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Biomedical subjects

D Davidson

Publications and source records attributed to D Davidson.

At least 19 recordsLinked to original sources
PubMed1999

The role of bilateral talectomy in the management of bilateral rigid clubfeet.

Severe clubfoot is a common sequela of arthrogryposis multiplex congenita and myelomeningocele. Talectomy is a practical surgical procedure to assist in the correction of severe, rigid equinovarus foot deformity. However, the results of talectomy may be less predictable in rigid bilateral equinovarus foot deformity than in the treatment of unilateral clubfoot. To determine the outcome of talectomy in the treatment of bilateral rigid clubfoot, we reviewed the cases of all patients at our center who underwent bilateral talectomy. Seven children were treated for bilateral talipes equinovarus with talectomy. The patient group consisted of 3 children with arthrogryposis, 3 with myelomeningocele, and 1 with Duchenne muscular dystrophy. The age at surgery averaged 6 years and ranged from 1 year and 10 months to 15 years and 7 months. The length of follow-up averaged 5 years and 6 months and ranged from 3 years to 12 years and 6 months. Three feet had a good and 7 feet a satisfactory correction of the deformity. Four feet had poor results. Bilateral talectomy was found overall to be a successful and predictable procedure, with low morbidity for the attainment of functional feet.

Adolescent↗
PubMed1999

Effects of naltrexone on alcohol self-administration in heavy drinkers.

The mechanisms underlying the suppressant effects of naltrexone (NTX) on ad libitum alcohol drinking in a bar/restaurant setting were investigated in heavy beer drinkers. Fifty-one male and female heavy drinkers (mean age = 22) received 50 mg of NTX or placebo (PBO), p.o., on two separate occasions in a randomized, double-blind crossover protocol. After 7 days of taking medication, subjects were provided with the opportunity to consume beer ad libitum during two, 90-min test sessions that were held 1 to 2 weeks apart. Blood samples were collected on test days to ensure medication compliance and to measure blood levels of NTX and the active beta-naltrexol. Less beer was consumed during NTX treatment. NTX decreased urges to consume alcohol. NTX-treated subjects also took significantly longer to finish each glass of beer and were more likely to terminate beer drinking early. Self-report stimulation and ratings of positive mood states were lower during NTX treatment. Negative side effects of NTX, such as nausea and headache, were reported more frequently with NTX. Not all of the subjects decreased their beer intake on NTX, and some subjects drank more beer. Nonresponders to NTX were not related to blood levels of the active metabolite beta-naltrexol or to a family history of alcoholism. Overall, the results of this study suggest that NTX affects a number of the components of alcohol drinking sequence, including lowering cravings, decreasing the positive reinforcing effects of alcohol, and increasing headache and nausea, each of which may contribute to reducing alcohol intake.

Adult↗
PubMed1998

An interview with Dick Davidson. Interview by Mary Grayson.

Dick Davidson, president of the American Hospital Association since 1991, has witnessed--and advocated--a revolution among the members. Hospitals have become much more than providers of acute care. Many of them now strive to manage a continuum of coordinated services to their communities. Their next big step is learning to manage risk for Medicare patients by becoming provider sponsored organizations. None of this is made easier, Davidson believes, by the public's sagging confidence in hospitals. In fact, he sees regaining that trust and respect as health care's top priority.

American Hospital Association↗
PubMed1998

Naltrexone effects on diazepam intoxication and pharmacokinetics in humans.

The opiate antagonist naltrexone (NTX) blocks relapse drinking in alcoholics and modifies some of the subjective effects of alcohol intoxication. Benzodiazepines have demonstrated cross-dependence and cross-tolerance to alcohol. Furthermore, benzodiazepine intoxication has effects on mood and psychomotor performance that are similar to alcohol intoxication. The effects of NTX on diazepam intoxication were investigated in non-drug abusing individuals. Eighteen men and eight women were randomly assigned to receive either 50 mg NTX or placebo PO, on two different occasions in a within-subjects, crossover, double-blind protocol. Diazepam was taken by mouth, 90 min after NTX. At -90, 45, 75, 135, 210 min, subjects were tested with repeated assessments of several mood and sensation scales and a computer-generated psychomotor test battery (CTB). Blood samples were also obtained and analyzed for serum diazepam levels. Diazepam induced several sensations and mood effects similar to those induced by alcohol. Negative mood states such as sedation, fatigue, and anxiety were higher for NTX than for placebo. Positive mood states such as friendliness, vigor, liking the effects of diazepam, and feeling high from diazepam were all lower for NTX than for placebo. There were no group differences on the CTB performance. NTX delayed the time to reach peak diazepam levels, so that peak levels occurred at 75 min for placebo compared to 135 min for NTX. A sub-analysis was conducted with 14 subjects who were FHP for alcoholism, but no differences were found on these outcome measures.

Adult↗
PubMed1998

Subungual exostosis: diagnosis and treatment in children.

Subungual exostosis is a benign bone tumor of the distal phalanx occurring beneath or adjacent to the nail. The exostosis occurs most commonly in the toes, most frequently involving the distal phalanx of the hallux. The majority of the lesions occur in the second or third decade of life. From 1975 to 1995, 21 children were treated for subungual exostosis at the Children's Hospital of Eastern Ontario, 20 of whom underwent local excision. One patient required an amputation of the affected distal phalanx due to recurrence of the lesion. The subungual exostosis occurred on the hallux in 14 children, the second toe in three children, the third toe in two children, and the fourth toe in two children. No lesion was encountered in the little toe. The exostosis is very rare in patients under 7 years of age; the average age in this review being 12 years and 6 months. The lesion recurred in three children. Removal of the nail over the exostosis facilitates the mandatory entire removal of the lesion.

Adolescent↗
PubMed1998

Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group.

OBJECTIVES: To assess the dose-related effects of inhaled nitric oxide (I-NO) as a specific adjunct to early conventional therapy for term infants with persistent pulmonary hypertension (PPHN), with regard to neonatal outcome, oxygenation, and safety. METHODS: Randomized, placebo-controlled, double-masked, dose-response, clinical trial at 25 tertiary centers from April 1994 to June 1996. The primary endpoint was the PPHN Major Sequelae Index ([MSI], including the incidence of death, extracorporeal membrane oxygenation (ECMO), neurologic injury, or bronchopulmonary dysplasia [BPD]). Patients required a fraction of inspired oxygen [FIO2] of 1.0, a mean airway pressure >/=10 cm H2O on a conventional ventilator, and echocardiographic evidence of PPHN. Exogenous surfactant, concomitant high-frequency ventilation, and lung hypoplasia were exclusion factors. Control (0 ppm) or nitric oxide (NO) (5, 20, or 80 ppm) treatments were administered until success or failure criteria were met. Due to slowing recruitment, the trial was stopped at N = 155 (320 planned). RESULTS: The baseline oxygenation index (OI) was 24 +/- 9 at 25 +/- 17 hours old (mean +/- SD). Efficacy results were similar among NO doses. By 30 minutes (no ventilator changes) the PaO2 for only the NO groups increased significantly from 64 +/- 39 to 109 +/- 78 Torr (pooled) and systemic arterial pressure remained unchanged. The baseline adjusted time-weighted OI was also significantly reduced in the NO groups (-5 +/- 8) for the first 24 hours of treatment. The MSI rate was 59% for the control and 50% for the NO doses (P = .36). The ECMO rate was 34% for control and 22% for the NO doses (P = .12). Elevated methemoglobin (>7%) and nitrogen dioxide (NO2) (>3 ppm) were observed only in the 80 ppm NO group, otherwise no adverse events could be attributed to I-NO, including BPD. CONCLUSION: For term infants with PPHN, early I-NO as the sole adjunct to conventional management produced an acute and sustained improvement in oxygenation for 24 hours without short-term side effects (5 and 20 ppm doses), and the suggestion that ECMO use may be reduced.

Administration, Inhalation↗
PubMed1998

Synovitis secondary to giardiasis in children.

Giardia lamblia, a gastrointestinal protozoan, is one of the most common disease-causing parasites in the world. Giardiasis is primarily encountered in areas with poor sanitation, but it is also seen in more developed countries. A possible sequela of Giardia infections of the bowel is reactive arthritis or synovitis. Few reports of synovitis secondary to giardiasis exist in the literature. Arthropathy secondary to giardiasis is uncommon, but may be underdiagnosed. In this study, Giardia synovitis was diagnosed in two children at a major children's hospital over a 20-year period. Both were boys, aged 7 years, 6 months and 1 year, 8 months at the time of presentation. The knee was the affected joint in both patients, and both cases were initially misdiagnosed as septic arthritis. The synovitis subsided with treatment of the giardiasis, one with cefuroxime and the other with cefuroxime and metronidazole. The diagnosis of Giardia synovitis should be suspected by the presence of Giardia cysts in the stool, similar symptoms in other family members, a synovial white count under 40,000, and an increase in the eosinophil count. Although uncommon, giardiasis can cause severe synovitis that may be confused with a septic joint.

Animals↗
PubMed1998

The white blood cell and plasma fibrinogen in thrombotic stroke. A significant correlation.

OBJECTIVES: Thrombotic stroke is a common disorder with considerable mortality and morbidity. Risk factors for stroke include cigarette smoking, hypertension and hyperlipidaemia and these have been linked to abnormalities of haemorrheology and coagulation such as increased fibrinogen. Other haemorrheological abnormalities have also been documented. These include an elevation in the white blood cell (WBC) count. The aim of our study was to evaluate plasma fibrinogen, WBC aggregation and the release of free radicals in thrombotic stroke. EXPERIMENTAL DESIGN: Thirty-four patients with thrombotic stroke were enrolled in the study. The data were compared to 58 matched controls. SETTING: This study was carried out in Ninewells Hospital, Dundee on patients previously admitted to the medical wards with acute stroke. MEASURES: Plasma fibrinogen, WBC aggregation and plasma malondialdehyde (MDA) were measured in this study. RESULTS: As expected, the stroke patients have a significantly higher fibrinogen level (4.3+/-1.2 g/dl versus 3.1+/-0.6, p<0.001). WBC aggregation is also increased in the patient group (47.5+/-10.4% versus 42.7+/-10.6, p=0.036), as is plasma MDA (8.6+/-2.0 micromol/l versus 7.1+/-1.07, p<0.001). The factor VIII von Willebrand factor antigen measured as a marker as vascular damage was also significantly higher in the patient group (251+/-87% versus 182+/-64, p<0.001). There was also a statistically significant correlation between fibrinogen level and WBC aggregation, and fibrinogen and MDA. These are both statistically significant p=0.012 and p<0.001 respectively. CONCLUSIONS: We believe our study suggests that enhanced WBC aggregation/adhesion with release of free radicals may be another mechanism whereby fibrinogen exerts its known detrimental effect in stroke development. This may allow planning of therapeutic strategies as yet undeveloped.

Aged↗
PubMed1997

Inhibitory tyrosine protein kinase p50csk is associated with protein-tyrosine phosphatase PTP-PEST in hemopoietic and non-hemopoietic cells.

p50(csk) is a cytosolic tyrosine protein kinase expressed in all cell types. Accumulating data show that it inhibits multiple cellular processes, as a consequence of its ability to repress the enzymatic activity of Src family tyrosine protein kinases. We previously demonstrated that, via its Src homology 3 (SH3) domain, Csk is tightly bound to PEP, a protein-tyrosine phosphatase (PTP) exclusively expressed in hemopoietic cells. In this report, we have tested the possibility that Csk also interacts with PTP-PEST, a ubiquitous PTP sharing structural homology with PEP. Our studies revealed that Csk was associated with PTP-PEST in a variety of cell types, including non-hemopoietic cells. This interaction involved the SH3 region of p50(csk) and a proline-rich region (PPPLPERTPESFVLADM) outside the catalytic region of PTP-PEST. Even though both PTP-PEST and PEP were associated with Csk, significant differences were noted between these two PTPs. PTP-PEST, but not PEP, was also complexed with Shc, an adaptor molecule implicated in the Ras pathway. Moreover, PTP-PEST and PEP were found to accumulate primarily in distinct intracellular compartments in cell fractionation studies. In combination, these findings indicated that, like PEP, PTP-PEST is probably involved in Csk-mediated functions in mammalian cells. Moreover, they suggested that the roles of Csk-PTP-PEST and Csk-PEP are likely to be different.

Amino Acid Sequence↗
PubMed1997

Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth.

Angiostatin is a potent angiogenesis inhibitor which has been identified as an internal fragment of plasminogen that includes its first four kringle modules. We have recently demonstrated that the anti-endothelial cell proliferative activity of angiostatin is also displayed by the first three kringle structures of plasminogen and marginally so by kringle 4 (Cao, Y., Ji, R.-W., Davidson, D., Schaller, J., Marti, D., Sohndel, S., McCance, S. G., O'Reilly, M. S. , Llinás, M., and Folkman, J. (1996) J. Biol. Chem. 271, 29461-29467). We now report that the kringle 5 fragment of human plasminogen is a specific inhibitor for endothelial cell proliferation. Kringle 5 obtained as a proteolytic fragment of human plasminogen displays potent inhibitory effect on bovine capillary endothelial cells with a half-maximal concentration (ED50) of approximately 50 nM. Thus, kringle 5 would appear to be more potent than angiostatin on inhibition of basic fibroblast growth factor-stimulated capillary endothelial cell proliferation. Appropriately folded recombinant mouse kringle 5 protein, expressed in Escherichia coli, exhibits a comparable inhibitory effect as the proteolytic kringle 5 fragment. Thus, kringle 5 domain of human plasminogen is a novel endothelial inhibitor that is sufficiently potent to block the growth factor-stimulated endothelial cell growth.

Amino Acid Sequence↗
PubMed1997

Chk, a Csk family tyrosine protein kinase, exhibits Csk-like activity in fibroblasts, but not in an antigen-specific T-cell line.

The Csk family of tyrosine protein kinases comprises two members named Csk and Chk. These enzymes phosphorylate the carboxyl-terminal tyrosine of Src-related kinases in vitro, thereby repressing their activity. Csk has been found to be necessary for normal embryonic development, and to be a potent negative regulator of antigen receptor signaling in T-lymphocytes. As the functions of Chk in mammalian cells are not known, we examined its ability to carry out Csk-like functions in vivo. Like p50csk, Chk reduced the elevated phosphotyrosine levels and the augmented activity of Src family kinases in Csk-deficient fibroblasts. Contrary to Csk, however, Chk was inefficient at repressing antigen receptor-induced signals in a T-cell line (BI-141). We also noted that Chk, but not Csk, failed to stably associate with cellular membranes following addition of a membrane targeting signal to its amino terminus. This observation suggested that Chk may contain dominant targeting sequences disallowing its recruitment to cellular membranes. Hence, these data demonstrate that Chk can mediate some, but not all, Csk-related functions in vivo. Moreover, they suggest that the "restricted" function of Chk may relate at least in part to its inability to be recruited to certain cellular locales.

Animals↗
PubMed1997

The mouse atlas and graphical gene-expression database

The large amounts of gene-expression data on mouse development are now too extensive to be stored in any format other than that of a database. Furthermore, as this data is intrinsically graphical and as, in the early developmental stages at least, its boundaries do not map directly to those of anatomical tissues, the natural way to store it is in graphical format. We are therefore constructing a database able to handle such graphical gene-expression data by mapping it onto 3-D reconstructions of mouse embryos whose tissues have been delineated. This article reviews the progress that has been made in this project and describes its two major components, CD-ROMs of the 3-D reconstructions to be held on the user's computer and a gene-expression database that will be maintained at a host site, the two being linked over the internet by a complex Java-based interface for submitting data and querying the database.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited

Journal Article↗
PubMed1997

Two enhancer domains control early aspects of the complex expression pattern of Msx1.

To understand how the complex embryonic expression pattern of the Msx1 gene is produced a transgenic analysis of 13 kb of DNA around the Msx1 locus was carried out. Most of the extensive expression pattern of the Msx1 gene was reproduced in transgenics using the LacZ gene fused to 5 kb of Msx1 5' flanking DNA. Two enhancer domains were identified which produced this pattern. The distal element produced expression in the first arch and the nasal epithelium and was restricted to 240 bp. However, the proximal element which produced expression in superficial nasal epithelium, dorsal and ventral myotome, limb mesenchyme, eye, ear, roof plate, second arch, genital ridge and epiphysis, was contained in only 78 bp.

Animals↗
PubMed1997

Monolingual and bilingual children's use of the mutual exclusivity constraint.

The use of the mutual exclusivity constraint was examined in three-year-old and six-year-old children who were either monolingual in English (N = 32) or bilingual in English/Urdu (N = 32) or in English/Greek (N = 32). Three tests of the constraint were used: disambiguation rejection, and restriction. On the disambiguation test, the mutual exclusivity bias was significantly more evident in five- and six-year-old monolingual children than in their same-age bilingual peers. Monolingual children were also more likely than bilingual children to reject a new name for a familiar object. However, using a restriction test, neither monolingual nor bilingual children readily accepted and restricted typical names for hybrid objects. Developmental differences were also found, as older (five- to six-year-old) monolingual children's responses on the tests were generally more consistent with the constraint than younger (three- to four-year-old) children's responses. Nevertheless, bilingual children did use the constraint, but not to the extent of monolingual children.

Child↗