Number of ovulations in Texel x Scottish hill ewes carrying the Inverdale fecundity (FecX(I)) gene.
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Animals↗
Biomedical subjects
M J Wood
Publications and source records attributed to M J Wood.
CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage.
AIMS: To assess the sensitivity and specificity of CSF spectrophotometry for the detection of xanthochromia in patients with clinical symptoms suggestive of subarachnoid haemorrhage (SAH) but normal cranial computed tomography (CT). METHODS: All consecutive patients undergoing both cranial CT and lumbar puncture for investigation of possible SAH at the Princess Alexandra Hospital, Brisbane, between January 2000 and April 2003 were included in the study. All case histories, radiology and laboratory results were retrospectively assessed. The sensitivity, specificity and positive predictive value of the spectrophotometry test were calculated. RESULTS: 253 patients were included in the study. Spectrophotometry was shown to have a sensitivity of 100% but a specificity of only 75.2%. The positive predictive value of spectrophotometry as an indicator of SAH was 3.3%. CONCLUSIONS: CSF spectrophotometry has an unacceptably low specificity and positive predictive value, which greatly limit its use as a clinical tool.
False Positive Reactions↗
Stabilizing natural selection on the early expression of a secondary sexual trait in a passerine bird.
Natural selection is a central tenet of evolutionary theory, yet the estimation of the direction and intensity of selection remains problematic. Here, we assess the strength of selection on the early expression of a secondary sexual ornament, bill colour, in male European blackbirds (Turdus merula) using 5 years of capture-mark-recapture (CMR) data. The best-fitting model consisted of a quadratic relationship between survival rate and bill colour, indicating stabilizing natural selection on the early expression of a secondary sexual trait. There was no evidence for sexual selection acting on bill colour in the first year. We suggest that the consideration of early selection and the adoption of refined statistical methods may reveal patterns of selection in the wild that have, as yet, remained undetected.
Age Factors↗
Staphylococcus lugdunensis vertebral osteomyelitis.
We report a case of vertebral osteomyelitis due to the coagulase-negative staphylococcus, Staphylococcus lugdunensis. This is only the second such case reported in the literature in an immunocompetent host. When the patient's lumbar spine inflammatory mass was drained, the coagulase-negative staphylococcus obtained was discarded as a likely contaminant. We discuss the situation when coagulase-negative staphylococci require further identification and look at the unique features of S. lugdunensis. Isolation of S. lugdunensis is usually significant, and the organism should not be discarded as a contaminant without careful consideration.
Aged↗
Conformational dimorphism and transmembrane orientation of prion protein residues 110-136 in bicelles.
A fragment corresponding to the putative membrane-associating domain of the prion protein (residues 110-136) was analyzed in phospholipid bicelles. Prion(110-136) associated with bicelles and exhibited a lipid- and pH-dependent conformational dimorphism between unstructured (pH 4.5) and alpha-helical (pH 7.5). Mutational analysis indicated that the charge state of a single histidine residue was largely responsible for the dimorphism. Amide-lipid NOEs and amide-water chemical exchange measurements revealed that the helical conformation of prion(110-136) spanned the bilayer, and were corroborated by solid-state deuterium NMR experiments indicating that the helical axis rested at a 16 degrees angle with respect to the bilayer normal.
Animals↗
Phase specific analysis of herpes zoster associated pain data: a new statistical approach.
Herpes zoster or shingles is a frequent occurrence in both elderly individuals and immunocompromised hosts. The pain associated with herpes zoster is the most debilitating complication of the disease. It can be described as acute pain and post-herpetic neuralgia or zoster associated pain (ZAP). The latter definition encompasses pain from the onset of disease through its resolution and provides a convenient analytic tool for evaluation of antiviral therapy. A heuristic examination of ZAP historical data suggests the existence of three phases of pain resolution: the acute, subacute and chronic phases. The subacute and chronic phases comprise the post-herpetic neuralgia (PHN) stage. Common analytic methods, such as a Kaplan-Meier survival function or a Cox's model, have been used to assess the pain. However, such approaches do not adequately allow for phase comparison. Notably, in the clinical trial setting the comparison of specific treatment effects on the latter stages of pain are of the greatest medical relevance since this is the most debilitating phase of the illness. In order to incorporate the phase-specific information in the modelling of time to cessation of ZAP, we assumed the hazard function was a stepwise constant. Utilizing the full likelihood function, we obtained the maximum likelihood estimate for the transition times (that is, change-points), and other parameters of medical importance. The standard error of the change-point estimates were obtained through a bootstrapping method. The asymptotic properties of the parameter estimates are also discussed. Hence, the rates of pain resolution across all phases can be examined in order to precisely define the existence of multiple phases. In addition, the covariates effect can be examined across phases and populations, thereby allowing us to translate potential efficacy of a standard therapy to different populations. These results can be utilized in the design of clinical trials or in targeting the outcome for a specific phase while controlling for the effect of other variables.
Acute Disease↗
Sociodemographic characteristics associated with medical appointment adherence among HIV-seropositive patients seeking treatment in a county outpatient facility.
BACKGROUND: Adherence is a major problem facing HIV-seropositive patients. Low adherence has been associated with faster disease progression as well as development of drug-resistant strains of HIV. Thus it is critical to understand factors associated with treatment compliance. This study examined the independent contributions of disease severity, age, gender, household income, homelessness, ethnicity, and sexual orientation on appointment adherence. METHODS: Participants (n = 671) scheduled for appointments in an outpatient county treatment facility for HIV-related medical care completed demographic questionnaires and clinic staff collected appointment attendance data. RESULTS: Multiple regression analyses indicated that patients diagnosed with AIDS, older in age, and receiving a higher income were more likely to keep medical appointments. Additionally, African American ethnicity and identifying as heterosexual were associated with missing scheduled medical appointments. CONCLUSIONS: These data suggest that cultural and sociodemographic characteristics influence patients' adherence to outpatient services. Implications for interventions aimed at increasing medical adherence are discussed.
Adult↗
Canadian nursing research in the new millennium.
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Canada↗
Declining clinical autopsy rates versus increasing medicolegal autopsy rates in Halifax, Nova Scotia.
The downward trend in the rate of clinical autopsies has been extensively documented in the literature. This decline is of concern when the benefits of the clinical autopsy are considered. In contrast, the rate of medicolegal autopsies has not been studied in such detail. What little reference there is to medicolegal autopsy rates suggests an absence of the same downward trend. A retrospective review of autopsy data over a 13-year period from the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, and from the Office of the Chief Medical Examiner of Nova Scotia was conducted. This review showed a difference between the rates of clinical and medicolegal autopsies for the metro Halifax area. The clinical autopsy rate was consistently less than 30% and declined to 15% in 1999, while the medicolegal autopsy rate was consistently greater than 40% and rose to 62% in 1999. The literature proposes many reasons for the decline in the clinical autopsy rate, but none for this difference between rates. The explanation proposed here is the changing and currently uncertain purpose of the clinical autopsy versus the clear, and consistent over time, purpose of the medicolegal autopsy.
Autopsy↗
HRT to prevent cardiovascular disease. What studies show, how to advise patients.
How should you advise postmenopausal patients who are considering estrogen therapy? Do the potential cardiovascular benefits outweigh the risks? Does hormone therapy improve the cardiovascular risk profile in women with established coronary artery disease? In this article, Drs Wood and Cox help clarify the current clinical data for and against hormone replacement therapy for prevention of cardiovascular disease. In addition, they discuss current treatment recommendations and future directions in hormone therapy.
Cardiovascular Diseases↗
Humoral immune responses to adenovirus vectors in the brain.
We have investigated the humoral immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of mice. Injection of these non-replicating vectors into the brain induced systemic antibody production to adenovirus vectors in dose dependent manner. Apparent antibody production to beta-galactosidase, the product of the lacZ gene, was detected later than anti-adenovirus antibody. Neutralizing antibody was not detected. This study demonstrates that E1-deleted adenovirus vectors injected into the brain trigger humoral immune responses to the adenovirus and its gene products, but they are not sufficient to block the infection of cells by adenovirus upon repeat injection.
Adenoviridae↗
Two mechanisms of K(+)-dependent potentiation in Kv2.1 potassium channels.
Elevation of external [K(+)] potentiates outward K(+) current through several voltage-gated K(+) channels. This increase in current magnitude is paradoxical in that it occurs despite a significant decrease in driving force. We have investigated the mechanisms involved in K(+)-dependent current potentiation in the Kv2.1 K(+) channel. With holding potentials of -120 to -150 mV, which completely removed channels from the voltage-sensitive inactivated state, elevation of external [K(+)] up to 10 mM produced a concentration-dependent increase in outward current magnitude. In the absence of inactivation, currents were maximally potentiated by 38%. At more positive holding potentials, which produced steady-state inactivation, K(+)-dependent potentiation was enhanced. The additional K(+)-dependent potentiation (above 38%) at more positive holding potentials was precisely equal to a K(+)-dependent reduction in steady-state inactivation. Mutation of two lysine residues in the outer vestibule of Kv2.1 (K356 and K382), to smaller, uncharged residues (glycine and valine, respectively), completely abolished K(+)-dependent potentiation that was not associated with inactivation. These mutations did not influence steady-state inactivation or the K(+)-dependent potentiation due to reduction in steady-state inactivation. These results demonstrate that K(+)-dependent potentiation can be completely accounted for by two independent mechanisms: one that involved the outer vestibule lysines and one that involved K(+)-dependent removal of channels from the inactivated state. Previous studies demonstrated that the outer vestibule of Kv2.1 can be in at least two conformations, depending on the occupancy of the selectivity filter by K(+) (Immke, D., M. Wood, L. Kiss, and S. J. Korn. 1999. J. Gen. Physiol. 113:819-836; Immke, D., and S. J. Korn. 2000. J. Gen. Physiol. 115:509-518). This change in conformation was functionally defined by a change in TEA sensitivity. Similar to the K(+)-dependent change in TEA sensitivity, the lysine-dependent potentiation depended primarily (>90%) on Lys-356 and was enhanced by lowering initial K(+) occupancy of the pore. Furthermore, the K(+)-dependent changes in current magnitude and TEA sensitivity were highly correlated. These results suggest that the previously described K(+)-dependent change in outer vestibule conformation underlies the lysine-sensitive, K(+)-dependent potentiation mechanism.
Biophysical Phenomena↗
Solution structure of the smallest cofactor-active fragment of thrombomodulin.
A glycosylated fragment of thrombomodulin containing two epidermal growth factor-like domains (TMEGF45) was analyzed by NMR. The 4th-domains structure of this two-domain fragment is similar to that of the individual domain previously determined. The 5th-domain, which has uncrossed disulfide bonds, is not as well determined in the two-domain fragment than the individual domain previously solved. The flexibility of the 5th-domain is consistent with low heteronuclear NOEs. In the individual 5th-domain, Met 388 was disordered, and key thrombin binding residues formed a hydrophobic core. By contrast, in TMEGF45, Met 388 is in the 5th-domain core, positioned by Phe 376 from the 4th-domain. As a result, key thrombin binding residues that were in the core of the individual domain are expelled. Upon thrombin binding, chemical shifts of two residues in the 4th-domain, the three interdomain linker residues, and nearly all of the 5th-domain are perturbed. Thus, TMEGF45 binds thrombin by an induced fit mechanism involving a flexible 5th-domain.
Acetylglucosamine↗
Neuroprotective autoimmunity-a double-edged sword?
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Animals↗
Prevention of the dystrophic phenotype in dystrophin/utrophin-deficient muscle following adenovirus-mediated transfer of a utrophin minigene.
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder caused by the lack of a subsarcolemmal protein, dystrophin. We have previously shown that the dystrophin-related protein, utrophin is able to compensate for the lack of dystrophin in the mdx mouse, the mouse model for DMD. Here, we explore whether utrophin delivered to the limb muscle of dystrophin/utrophin-deficient double knockout (dko) neonatal mice can protect the muscle from subsequent dystrophic damage. Utrophin delivery may avoid the potential problems of an immune response associated with the delivery of dystrophin to a previously dystrophin-deficient host. Dko muscle (tibialis anterior) was injected with a first generation recombinant adenovirus containing a utrophin minigene. Up to 95% of the fibres continued expressing the minigene 30 days after injection. Expression of utrophin caused a marked reduction from 80% centrally nucleated fibres (CNFs) in the uninjected dko TA to 12% in the injected dko TA. Within the region of the TA expressing the utrophin minigene, a significant decrease in the prevelance of necrosis was noted. These results demonstrate that the utrophin minigene delivered using an adenoviral vector is able to afford protection to the dystrophin/utrophin-deficient muscle of the dko mouse. Gene Therapy (2000) 7, 201-204.
Adenoviridae↗
Comparative safety of teicoplanin and vancomycin.
Although modern preparations of vancomycin are associated with a lower incidence of adverse events than the early preparations, a number of clinically significant problems remain. Consequently monitoring of serum concentrations is required. In a meta-analysis of comparative trials adverse events were significantly less likely to occur with teicoplanin (13.9%) than with vancomycin (21.9%) (P = 0.0003). This was particularly significant when nephrotoxicity was considered: 4.8% vs. 10.7%, for teicoplanin and vancomycin, respectively (P = 0.0005). Red man syndrome, which may be due to histamine release, occurs after rapid infusion of vancomycin but is very rare following teicoplanin administration. In USA trials, thrombocytopenia was more commonly seen with teicoplanin administration but this was almost exclusively in patients receiving much larger doses than are now recommended. The lower rate of adverse events supports the choice of teicoplanin over vancomycin in treating infections where the two antibiotics have similar efficacy.
Animals↗
Restoration of a normal reproductive lifespan after grafting of cryopreserved mouse ovaries.
Fresh and frozen ovaries from 10 day old C57BL/6J-Gpi-1(a) mice were grafted orthotopically into ovariectomized B6CBF1 (homozygous Gpi-1(b)) recipients. The recipients were mated with B6CBF1 males. The birth and size of each litter was recorded. The electrophoretic variant of glucose phosphate isomerase was determined for each neonate. Twelve of 13 recipients of fresh ovary and 10 of 12 recipients of frozen ovary were fertile. Of these, 10 (fresh) and eight (frozen) had litters derived from the ovarian grafts only, or from the graft and native ovary. The breeding characteristics of recipients of fresh and frozen grafts were similar. The reproductive lifespan of the recipients of fresh (6.2 litters) and frozen (8.4 litters) grafts was similar to that of unoperated C57BL/6-Gpi-1(a) control females mated with B6CBF1 males (6.3 litters). Litter size was similar in recipients of grafted ovaries (fresh, 5.4 pups/litter; frozen, 6.3 pups/litter) and C57BL/6-Gpi-1(a) females (6.3 pups/litter). The results suggest that cryopreservation per se does not affect the long-term viability of ovarian tissue and provides an option for storing female germ cells. This is the first unequivocal demonstration that a normal reproductive lifespan can be restored by orthotopic grafting of frozen ovary.
Animals↗
Prokinetic effects of erythromycin after antimotion sickness drugs.
Motion sickness and the antimotion sickness drugs scopolamine (SCP) and promethazine (PMZ) inhibit gastric emptying (GE). This study was conducted to determine if erythromycin would exert its well-known prokinetic effects in normal and motion-sick subjects given antimotion sickness drugs. Fifteen fasted volunteers (11 males, 4 females) participated in the study. In control tests, 8 subjects were given intramuscular (i.m.) saline (SAL, 0.5 ml), SCP (0.1 mg), or PMZ (25 mg). GE of liquid (300 ml) containing 1 mCi of Tc 99m diethylenetriaminepentaacetic acid (DTPA) was measured by sequential gastric scintigraphy 30 minutes after i.m. treatments. In other tests, GE was measured in 8 subjects after each i.m. treatment, followed 10 minutes later by 200 mg of erythromycin ethylsuccinate (ESS) suspension given orally. In a third group of tests, 7 subjects received an i.m. treatment, oral EES 10 minutes later, and were then brought to an advanced level of motion sickness short of vomiting. To induce motion sickness, blindfolded subjects made timed head movements while seated in a rotating chair. GE was measured immediately after rotation. GE half-life, rate constant, area under the curve (AUC), and lag time were calculated using conventional mathematical methods for analyzing exponential rate processes. GE parameters calculated for normal and motion-sick subjects given antimotion sickness drugs and EES were compared with those from subjects given i.m. treatments (control) only. In normal subjects, EES significantly (p < 0.05) increased the GE rate constant for all i.m. treatments and reduced the AUC for SAL, SCP, and PMZ by 49% (p < 0.05), 44% (p < 0.05), and 69% (p < 0.01), respectively. In motion-sick subjects, lag time was significantly (p < 0.05) increased, and the rate constant and AUC values were unchanged from control for all i.m. treatments. The authors conclude that oral EES reverses the gastrostatic actions of the antimotion sickness drugs but does not affect the inhibition of gastric emptying associated with motion sickness. The results suggest that motion sickness and antimotion sickness drugs reduce GE through different mechanisms.
Administration, Oral↗