isolates belong to the type 3 variant of HGV.

Base Sequence

Infectivity of lion and puma lentiviruses for domestic cats.

Infection of domestic cats with feline immunodeficiency virus (FIV) causes progressive immunological deterioration similar to that caused by human immunodeficiency virus (HIV). Lentiviruses related to but phylogenetically distinct from FIV have been detected in several non-domestic feline species. Serological cross-reactivity of these viruses raises the question as to whether inter-species transmission may occur. To address this issue, we asked whether lion lentivirus (FIV-Ple) or two strains of puma lentivirus (FIV-Pco) could replicate or cause disease in domestic cats. We found that domestic cats inoculated with FIV-Ple developed persistent cell-associated viraemia, transient cell-free viraemia and antiviral antibody. Clinical disease was not detected throughout a 6 month observation period. Two of four cats inoculated with FIV-Pco developed cell-associated viraemia, seroconverted and exhibited transient lymphadenopathy. No changes in white blood cell parameters or other haematological abnormalities were detected in any of the infected cats. Virus-specific RNA was detected in co-cultivated lymphocytes of all infected cats by RT-PCR. These findings reveal that non-domestic cat lentiviruses are infectious for domestic cats and can establish persistent infection in the absence of disease.

Animals

Conservation of human vs. feline genome organization revealed by reciprocal chromosome painting.

We employed fluorescence in situ hybridization (FISH) with probes established by flow sorting metaphase chromosomes of the domestic cat (Felis cattus, 2n = 38) to "paint" homologous segments on human chromosomes and, reciprocally, using human chromosome paints on feline metaphase preparations. The results revealed, by direct microscopic observation, widespread conservation of genome organization between the two mammalian orders and confirmed 90% of the homologous genes mapped to both species. Fourteen of 23 human chomosomes were hybridized with single cat probes, and 9 of 19 cat chromosomes were entirely labeled by a single human probe. All other chromosomes were labeled with only two or, at most, three probes of the respective species. Y-chromosome probes gave no signals. Approximately 30 syntenic segments were identified, and the number of translocations could be estimated to be on the order of one new translocation per 10 million years in the phylogenetic lines leading to human and cat. Using the principle of maximum parsimony, the primitive vs. derived human chromosome segments were identified by comparison to the feline, cattle, and pig genomes, a first step in reconstructing the evolutionary heritage of the mammalian radiations. The results suggest that reciprocal chromosome painting will help reconstruct the history of genomic changes by determining the polarity of chromosomal rearrangements and establishing the ancestral karyotype for each principle branching point in mammalian evolution.

Animals

Suprascapular neuropathy. Results of non-operative treatment.

We retrospectively reviewed the results of non-operative treatment of suprascapular neuropathy in fifteen patients seen between November 1983 and February 1991. The clinical diagnosis was confirmed with electrodiagnostic studies. The treatment consisted of a program of physical therapy to improve the range of motion of the shoulder and to strengthen the surrounding muscles. The average duration of follow-up was three years and eleven months (range, one year to eight years and ten months). The latest evaluation included electrodiagnostic studies of the affected extremity and dynamic isokinetic testing of both upper extremities. The result was excellent for five patients and good for seven. The three remaining patients had operative treatment because of persistent symptoms; one of these patients had an excellent result, one had a good result, and one had a poor result. The results suggest that, in the absence of a well defined lesion producing mechanical compression of the suprascapular nerve, suprascapular neuropathy should be treated non-operatively.

Adolescent

Biomechanical evaluation of the medial collateral ligament of the elbow.

UNLABELLED: Anatomical dissection and biomechanical testing were used to study twenty-eight cadaveric elbows in order to determine the role of the medial collateral ligament under valgus loading. The medial collateral ligament was composed of anterior, posterior, and occasionally transverse bundles. The anterior bundle was, in turn, composed of anterior and posterior bands that tightened in reciprocal fashion as the elbow was flexed and extended. Sequential cutting of the ligament was performed while rotation caused by valgus torque was measured. The anterior band of the anterior bundle was the primary restraint to valgus rotation at 30, 60, and 90 degrees of flexion and was a co-primary restraint at 120 degrees of flexion. The posterior band of the anterior bundle was a co-primary restraint at 120 degrees of flexion and a secondary restraint at 30 and 90 degrees of flexion. The posterior bundle was a secondary restraint at 30 degrees only. The reciprocal anterior and posterior bands have distinct biomechanical roles and theoretically may be injured separately. The anterior band was more vulnerable to valgus overload when the elbow was extended, whereas the posterior band was more vulnerable when the elbow was flexed. The posterior bundle was not vulnerable to valgus overload unless the anterior bundle was completely disrupted. The intact elbows rotated a mean of 3.6 degrees between the neutral position and the two-newton-meter valgus torque position. Cutting of the entire anterior bundle caused an additional 3.2 degrees of rotation at 90 degrees of flexion, where the effect was greatest. CLINICAL RELEVANCE: Physical findings in a patient who has an injury of the anterior bundle may be subtle, and an examination should be performed with the elbow in 90 degrees of flexion for greatest sensitivity. As the anterior bundle is the major restraint to valgus rotation, reconstructive procedures should focus on anatomical reproduction of that structure. Parallel limbs of tendon graft placed from the inferior aspect of the medial epicondyle to the area of the sublimis tubercle will simulate the reciprocal bands of the anterior bundle. Temporary immobilization with the elbow in flexion may relax the critically important anterior band of the reconstruction during healing.

Biomechanical Phenomena