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Biomedical subjects

A Jones

Publications and source records attributed to A Jones.

At least 289 records · Page 16Linked to original sources

Senior surgeons and radiologists should assess emergency patients on presentation: a prospective randomized controlled trial.

The objective of this study was to determine whether abdominal ultrasound and plain film radiography (evaluated by senior radiologists) substantially enhances senior surgical assessment in reducing surgical admissions. A randomized controlled trial was carried out in a teaching hospital; ninety-five emergency referrals to general surgery (mean age 51 years, 37% males), presenting with intrabdominal disturbances not requiring immediate surgery, were selected for study. The major outcome measure was the number of patients not admitted as in-patients. Thirty per cent of the intervention group and 10% of the controls did not need admission (95% confidence interval on this 29% difference, 12-38%). There were no important differences in the mean waiting time in casualty (26 min vs. 25 min), length of admission (4.1-5.9 days), surgical intervention (seven vs. 11 patients), readmission with similar pathology within 3 months (seven vs. three patients), and mortality as an in-patient or within 3 months of discharge. Abdominal ultrasound and plain film radiography, assessed by senior radiologists, enhances senior surgical assessment in reducing unnecessary surgical admissions.

Abdomen↗

Directing gene expression to cerebellar granule cells using gamma-aminobutyric acid type A receptor alpha6 subunit transgenes.

Expression of the gamma-aminobutyric acid type A receptor alpha6 subunit gene is restricted to differentiated granule cells of the cerebellum and cochlear nucleus. The mechanisms underlying this limited expression are unknown. Here we have characterized the expression of a series of alpha6-based transgenes in adult mouse brain. A DNA fragment containing a 1-kb portion upstream of the start site(s), together with exons 1-8, can direct high-level cerebellar granule cell-specific reporter gene expression. Thus powerful granule cell-specific determinants reside within the 5' half of the alpha6 subunit gene body. This intron-containing transgene appears to lack the cochlear nucleus regulatory elements. It therefore provides a cassette to deliver gene products solely to adult cerebellar granule cells.

Animals↗

Missense mutations affecting a conserved cysteine pair in the TH domain of Btk.

Tec family protein tyrosine kinases have in their N-terminus two domains. The PH domain is followed by Tec homology (TH) domain, which consists of two motifs. The first pattern, Btk motif, is also present in some Ras GAP molecules. C-terminal half of the TH domain, a proline-rich region, has been shown to bind to SH3 domains. Mutations in Bruton's tyrosine kinase (Btk) belonging to the Tec family cause X-linked agammaglobulinemia (XLA) due to developmental arrest of B cells. Here we present the first missense mutations in the TH domain. The substitutions affect a conserved pair of cysteines, residues 154 and 155, involved in Zn2+ binding and thereby the mutations alter protein folding and stability.

Adult↗

Initial frequency of alleles for resistance to Bacillus thuringiensis toxins in field populations of Heliothis virescens.

The risk of rapid pest adaptation to an insecticide is highly dependent on the initial frequency of resistance alleles in field populations. Because we have lacked empirical estimates of these frequencies, population-genetic models of resistance evolution have relied on a wide range of theoretical estimates. The recent commercialization of genetically engineered cotton that constitutively produces an insecticidal protein derived from the biocontrol agent, Bacillus thuringiensis (Bt) has raised concern that we lack data needed to quantify the risk of insect pests such as Heliothis virescens rapidly adapting to this ecologically valuable class of toxins. By individually mating over 2,000 male H. virescens moths collected in four states to females of a Bt toxin-resistant laboratory strain, and screening F1 and F2 offspring for tolerance of the toxic protein, we were able to directly estimate the field frequency of alleles for resistance as 1.5 x 10(-3). This high initial frequency underscores the need for caution in deploying transgenic cotton to control insect pests. Our single-pair mating technique greatly increases the efficiency of detecting recessive resistance alleles. Because alleles that decrease target site sensitivity to Bt toxins and other insecticides are often recessive, this technique could be useful in estimating resistance allele frequencies in other insects exposed to transgenic insecticidal crops or conventional insecticides.

Journal Article↗

Clinical evaluation is better: myoglobin estimation used singly as a discriminant for early acute myocardial infarction does not well identify patients who will benefit from thrombolytic therapy.

We have examined the use of serum myoglobin concentration in the management of cases of suspected acute myocardial infarction (AMI). In a series of 51 patients myoglobin, used as a discriminant, correctly identified 97% (28/29) of cases as AMI with one false positive. Initial clinical judgement based on history, examination and the electrocardiogram correctly identified 66% (19/29) of cases with one false positive. These patients were given streptokinase. However, in these further identified AMI patients, 78% (7/9) had small enzyme rises with non-Q wave infarction and/or non-ST elevation and therefore may not have benefited from thrombolytic therapy in contrast to the Q wave/raised ST segment infarcts with large enzyme rises identified by clinical means. Enthusiasm for myoglobin estimation, where used as a discriminant for AMI, as a direct pointer to thrombolysis in the early diagnosis of AMI should be tempered by this finding.

Aged↗

Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression.

Cerebellar granule cells express six GABAA receptor subunits abundantly (alpha1, alpha6, beta2, beta3, gamma2, and delta) and assemble various pentameric receptor subtypes with unknown subunit compositions; however, the rules guiding receptor subunit assembly are unclear. Here, removal of intact alpha6 protein from cerebellar granule cells allowed perturbations in other subunit levels to be studied. Exon 8 of the mouse alpha6 subunit gene was disrupted by homologous recombination. In alpha6 -/- granule cells, the delta subunit was selectively degraded as seen by immunoprecipitation, immunocytochemistry, and immunoblot analysis with delta subunit-specific antibodies. The delta subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a post-translational loss of the delta subunit. These results provide genetic evidence for a specific association between the alpha6 and delta subunits. Because in alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot rescue the delta subunit, certain potential subunit combinations may not be found in wild-type cells.

Animals↗

Family therapy in a critical care unit.

This article explores the use of family therapy in a general hospital setting. The author, a liaison mental health nurse, describes with the use of a case study how he helped a family to examine, understand and address emotional pain and suffering in response to the anticipated death of a family member following traumatic injury.

Family↗

Clinical spectrum of X-linked hyper-IgM syndrome.

We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.

Bone Marrow Transplantation↗

Characterization of ciguatoxins and ciguatoxin congeners present in ciguateric fish by gradient reverse-phase high-performance liquid chromatography/mass spectrometry.

Reverse-phase high-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to identify Pacific ciguatoxins (P-CTX) and P-CTX congeners present in a highly purified extract from the viscera of ciguateric moray eels (Lycodontis javanicus) collected in the central Pacific Ocean. Fourteen P-CTX or P-CTX congeners were identified with protonated molecular ions [M + H]+ m/z 1095.7 (two), 1111.6 (six) or 1127.7 (six), including dominant ions for P-CTX-1, -2 and -3. In addition to the protonated species, each of these ciguatoxins gave rise to prominent [M + NH4]+ and [M + Na]+ ions. The 11 new P-CTX congeners, not readily detected by mouse bioassay, were present in trace amounts (2-13% of P-CTX-2 levels) and identified as several oxidized P-CTX-1, -2 and -3, and a possible diasteriomer of P-CTX-1. Acetonitrile-water gradients buffered with 1 mM ammonium acetate improved the separation and detection of the minor ciguatoxins compared with an acetonitrile-water gradient modified with 0.1% TFA. Turbo-assisted HPLC/MS had sufficient sensitivity to detect P-CTX-1 in a crude extract from the flesh of an Australian ciguateric fish. Compounds with masses equivalent to other isolated ciguatoxins, including Caribbean-CTX-1, gambiertoxin-4A and P-CTX-3C, were not detected in these samples. HPLC/MS can readily identify multiple ciguatoxins accumulated by fish and has the potential to be used as a confirmatory analytical method for characterizing the low levels of ciguatoxins contaminating ciguateric fish.

Animals↗

Medication, chronic illness and identity: the perspective of people with asthma.

The issue of compliance with prescribed medication has traditionally been dominated by the perspective of the health professional although increasingly sociologists, using qualitative methods, have begun to present the patients' point of view. However, little has been published on asthma, despite the numbers of people suffering from this chronic condition and the amount of medication regularly prescribed. This paper focuses on the perspective of a sample of S. Wales (U.K.) asthma patients who have all been prescribed prophylactic medication in the last 12 months and explores their attitudes to medication in the context of their everyday lives, using inductive qualitative research methods. Two main groups were identified: the deniers and the accepters. They differed fundamentally in their readiness to accept the identity of asthma sufferer which, in turn, was associated with very different beliefs about the nature of their problem and the meaning of the medication prescribed for it. There was also marked differences in their strategies of self-presentation and disclosure and their pattern of medication use, particularly for prophylactic medication. A third group, the pragmatists, were also identified as a possible sub-group of the accepter category who are less open within self-presentation and less consistent in their beliefs about asthma but do not reject the label entirely. Identity work, i.e. the way the respondents interpreted the social identity of asthma sufferers and managed to reconcile it with other social identities, is proposed as the most useful way of understanding the observed variation in the way people diagnosed as asthmatic conceptualise and use their medication.

Adolescent↗

Post-operative central hypersensitivity and pain: the pre-emptive value of pethidine for ovariohysterectomy.

The effect of timing of analgesic drug administration on the severity of post-operative pain was investigated in dogs undergoing ovariohysterectomy using both subjective visual assessment scoring systems (VAS) and objective mechanical nociceptive threshold measurements using a novel handheld anti-nociceptiometric device. Forty dogs undergoing routine elective ovariohysterectomy were included in a randomised and double-blind study and assigned to one of three groups: (i) pre-operative analgesics; (ii) post-operative analgesics; (iii) no analgesics (saline injections). The analgesic used was pethidine (a short acting predominantly mu-opioid agonist), at a dose of 5.0 mg/kg (intramuscular). The post-operative administration of pethidine resulted in significantly higher sedation scores and significantly lower pain scores in the early post-operative period, but the dogs given pethidine pre-operatively had significantly lower pain scores than both the other groups at 8, 12 and 20 h post-extubation (P < 0.01, ANOVA). Mechanical thresholds measured at the distal tibia demonstrated the development of allodynia at 12 and 20 h post-extubation, and this was significantly prevented by the pre- (P < 0.01 at 12 h, P < 0.05 at 20 h, Kruskal-Wallis and post hoc Dunn's), but not by the post-operative administration of pethidine. Mechanical nociceptive thresholds measured at the ventral midline (site of surgery) demonstrated post-operative hyperalgesia in all groups; this hyperalgesia was least in the pre-operative pethidine group. In summary, this study clearly shows pethidine to be an effective analgesic in dogs, albeit of short duration of action, when administered post-operatively, and, importantly, that it has a positive benefit in terms of post-operative outcome measures, when administered pre-operatively, possibly as a result of blocking or preventing the development of central sensitisation following surgical stimulation.

Abdomen↗