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Biomedical subjects

A Wheeler

Publications and source records attributed to A Wheeler.

17 recordsLinked to original sources
PubMed2004

A microsatellite genetic linkage map for Xiphophorus.

Interspecies hybrids between distinct species of the genus Xiphophorus are often used in varied research investigations to identify genomic regions associated with the inheritance of complex traits. There are 24 described Xiphophorus species and a greater number of pedigreed strains; thus, the number of potential interspecies hybrid cross combinations is quite large. Previously, select Xiphophorus experimental crosses have been shown to exhibit differing characteristics between parental species and among the hybrid fishes derived from crossing them, such as widely differing susceptibilities to chemical or physical agents. For instance, genomic regions harboring tumor suppressor and oncogenes have been identified via linkage association of these loci with a small set of established genetic markers. The power of this experimental strategy is related to the number of genetic markers available in the Xiphophorus interspecies cross of interest. Thus, we have undertaken the task of expanding the suite of easily scored markers by characterization of Xiphophorus microsatellite sequences. Using a cross between Xiphophorus maculatus and X. andersi, we report a linkage map predominantly composed of microsatellite markers. All 24 acrocentric chromosome sets of Xiphophorus are represented in the assembled linkage map with an average intergenomic distance of 7.5 cM. Since both male and female F1 hybrids were used to produce backcross progeny, these recombination rates were compared between "male" and "female" maps. Although several genomic regions exhibit differences in map length, male- and female-derived maps are similar. Thus Xiphophorus, in contrast to zebrafish, Danio rerio, and several other vertebrate species, does not show sex-specific differences in recombination. The microsatellite markers we report can be easily adapted to any Xiphophorus interspecies and some intraspecies crosses, and thus provide a means to directly compare results derived from independent experiments.

Animals↗
PubMed2002

Cochlear implants in children with craniofacial syndromes: assessment and outcomes.

The aim of this retrospective study was to review the outcomes for children with craniofacial syndromes who had received a cochlear implant. The group comprised four children (three girls, one boy) aged between 3.3 and 10.1 years (mean 6.3 years) at time of implantation with the Cochlear CI-22M device. Two children had the CHARGE association. one had Goldenhar's syndrome and one had brachio-oculo-facial syndrome. All had full electrode insertion at time of surgery. At follow-up, three of the children demonstrated benefit in detection, recognition and identification of environmental sounds, and they continued to gain receptive spoken language skills, although none had intelligible speech. The group required careful mapping and higher levels of electrical stimulation of the implant compared to normal child implantees. Stimulation of the facial nerve was a problem with one child. The pre-implantation assessment of these children requires extensive interdisciplinary discussion and careful radiological investigation. Cases should be carefully selected. Parents should receive realistic counselling about outcomes and the time commitment necessary, as habilitation of these children can take twice as long as that of children without additional special needs. Post-implantation, these children continue to require well-coordinated medical and interdisciplinary management.

Auditory Threshold↗
PubMed2000

The effects of intrapleural polyclonal anti-tumor necrosis factor alpha (TNF alpha) Fab fragments on pleurodesis in rabbits.

The mechanism by which various agents produce a pleurodesis is unknown. The purpose of this project was to determine whether the pleurodesis that results from the intrapleural administration of talc or doxycycline depends on tumor necrosis factor alpha (TNF alpha). In a randomized, blinded, placebo-controlled study, 34 New Zealand white rabbits were given 400 mg talc or 10 mg/kg doxycycline intrapleurally as a sclerosant through a chest tube. Half the rabbits in each group were also given 2,000 units of ovine, polyclonal affinity purified anti-TNF alpha Fab, or saline as placebo immediately after and 12 h after the injection of the sclerosant. Chest tubes were aspirated at 12-h intervals until their removal at 4 days. Rabbits were killed at 28 days. The pleural fluid volume, cell counts, lactate dehydrogenase (LDH) and pleurodesis scores were compared among groups. Both talc and doxycycline produced an exudative pleural effusion. The pleural fluid volume and the pleural fluid LDH levels were significantly (p < 0.05) greater in the group given doxycycline. The administration of anti-TNF alpha Fab had no significant effect on pleural fluid volume or leukocyte count in either group. However, the administration of anti-TNF alpha Fab resulted in a significant decrease (p = 0.004) in the pleurodesis score for the animals given talc (3.2 +/- 0.8 without Fab and 1.8 +/- 0.9 with Fab). In contrast, the pleurodesis score was virtually identical in the doxycycline group with (3.5 +/- 0.5) and without (3.4 +/- 0.7) Fab. The administration of anti-TNF alpha Fab diminishes the pleurodesis induced by talc but not that resulting from doxycycline. These findings suggest that different mechanisms are involved with the two different sclerosants.

Animals↗
PubMed2000

Changing pattern of organ dysfunction in early human sepsis is related to mortality.

OBJECTIVE: We examined the pattern of organ system dysfunction, the evolution of this pattern over time, and the relationship of these features to mortality in patients who had sepsis syndrome. DESIGN: Prospective, multicenter, observational study. SETTING: Intensive care units in tertiary referral teaching hospitals. PATIENTS: A total of 287 patients who had sepsis syndrome were prospectively identified in intensive care units. MATERIALS AND MEASUREMENTS: Cardiovascular, pulmonary, neurologic, coagulation, renal, and hepatic dysfunction were assessed at onset and on day 3 of sepsis syndrome. Organ dysfunction was classified as normal, mild, moderate, severe, and extreme dysfunction. We calculated the occurrence rate and associated 30-day mortality rate of organ dysfunction at the onset of sepsis syndrome. We then measured the change in organ dysfunction from onset to day 3 of sepsis syndrome and determined, for individual organ systems, the associated 30-day mortality rate. RESULTS: At the onset of sepsis syndrome, clinically significant pulmonary dysfunction was the most common organ failure, but was not related to 30-day mortality. Clinically significant cardiovascular, neurologic, coagulation, renal, and hepatic dysfunction were less common at the onset of sepsis syndrome but were significantly associated with the 30-day mortality rate. Worsening neurologic, coagulation, and renal dysfunction from onset to day 3 of sepsis syndrome were associated with significantly higher 30-day mortality than with improvement or no change in organ dysfunction. CONCLUSIONS: Increased mortality rate in sepsis syndrome is associated with a pattern characterized by failure of nonpulmonary organ systems and, in particular, worsening neurologic, coagulation, and renal dysfunction over the first 3 days. Although initial pulmonary dysfunction is common in patients with sepsis syndrome, it is not associated with an increased mortality rate.

Aged↗
PubMed1996

A controlled trial of 5-hydroxy-L-tryptophan for ataxia in progressive myoclonus epilepsy.

To study the role of serotonin in the ataxia of progressive myoclonus epilepsy, eight patients received oral 5-hydroxy-L-tryptophan (L-5-HTP) or placebo plus carbidopa for 1 month in a controlled, double-blinded, dose-ranging, cross-over, add-on study. Ataxia was evaluated using objective and subjective scales. All of the subjects had significantly slower motor performance on timed, repetitive tasks than controls and had moderately severe ataxia. L-5-HTP was not efficacious for ataxia or speed of motor performance. Serotonergic drugs that work through mechanisms different than L-5-HTP may be more effective in correcting the abnormal serotonergic neurotransmission suggested by reduction of serotonin metabolites in cerebrospinal fluid in patients with progressive myoclonus epilepsy.

5-Hydroxytryptophan↗
PubMed1995

Anti-tumor necrosis factor-alpha prevents decreased ventricular contractility in endotoxemic pigs.

It is not known how the decrease in left ventricular contractility following endotoxin exposure is mediated, or whether this decrease is preventable by antibodies to tumor necrosis factor-alpha (TNF alpha). Four groups of six anesthetized and instrumented pigs were pretreated with ovine polyclonal antibody to human TNF alpha (anti-TNF alpha), nonspecific IgG, or saline, and then treated with either endotoxin or saline. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (Emax) of the end-systolic pressure-volume relationship. Four hours after the start of endotoxin infusion in the nonspecific IgG pretreated group, Emax had decreased by 44 +/- 6% (p < 0.05), mean arterial pressure had decreased from 115 +/- 7 mm Hg to 70 +/- 10 mm Hg (p < 0.05), and cardiac output was rapidly decreasing after an initial increase (p < 0.05). Anti-TNF alpha significantly reduced the decrease in Emax (11 +/- 9%, p < 0.05), and the systemic hypotension (108 +/- 15 mm Hg to 99 +/- 6 mm Hg, p < 0.05), at 4 h, and prevented the late decrease in cardiac output. This suggests that TNF alpha is an important early mediator in sepsis leading to decreased left ventricular contractility.

Animals↗
PubMed1994

Current management of disseminated intravascular coagulation.

Disseminated intravascular coagulation is a complex process seen in a wide variety of clinical disorders. The oncology patient may develop this syndrome either as a result of the neoplasm itself or of the treatment of the neoplasm. An understanding of the pathophysiology of disseminated intravascular coagulation is essential for diagnosis and treatment. Diagnosis is accomplished by correlating clinical and laboratory data. Treatment remains controversial, but reversal of the triggering mechanism is the single most important factor in successful treatment. Other interventions, including the use of heparin, antithrombin III, and hirudin, are being studied. Much remains to be understood about disseminated intravascular coagulation, and controlled clinical trials are needed to define optimal treatment.

Antithrombin III↗
PubMed1987

Fully automated antithrombin-III assays by synthetic substrate on the Multistat III.

Antithrombin-III assays are performed to assess response to heparin therapy and efficacy of antithrombin concentrate therapy and in diagnosing hereditary thrombophilia, deep venous thrombosis, pulmonary embolus, and disseminated intravascular coagulation. Synthetic substrate assays for antithrombin-III are the methods of choice; however, most existing assay systems are semiautomated. A fully automated, antithrombin-III assay using the Kabi Chromogenic Synthetic Substrate S-2238 COATEST on the MULTISTAT III has been developed. This assay was compared with the Dade Protopath fluorometric assay. The correlation (r-sq) between the two assay systems was 0.82. Additionally, a three-way assay comparison was also performed, incorporating a new fluorometric substrate for antithrombin-III. The three-way comparative assays revealed correlation as follows: MULTISTAT III fluorometric assay and the MULTISTAT III/Kabi COATEST assay r-sq = 0.90; MULTISTAT III fluorometric assay and the Dade fluorometric assay r-sq = 0.86; and the MULTISTAT III/Kabi COATEST assay and the Dade Protopath fluorometric assay r-sq = 0.95. These automated assays were extremely cost effective and were a fraction of the cost of performing other types of antithrombin-III assays.

Antithrombin III↗
PubMed1986

Nucleotide sequences of a feline leukemia virus subgroup A envelope gene and long terminal repeat and evidence for the recombinational origin of subgroup B viruses.

Molecular clones of the subgroup A feline leukemia virus FeLV-A/Glasgow-1 have been obtained. Nucleotide sequence analysis of the 3' end of the proviral genome and comparison with the published sequence of FeLV-B/Gardner-Arnstein showed that the most extensive differences are located within the 5' domain of the env gene. Within this domain, several divergent regions of env are separated by more conserved segments. The 3' end of env is highly conserved, with only a single amino acid coding difference in p15env. The proviral long terminal repeats are also highly conserved, differing by only eight base substitutions and one base insertion. Specific probes constructed from the FeLV-A or FeLV-B env genes were used to compare the env genes of various exogenous FeLV isolates and the endogenous FeLV-related proviruses of normal cat DNA. An FeLV-A-derived env probe showed no hybridization to normal cat DNA but detected all FeLV-A and FeLV-C isolates tested. In contrast, an FeLV-B env probe detected independent FeLV-B isolates and a family of endogenous FeLV-related proviruses. Our observations provide strong evidence to support the hypothesis that FeLV-B viruses have arisen by recombination between FeLV-A and endogenous proviral elements in cat DNA.

Antigens, Viral↗
PubMed1985

A comparative study of the DuPont antithrombin III and fibrinogen assay systems.

Antithrombin III (AT-III) levels are useful for diagnosing thrombosis and for assessing antithrombotic therapy. Fibrinogen levels also are useful in numerous thrombohemorrhagic disorders and for noting cessation of fibrinolysis after thrombolytic therapy. With the availability of these assays on the DuPont aca, a comparative study of AT-III and fibrinogen assays was performed. DuPont assays were compared to Dade Protopath (AT-III) and Auto-Fi (fibrinogen) assays. In 38 instances a third comparative AT-III assay also was used, namely the Kabi S-2238 method (COATEST). Poor correlation existed between the DuPont AT-III and Protopath AT-III, r - sq = 0.53 to 0.61. There also was poor correlation between the DuPont and S-2238 AT-III assay, r - sq = 0.59. Excellent correlation was noted with the Protopath and Kabi AT-III assays, r - sq = 0.90. There was poor correlation between DuPont and Dade fibrinogen levels, r - sq = 0.55. When comparing AT-III values, the DuPont level was consistently higher. DuPont fibrinogen levels also were consistently higher. The DuPont AT-III and fibrinogen levels correlate poorly with existing assays, and higher results than those noted with the other methods appear common. Spuriously high values noted with the DuPont system could misguide clinicians caring for patients with thrombohemorrhagic diseases where they would expect low levels of AT-III or fibrinogen.

Antithrombin III↗
PubMedDate not supplied

Controlled pilot study of piracetam for pediatric opsoclonus-myoclonus.

Piracetam is an effective symptomatic treatment for some types of myoclonus in adults. To survey the efficacy and safety of piracetam in pediatric opsoclonus-myoclonus, we conducted an open, randomized, two-period, dose-ranging, double-blind, crossover, clinical trial of five children comparing the antimyoclonic properties of oral piracetam to placebo. We devised and validated a new rating scale, specifically for pediatric opsoclonus-myoclonus. Two parents while blinded were able to identify the active phase by improvement in behavior, but another thought the behavior was worse. None of the patients showed improvement in myoclonus. The adult-equivalent dose of piracetam used in this study, which is threefold higher than that used in previous pediatric studies, was well tolerated and safe. We found our rating scale to be a reliable and useful tool for future studies of opsoclonus-myoclonus in children.

Ataxia↗