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Biomedical subjects

I Davis

Publications and source records attributed to I Davis.

At least 37 records · Page 2Linked to original sources

Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group.

BACKGROUND: Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo. METHODS: Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment. RESULTS: A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52). CONCLUSIONS: No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.

Adjuvants, Immunologic↗

Nonstructural protein-2 and the replication of canine parvovirus.

The nonstructural protein-2 (NS2) of canine parvovirus (CPV) is produced from the left-hand open reading frame of the viral genome and contains 87 amino-terminal amino acids in common with nonstructural protein 1 (NS1) joined to 78 amino acids from an alternative open reading frame. In the minute virus of mice parvovirus NS2 plays a role in controlling capsid protein assembly and translation in a host-specific manner. The predicted NS2 of CPV is divergent from the proteins of the rodent parvoviruses, and the protein and its functions have not been described. We characterized the large and the small splices of CPV using reverse transcriptase-PCR, NS2 was identified using anti-peptide antibodies against the predicted C-terminal sequence and also by expressing the protein from a plasmid vector. The protein could be detected at low levels in the nucleus and the cytoplasm of a proportion of CPV-infected cells, as well as in cells transfected with the expression plasmid. Virus genomes were prepared with mutations in the splice donor or acceptor sites of the NS2-specific intron or with three different termination codons in the NS2-unique exon. Both splice donor and acceptor mutations resulted in the use of previously cryptic splice sites, and the virus containing the splice donor mutation replicated inefficiently. However, the other four mutant viruses were all viable and replicated efficiently in cat and dog cells, and two mutant viruses that were tested appeared to assemble their capsids in the same manner as did the wildtype. After inoculation of dogs an NS2 mutant virus with a termination codon in the NS2-unique exon replicated to titers similar to those seen for wildtype CPV in several tissues examined.

Alternative Splicing↗

Reducing emotional conflict during the organ donor process.

It is widely recognized that nurses support and play a paramount role in the organ donor process. Nurses are faced with conflict as they deal with a grieving family while at the same time providing aggressive medical treatment to a clinically dead patient. Nurses' attitudes regarding the organ donor process will affect the process and families either positively or negatively. The organ donor coordinator in our hospital and the transplant community support the nurse, who in turn supports the family before, during and after the process. The family needs, emotional conflict and difficult decisions will be identified as perceived by a critical care nurse who was a member of an organ donor family.

Adult↗

Polynucleotide immunization of nonhuman primates against carcinoembryonic antigen.

In preparation for a Phase I trial of DNA immunization against carcinoembryonic antigen (CEA) in patients with colorectal carcinoma, we have produced a single plasmid DNA encoding CEA and hepatitis B surface antigen (HBsAg) under transcriptional regulatory control of two separate cytomegalovirus promoters within separate eukaryotic expression cassettes, designated pCEA/HBsAg. Hepatitis B surface antigen was included to provide an internal positive control for the efficacy of this immunization strategy without regard to the issue of breaking tolerance to a self-antigen. In the present work, we sought to examine the immunogenicity of this plasmid in a nonhuman primate model with close phylogenetic relationship to humans. Groups of pig-tailed macaques were immunized with pCEA/ HBsAg by i.m. injection or particle bombardment of the skin according to a dose and schedule thought to be optimal for the respective technique of DNA immunization. Both administration techniques produced humoral and lympho-proliferative responses of comparable magnitude. However, delayed type hypersensitivity to CEA and CEA-specific interleukin-2 release were observed only in the i.m. group, suggesting a qualitative difference in the character of the immune response elicited by the two techniques of DNA immunization. The antibody responses to CEA and HBsAg were surprisingly persistent in that all immunized animals maintained moderate antibody titers against both antigens for more than 15 months after the last boost. No toxicity was observed during 2 years of follow-up, including no measurable levels of anti-DNA antibody. This antitumor immunization strategy is presently being examined in patients with metastatic colorectal carcinoma using pCEA/HBsAg administered by i.m. injection.

Animals↗

Asymmetric localization of Drosophila pair-rule transcripts from displaced nuclei: evidence for directional nuclear export.

Drosophila pair-rule transcripts accumulate exclusively apical of the layer of peripheral nuclei in syncytial blastoderm stage embryos. Here, we use aneuploid embryos to test zygotic gene requirements for pair-rule transcript localization. As apical localization is maintained in all genotypes tested, the required components must be maternally encoded. In aneuploid embryos with multiple layers or cortical nuclei, pair-rule transcripts lie apical of both superficial and internalized nuclei. In the latter case, the transcripts are 'pseudo-apical', i.e. apical of the nuclei from which they derive, but basal of superficial nuclei. We show that internalized nuclei maintain their apico-basal nuclear orientation, and that they lack the apical cytoskeletal assemblies which lie adjacent to superficial nuclei. These results support a mechanism of localizing pair-rule transcripts by directional (vectorial) nuclear export.

Aneuploidy↗

Efficacy of corneal eye shields in protecting patients' eyes from laser irradiation.

BACKGROUND: The continuing development of new types and applications of lasers has appeared to surpass the development of specific eye protection for these lasers. There are a variety of eye shields on the market, but few are specifically designed for laser protection. OBJECTIVE: Our purpose was to test a variety of eye shields by two parameters, light transmission and temperature rise, and to determine from these measurements the most protective shield for patients. METHODS: We tested four plastic shields, one metal shield, and two sets of tanning goggles for temperature rise and light transmission when irradiated with a beam from a flashlamp-pumped, pulsed-dye laser. RESULTS: The temperature rise at the surface of the shield opposite the laser impacts was no more than 0.2 degree C in any case. White light was transmitted at significant levels through several of the shields, but yellow light transmittance was noted only through the green eye shield. CONCLUSION: Our measurements indicate that all except the green shield appeared safe from transmission of the 585-nm radiant energy. However, the optimal laser eye shield, in our opinion, would be a composite of several different shields' characteristics.

Color↗

A nuclear GFP that marks nuclei in living Drosophila embryos; maternal supply overcomes a delay in the appearance of zygotic fluorescence.

The central role of gene expression in regulating development has largely been studied by in situ hybridization and antibody staining techniques in fixed material. However, rapid temporal and spatial changes in gene expression are often difficult to correlate with complex morphogenetic movements. A green fluorescent protein (GFP) from the jellyfish, Aequorea victoria, can be used as a real-time reporter for gene expression and could aid analysis of dynamic events during embryogenesis. Here, we describe a transgenic Drosophila line ubiquitously expressing a nuclear GFP fusion protein that highlights morphogenesis, cell movement, and mitosis in living embryos. The fusion protein is highly fluorescent when maternally supplied, but there is a long delay between its zygotic expression and the appearance of fluorescence. GFP is thus an excellent marker for the expression of stable gene products, but a poor reporter for dynamic zygotic gene expression in early Drosophila embryos.

Animals↗

Use of a Delphi technique to prioritize clinical nursing research needs.

School of nursing faculty and nursing service personnel at an academic medical center in the South, collaboratively using a Delphi method, were able to prioritize the top three unit based clinical nursing research needs. The benefits were evident as research conducted at the staff level linked the research efforts with the quality improvement efforts on the Labor, Delivery and OB Receiving Units. The Delphi method, a consensus building technique, offered a clear, concise, accurate and non-threatening approach for staff nurses to participate in research.

Clinical Nursing Research↗

Triage by laparoscopy in patients with penetrating abdominal trauma.

Laparoscopy was performed on 33 patients with penetrating abdominal injuries to identify those with peritoneal penetration. Diagnostic or therapeutic manoeuvres were not attempted; evidence of peritoneal penetration mandated exploratory laparotomy. Twenty-two patients had gunshot wounds and 11 stab wounds. Ten patients had multiple penetrating injuries. Intraperitoneal injury was not evident by clinical assessment in any patient and all were haemodynamically stable. Twenty-three patients underwent negative laparoscopy and no intraperitoneal injury was subsequently detected. Laparoscopy demonstrated peritoneal penetration in ten patients and subsequent laparotomy detected intraperitoneal injuries in nine. No complications of laparoscopy occurred. In stable patients with penetrating trauma and no clinical evidence of intraperitoneal injury, laparoscopy effectively and safely detects those with peritoneal penetration.

Abdominal Injuries↗

Response to inhibition of angiotensin-converting enzyme in human immunodeficiency virus-associated nephropathy: a case report.

The most common chronic nephropathy seen with human immunodeficiency virus (HIV) infection is characterized by heavy proteinuria and rapid deterioration of renal function. We here report the findings in an HIV-seropositive patient with nephrotic-range proteinuria and biopsy-proven HIV-associated nephropathy treated with the angiotensin-converting enzyme (ACE) inhibitor, fosinopril. During treatment periods, the patient demonstrated a significant decrement in 24-hour urinary protein excretion without change in renal function. The patient acted as her own control. After discontinuation of the drug, the 24-hour protein excretion deteriorated to pretreatment levels. ACE inhibition has been reported to decrease proteinuria and to have a beneficial influence on the progression of renal failure in diabetic and nondiabetic renal disease. To date, there is no known therapy for HIV-associated nephropathy. Our preliminary results in this patient suggest the need for long-term studies to assess whether this form of therapy can improve proteinuria over longer periods and, at the same time, ameliorate the progressive form of nephropathy seen in selected HIV-seropositive patients.

AIDS-Associated Nephropathy↗

Topographical analysis of cortical evoked activity during a variable demand spatial processing task.

This experiment studied changes in brain activity as subjects performed a variable demand spatial rotation task. The task involved the sequential presentation of a template histogram and a spatially rotated comparison histogram. Task difficulty was manipulated by varying the number of bars and the degree of rotation. Topographical analysis of the brain event-related activity data indicated the presence of negative components that were maximal at the vertex within 80 ms and bilaterally in the temporal lobes within 140 ms of stimulus onset and that appeared to be insensitive to changes in task difficulty. Demand-sensitive potentials were recorded, however. Positive components corresponding to P200 and P300 activity were recorded symmetrically around site PZ. The P200 component declined in amplitude, but showed no changes in latency as task demand increased. P300 activity declined in both amplitude and latency as the task became more difficult. Finally, a positive component was recorded over right central cortex approximately 490 ms after stimulus onset. This component declined in amplitude but increased in latency as task difficulty increased.

Adult↗