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Biomedical subjects

D Davidson

Publications and source records attributed to D Davidson.

At least 55 records · Page 3Linked to original sources
PubMed2000

A pharmacokinetic and tolerability evaluation of two continuous subcutaneous infusion systems compared to an oral controlled-release morphine.

The pharmacokinetic profiles, safety, and tolerability of continuous subcutaneous infusion with a novel drug deliver system (the MEDIPAD system) was compared to a standard infusion pump (the CADD-Micro) and to controlled-release tablets (MS Contin) for the administration of morphine sulfate. This was a single-center, open-label, three-treatment study conducted in 24 male and female healthy volunteers. The mean age was 40.6 yr (SD = +/- 12.27). A three treatment design was chosen to compare differences between modes of administration within each subject to minimize the impact of intersubject variability: Treatment A was a continuous 48-hr subcutaneous infusion of morphine sulfate (165.6 mg at a rate of 3. 45 mg/hr) with the MEDIPAD system attached to the chest, Treatment B was a series of four oral doses of morphine sulfate (120 mg each) at 12-hr intervals, and Treatment C was a continuous 48-hr subcutaneous infusion of morphine sulfate (163.2 mg at a rate of 3.40 mg/hr) with the CADD-Micro device attached to the chest. Subjects began treatment after eligibility was established and informed consent was obtained. The primary pharmacokinetic parameters (AUC, C(max)) for the two devices were similar; 90% confidence intervals showed that the MEDIPAD system was bioequivalent to the CADD-Micro in terms of both rate and extent of morphine absorption. The mean morphine plasma concentration versus time plot suggested that plasma concentrations rise more rapidly with the MEDIPAD device than with the CADD-Micro or oral administrations. The MEDIPAD system showed mild application and injection site reactions; there were no site reactions for the CADD-Micro or oral doses. As expected nausea, somnolence, and abdominal pain occurred more frequently in the oral treatment than the two infusion devices. These data suggest that the MEDIPAD system, which is currently undergoing clinical evaluation, is an acceptable alternative to the traditional oral treatment of morphine sulfate for delivery of analgesics as it allows rapid absorption of morphine; is small, easy to use, and disposable; and achieves plasma levels that are essentially equal to other standard infusion pumps.

Administration, Oral↗
PubMed2000

Three-dimensional reconstruction of tetraploid<-->diploid chimaeric mouse blastocysts.

Studies of tetraploid<-->diploid (4n<-->2n) mouse chimaeras have demonstrated unequal contributions of 4n cells to different tissues of the midgestation conceptus. Such a pattern has also been reported in chimaeras as early as E3.5d, which show an enhanced contribution of 4n cells to the mural trophectoderm (Everett & West, 1996). In this study, sectioned 4n<-->2n and 2n<-->2n control chimaeric blastocysts were digitised and reconstructed in 3 dimensions (3-D). The 3-D images revealed only limited mixing of cells from the 2 contributing embryos of individual blastocysts in both chimaera groups. Consequently, the distribution pattern of the 2 cell types was dependent on the spatial relationship between the orientation of the blastocyst and the boundary between the 2 clusters of cells. The distribution patterns observed were not strikingly different for 4n<-->2n and 2n<-->2n chimaeras, each showing some transgenic positive cell contribution in all 3 identifiable developmental lineages. It was notable, however, that in all 4n<-->2n blastocysts at least some 4n cells were located adjacent to the blastocyst cavity. Such a consistent pattern was not evident in 2n<-->2n chimaeras. This study has demonstrated the value of 3-D reconstructions for the analysis of spatial relationships of 2 cell populations in chimaeric mouse blastocysts.

Animals↗
PubMed2000

Interruption and bizarreness effects in the recall of script-based text.

Recall of script, script-irrelevant, and script-interruptive actions in script-based stories was examined in four experiments. By varying the plausibility of the script-irrelevant and the script-interruptive actions, the bizarreness effect (i.e., enhanced recall for bizarre, implausible actions) was assessed within the context of script-based text. In addition, presentation of script-interruptive actions actions allowed for an assessment of the interruption effect (i.e., enhanced recall for interruptive actions). A bizarreness effect was found, to the extent that implausible script-irrelevant actions were better recalled than their more plausible counterparts and script actions. However, implausible actions were not better recalled than script-interruptive actions, nor did bizarreness significantly enhance recall of script-interruptive actions. These results are discussed in terms of recent assumptions underlying interruptions underlying interruption and bizarreness effects, and in terms of recent assumptions about how scripted and nonscripted actions are retained in memory.

Adult↗
PubMed2000

Sentinel lymph node biopsy for melanoma: experience with 234 consecutive procedures.

Sentinel lymph node biopsy is increasingly used to identify occult metastases in regional lymph nodes of patients with melanoma. Selection of patients for sentinel lymph node biopsy and subsequent lymphadenectomy is an area of debate. The purpose of this study was to describe a large clinical series of these biopsies for cutaneous melanoma and to identify patients most likely to gain useful clinical information from sentinel lymph node biopsy. The Indiana University Melanoma Program computerized database was queried to identify all patients who underwent this procedure for clinically localized cutaneous melanoma. It was performed using preoperative technetium Tc 99m lymphoscintigraphy and isosulfan blue dye. Pertinent demographic, surgical, and histopathologic data were recorded. Univariate and multivariate logistic regression and classification table analyses were performed to identify clinical variables associated with sentinel node and nonsentinel node positivity. In total, 234 biopsy procedures were performed to stage 291 nonpalpable regional lymph node basins. Mean Breslow's thickness was 2.30 mm (2.08 mm for negative sentinel lymph node biopsy, 3.18 mm for positive). The mean number of sentinel nodes removed was 2.17 nodes per basin (range, 1 to 8). Forty-seven of 234 melanomas (20.1 percent) and 50 of 291 basins (17.2 percent) had a positive biopsy. Positivity correlated with AJCC tumor stage: T1, 3.6 percent; T2, 8.1 percent; T3, 27.4 percent; T4, 44 percent. By univariate logistic regression, Breslow's thickness (p = 0.003, continuous variable), ulceration (p = 0.003), mitotic index > or = 6 mitoses per high power field (p = 0.008), and Clark's level (p = 0.04) were significantly associated with sentinel lymph node biopsy result. By multivariate analysis, only Breslow's thickness (p = 0.02), tumor ulceration (p = 0.02), and mitotic index (p = 0.02) were significant predictors of biopsy positivity. Classification table analysis showed the Breslow cutpoint of 1.2 mm to be the most efficient cutpoint for sentinel lymph node biopsy result (p = 0.0004). Completion lymphadenectomy was performed in 46 sentinel node-positive patients; 12 (26.1 percent) had at least one additional positive nonsentinel node. Nonsentinel node positivity was marginally associated with the presence of multiple positive sentinel nodes (p = 0.07). At mean follow-up of 13.8 months, four of 241 sentinel node-negative basins demonstrated same-basin recurrence (1.7 percent). Sentinel lymph node biopsy is highly reliable in experienced hands but is a low-yield procedure in most thin melanomas. Patients with melanomas thicker than 1.2 mm or with ulcerated or high mitotic index lesions are most likely to have occult lymph node metastases by sentinel lymph node biopsy. Completion therapeutic lymphadenectomy is recommended after positive biopsy because it is difficult to predict the presence of positive nonsentinel nodes.

Adolescent↗
PubMed2000

Dok-3, a novel adapter molecule involved in the negative regulation of immunoreceptor signaling.

Adapters are typically viewed as molecules coordinating the recruitment of positive effectors of cell signaling. Herein, we report the identification of Dok-3, a novel adapter molecule belonging to the Dok family. Our studies show that Dok-3 is highly expressed in several hemopoietic cell types, including B cells and macrophages. It undergoes rapid tyrosine phosphorylation in response to immunoreceptor-mediated cellular activation, seemingly as a result of the action of Src family kinases. This phosphorylation induces the binding of Dok-3 to at least two inhibitory molecules, the 5' inositol phosphatase SHIP and the protein tyrosine kinase Csk. We also demonstrate that augmented expression of wild-type Dok-3 in a B-cell line results in an inhibition of immunoreceptor-mediated nuclear factor of activated T-cells (NFAT) activation and cytokine release, while introduction of a Dok-3 mutant with impaired ability to associate with SHIP and Csk enhances B-cell responsiveness. Taken together, these results indicate that Dok-3 is an adapter involved in the recruitment of inhibitory molecules and that it may play a significant role in the negative regulation of immunoreceptor signaling in hemopoietic cells such as B cells and macrophages.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Estimation of the flow of microbial nitrogen to the duodenum using milk uric acid or allantoin.

Data were collected from 10 experiments with duodenally cannulated Holstein dairy cows (271 combinations of cow and period) to evaluate the relationship between milk purine metabolites and microbial nitrogen flow. Experiments evaluated the effects of dietary factors on microbial N production and included: 1) supplemental sources of ruminally protected amino acids; 2) grass silage treated with fibrolytic enzymes; 3) bacterial inoculation of corn silage; 4) a comparison of corn and barley grain; 5) ruminal starch availability as affected by corn silages of varying maturity; and, 6) ruminal starch availability as affected by corn silages harvested at varying chop length and with or without mechanical processing. The coefficient of determination for individual experiments for the relationship between microbial nitrogen flow and allantoin or uric acid excretion in milk ranged from -0.01 to 0.77 and -0.06 to 0.22 respectively. Across all experiments, the coefficients of determination between microbial nitrogen flow and allantoin or uric acid excretion in milk were r2 = 0.09 and 0.01 respectively. Milk allantoin output was used to develop a prediction equation estimating microbial nitrogen flow to the duodenum. The greatest predictive value (r2 = 0.25) relationship was observed across non-bST experiments and included the factors of allantoin excretion, milk yield, dry matter intake, and days in milk. When milk yield was included in the model, the predictive value improved (r2 = 0.44). Based on these data, milk uric acid excretion alone cannot be used to predict microbial N production accurately [corrected].

Allantoin↗
PubMed2000

Subcutaneous granuloma annulare of the extremities in children.

OBJECTIVE: To familiarize surgeons to the natural history and treatment of granuloma annulare of the extremities in children. DESIGN: Case review and follow-up by appointment and questionnaire. SETTING: The Children's Hospital of Eastern Ontario, a tertiary referral centre. PATIENTS: Twenty-seven children (23 girls, 4 boys) seen between 1983 and 1998 with subcutaneous granuloma annulare, proven pathologically. The mean age at initial presentation was 8.3 years (range from 1.8 years to 16.7 years). The mean follow-up was 45 weeks (range from 1 week to 5 years). INTERVENTION: Biopsy excision of the lesions. OUTCOME MEASURES: The incidence multiple lesions, the commonest site of occurrence and the incidence of recurrence. RESULTS: Six children presented with multiple lesions for a total of 46 lesions. The anterior pretibial area was the most frequently affected site (16 lesions), followed by the ankle (6 lesions) and the long finger (4 lesions). Five patients suffered recurrence of the lesion, with a total of 7 lesions recurring. CONCLUSIONS: Subcutaneous granuloma annulare is a benign inflammatory skin lesion occurring most frequently in the anterior pretibial area in children, predominantly girls. The incidence of recurrence and of multiple lesions is high. Biopsy is required for definitive diagnosis. The lesion resolves spontaneously without treatment.

Adolescent↗
PubMed2000

Strategic planning: myth or reality.

The reality of strategic planning often falls prey to the unplanned external or internal forces at work in health care. A strategic plan may sit on the shelf as though it were an end unto itself. This article discusses what might need to happen differently to change the outcome of planning generally and describes some of the strengths and weaknesses of planning at the system level.

Commerce↗
PubMed1999

Visual scanpaths in schizophrenia: is there a deficit in face recognition?

There is substantial evidence that schizophrenics have deficits in face processing. We hypothesised that this difficulty is due to abnormalities in the visual scanning of faces. The specificity of these abnormalities to recognisable faces, the effect of task difficulty and their relationships to three primary symptom dimensions were examined. An infrared corneal reflection technique was used to record the visual scanpaths of 63 schizophrenics and 60 non-psychiatric controls while viewing non-degraded ('recognisable') and degraded ('not recognisable') faces. In the concurrent recognition task, subjects were asked to select the previously viewed face from among seven (exposure 1) or three (exposure 2) options. Both groups were unable to accurately recognise degraded faces, but schizophrenics were less accurate than controls for non-degraded faces in the more difficult task condition. Schizophrenics maintained a relatively 'restricted' scanpath style across both faces, but scanpath disturbances were most apparent for non-degraded faces. Analysis of fixation distribution to non-degraded faces showed that, unlike controls, schizophrenics did not concentrate their fixations on salient features. Scanpath aberrations showed only minimal associations with symptom dimensions. These results suggest that schizophrenic individuals have a specific deficit in the visual scanning of faces, that is a distinct case of a fundamental problem in complex object processing.

Adult↗
PubMed1999

A three-dimensional model of the mouse at embryonic day 9.

This paper describes a digital, three-dimensional model of the mouse embryo at E9. The model was made by reconstruction from images of serial histological sections digitally warped to remove distortions and has a resolution of approximately 9 microns. The model can be digitally resectioned in any plane to provide images which resemble conventional histological sections. The main tissues have been identified and delineated by digital painting so that the anatomical components can be visualized and manipulated in 3-D surface- and volume-rendered views. This provides a three-dimensional definition of anatomy that will provide a useful tool for interpreting and understanding spatial data in mouse embryos. The anatomy of the model is discussed where it provides landmarks for interpretation and navigation or where it is unexpected in light of existing descriptions of the E9 mouse embryo. The complete anatomy is not presented in this paper but will be available on CD-ROM. A detailed description of the technical aspects of the construction of the model is included in an appendix. The model is the first of a series that will form the basis for an atlas/database of mouse development. This reconstruction and its associated anatomy are available in a variety of data formats with some supporting software from http:@genex.hgu.mrc.ac.uk/.

Anatomy, Cross-Sectional↗
PubMed1999

Clnk, a novel SLP-76-related adaptor molecule expressed in cytokine-stimulated hemopoietic cells.

We have identified a novel Src homology 2 domain-containing leukocyte protein of 76 kD (SLP-76)-related molecule which we have termed Clnk (for cytokine-dependent hemopoietic cell linker). Unlike its relatives SLP-76 and B cell linker protein (Blnk), Clnk is not expressed uniformly within a given hemopoietic cell lineage. Even though it can be detected in several cell types, including T cells, natural killer cells, and mast cells, its expression seems to be strictly dependent on sustained exposure to cytokines such as interleukin (IL)-2 and IL-3. Strong support for the notion that Clnk is involved in immunoreceptor signaling was provided by the observation that it inducibly associated with at least one tyrosine-phosphorylated polypeptide (p92) in response to immunoreceptor stimulation. Moreover, transient expression of Clnk caused an increase in immunoreceptor-mediated signaling events in a T cell line. Taken together, these results show that Clnk is a novel member of the SLP-76 family selectively expressed in cytokine-stimulated hemopoietic cells. Furthermore, they suggest that Clnk may be involved in a cross-talk mechanism between cytokine receptor and immunoreceptor signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Hospital discharge. Smooth passage.

The introduction of care co-ordinators into a medical directorate two years ago has reduced bed blocking and cut length of stay from 8.5 to 5.9 days. All those appointed were already working in the hospital. There have been some tensions over boundaries with nursing and social work.

Case Management↗
PubMed1999

The spinal manifestations of Stickler's syndrome.

STUDY DESIGN: A review of current knowledge, clinical publications, and recent concepts of the causes of Stickler's syndrome was correlated with a clinical review of the condition at the Children's Hospital of Eastern Ontario, Canada. OBJECTIVES: To acquaint orthopedic spine surgeons with the natural history, associated anomalies, and high incidence of spinal deformity and scoliosis in children with Stickler's syndrome. SUMMARY OF BACKGROUND DATA: Stickler's syndrome is a hereditary, progressive arthro-ophthalmopathy with an autosomal dominant inheritance pattern. The estimated incidence is 1 in 10,000 people, which is slightly more common than Marfan syndrome. METHODS: The experience with Stickler's syndrome was reviewed in seven children, 2-15 years of age, with particular attention to the spinal abnormalities secondary to the connective tissue dysplasia. RESULTS: Six of the children had kyphosis or scoliosis, and four had wedging or flattening of the vertebrae or platyspondylia. In general, the spinal changes became more prominent in the older children with Stickler's syndrome, with the spinal vertebrae affected by the generalized epiphyseal dysplasia. The treatment of scoliosis and kyphosis is no different in children with Stickler's syndrome. The most difficult aspect is in diagnosing the condition. CONCLUSIONS: The importance of recognizing the syndrome is to allow for the investigation and treatment of the many other associated connective tissue disorders associated with Stickler's syndrome, such as the high incidence of retinal detachment, mitral valve prolapse, and mandibular hypoplasia that may result in problems with anesthesia should the spine require surgical stabilization.

Adolescent↗
PubMed1999

Seat belt fracture with late development of an enterocolic fistula in a child. A case report.

STUDY DESIGN: A case report of a 9-year-old boy treated at a pediatric trauma center for a flexion-extension spiral fracture with late development of an enterocolic fistula subsequent to a high-velocity motor vehicle accident. OBJECTIVES: To increase the awareness of possible delayed bowel complications associated with flexion-distraction injuries of the spine in children. SUMMARY OF BACKGROUND DATA: Flexion-distraction fractures of the spine in children wearing lap seat belts, so-called "Chance" fractures, are an increasingly common result of high-velocity collisions. This type of fracture, referred to as a seat-belt fracture, is often associated with duodenal or jejunal tears. Although such intra-abdominal injuries are common in such fractures secondary to this type of trauma, the occurrence of an enterocolic fistula has never been reported. METHODS: A review of all pediatric Chance fractures managed at the Children's Hospital of Eastern Ontario, as well as a literature review of all reported series of flexion-distraction injuries to the spine in children, were performed. RESULTS: The subtle and prolonged symptomatology of this lesion and its similarity to a cast syndrome is emphasized. CONCLUSION: Because the orthopedic surgeon is usually the primary care-giver for children with this type of seat-belt trauma, an appreciation of the possibility of a delayed onset enterocolic fistula with its symptomatology is essential to avoid prolonged morbidity.

Accidents, Traffic↗
PubMed1999

Interactions of CD45-associated protein with the antigen receptor signaling machinery in T-lymphocytes.

CD45 is a transmembrane protein tyrosine phosphatase playing an essential role during T-cell activation. This function relates to the ability of CD45 to regulate p56(lck), a cytoplasmic protein tyrosine kinase necessary for T-cell antigen receptor (TCR) signaling. Previous studies have demonstrated that CD45 is constitutively associated in T-lymphocytes with a transmembrane molecule termed CD45-AP (or lymphocyte phosphatase-associated phosphoprotein). Even though the exact role of this polypeptide is unclear, recent analyses of mice lacking CD45-AP have indicated that its expression is also required for optimal T-cell activation. Herein, we wished to understand better the function of CD45-AP. The results of our studies showed that in T-cells, CD45-AP is part of a multimolecular complex that includes not only CD45, but also TCR, the CD4 and CD8 coreceptors, and p56(lck). The association of CD45-AP with TCR, CD4, and CD8 seemed to occur via the shared ability of these molecules to bind CD45. However, binding of CD45-AP to p56(lck) could take place in the absence of other lymphoid-specific components, suggesting that it can be direct. Structure-function analyses demonstrated that such an interaction was mediated by an acidic segment in the cytoplasmic region of CD45-AP and by the kinase domain of p56(lck). Interestingly, the ability of CD45-AP to interact with Lck in the absence of other lymphoid-specific molecules was proportional to the degree of catalytic activation of p56(lck). Together, these findings suggest that CD45-AP is an adaptor molecule involved in orchestrating interactions among components of the antigen receptor signaling machinery. Moreover, they raise the possibility that one of the functions of CD45-AP is to recognize activated Lck molecules and bring them into the vicinity of CD45.

Animals↗