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Biomedical subjects

P Ryan

Publications and source records attributed to P Ryan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Venlafaxine in depressed geriatric outpatients: an open-label clinical study.

A 12-month open-label clinical trial was conducted to evaluate patient acceptance and safety of venlafaxine, a novel antidepressant, in ambulatory geriatric depressed patients. The sample consisted of 58 depressed patients aged 65 years and older who needed long-term antidepressant treatment. The setting was multiple study sites in California, Florida, New York, Utah, and Washington. All patients took venlafaxine; 52 qualified for the intent-to-treat analysis, and 24 completed 12 months of treatment. Repeated-measures analysis of variance within subjects showed significant improvements in Clinical Global Impressions severity and improvement, Modified Symptom Checklist, and Quality of Life Questionnaire scores. One patient developed a rash that was judged to be a serious drug-related side effect. The most common side effects were headache (n = 25), nausea (n = 21), insomnia (n = 18), dry mouth (n = 18), and sweating (n = 18). The results demonstrate the safety and patient acceptance of venlafaxine in depressed geriatric outpatients for acute and maintenance treatment.

Aged↗
PubMed1994

Can a signal sequence become too hydrophobic?

We have characterized several mutants that contain alterations in the hydrophilic domain (N region) of the pseudorabies virus glycoprotein gC signal sequence. In general, our results agree with previous findings and indicate that basic residues in the N region are not essential for efficient export of gC in infected cells. While reducing the N region to a net neutral charge led to a slight impairment of membrane translocation, a substantial gC export defect was not observed until a net negative charge was introduced. However, there was one exception to this pattern. The substitution of a leucine for an arginine at the carboxyl terminus of the N region led to a considerable export defect despite maintaining a net positive charge. As a consequence of the substitution, the mutant signal sequence was 1.5 times more hydrophobic than wild type, but we found that the defect could be largely corrected if an additional alteration that lessened the overall hydrophobicity of the gC signal sequence was incorporated. We suggest that an upper limit of hydrophobicity may exist for eukaryotic signal sequences; exceeding this value could lead to an export defect.

Amino Acid Sequence↗
PubMed1994

Neural tube defects and maternal serum zinc and copper concentrations in mid-pregnancy: a case-control study.

OBJECTIVE: To assess the relationship between mid-pregnancy maternal serum zinc and copper concentrations and neural tube defects. DESIGN: A prospective case-control study during 1978-1988 within a statewide hospital-based neural tube defect screening program measuring maternal serum alpha-fetoprotein levels at mid-pregnancy. SUBJECTS: Cases were 69 women with fetuses with confirmed neural tube defects. Controls were 592 women with fetuses without neural tube defects who were individually matched to cases for hospital, calendar date of screening, age and parity; there was a variable control-to-case ratio. RESULTS: For both unmatched and adjusted matched analyses, mean maternal serum zinc concentration was higher in cases than controls (P = 0.02 and P = 0.03, respectively). There were no case-control differences for serum copper concentrations. Conditional logistic regression analysis showed a (statistically non-significant) 50% increase in risk of neural tube defects in women whose serum zinc concentration was more than two standard deviations above the population mean. CONCLUSION: Within the normal range of maternal serum zinc and copper concentrations there is no variation in risk of neural tube defects. However, women with very high serum zinc levels may have an increased risk of neural tube defects. This could reflect deficient maternal-to-fetal transfer of zinc in some of those individuals. Any such phenomenon would be manifest in observational, but not experimental, studies.

Adult↗
PubMed1994

Characterization of the prv43 gene of pseudorabies virus and demonstration that it is not required for virus growth in cell culture.

We have determined the complete DNA sequence of the prv43 gene of a swine herpesvirus, pseudorabies virus. prv43 is 1119 bp in length with a G+C content of 74.5% and is predicted to encode a multiply hydrophobic protein with a molecular mass of 38 kDa. prv43 is colinear with the herpes simplex virus type 1 UL43 locus, and the prv43 and UL43 gene products are predicted to be 47% similar and 23% identical. prv43 is an early gene, producing a 1.2-kb transcript that is easily detected at 2 hr postinfection but not at 6 hr postinfection. We have constructed a prv43 deletion mutant that does not express a prv43 transcript. This mutant did not appear to be defective for viral growth and demonstrated that the gene is nonessential for virus growth in cell culture.

Amino Acid Sequence↗
PubMed1994

The use of inhaled radioisotopes for measuring the effect of sputum induction on tracheobronchial clearance rates.

Inhaled radioisotopes were employed to study the role of tracheobronchial clearance in sputum induction, a technique used to diagnose Pneumocystis carinii pneumonia in patients with acquired immune deficiency syndrome (AIDS). Seven normal nonsmoking male subjects inhaled a nebulized aerosol of technetium-labelled human serum albumen, which was cleared from the lung solely by tracheobronchial clearance. The aerosol's particle size distribution ensured both alveolar and proximal airway deposition, the site of P. carinii organisms and tracheobronchial clearance mechanisms, respectively. Pulmonary emission counts were measured for 12 continuous 5-min periods before, and immediately after, sputum induction with nebulized 3% saline. A further 10-min scan was performed at 24 h to determine the alveolar fraction of deposited aerosol. Tracheobronchial clearance rates (log10[activity]/time) were calculated after log linear regression, for the time periods before, during and after sputum induction, having corrected for isotope decay and alveolar deposition. Results were analysed by the Wilcoxon rank sum test. Tracheobronchial clearance rates increased significantly in all subjects during sputum induction, with a mean 65.5% reduction in pulmonary activity over this period. Mean clearance gradients for the three time periods before, during and after sputum induction were -1.2 x 10(-3) min-1, -15.0 x 10(-3) min-1 and 0.4 x 10(-3) min-1, respectively (P < 0.025), which probably underlies the principal mechanism for success of the technique.

Administration, Inhalation↗
PubMed1994

Spontaneous fusions to prv43 can suppress the export defect of pseudorabies virus gIII signal peptide mutants.

We have devised an enrichment scheme for the isolation of export-competent derivatives of pseudorabies virus glycoprotein gIII signal peptide mutants. Enrichment is based upon a growth advantage imparted upon gIII-containing virions compared with virions lacking the glycoprotein. Each of identified derivatives suppressed the gIII signal peptide defect by fusing the gIII gene in frame to the prv43 gene that lay immediately upstream; the result was the synthesis of a Prv43-gIII hybrid protein. The deduced Prv43 protein is predicted to span a membrane multiple times, and it appeared that the gIII portion of each hybrid used a hydrophobic domain of Prv43 protein to initiate its export. For at least two of the isolates, the hybrid protein was efficiently translocated across the endoplasmic reticulum membrane but appeared to be poorly exported out of the endoplasmic reticulum. Nonetheless, the prv43-gIII fusions encoded a gIII species that was localized to the virus envelope. Because the gIII portion of each hybrid protein must be exposed on the virion surface to provide a growth advantage, our results also suggest a preliminary membrane topology for wild-type Prv43 protein.

Amino Acid Sequence↗
PubMed1994

Cancer pain: knowledge, attitudes of pharmacologic management.

The knowledge of, attitudes toward, and perceived barriers to pharmacologic management of cancer pain were compared between oncology nurses (N = 128) and long-term care facility (LTCF) nurses (N = 72) using an 82-item questionnaire. The oncology nurses were significantly more knowledgeable about pharmacologic management of cancer pain than were the nurses in LTCFs. However, the two groups did not differ in their attitudes toward pain management, with the exception that nurses in LTCFs were more likely to believe that patients over-report their pain. LTCF nurses were more likely than the oncology nurses to believe that inadequate assessment of pain, lack of equipment, and lack of skills to use equipment were impediments to pain management.

Adult↗
PubMed1993

Nosocomial pneumonia during stress ulcer prophylaxis with cimetidine and sucralfate.

BACKGROUND: Recent studies have questioned the use of histamine (H2) receptor antagonist in stress ulcer prophylaxis because of an increased incidence of nosocomial pneumonia and subsequent death. DESIGN: This prospective randomized study compared prophylaxis with cimetidine vs sucralfate. SETTING: Medical/surgical intensive care unit in Springfield, Mass. PATIENTS: One hundred fourteen patients were enrolled. INTERVENTIONS: Cimetidine, administered as a primed continuous infusion using a 300-mg bolus followed by 37.5 mg/h, was compared with sucralfate, administered via nasogastric tube, at a dosage of 1 g every 6 hours suspended in 20 mL of sterile water. MAIN OUTCOME MEASURES: End points of the study included nosocomial pneumonia, gastrointestinal hemorrhage, and death. RESULTS: Fifty-six patients were randomized to receive cimetidine and their rate of pneumonia was 12.5%; upper gastrointestinal hemorrhage, 3.6%; and mortality, 33.9%. Fifty-eight patients were given sucralfate, and their rate of pneumonia was 13.8%; upper gastrointestinal hemorrhage, 3.4%; and mortality, 37.9%. There were no significant differences between these study end points. In patients who had pneumonia, 80% of isolates were aerobic gram-negative bacilli. CONCLUSIONS: These observations suggest that the rate of nosocomial pneumonia is not increased in patients in the intensive care unit who receive prophylaxis with cimetidine to prevent stress ulcer bleeding.

Administration, Oral↗
PubMed1993

Overall signal sequence hydrophobicity determines the in vivo translocation efficiency of a herpesvirus glycoprotein.

We have described three mutant strains of Pseudorabies virus that contain mutations in the signal sequence coding region of a nonessential envelope glycoprotein, gIII. The alterations disrupt, truncate, or eliminate the hydrophobic core domain of the signal sequence. Each mutant was assayed for its ability to promote the translocation of gIII across the endoplasmic reticulum membrane and the subsequent localization of the mature form of the glycoprotein to the infected cell surface or the virus envelope. Our results confirm and extend findings in other systems that the overall hydrophobicity of the signal sequence core region is a major determinant of translocation efficiency. We were unable to correlate simply the length of the core or the average hydrophobicity of core residues with export efficiency. Because our work involved the use of infectious virus mutants, we were able to identify a virus defect associated with a complete block in gIII export. This defect will facilitate a pseudo-reversion analysis of gIII signal sequence function.

Amino Acid Sequence↗
PubMed1993

Tumours of the brain and presence of antibodies to Toxoplasma gondii.

The possible association between prior infection with the protozoan Toxoplasma gondii and development of brain tumours was investigated as part of two Australian population-based case-control studies of adult brain tumours. One study, based in Adelaide, South Australia, collected blood from 73 subjects with glioma, 53 subjects with meningioma and 348 controls. The other study, based in Melbourne, Victoria, collected blood from 44 subjects with glioma and 67 controls. All tumours had been verified histologically. IgG antibodies to T. gondii were measured using Enzyme Linked Immunosorbent Assay (ELISA) techniques. In both the centre-specific and combined analyses, there was no difference between subjects with glioma and controls in the prevalence of antibody test-positivity (35% test-positive in glioma versus 33% in controls, age-, sex- and centre-adjusted odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.64-1.56). In the Adelaide study, there was a statistically significant increased risk of meningioma associated with antibody test-positivity (47% test-positive in meningioma versus 31% in controls, P = 0.02, adjusted OR = 2.09, 95% CI: 1.14-3.83). Our results do not support the hypothesis that antibody positivity to T. gondii is a risk factor for glioma, but suggest that it might be associated with meningioma.

Adult↗
PubMed1993

The amino-terminal one-third of pseudorabies virus glycoprotein gIII contains a functional attachment domain, but this domain is not required for the efficient penetration of Vero cells.

We have examined the attachment and penetration phenotypes of several glycoprotein gIII mutants of pseudorabies virus (PRV) and have identified the first one-third of gIII as a region that mediates efficient virus attachment to PK15 and Vero cells. This portion of gIII, amino acids 25 through 157 of the wild-type sequence, appeared to support attachment by binding to heparinlike molecules on cell surfaces. Virions containing the first one-third of gIII were sensitive to heparin competition and showed greatly reduced infectivity on cells treated with heparinase. PRV virions lacking the first one-third of the mature glycoprotein exhibited only residual binding to cells if challenged by vigorous washing with phosphate-buffered saline at 2 h postinfection at 4 degrees C. This residual binding was resistant to heparin competition, and strains lacking the first one-third of gIII were able to infect cells treated with heparinase as effectively as untreated cells. When we determined the penetration phenotypes for each strain, we found that gIII-mediated virus attachment was necessary for timely penetration of PK15 cells but remarkably was not required for efficient virus penetration of Vero cells. Moreover, wild-type PRV was actually prohibited from rapid penetration of Vero cells by a gIII-heparan sulfate interaction. Our results indicate that initial virus binding to heparan sulfate via glycoprotein gIII is not required for efficient PRV infection of all cell types and may in fact be detrimental in some instances.

Amino Acid Sequence↗
PubMed1993

A suburban focus of endemic typhus in Los Angeles County: association with seropositive domestic cats and opossums.

Thirty-three cases of locally acquired murine typhus were reported in Los Angeles County residents from May 1984 through February 1988. Only eight cases were reported over the previous 20-year period. Thirty (91%) cases resided within a suburban area encompassing approximately 50 km2 in northcentral Los Angeles or had contact with an animal from this area. Serologic testing (complement fixation and indirect fluorescent antibody) of selected animals in close association with human cases revealed a high prevalence of seropositivity among domestic cats and opossums. Nine (90%) of 10 resident cats tested had demonstrable antibody titers compared with none (0%) of 20 cats from a control area (P < 0.001). Suburban typhus cases were more likely than neighborhood controls to own a cat or dog (odds ratio = 6.9, 95% confidence interval = 1.8, 25.9, P = 0.002). Sixteen (42%) of 38 opossums trapped in close proximity to the residences of cases were seropositive versus none (0%) of 36 opossums from control areas (P < 0.001) A low frequency (2.8%) of seropositivity was found in commensal rodents, and the classic vector of murine typhus, Xenopsylla cheopis, was not found. Ectoparasite indices form seropositive opossums revealed heavy infestations with the cat flea, Ctenocephalides felis (mean flea count = 104.7), a species that readily bites humans. These data provide evidence that a suburban focus of murine typhus exists in Los Angeles that differs substantially from the classic transmission cycle, and that cats, opossums and C. felis may play an important role in the occurrence of human cases.

Adolescent↗
PubMed1993

Southern California Edison's performance standards: an employer's key to quality care delivery.

One of the most significant lessons learned from this process is that setting objectives with performance standards is the key to continuous quality improvement. The critical differences between health administration and health management are threefold: (1) performance standards are developed with clarity, (2) care delivery is monitored and measured against these standards, and (3) improvements are made based on information from these measurements.

California↗