Severe breathlessness, mouth ulcers and skin blistering in a female.
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Bronchiolitis Obliterans↗
Biomedical subjects
J Weir
Publications and source records attributed to J Weir.
Thoracic lymphatic pumping and the efficacy of influenza vaccination in healthy young and elderly populations.
The authors investigated whether thoracic lymphatic pumping (TLP) after FluShield vaccination enhanced the production of anti-influenza immunoglobulins in elderly individuals, who are at particular risk for influenza. Osteopathic students and non-TLP-treated elderly subjects served as controls. Serum antibody titers were quantified with enzyme-linked immunosorbent assay, and hemagglutination inhibition assay, both of which generated comparable results. While approximately 70% of the younger controls had increased anti-influenza immunoglobulin production on vaccination, only 30% to 35% of the aged population had increased antibody production. There was no significant enhancement in anti-influenza immunoglobulin production in the TLP-treated subjects. The authors' findings suggest that TLP in conjunction with influenza vaccination does not enhance immunization against influenza in otherwise healthy and active populations. However, such techniques may be of value when applied in conjunction with vaccination to nonambulatory patients or on actual influenza exposure of at-risk individuals.
Adult↗
Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat.
Vertebrate photoreceptor cells are the basic sensory apparatus of the retina, capable of converting the energy of absorbed photons into neuronal signals. The proximal portions of mammalian photoreceptor outer segments are synthesized daily by cell bodies, and outer segment tips are shed with a circadian rhythm, resulting in a complete turnover of outer segments about every 9 days. The shed outer segments are phagocytosed by adjacent retinal pigment epithelial (RPE) cells, and metabolites are recycled to photoreceptors. The Royal College of Surgeons (RCS) rat is a widely studied, classic model of recessively inherited retinal degeneration in which the RPE fails to phagocytose shed outer segments, and photoreceptor cells subsequently die. We have used a positional cloning approach to study the rdy (retinal dystrophy) locus of the RCS rat. Within a 0.3 cM genetic inclusion interval, we have discovered a small deletion of RCS DNA that disrupts the gene encoding the receptor tyrosine kinase Mertk. The deletion includes the splice acceptor site upstream of the second coding exon of Mertk and results in a shortened transcript that lacks this exon. The aberrant transcript joins the first and third coding exons, leading to a frameshift and a translation termination signal 20 codons after the AUG. The concordance of these and other data indicate that Mertk is probably the gene for rdy. Our results provide genetic evidence for an essential role of a receptor tyrosine kinase in a specialized form of phagocytosis and suggest a molecular model for ingestion of outer segments by RPE cells.
Animals↗
Notch signaling and the emergence of auditory hair cells.
OBJECTIVE: Recent insights into the mechanisms that determine a hair cell's fate have emerged from studies on invertebrate sensory organs and the avian inner ear. These mechanisms have important implications for our understanding of the possible therapeutic management of sensorineural deafness. This article reviews the current state of our knowledge regarding mammalian auditory hair cell fate specification. DESIGN: Data were obtained from the MEDLINE database and data presented at the Molecular Biology of Hearing and Deafness Meeting (Bethesda, Md, October 1998). Articles reporting information about cell fate specification and Notch and its ligands were selected. MAIN OUTCOME MEASURES: Data pertaining to cell fate mechanisms, Notch and its ligands, and application to hearing were extracted. RESULTS: The Notch/ligand mechanism is responsible for the specification of the hair cell phenotype. CONCLUSIONS: Major progress has been made in understanding this fundamental process, and its application to hair cell determination is only now being realized. Possible applications could involve the "switching" of supporting cells to hair cells, thus replenishing those hair cells damaged in sensorineural hearing loss.
Hair Cells, Auditory↗
Identification of differentiating cochlear hair cells in vitro.
HYPOTHESIS: The expression of hair cell-specific genes involved in differentiation was studied in the cell line UB/OC-1 (University Bristol/Organ of Corti). BACKGROUND: Studies of gene expression in cochlear hair cells are restricted by the small number of cells available and by their experimental inaccessibility. The cell line was derived from the H2K(b)tsA58 transgenic mouse, which harbors a conditionally expressed immortalizing gene. Two genes that are characteristic of hair cells were upregulated during differentiation of UB/OC-1 cells in vitro. They are the transcription factor Brn3.1, which is essential for hair cell differentiation, and the alpha9 subunit of the nicotinic acetylcholine receptor that is involved in olivocochlear efferent innervation. METHODS: The expression of Brn3.1 and alpha9, at different time points under differentiating conditions, was analyzed by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR). Western blot analysis and immunofluorescence analysis were performed on the cell line with anti-Brn3.1 antibody. RESULTS: Reaction products for alpha9 were detected after 3 to 6 days under differentiating conditions. Low levels of Brn3.1 were detectable under proliferating conditions and increased under differentiating conditions. All cells expressed Brn3.1 under differentiating conditions. This temporal pattern of gene expression is very closely similar to that found in vivo. CONCLUSION: The cochlear hair cell line UB/OC-1 provides a valuable experimental system because it conditionally expresses genes essential for normal differentiation and electrophysiology. It should prove valuable in the identification and characterization of genes involved in development and may provide material for screening new therapeutic methods of stimulating recovery and regeneration of hair cells.
Animals↗
Deliberate self-poisoning presenting at a rural hospital in Northern Ireland 1976-1996: relationship to prescribing.
PURPOSE: This study reports on a project to monitor deliberate self-poisoning in a rural area of Northern Ireland over a 20-year period. Comparison is made with reports from large urban centres. In addition, a local prescribing database allows assessment of any association between psychotropic drug prescription and use for deliberate self-poisoning. MATERIALS AND METHODS: Frequency of self-poisoning, demographic details and drugs used were recorded for all episodes of deliberate self-poisoning occurring at Craigavon Area Hospital for the years 1976, 1986, 1991 and 1996. It was possible to compare prescriptions of psychotropic drugs with their use for deliberate self-poisoning between the years 1991 and 1996 in the region served by the hospital, using the Defined Daily Dose (DDD) system. RESULTS: In this rural area the pattern of deliberate self-poisoning has changed, as in urban centres, with a rise in frequency and the male/female ratio approaching unity. The pattern of drug use has altered, with paracetamol overtaking benzodiazepines as the most commonly used agent. More recently, antidepressants have become the second most frequently used drug class for this purpose. Psychotropic medications used for self-poisoning altered in proportion to their prescription between the years 1991 and 1996. CONCLUSIONS: In the face of a continuing rise in deliberate self-poisoning, which is effecting both urban and rural areas, care should be taken to prescribe the least toxic agent available as this is associated with likely frequency of self-poisoning for most classes of psychotropic drug.
Adult↗
Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa.
Mutation of a receptor tyrosine kinase gene, Mertk, in the Royal College of Surgeons (RCS) rat results in defective phagocytosis of photoreceptor outer segments by the retinal pigment epithelium (RPE) and retinal degeneration. We screened the human orthologue, MERTK, located at 2q14.1 (ref. 10), in 328 DNA samples from individuals with various retinal dystrophies and found three mutations in three individuals with retinitis pigmentosa (RP). Our findings are the first conclusive evidence implicating the RPE phagocytosis pathway in human retinal disease.
Adult↗
Inflammatory abdominal aortic aneurysms: diagnosis with gadolinium enhanced T1-weighted imaging.
AIM: Inflammatory abdominal aortic aneurysms (IAAA) are a variant of abdominal aortic aneurysms, which are associated with an increased morbidity. The diagnosis of IAAA has traditionally been established with a combination of clinical and laboratory findings together with contrast enhanced CT. There is a high incidence of renal impairment in this group, and therefore contrast enhanced CT may be harmful. PATIENTS AND METHODS: Five patients with IAAA underwent T1-weighted spin echo and gradient echo gadolinium enhanced abdominal MRI. A total of eight examinations were performed, including three patients who underwent repeat MRI following steroid therapy. RESULTS: The inflammatory cuff was clearly identified following gadolinium administration in all eight examinations. The cuff enhanced homogeneously in all patients with no alteration in appearance following steroid therapy. The intravenous administration of gadolinium DTPA enabled clearer definition of locally involved structures. CONCLUSION: Gadolinium enhanced MRI readily demonstrates features of IAAA. In view of potential renal impairment in this patient group, we recommend this technique in preference to contrast enhanced CT in the initial investigation of inflammatory abdominal aortic aneurysms.
Aged↗
Erythrocyte transfusion causes immunosuppression after total hip replacement.
A prospective study of 34 patients undergoing total hip replacement was done to determine whether homologous erythrocyte transfusion causes postoperative immunosuppression. In the transfused patient group (14 patients), there was a reduction in CD3+ and CD3+4+ cell numbers at Day 2, returning to preoperative levels by Day 7. In contrast, in the untransfused patient group (20 patients), there was no significant depression in these lymphocyte subgroups at Day 2 and an increase in total lymphocyte, CD3+, CD3+4+, and CD3+4-8- cell numbers at Day 7. In both patient groups there was postoperative leukocytosis, granulocytosis, and monocytosis at Days 2 and 7, with no significant change in postoperative B (CD19+) cell numbers, natural killer cells, or the minor T cell populations of CD3+4+8+ and CD3+25+. The lymphocyte functional test of Candida recall was significantly impaired at Day 7 in the transfused patient group, where Candida recall is a memory T cell response to an antigen extracted from the yeast Candida Albicans. These findings suggest that homologous erythrocyte transfusion after hip replacement surgery causes cell mediated immune suppression. The main clinical implication of the current study is that perioperative homologous erythrocyte transfusion may place patients at greater risk of infectious complications, including infection of the prosthesis.
Arthroplasty, Replacement, Hip↗
Three-dimensional computer-simulated prostate models: lateral prostate biopsies increase the detection rate of prostate cancer.
OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. METHODS: We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. RESULTS: The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-region biopsy protocol had a 90.5% detection rate and the 14-pattern, which includes all the biopsies used in the patterns above, only added 1 additional positive case (99.5%). Transitional zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. Only one positive model was obtained when the transitional zone biopsies were added. The lateral sextant pattern had a detection rate of 95.5%, and the 4-pattern lateral biopsy protocol had a 93.5% detection rate. CONCLUSIONS: Our results suggest that all the biopsy protocols that use laterally placed biopsies based on the 5-region anatomic model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.
Biopsy, Needle↗
Quantifying comorbidity in a disease-specific cohort: adaptation of the total illness burden index to prostate cancer.
OBJECTIVES: Numerous studies have demonstrated the importance of comorbid illness when analyzing medical outcomes. The purpose of this study was to adapt a generic comorbidity index, the Total Illness Burden Index (TIBI), for use in men with prostate cancer, and to evaluate the usefulness of the new instrument in adjusting for the impact of comorbidity on functional outcomes in a prostate cancer cohort. METHODS: The TIBI uses patients' self-report of symptoms and diagnoses to determine not only the presence but also the severity of comorbidities in each of 16 body system domains. To create the TIBI-P (prostate cancer modification), some domains were added and others were modified according to clinical criteria. The TIBI-P was completed by 1638 men with prostate cancer followed up longitudinally in 29 urology practices in the United States. TIBI-P scores were calculated for each patient and analyzed with scores on the SF-36 quality-of-life questionnaire and with patient report of days confined to bed. RESULTS: After adjusting for age and income, lower SF-36 scale scores and increases in confinement to bed were associated with a greater burden of comorbid illness as measured by the TIBI-P, independent of the extent of prostate cancer. The TIBI-P explained 24% of the variance in the SF-36 physical functioning domain score. CONCLUSIONS: The TIBI-P is a powerful measure of the impact of comorbid illness on the quality of life and functioning among patients with prostate cancer. This index may prove valuable in research on clinical and economic outcomes of prostate cancer.
Aged↗
The structure and paramutagenicity of the R-marbled haplotype of Zea mays.
Paramutation is the meiotically heritable silencing of a gene that can occur in particular heterozygous combinations. The R-marbled (R-mb) haplotype is paramutagenic: it causes paramutable r1 haplotypes like R-r to become heritably silenced. R-mb was found to comprise three distinct r1 genes arranged as direct repeats. The most distal gene of R-mb, Scm, contains a novel transposable element, Shooter (Sho). Excision of the Sho element early in aleurone development results in the characteristic "marbled" aleurone pigmentation pattern conferred by R-mb. The effect of gene copy number on the paramutagenic strength of R-mb was tested. Paramutagenic strength of R-mb is directly correlated with r1 gene copy number. Paramutagenic strength of R-mb is directly correlated with r1 gene copy number. Paramutagenic strength of R-mb was not affected by removal, through crossing over, of the Sho transposon. Finally, R-mb does not appear to contain the transposable element, Doppia, which is associated with paramutability of R-r, and has been suggested to play a role in paramutagenicity of another paramutagenic haplotype, R-stippled.
Base Sequence↗
High incidence of left atrial thrombus in renal transplant recipients.
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Adult↗
Prevalence of protein-energy malnutrition at diagnosis in children with acute lymphoblastic leukemia.
BACKGROUND: The purpose of the present study was to test the hypothesis that protein-energy undernutrition is common in patients with acute lymphoblastic leukemia at diagnosis. Previous studies have failed to establish whether undernutrition is a common feature at diagnosis. METHODS: Body mass index (BMI, weight/height2), expressed as a standard deviation score (SDS) relative to contemporary United Kingdom reference data, was used as the index of nutritional status. The index was calculated in a national cohort of standard-risk patients (n = 1019) treated in the same protocol in the United Kingdom. RESULTS: Prevalence of undernutrition (defined as BMI SDS <-2.0) exceeded expected frequencies in boys (7.6%) and girls (6.7%). These differences were statistically significant (p < 0.001), with a 95% confidence interval for the prevalence of undernutrition of 5.8% to 9.0%. CONCLUSIONS: Undernutrition is relatively common in patients with newly diagnosed acute lymphoblastic leukemia, with a threefold excess of patients below the cutoff used to define undernutrition. Screening for undernutrition at diagnosis of acute lymphoblastic leukemia is indicated, and the BMI SDS is a simple index of nutritional status that could be readily calculated using measurements routinely made at diagnosis. The same simple screening technique could also be used clinically to detect and manage or prevent overnutrition (obesity), which is common in these patients after diagnosis.
Adolescent↗
Sore throat after central venous cannulation.
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Catheterization, Central Venous↗
Provision of an out-of-hours imaging service: expectations vs reality.
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Attitude of Health Personnel↗