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Biomedical subjects

J Andrews

Publications and source records attributed to J Andrews.

At least 91 records · Page 5Linked to original sources
PubMed1999

Cytomegalovirus (CMV) resistance in patients with CMV retinitis and AIDS treated with oral or intravenous ganciclovir.

Treatment of cytomegalovirus (CMV) retinitis with oral ganciclovir results in relatively low plasma concentrations of drug, which theoretically could cause more frequent viral resistance compared with intravenous (iv) ganciclovir. By use of a plaque-reduction assay to quantify phenotypic sensitivity to ganciclovir, virus isolates were studied from patients with CMV retinitis participating in four clinical trials of oral ganciclovir. Before treatment, 69% of patients were culture-positive but just 1.1% of patients yielded a resistant CMV, defined as a median inhibitory concentration (IC50) >6 microM. On treatment, the first resistant isolate was recovered at 50 days. Overall, 3.1% of patients receiving iv ganciclovir and 6. 5% of those taking oral ganciclovir shed resistant CMV (median ganciclovir exposures of 75 and 165 days, respectively). Since IC50s for clinical isolates increased proportionately with treatment duration, it is likely that viral resistance would be more frequent with longer treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Production of influenza-stimulated tumor necrosis factor-alpha by monocytes following acute influenza infection in humans.

Tumor necrosis factor-alpha (TNF-alpha) is often measured in the serum or plasma of patients with severe infections, and marked elevation correlates with poor outcome. The relationship of TNF-alpha to protection from disease is frequently not observed because prospective studies of infectious agents are difficult to perform. We took advantage of a human antiviral influenza challenge study to correlate TNF-alpha production with seroconversion and symptom development. TNF-alpha production was measured by ELISA in the plasma compartment or was measured by intracellular production at the single cell level in the monocyte gated population. Monocyte TNF-alpha was associated with asymptomatic seroconversion, whereas there was no change in the plasma at the times measured. Measurement of TNF-alpha at the single cell level by flow cytometry may allow for better differentiation of the protective role of this cytokine in future studies.

Adolescent↗
PubMed1999

Refrigerated storage improves the stability of the complete blood cell count and automated differential.

A CBC count was performed on 113 random patient and 21 control specimens before and after 24-hour room temperature (RT) storage; 98 random patient and 20 control specimens also were analyzed before and after 24 hour 4 degrees C storage. The Cell-Dyn 3500 (Abbott Laboratories, Abbott Park, IL) was used for analysis. RT storage showed a decline in WBC count using the optical but not the impedance method, resulting in a large number of WBC flags. An increase in mean corpuscular volume also was seen for patient specimens. The automated WBC differential showed a decrease in the percentage of neutrophils and an increase in the percentage of lymphocytes, owing primarily to neutrophil degeneration. These changes also were seen in the manual differential to a similar degree. Storage of specimens at 4 degrees C largely prevented all of these changes. The implementation of refrigerated specimen storage is a simple, inexpensive method to improve the accuracy of CBC results for aged specimens on automated hematology analyzers.

Autoanalysis↗
PubMed1999

Antimicrobial resistance in gram-positive pathogens isolated in the UK between October 1996 and January 1997.

Antimicrobial resistance in gram-positive pathogens from 30 centres in the UK (ten Teaching, ten Associate Teaching and ten District General Hospitals) was studied over a 4 month period between October 1996 and January 1997. High-level resistance (HLR) and low-level resistance (LLR) to penicillin amongst pneumococci was 3.3% and 3.4%, respectively. However, considerable variation in resistance rates was observed depending on geographical location (LLR range 0-15.4% and HLR range 0-30.8%). Considerable variation in resistance rates was also observed for Staphylococcus aureus to methicillin, with rates ranging from 0% to 56.7% depending on locality. Using conventional MIC methodology, none of the isolates of S. aureus was considered as having reduced sensitivity to vancomycin. However, eight isolates grew on Brain Heart Infusion Agar containing vancomycin (4 mg/L) after prolonged incubation and are therefore worthy of further investigation by electron microscopy. With Enterococcus faecalis, resistance rates were similar between the three types of hospital and only four isolates were considered resistant to glycopeptide antibiotics (one vanA and three vanB phenotype).

Anti-Bacterial Agents↗
PubMed1999

Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

Anti-Infective Agents↗
PubMed1999

Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants.

PURPOSE: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS: A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK > or = 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK > or = 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P =.001); 24% of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P =.001). CONCLUSION: Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.

Adolescent↗
PubMed1999

Human corneal ablation threshold using the 193-nm ArF excimer laser.

PURPOSE: To determine the human corneal threshold ablation energy density for the 193-nm ArF excimer laser, approximating clinical conditions. METHODS: The VISX Star (Santa Clara, CA) 193-nm argon fluoride excimer laser was used to ablate the cornea in human eye bank eyes under clinical conditions. Corneas were exposed to energy densities of 10, 20, 30, 35, 40, 45, and 140 to 160 mJ/cm2. Corneas were fixed for light and transmission electron microscopy immediately after laser exposure. RESULTS: Different ablation thresholds for various corneal structural elements were observed. The ablation threshold for the collagen in the corneal stroma was determined to be 30 mJ/cm2. Keratocytes had ablation thresholds of 40 mJ/cm2. These different ablation thresholds accounted for the production of stromal peaks and valleys, with the keratocytes atop the peaks. CONCLUSIONS: Different corneal structural elements have different ablation threshold energy densities.

Collagen↗
PubMed1999

Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET.

BACKGROUND: Amplified DNA probes provide powerful tools for the detection of infectious diseases, cancer, and genetic diseases. Commercially available amplification systems suffer from low throughput and require decontamination schemes, significant hands-on time, and specially trained laboratory staff. Our objective was to develop a DNA probe system to overcome these limitations. METHODS: We developed a DNA probe system, the BDProbeTecTMET, based on simultaneous strand displacement amplification and real-time fluorescence detection. The system uses sealed microwells to minimize the release of amplicons to the environment. To avoid the need for specially trained labor, the system uses a simple workflow with predispensed reagent devices; a programmable, expandable-spacing pipettor; and the 96-microwell format. Amplification and detection time was 1 h, with potential throughput up to 564 patient results per shift. We tested 122 total patient specimens obtained from a family practice clinic with the BD ProbeTecET and the Abbott LCx(R) amplified system for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Based on reportable results, the BDProbeTecET results for both organisms were 100% sensitive and 100% specific relative to the LCx. CONCLUSIONS: The BDProbeTecET is an easy-to-use, high-throughput, closed amplification system for the detection of nucleic acid from C. trachomatis and N. gonorrhoeae and other organisms.

Chlamydia trachomatis↗
PubMed1999

Medical packaging: more for less?

The market for medical devices is governed by the need to have validated products and processes, clean manufacturing environments and proven shelf-life. All this, often for products that are disposable, low-unit-cost items and, as such, highly price sensitive. This, in turn, has an impact on the businesses supplying the market. This article considers one such supply market, packaging, and the steps taken by packaging manufacturers to respond to these pressures while maintaining long-term, viable products.

Cost-Benefit Analysis↗
PubMed1999

Attaining role confirmation in nurse practitioner practice.

Although nurse practitioners (NPs) as a collective group have reached the stage of role confirmation, in new settings they must transition through several phases of role development. The role confirmation issues for a team of NPs who were hired to work in a large academic teaching hospital in the Southeastern part of the United States are explored over a 3-year period. Characteristics of the organization and strategies that the NPs implemented over time impacted favorably on the evolution of the NP role in that setting. The NPs gained prescriptive privileges, independent practice, and market-place salaries. Effective negotiation and marketing strategies enhanced both personal and professional development.

Academic Medical Centers↗
PubMed1998

Numbers of deaths related to intrapartum asphyxia and timing of birth in all Wales perinatal survey, 1993-5.

OBJECTIVES: To investigate the relation between the timing of birth and the occurrence of death related to an intrapartum event. DESIGN: Analysis of 107,206 births to Welsh residents in 1993-5, including 608 cases of stillbirth and 407 of neonatal death identified in the all Wales perinatal survey, the cause of death classified with the clinicopathological system. SUBJECTS: 79 normally formed babies stillborn or who died in the neonatal period, birth weight > 1499 g, for whom cause of death was related to an intrapartum event. MAIN OUTCOME MEASURES: Relative risk of death due to an intrapartum event according to the hour, day, and month of birth. RESULTS: Mortality was higher in babies born between 9.00 pm and 8.59 am than in those born between 9.00 am and 8.59 pm; relative risk (95% confidence interval) 2.18 (1.37 to 3.47). July and August births also had a higher death rate than births in other months; relative risk 1.99 (1.23 to 3.23). Weekened births had a higher death rate but it was not significant. CONCLUSIONS: The excess of deaths at night and during months when annual leave is popular may indicate an overreliance on inexperienced staff at these times. Errors of judgement may also be related to physical and mental fatigue, demanding a more disciplined systematic approach at night. Mistakes may be ameliorated by increasing shiftwork, but shifts should be carefully designed to avoid undue disruption of circardian rhythms. In addition, greater supervision by senior staff may be required at night and during summer months.

Asphyxia Neonatorum↗
PubMed1998

New AUG initiation codons in a long 5' UTR create four dominant negative alleles of the Drosophila C2H2 zinc-finger gene ovo.

Promoters active in the germline produce OVO-A and OVO-B mRNAs encoding isoforms of a putative transcription factor. The isoforms have a common C2H2 zinc-finger domain but different N-termini that include potential effector domains. Single point mutations in three dominant-negative ovoD mutations result in new in-frame initiation codons in OVO-B mRNAs and amino acid substitutions within charged regions of OVO-A proteins. Three lines of evidence suggest that the dominant activity is due to the new initiation codons in OVO-B mRNAs and not the amino acid substitutions in OVO-A. First, we made a fourth ovoD allele by inserting a new in-frame AUG. This ovoD4 allele encodes a nearly full-length OVO-A isoform from OVO-B mRNAs. Second, engineered stop codons in ovoD1 downstream of the new AUG abolished dominant negative activity. Third, a substantial deletion of an OVO-A region encoding a highly charged amino acid domain fully rescued loss-of-function ovo alleles. These data suggest that ovoD mutations result in inappropriate expression of OVO-A in the female germline.

Alleles↗
PubMed1998

Drosophila OVO zinc-finger protein regulates ovo and ovarian tumor target promoters.

The ovo+ and ovarian tumor+ genes function in the germline sex determination pathway in Drosophila, but the hierarchical relationship between them is unknown. We found that increased ovo+ copy number resulted in increased ovarian tumor expression in the female germline and increased ovo expression in the male germline. The ovo locus encodes C2H2 zinc-finger proteins. Bacterially expressed OVO zinc-finger domain bound to multiple sites at or near the ovo and ovarian tumor promoters strongly suggesting that OVO is directly autoregulatory and that ovarian tumor is a direct downstream target of ovo in the germline sex determination hierarchy. Both positive and negative regulation by OVO proteins appears likely, depending on promoter context and on the sex of the fly. Our observation that two strong OVO-binding sites are at the initiator of the TATA-less ovo-B and ovarian tumor promoters raises the possibility that OVO proteins influence the nucleation of transcriptional pre-initiation complexes.

Amino Acid Sequence↗
PubMed1998

Interactional processes in families with depressed and non-depressed adolescents: reinforcement of depressive behavior.

Problem-solving interactions were observed in 86 families of depressed adolescents and 408 families of non-depressed adolescents. Sequential analyses indicated that mothers of depressed adolescents were more likely than mothers of non-depressed adolescents to increase facilitative behavior in response to adolescent depressive behavior. Additionally, fathers of depressed adolescents were more likely than their counterparts in families of non-depressed adolescents to decrease aggressive behavior subsequent to adolescent depressive behavior. These analyses suggest that parents of depressed adolescents may be inadvertently reinforcing depressive behavior. Decreases in adolescent depressive symptomatology from year 1 to year 2 were not accompanied by changes in family interaction patterns.

Adolescent↗