Tuberculosis in cattle and badgers.
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Animals↗
Biomedical subjects
J Gallagher
Publications and source records attributed to J Gallagher.
Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis.
OBJECTIVE: Proteoglycan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA), both in terms of its pathology and its genetics. PGIA can only be induced in susceptible murine strains and their F2 progeny. As with RA, the genetics are complex, containing both major histocompatibility complex (MHC)-related and non-MHC-related components. Our goal was to identify the underlying non-MHC-related loci that confer PGIA susceptibility. METHODS: We used 106 polymorphic markers to perform simple sequence-length polymorphism analysis on F2 hybrids of susceptible (BALB/c) and nonsusceptible (DBA/2) strains of mice. Because both strains of mice share the H2d haplotype, this cross permits identification and analysis of non-MHC-related genes. RESULTS: We identified a total of 12 separate quantitative trait loci (QTL) associated with PGIA, which we have named Pgia1 through Pgia12. QTLs associated with the inflammatory symptoms of PGIA were linked to chromosomes 7, 9, 15 (2 separate loci), 16, and 19. QTLs associated with autoantibody production were identified on chromosomes 1, 2, 7, 8, 10, 11, 16, and 18. QTLs on chromosomes 7 and 16 showed linkage to both inflammation and autoantibody production, suggesting a shared regulatory component in arthritis induction. The first inflammation QTL on chromosome 15 and the autoantibody QTL on chromosome 7 originate from the DBA/2 background, which indicates that as in RA, susceptibility genes can originate from heterogeneous backgrounds. CONCLUSION: These data demonstrate the complexity of PGIA, where QTLs may be involved in multiple traits or even originate from a genetic background previously determined to be resistant.
Animals↗
A Phase I study of continuous infusion doxorubicin and paclitaxel chemotherapy with granulocyte colony-stimulating factor for relapsed epithelial ovarian cancer.
A Phase I study of paclitaxel and doxorubicin administered as concurrent 96-h continuous i.v. infusion was performed to determine the maximum tolerated dose (MTD), principal toxicities, and pharmacokinetics of this combination in women with relapsed epithelial ovarian cancer. The paclitaxel dose was fixed at 100 mg/m2 (25 mg/m2/day for 4 days). The dose of doxorubicin was escalated from 30 mg/m2 (7.5 mg/m2/day for 4 days) in increments of 10 mg/m2 until dose-limiting toxicity was observed. All patients received granulocyte colony-stimulating factor 5 microg/kg/day prophylactically. Apparent steady-state plasma levels of both drugs were determined in the final cohort of patients treated at the MTD. A total of 17 patients received 52 cycles of therapy. The median age was 58 years, and all patients had previously received one to five different regimens (median, 2) of chemotherapy, including both platinum and paclitaxel. The treatment was tolerated well, with grade 1-2 nausea being the most frequent side effect (73% of cycles). Anemia, neutropenia, thrombocytopenia, and mucositis became dose limiting at the fourth dose level, defining the MTD of doxorubicin in this regimen as 50 mg/m2. There were four partial responses and one complete response in 15 evaluable patients. Apparent steady-state plasma concentrations (mean +/- SD) of paclitaxel and doxorubicin in the three patients treated at the MTD were 33.9 +/- 12.5 nM and 15.7 +/- 1.3 nM, respectively. Paclitaxel and doxorubicin by continuous infusion is a well-tolerated and active chemotherapy regimen for recurrent ovarian cancer.
Adult↗
Hemolytic uremic syndrome: defining the need for long-term follow-up.
BACKGROUND: Diarrhea-associated (D+) hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Progressive renal insufficiency has been documented on prolonged follow-up of selected patients. However, it is uncertain whether all children recovering from varying degrees of HUS require long-term follow-up. PATIENTS AND METHODS: We reviewed the outcome of 114 patients with D+ HUS presenting to a regional pediatric unit between January 1986 and December 1996. Yearly clinical review post illness included measurement of blood pressure and urinalysis for proteinuria with planned GFR assessments by 51Cr EDTA slope clearance at 1 and 5 years. RESULTS: Treatment of the HUS was conservative in 27%, by peritoneal dialysis in 62%, hemodialysis in 4% and both peritoneal and hemodialysis in 7%. Ninety-two patients were assessed at 1 year - of these, 1 remained on chronic peritoneal dialysis, 5 (5%) had moderate to severe chronic renal failure (CRF) (GFR 25 - 50 ml/min/1.73 m2), 20 (22%) had mild CRF (GFR 50-80) and 66 (72%) had normal renal function (> or =80 ml/min/1.73 m2). Forty patients have had GFRs performed at 1 and 5 years. Of the 28 patients with a normal GFR at 1 year, 3 deteriorated into mild CRF at 5 years. One patient has a single kidney and one had significant proteinuria at 1 year, factors which would have led to long-term follow-up. There was a negative correlation between number of days of dialysis and GFR at 1 year with a Pearson's correlation coefficient of -0.453 (p<0.01). CONCLUSION: We conclude that renal function at I year following HUS cannot be predicted with any certainty from the initial illness and should be formally assessed. However, renal function was within normal limits and remained stable between 1 and 5 years following HUS in most children. The results suggest that longer-term follow-up can probably be restricted to those with proteinuria, hypertension, abnormal ultrasound and/or impaired GFR at 1 year.
Child↗
Role of infected, non-diseased badgers in the pathogenesis of tuberculosis in the badger.
The lungs and kidneys of 15 badgers which had no visible lesions of tuberculosis but from which Mycobacterium bovis was isolated from pooled collections of lymph nodes were serially sectioned. Lesions of tuberculosis were detected by histopathology in the the lungs of 13 and in the kidneys of one of them. The lesions were mostly typical early stage granuloma-lesions which were considered to be the primary foci of infection. These lesions suggest an early containment phase of arrested development previously not observed and provide further evidence on which to propose a hypothesis for the pathogenesis of tuberculosis in the badger.
Animals↗
Protease activity of 1,10-phenanthroline-copper(I). Targeted scission of the catalytic site of carbonic anhydrase.
To investigate the mechanism of scission of proteins by the chemical cleaving agent 1,10-phenanthroline-copper, the active sites of human carbonic anydrase I and bovine carbonic anhydrase II have been targeted for cleavage by a tight binding sulfonamide inhibitor tethered to the metal complex. The inhibitor-phenanthroline-copper conjugate binds to the carbonic anhydrases with sub-micromolar Kd's and, upon addition of a reducing agent, causes scission specifically within the active site of the enzymes to yield a discrete set of cleavage fragments. N- and C-terminal sequencing and mass spectrometric analysis of several fragments indicate that the C-terminal cleavage fragments have free amino groups at their N termini, thereby allowing facile location of the cut sites through standard Edman degradation. The N-terminal cleavage fragments do not have a free carboxyl group at their C termini. It is proposed that scission occurs by abstraction of H at Calpha, followed by oxidation at Calpha by the neighboring cupric ion and cleavage of the Calpha-C(O) bond to give an N-terminal fragment containing a C-terminal acyl amide, and an unstable C-terminal fragment containing an N-terminal isocyanate group which undergoes hydrolysis to a free amino terminus. Modeling of the inhibitor-phenanthroline-copper conjugate within the active site of human carbonic anhydrase I shows that the sites of cleavage that have been identified are fully consistent with the available structural data.
Amino Acid Sequence↗
Severe tiger snake envenomation in a wilderness environment.
A 44-year old bushwalker was envenomed in an isolated area late in the afternoon, and a succession of difficulties with his rescue resulted in his not reaching hospital until nearly 24 hours later. This case highlights the problems of prolonged delays before treatment for envenomation, and points to the advantages of physician-staffed emergency helicopter services carrying snake antivenoms into the field.
Adult↗
Chickenpox ARDS in a health care worker following occupational exposure.
A case is described of chickenpox acute respiratory distress syndrome in an ambulance driver after the inter-hospital transfer of a patient known to have chickenpox pneumonia. Following this exposure, he neither avoided patient contact nor received varicella zoster immune globulin. He subsequently required 13 days of ventilatory support before making a full recovery. The case described supports the contention that health care workers should be screened by serology for immunity to chickenpox before patient contact occurs, with subsequent vaccination of those who are non-immune, when the vaccine becomes available.
Adult↗
A critical analysis of on-scene helicopter transport on survival in a statewide trauma system.
BACKGROUND: Recently, questions have been raised regarding the effectiveness of helicopters in trauma care. We conducted a retrospective study to evaluate the effect of on-scene helicopter transport on survival after trauma in a statewide trauma system. METHODS: Data were obtained from a statewide trauma registry of 162,730 patients treated at 28 accredited trauma centers. Patients transported from the scene by helicopter (15,938) were compared with those transported by ground with advanced life support (ALS) (6,473). Interhospital transfers and transports without ALS were excluded. Statistical analysis was performed using one-way analysis of variance and logistic regression. RESULTS: Patients transported by helicopter were significantly (p < 0.01) younger, were more seriously injured, and had lower blood pressure. They were also more likely to be male and to have systolic blood pressure < 90 mm Hg. Logistic regression analysis revealed that when adjusting for other risk factors, transportation by helicopter did not affect the estimated odds of survival. CONCLUSION: A reappraisal of the cost-effectiveness of helicopter triage and transport criteria, when access to ground ALS squads is available, may be warranted.
Adolescent↗
Severe rhabdomyolysis after tiger snake bite.
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Adult↗
Estimation of the age of the ancestral arginine3500-->glutamine mutation in human apoB-100.
Familial defective apoB-100 (R3500Q) [FDB (R3500Q)] is caused by a mutation in the apoB gene (2p23.24). Almost all individuals with this disorder are of European descent, and in almost all cases the mutation is on a chromosome with a rare haplotype (194) at the apoB locus, suggesting that all FDB (R3500Q) probands are descended from a common ancestor in whom the original mutation occurred. The distribution of the mutation is consistent with an origin in Europe 6000-7000 years ago. We have estimated the amount of recombination between the apoB gene and markers on chromosome 2 in 34 FDB (R3500Q) probands in whom the mutation is on a 194 haplotype. Significant linkage disequilibrium was found between the apoB gene and marker D2S220. We have identified three YACs that contain the apoB gene and D2S220. The shortest restriction fragment common to the three YACs that contained both loci was 240 kb long. No shorter fragments with both loci were identified. On the assumption that 1000 kb corresponds to 1 cM, we deduce that the recombination distance between D2S220 and the apoB gene is about 0.24 cM. Combining this value with the linkage disequilibrium observed between the two loci in the probands, we estimate that the ancestral mutation occurred about 270 generations ago. We postulate that the original mutation occurred in the common ancestor of living FDB (R3500Q) probands, who lived in Europe about 6750 years ago. The errors in this estimate are discussed.
Apolipoprotein B-100↗
Follicular variant of papillary carcinoma of the thyroid: fine-needle aspirates with histologic correlation.
Crile and Hazard reported in 1953 a follicular pattern of papillary thyroid carcinoma. Little has been said about this pattern in the cytologic literature. From more than 8,000 thyroid aspirates in our files, we reviewed all those diagnosed as "follicular variant of papillary carcinoma," "suspect follicular variant of papillary carcinoma," and "follicular neoplasm vs. follicular variant of papillary carcinoma." Also, we reviewed all aspirates in which a diagnosis of follicular variant of papillary carcinoma had been made on surgically excised glands, regardless of the cytologic diagnosis; 63 aspirates from 45 patients were collected. All smears were air-dried and stained with Diff-Quik. Most smears were very cellular ("tumor cellularity"), and the neoplastic follicular cells formed empty follicles, rosettes, tubules, and papillary structures. Nuclei were twice the size of red blood cells, had smooth contours, were hyperchromatic, and varied in shape but not much in size. Nuclear overlapping was common. Some nuclei had one small and almost pointed end, thereby resembling arrowheads. Intranuclear inclusions, multinucleated histiocytes, and psammoma bodies were uncommon. Pink-stained colloid was frequent.
Adult↗
The mechanisms for adult-onset apraxia and developmental dyspraxia: an examination and comparison of error patterns.
OBJECTIVES: The purpose of this study was to determine whether persons with developmental dyspraxia and apraxia make similar errors during the performance of four types of tasks. METHOD: Three groups of subjects with dyspraxia or apraxia (i.e., children with learning disabilities and dyspraxia, young adults with learning disabilities and dyspraxia, older adults with left-hemisphere brain damage with apraxia) and three groups of age-matched control subjects (i.e., children, young adults, older adults) were observed performing transitive, intransitive, verbal command, and imitation tasks. Performance was scored on the basis of the types of errors made. Errors were classified as conceptual (nonrelated, unrecognizable, sequencing) or production (omission, perseveration, related, internal configuration, external configuration, incorrect movement, body part as object). RESULTS: No significant difference was found between conceptual and production error patterns for any group. In addition, there was no significant difference between the dyspraxia and apraxia groups or among the control groups on the specific types of production errors made. However, the dyspraxia and apraxia groups differed in the type of conceptual error made on the intransitive task. The body-part-as-object error was the most frequently made error on the transitive, verbal command, and imitation tasks, whereas the movement error was the most frequently made error on the intransitive task. CONCLUSION: Subjects with dyspraxia or apraxia make similar errors, suggesting that the praxis behaviors are similar.
Adult↗
Religious freedom, reproductive health care, and hospital mergers.
This article examines the impact of hospital mergers and the formation of health care networks involving religious hospitals on the provision of reproductive health care. Although instances of access to such services being curtailed at non-Catholic religious facilities have been reported, no systematic study of hospitals owned by other religious denominations has yet been done. Accordingly, the author focuses on Roman Catholic institutions and policies. Efforts by Roman Catholic Bishops to enforce the Ethical and Religious Directives for Catholic Health Care Services on new institutional partners has led to the elimination of or severe restrictions on patient access to abortion, contraception, infertility treatments, and even to emergency contraception for rape victims. The article suggests steps that physicians, patients, and community organizations and activists can take to safeguard reproductive health care as new institutional and professional relationships are formed.
Catholicism↗
Vero cytotoxin-producing E coli O157 infection associated with farms.
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Agriculture↗
Flumazenil reversal of psychomotor impairment due to midazolam or diazepam for conscious sedation for upper endoscopy.
BACKGROUND: Flumazenil is a competitive benzodiazepine antagonist that acts to reverse their sedative and hypnotic effects. It is indicated in the management of benzodiazepine overdose, but its role in the routine reversal of endoscopic conscious sedation has not been defined. METHODS: Patients undergoing diagnostic upper endoscopy who received sedation with either diazepam or midazolam alone were given flumazenil 0.2 mg incrementally immediately following the procedure until awake. They were then asked to repeat three psychomotor tests measuring cognitive and motor skills, with their baseline scores compared with postprocedure scores over a 3-hour period. RESULTS: Full psychomotor function was restored to baseline values within 30 minutes after flumazenil in 79% of patients, with no differences in the reversal of psychomotor skill impairment observed between diazepam and midazolam sedation. There was no evidence of rebound sedation seen for up to 3 hours. No significant anterograde amnesia was evident in 78% of individuals. CONCLUSIONS: These results demonstrate that flumazenil's effects on reversing psychomotor impairment are similar when midazolam or diazepam are used for conscious sedation. However, the potential usefulness of routine flumazenil reversal of conscious sedation will require further evaluation of specific psychomotor performance skills (such as driving a car) before we lift the admonition against leaving the endoscopic suite unattended, driving a vehicle, or operating complicated machinery for several hours.
Adult↗
Power of one: nurses and tobacco control.
OBJECTIVES: To review major events in cigarette marketing and smoking practices, and to examine courses of action that can be taken by nurses to impact public health and safety. DATA SOURCES: Journal articles and news reports relating to the tobacco industry and tobacco regulations. CONCLUSION: Every segment of society suffers economic and health consequences of tobacco use, yet the tobacco industry continues to successfully market and promote the use of tobacco. Successful approaches to control tobacco use can be initiated at the federal, state, or local level. IMPLICATIONS FOR NURSING PRACTICE: Any nurse can take positive action toward tobacco control in numerous ways: by increasing awareness of the need for tobacco control; initiating personal action such as education and contacting legislators; and supporting public action through joining groups or coalitions whose efforts are directed at tobacco control.
Advertising↗
Recognition of tetrahedral 1,10-phenanthroline-cuprous chelates by transcriptionally active complexes does not depend on the sequence of the promoter.
BACKGROUND: The open complex formed at the initiation site of transcription within the active site of RNA polymerase is unique to actively transcribing genes and is thus an ideal target for the design of transcription inhibitors. Many redoxactive tetrahedral cuprous chelates of 1,10-phenanthroline (OP) or derivatives cleave the single-stranded template, principally at sequence positions -7 to -3, whereas the redox-inactive tetrahedral cuprous chelate of 2, 9-dimethyl-OP (neocuproine) blocks transcription, but does not cleave. The octahedral (OP)3-Fe2+ chelate has no effect. Different promoters can give different cleavage patterns. We therefore searched for structural determinants of the open complex that are important in the cleavage reaction. RESULTS: Using site-directed mutagenesis, we systematically altered the nucleotides at the cleavage sites of the Escherichia coli lac UV-5-RNA polymerase open complex (positions -6 to -4), which are highly variable in E. coli promoters. Surprisingly, these changes had little effect on catalytic activity, on transcription inhibition by the cuprous complex of neocuproine and on the cleavage patterns generated by the cuprous chelates of OP derivatives. The scission pattern of a lac UV-5 promoter mutant in which the cleavage sites have the sequence of the trp EDCBA promoter is that of the lac UV-5 promoter, not the trp EDCBA promoter. CONCLUSIONS: Nucleotide-specific interactions are not responsible for the observed cleavage patterns. The recognition of the tetrahedral OP chelate must be due to a specific structure of the single-stranded regions, determined by RNA polymerase-DNA interactions in the upstream regulatory region.
Chelating Agents↗