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Biomedical subjects

I D Davis

Publications and source records attributed to I D Davis.

31 records · Page 2Linked to original sources
PubMed1998

Pediatric renal biopsy: should this procedure be performed in an outpatient setting?

Although several retrospective reports suggest that pediatric outpatient renal biopsies may be done in a safe and cost-effective manner, risk factors and the natural history of major complications following this procedure have not been clearly delineated. In an effort to determine the minimal observation period required to detect major post-renal biopsy complications in children and to establish clinical parameters predictive of these complications, a retrospective review of 177 percutaneous renal biopsies was performed. The overall major complication rate was 3.4%, while the minor complication rate was 14.1%. The mean percentage change in hemoglobin 4-10 h postbiopsy in patients with major bleeding complications was significantly greater than patients with minor bleeding complications. Using a 16% drop in hemoglobin 4-10 h postbiopsy, the sensitivity and specificity of identifying a major bleeding complication was 100% and 98%, respectively, while the positive and negative predictive value was 68% and 100%, respectively. All patients with major complications due to excess sedation or immediate bleeding were diagnosed within 11 h of the biopsy. Automated renal biopsies offered several safety and efficiency advantages compared with non-automated methods. Our results suggest that outpatient pediatric renal biopsies should be encouraged provided certain precautions are taken to reduce the risk of developing major complications.

Ambulatory Surgical Procedures↗
PubMed1998

Pediatric renal transplantation: indications and special considerations. A position paper from the Pediatric Committee of the American Society of Transplant Physicians.

Renal transplantation of children with chronic renal insufficiency (CRI) and end-stage renal disease (ESRD) appears to be the optimal form of renal replacement therapy. This report, which expresses the opinions of the nephrology members of the Pediatric Committee of the American Society of Transplant Physicians, discusses the indications for pediatric renal transplantation and identifies the unique aspects of caring for children with CRI and ESRD. Indications for pediatric renal transplantation include: 1) symptoms of uremia not responsive to standard therapy; 2) failure to thrive due to limitations in total caloric intake; 3) delayed psychomotor development; 4) hypervolemia; 5) hyperkalemia; and 6) metabolic bone disease due to renal osteodystrophy. The urgency and timing of renal transplantation in children must be considered in the context of a number of issues unique to children with CRI and ESRD such as delayed cognitive and educational performance, growth retardation, delayed puberty, etiology of ESRD, and timing of immunizations. In addition, these children frequently display various inherited and sporadic syndromes with multiorgan involvement requiring the expertise of a variety of pediatric subspecialists including the pediatric urologist, who plays a critical role in the evaluation of children with obstructive uropathy and other anomalies of the genito-urinary system. The advantages of a living-related donor are also delineated. The importance of adequate immunosuppression on graft function, early recognition of the signs and symptoms acute rejection, preventive strategies for minimizing the morbidity and mortality from viral infections in the post-transplant period, and the impact of transplantation on cognitive function, educational status, and catch-up growth are also discussed. To address these complex issues, transplant care of pediatric patients must be provided by a multidisciplinary team of pediatric health care professionals.

Child↗
PubMed1997

The paracrine role of tumour-derived mIL-4 on tumour-associated endothelium.

Interleukin-4 (IL-4) has been demonstrated to possess anti-tumourigenic properties in vivo which is initially attributed to the infiltration of eosinophils proposed to occur by IL-4 binding to its receptors on endothelial cells, thereby mediating eosinophil adhesion. We have investigated whether the binding of IL-4 to receptors on endothelial cells could elicit other biological responses which may also play a role in tumour inhibition, such as angiogenesis. We have demonstrated that mouse IL-4 (mIL-4) down-regulates the expression of one of the receptors for VEGF, VEGF-R2, on endothelial cells in vitro. By generating stable transfectants of C6 glioma cells that express mIL-4 under a tetracycline-responsive promoter system, we were able to apply tight regulatory control of mIL-4 expression in vivo. Subcutaneous implantation of mIL-4/C6 cell lines in nu/nu mice revealed that tumour growth is inhibited by mIL-4 expression. mIL-4-expressing tumours were demonstrated to have a reduced level of vascularisation compared with controls, in addition to a high degree of eosinophil infiltration. Our results suggest that mIL-4 has bimodal biological roles in potentiating tumour inhibition in athymic mice: the suppression of angiogenesis and the augmentation of the host local immune response.

Animals↗
PubMed1997

Interferon-alpha gene therapy for cancer: retroviral transduction of fibroblasts and particle-mediated transfection of tumor cells are both effective strategies for gene delivery in murine tumor models.

Stable transfection of tumor cells with IFN-alpha genes has been shown to result in abrogation of tumor establishment and induction of antitumor immunity. However, strategies suitable for the clinical application of IFN-alpha gene therapy for cancer have not been reported. In this study, we investigated two gene delivery systems capable of mediating the local paracrine production of high levels of biologically active IFN-alpha in murine tumor models: retroviral transduction of fibroblasts and particle-mediated transfection of tumor cells. In spite of the antiproliferative effects of IFN-alpha, it was possible to obtain stable retroviral producer cell lines and transduce a variety of murine tumor cells including syngeneic fibroblasts to stably secrete 2000-5000 U (40-100 ng) murine IFN-alpha/10(6) cells/24 h. IFN-alpha transduction of tumor cells abrogated tumorigenicity in establishment models and induced antitumor immunity in several murine tumor model systems. Importantly, IFN-alpha gene delivery using retrovirally transduced syngeneic fibroblasts was capable of suppressing the establishment of the poorly immunogenic TS/A mouse mammary adenocarcinoma and induced antitumor immunity. Particle mediated transient transfection of tumor cells using the gene gun led to the production of up to 20,000 U IFN-alpha/10(6) cells during the first 24 h and proved to be equally effective in suppressing establishment of TS/A adenocarcinoma and inducing antitumor immunity. These results suggest that retroviral transduction of autologous fibroblasts can serve as an effective gene delivery method for IFN-alpha gene therapy of cancer. Particle-mediated transfection of freshly isolated tumor cells may represent a clinically attractive alternative approach for nonviral gene delivery. Both strategies circumvent the difficulties in routinely establishing primary tumor cell lines from the vast majority of human cancers.

Animals↗
PubMed1996

Controlled overexpression of selected domains of the P85 subunit of phosphatidylinositol 3-kinase reverts v-Ha-Ras transformation.

Selected domains of the regulatory p85 subunit of phosphatidylinositol 3-kinase have been expressed under the control of the tetracycline transactivator in NIH 3T3 fibroblasts transformed by the v-Ha-Ras oncogene. The domains expressed were the SH3 domain, the BCR homology domain, the region between the two SH2 domains which contains the p110 binding site (the inter SH2 (IS) domain), and the C-terminal (CT) domain (containing both SH2 domains and the IS domain). The levels of IS or SH3 domain expressed in the presence of tetracycline were sufficient to reverse the transforming effects of v-Ha-Ras, and no further inhibition of proliferation was observed when expression was increased 7-fold by removal of tetracycline. In contrast inhibition of proliferation by the CT domain was observed only when the level of expression was increased 5-fold by removal of tetracycline. Overexpression of the BCR domain of p85 had no effect on v-Ha-Ras transformation. Expression of the IS domain disrupted the interaction of the p85 regulatory subunit with the p110 catalytic subunit. These results indicate that the association of the p85 subunit of PI 3-kinase with the p110 subunit is necessary for v-Ha-Ras-induced transformation in NIH 3T3 cells.

3T3 Cells↗
PubMed1995

A potent human interleukin-4 antagonist stimulates the proliferation of murine cells expressing the human interleukin-4 binding chain.

A single-amino-acid substitution mutant form of human interleukin-4 (hIL-4), Y124D.hIL-4, has been described previously as an antagonist of the effects of hIL-4 on various human cells. The murine T-cell leukemic cell line CT.h4S, which expresses the human IL-4 receptor, proliferates in response to both hIL-4 and murine IL-4. Although Y124D.hIL-4 antagonizes the proliferative effects of hIL-4 on human phytohaemagglutinin-stimulated peripheral blood mononuclear cells, Y124D.hIL-4 is a potent stimulator for CT.h4S cells. Molecular modelling studies were performed to investigate the stability of different conformations of residue 124 as well as the efficiency of different molecular mechanics force fields in homology modelling. We suggest that the aspartate substitution alters the C-terminal end of the D-helix in such way that the analogue still binds to the human IL-4 receptor alpha-chain and signals through the murine gamma c-chain. In contrast, the Y124D.hIL-4/IL-4 receptor complex cannot signal through the human gamma c-chain.

Amino Acid Sequence↗
PubMed1993

Intrapartum fetal heart rate assessment: monitoring by auscultation or electronic means.

OBJECTIVE: Our purpose was to assess the frequency with which auscultation could be used as the primary mode of fetal assessment during labor in a busy labor and delivery suite by means of published criteria. STUDY DESIGN: During a 3-month period, 862 patients in labor with live fetuses between 24 and 43 weeks of gestation were available for auscultation in the prospective study. Auscultation was initiated during a contraction and extended for 30 seconds after uterine activity ceased. It was repeated every 15 minutes in the first stage and every 5 minutes in the second stage of labor. RESULTS: In 420 patients this modality was not begun because of inability of the nurses to meet 1:1 staffing requirements. In 19 patients auscultation was not performed because of obesity (12) or patient refusal (7). Of the 423 assessed by auscultation 392 were unable to complete monitoring caused by the frequency requirement (n = 212) or the recording criteria (n = 163). Of the 31 patients where auscultation was successfully completed, there was a 1:1 nurse ratio during the entire labor. CONCLUSIONS: Auscultation with stringent evaluation and recording frequency is not feasible under normal labor and delivery room conditions unless 1:1 nursing care is always available.

Adult↗
PubMed1992

The pathologic spectrum of the nephropathy associated with alpha 1-antitrypsin deficiency.

To further define the clinicopathologic spectrum and pathogenetic mechanism of the nephropathy associated with alpha 1-antitrypsin (A1AT) deficiency, we evaluated renal specimens from 34 patients with chronic hepatic disease, including 20 with A1AT deficiency (study patients), and correlated these findings with urinalysis evaluation. Glomerular lesions were noted in 79% (15 of 19) of A1AT patients with the PiZZ phenotype, including seven with mesangio-capillary glomerulonephritis (MPGN and focal segmental MPGN), six with mesangial proliferative glomerulonephritis (Mes GN), one with diffuse endocapillary proliferative glomerulonephritis (DPGN), and one with focal segmental mesangial proliferative glomerulonephritis with segmental necrosis (FS Nec GN). One A1AT patient with the PiMZ phenotype did not demonstrate glomerular abnormalities. Focal segmental Mes GN was found in 43% (six of 14) of patients in an age-matched group with chronic hepatic failure unrelated to A1AT deficiency. In nine study patients, glomerular pathology was noted in the presence of a normal urinalysis. Immunofluorescence studies revealed the presence of immunoproteins and the A1AT protein isoelectric forms, PiM and PiZ, in the subendothelial region of glomerular basement membranes in A1AT patients with MPGN, Mes GN, and DPGN. Our results emphasize the heterogeneity of glomerular lesions associated with A1AT deficiency and hepatic disease and the relatively high incidence of MPGN in these children. The presence of abnormal PiZ protein in the subendothelial region of the glomerular basement membrane in A1AT patients with glomerulonephritis suggests a possible role for this protein in the pathogenesis of this lesion.

Adolescent↗
PubMed1991

Biochemical and histochemical characterization of a murine tubular antigen.

Cellular components of the developing fetal nephron express certain cell surface antigens at discrete stages of nephron development. To further evaluate the expression of antigens by tubular epithelium, a rat monoclonal antibody (BL26) was developed against murine fetal kidney. BL26 identified a differentiation antigen expressed by epithelial cells of the ureteric bud and late S-body in developing nephrons and by endothelium, mesangium, and distal tubular epithelium in mature nephrons. The polypeptide identified by BL26 was shown to be synthesized by fetal kidney and renal adenocarcinoma cells. The polypeptide contained no detectable carbohydrate modifications but was found in two isoforms, an acylated (26,000-Da) form and a nonacylated (24,000-Da) form. The murine antigen recognized by BL26 and the human CD9 moiety, an acylated polypeptide with a tissue distribution similar to that of the BL26 antigen, comigrated in polyacrylamide gels. We speculate that expression of the BL26 antigen and CD9 reflects processes relating to the activation of epithelial cells.

Animals↗
PubMed1990

Successful renal transplantation accelerates development in young uremic children.

To examine the impact of renal transplantation on subsequent development of children with chronic renal failure, 37 children undergoing primary renal transplantation at or before 30 months of age whose allograft functioned for at least 1 year were prospectively studied. Psychometric tests were performed an average of 4 months before transplantation; reevaluation was done an average of 14 months after surgery. Comparison of individual pretransplantation and posttransplantation mental development scores in 33 patients, assessed by either Bayley Mental Development Index or Stanford-Binet Intelligence Quotient, revealed an average increase of 12.6 (P less than .001). After transplantation, there was a significant improvement in mental performance in 12 of 18 patients (P less than .02) from the range of mild delay (Mental Development Index or Stanford-Binet IQ score = 50 to 69) to the range of normal mental development (greater than or equal to 70). The Bayley Psychomotor Development Index scores were frequently lower than Mental Development Index scores and also increased an average of 14.4 (P less than .01) after transplantation in all 12 patients with paired data. Significant individual improvement in occipital-frontal circumference standard deviation score (P less than .001) was noted in 24 children after transplantation. It is concluded that successful renal transplantation in young children with chronic renal failure is often associated with significant improvements in cognitive and psychomotor function, as well as improved cephalic growth.

Child Development↗