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Biomedical subjects

M Brennan

Publications and source records attributed to M Brennan.

At least 37 records · Page 2Linked to original sources

Cytokine expression in human labial minor salivary gland epithelial cells in health and disease.

Microdissection of biopsy material from labial minor salivary glands followed by RT-PCR demonstrates extensive production of cytokines IL-2, 1L-6, IL-10, TNF-alpha, TGF-beta, and IFN-gamma in both normal glands and in glands affected by Sjögren's syndrome. Continuation of these studies should expand our knowledge of normal salivary gland function and the pathogenesis of Sjögren's syndrome.

Autoimmune Diseases↗

Epidemiology of epidemic diphtheria in three regions, Russia, 1994-1996.

BACKGROUND: A massive diphtheria epidemic which began in the former Soviet Union in 1990 is the first large-scale diphtheria epidemic in developed countries in more than 30 years and has primarily affected adults. In response, health authorities attempted to maximize vaccination for children and conducted an unprecedented campaign to vaccinate adults. METHODS: We analyzed diphtheria surveillance data (case report forms and diphtheria vaccine coverage data) from three Russian regions from January 1994 to December 1996 and estimated vaccine effectiveness by the screening method. RESULTS: We reviewed records from 2243 (97.2%) of 2307 reported cases. The highest cumulative incidence in the period was among children aged 5 to 9 years (106 cases per 100,000 population); adults aged 40-49 years had the highest adult incidence for disease (88 cases per 100,000) and the highest incidence of any age group of clinically severe disease (29 cases per 100,000) and death (5.1 deaths per 100,000). The incidence among women aged 2049 years (82 per 100,000 women) was higher than among men (47 per 100,000, p<0.01). The annual incidence decreased from 25.2 cases per 100,000 population in 1994 to 9.4 cases per 100,000 in 1996. The decrease occurred as adult coverage increased from an estimated 25-30% in December 1992 to 88% in December 1995. Vaccine effectiveness was high among both children and adults. CONCLUSIONS: The Russian diphtheria epidemic primarily affected adults, especially women; this pattern is likely representative of diphtheria epidemics in immunized populations. Raising childhood immunization coverage and mass adult vaccination was effective in controlling the Russian epidemic. An improved understanding of the current epidemiology of diphtheria will be useful to design public health responses to prevent or control modern epidemics.

Adolescent↗

Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults, 1990-1996.

Since 1990, the reported incidence of pertussis has increased in the United States with peaks occurring every 3-4 years. On the basis of analysis of pertussis cases reported to the Centers for Disease Control and Prevention, the incidence remained stable among children aged younger than 5 years, most of whom were protected by vaccination. In contrast to 1990-1993, during 1994-1996, the average incidence among persons aged 5-9 years, 10-19 years, and 20 years or older increased 40%, 106%, and 93%, respectively. Since 1990, 14 states reported pertussis incidences of > or =2 cases per 100,000 population during at least 4 years between 1990 and 1996; seven of these states also reported that a high proportion of cases occurred in persons aged 10 years or older. Analysis of national data on pertussis did not provide sufficient information to fully elucidate the relative importance of multiple possible explanations for the increase in the incidence of pertussis in adolescents and adults. Improvement in diagnosis and reporting of pertussis in this age group, particularly in some states, is an important factor contributing to the overall increase.

Adolescent↗

Use of flexible intermediate and intensive care to reduce multiple transfers of patients.

OBJECTIVE: To test an alternative flexible approach to traditional fixed intermediate and intensive care to minimize transfers of patients. METHODS: Patients admitted to a 28-bed nursing unit with intermediate care potential and a 12-bed intensive care unit at a 300-bed teaching community hospital were studied. The group included 524 patients with a discharge diagnosis code for mechanical ventilation. During eight 3-week cycles, 1073 transfers of patients were tabulated. A plan-do-study-act method was used to improve weaning from mechanical ventilation and reduce the number of inappropriate days in intensive care. Admissions and transfers to the 2 units for all patients during the eight 3-week cycles were compared over time. Length of stay and mortality were noted for all patients treated with conventional and noninvasive ventilation. RESULTS: Direct admissions to the flexible intermediate unit increased with no overall change in admissions to the intensive care unit. Fewer patients needed conventional ventilation, and more in both units were treated with noninvasive ventilation. The median number of transfers per patient treated with mechanical ventilation decreased from 1.94 to 1.20. Length of stay and mortality also decreased among such patients. Some cost savings were attributable to the decrease in the number of transfers. Transfers out of the hospital directly from the intensive care unit increased from 2.24% to 4.43%. CONCLUSIONS: In a community teaching hospital, flexible care policies decreased the number of in-hospital transfers of patients treated with mechanical ventilation.

Critical Care↗

Overexpression, purification, and stereochemical studies of the recombinant (S)-adenosyl-L-methionine: delta 24(25)- to delta 24(28)-sterol methyl transferase enzyme from Saccharomyces cerevisiae.

The ERG6 gene that encodes (S)-adenosyl-L-methionine: delta 24(25)-to delta 24(28)-sterol methyl transferase (SMT) enzyme from Saccharomyces cerevisiae was introduced into plasmid pET23a(+) and the resulting native protein was overexpressed in BL21 (DE3) host cells under control of a T7 promoter. This enzyme was purified to apparent homogeneity by ammonium sulfate precipitation, anion exchange, and hydrophobic interaction chromatography. N-Terminal sequence analysis of the first 10 amino acids of the purified SMT protein confirmed the identity of the start triplet and expected primary structure. The enzyme exhibited a turnover number of 0.01/s and an isoelectric point of 5.95. A combination of Superose 6 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the purified SMT enzyme possessed a native molecular weight of 172,000 and was tetrameric. The purified SMT enzyme generated kinetics in which velocity versus substrate curves relative to zymosterol (preferred sterol acceptor molecule) and AdoMet were sigmoidal rather than hyperbolic, indicating enzyme cooperativity among the subunits. Studies on product formation using [27-13C]zymosterol and [2H3-methyl]AdoMet incubated with the pure SMT enzyme confirmed the reaction mechanism of sterol methylation to involve a 1,2-hydride shift of H-24 to C-25 from the Re-face of the original 24,25- double bond. Deduced amino acid sequence comparisons of the SMT polypeptide from S. cerevisiae with related sterol methyl transferase enzymes of plant and fungal origin indicate that there is a significant degree of similarity between these enzymes. Specifically, there is a conserved sequence (in yeast from amino acids ca. 79 to 92 which contains an YEXGWG motif; referred to as Region I) that is not present in other AdoMet-dependent methyl transferase enzymes.

Amino Acid Sequence↗

Coronary artery injection technique: a quantitative in vivo investigation using modern catheters.

To date, there have been no quantitative in vivo assessments of contrast volumes and injection rates using modern high flow catheters during coronary angiography. Contrast volumes (n = 554), injection durations (n = 563), and injection rates (n = 498) were collected during 88 cardiac catheterizations. With increasing cathetersize (6, 7, and 8 French), injection volume increased (P < 0.0001), duration decreased (P < 0.0001), and rate increased (P < 0.0001). Compared with injections into the right coronary artery, left coronary artery injections were larger (7.1 +/- 0.1 cc vs. 4.8 +/- 0.1 cc, p < 0.0001), longer (3.6 +/- 0.05 sec vs 3.0 +/- 0.07 sec, P < 0.0001) and faster (2.1 +/- 0.04 cc/sec vs. 1.7 +/- 0.06 cc/sec, P < 0.0001). Patients with a significant stenosis in the left main or proximal right coronary artery received less contrast (P < 0.0001) more slowly (P < 0.0001) over a similar duration of injection (P = NS). When collaterals arose from the injected artery, angiographers injected more contrast (P < 0.001) over a longer period (P < 0.0001) more slowly (P < 0.0001). Catheter size and the injected vessel's location and anatomy significantly affect coronary catheterization injection technique.

Angioplasty, Balloon, Coronary↗

The clinical relevance of hemoglobin, platelet, and serotonin changes in sequestered and circulating blood during cardiopulmonary bypass.

OBJECTIVE: To determine how hemoglobin (Hb), platelet, and serotonin concentrations change during cardiopulmonary bypass (CPB) in sequestered blood from the pulmonary artery compared with circulating systemic blood; and to determine the correlation between platelet and serotonin variability at the two sites and clinical outcome measurements related to hemodynamics and blood loss. DESIGN: A prospective clinical study. SETTING: A university hospital. PARTICIPANTS: Twenty patients undergoing elective aortocoronary bypass. INTERVENTIONS: Measurements of Hb, platelet, and serotonin concentrations were performed before, during, and after CPB on paired blood samples from the pulmonary artery and the radial artery. Hemodynamic measurements were recorded before and after CPB and chest tube drainage was recorded postoperatively. MEASUREMENTS AND MAIN RESULTS: The Hb, platelet, and serotonin concentrations were all significantly different between radial artery and pulmonary artery samples at the different measurement times (p < 0.001, analysis of variance [ANOVA] for repeated measures). Hb, platelet, and serotonin concentrations were all significantly increased in the pulmonary artery at the time of aortic cross-clamping compared with the corresponding radial artery blood samples (p < 0.0005, ANOVA). During the period of ischemic arrest, Hb was unchanged in the pulmonary artery and remained significantly increased compared with systemic blood (p < 0.0005, ANOVA). Serotonin concentrations in both systemic and sequestered pulmonary artery blood had significant correlation with cardiac index (CI), right ventricular ejection fraction (REF), and systemic vascular resistance index (SVRI; p < or = 0.006, least squares analysis). Postoperative chest tube drainage most closely correlated with the platelet counts measured in both the radial and pulmonary arteries at the start of CPB (p < 0.05, least squares analysis). CONCLUSION: During CPB, there were significant differences in Hb, platelet, and serotonin concentrations in sequestered pulmonary artery blood compared with circulating systemic blood. The initial differences and subsequent changes were most likely attributable to decreased hemodilution and a different pattern of platelet activation in the pulmonary artery blood compared with the systemic blood. Despite the hematologic differences, serotonin concentration and platelet counts in the pulmonary artery blood had significant correlation to indices of cardiac function and postoperative chest tube drainage, respectively. Platelet and serotonin changes in sequestered pulmonary artery blood were also associated with some of the adverse consequences of CPB.

Analysis of Variance↗

Multidisciplinary achievement: the collaborative approach to rapid cycle ICU and hospital change.

Multidisciplinary teams are different from the traditional team format in that representation and participation from various disciplines characterize the structure. In April 1996, a multidisciplinary group from Muhlenberg Regional Medical Center's intensive care unit learned methodology at the Institute for Health Care Improvement (IHI) Breakthrough Series in Adult Intensive Care. With the format learned, improvements in diverse areas such as ventilator management, intermediate care, clinical laboratory utilization, and others were accomplished. Continued support from an expert staff and utilization of on-line communication tools characterized this 15-month quality improvement endeavor. The end of the breakthrough series spurred the development of a hospital-wide collaborative cost containment team.

Clinical Protocols↗

Evaluation of PCR for diagnosis of melioidosis.

Previously published PCR-based diagnostic tests for melioidosis were evaluated for clinical usefulness. A Burkholderia pseudomallei 16S rRNA-derived primer set had a sensitivity approaching 100% for clinical samples from 22 culture-confirmed cases of melioidosis and enabled diagnosis of 3 culture-negative cases. However, samples from 10 of 30 inpatients from Royal Darwin Hospital with other diagnoses were positive by PCR, giving a specificity of 67% and a positive predictive value of only 70%. Although there are a number of intriguing possible explanations for our results, concerns of inappropriate therapy resulting from a positive result by PCR have led us to forgo the advantage of rapid PCR diagnosis for melioidosis until a better system is validated.

Humans↗

Sjögren's syndrome: a model for dental care in the 21st century.

The diagnosis and treatment of Sjögren's syndrome, which poses many severe complications, should be of critical interest to dentists, who are often the first practitioners to detect symptoms. Dentistry is an integral part of health care delivery for patients with this condition. Management of Sjögren's syndrome can be seen as a model for the expanded scope of dental care in the future.

Autoimmune Diseases↗

Nursing students with disabilities.

Nursing is a self-licensing profession with an ever-increasing responsibility to develop and sustain public trust. Thus, there is a need for nurses not only to be accountable and trustworthy but to be perceived by the public as accountable and trustworthy. Recognizing the special need for trust in caregivers, the Faculty of Health Professions at Dalhousie University has recently instituted a policy enabling its schools to suspend or terminate a student from a program based on the student's professional unsuitability. Unsuitability could include a type of conduct (criminal behavior, substance abuse or unethical behavior) or a health impairment that affects the student's ability to meet performance requirements. The challenge for the health profession schools, including Nursing, is to develop specific guidelines for implementing the policy. Guidelines on performance requirements for students with disabilities will be particularly difficult to define.

Crime↗

Prognostic significance of peripheral blood and bone marrow tyrosinase messenger RNA in malignant melanoma.

The objectives of this study were to evaluate the prognostic significance of reverse transcription PCR (RT-PCR) detection of tyrosinase mRNA in the peripheral blood (PB) and bone marrow (BM) of patients with stage II-IV malignant melanoma (MM). Seventy-three PB samples and 109 BM aspirates from 123 assessable patients with stage II-IV MM were analyzed for tyrosinase mRNA using nested RT-PCR. Twenty-five controls without MM were also evaluated. The RT-PCR results were correlated with overall survival (OS) and clinical stage. Overall, 23 of the 123 patients with MM (19%) had tyrosinase mRNA in their blood and/or BM. RT-PCR positivity was present in the PB of 9 of 73 patients (12%), whereas 18 of 109 (16.5%) had tyrosinase mRNA in their BM. All controls were tyrosinase PCR negative. There was no correlation between RT-PCR results and clinical stage. Within stage II, BM PCR-positive patients had a shorter median survival (24 months) than BM PCR-negative individuals (median not reached), with a P approaching significance (P = 0.06). There was a statistically significant correlation between blood PCR positivity and decreased overall survival (P = 0.03) in all patients. Blood PCR positivity was associated with a significantly decreased OS in stage II and III (P = 0.01 and 0.02, respectively) and was not a predictor of OS in stage IV. In multivariate analysis, blood RT-PCR for tyrosinase mRNA was found to be an independent predictor of survival (P = 0.03; risk ratio, 2.87). RT-PCR can specifically detect tyrosinase mRNA in the PB and BM of patients with MM. Blood RT-PCR is an independent predictor of overall survival in stage II-III MM. Additional studies are needed to define the potential role of this assay in the management of patients with advanced melanoma.

Adult↗

Pain as a predictor of outcome in patients with operable pancreatic carcinoma.

BACKGROUND: The purpose of our study was to evaluate the relationship between pain and resectability and survival in patients with operable pancreatic carcinoma. METHODS: Pain, pain intensity, and pain location were prospectively assessed in newly diagnosed patients with operable adenocarcinoma of the pancreas. Patients were evaluated before their first operation at a large tertiary care cancer center. Pain factors were then correlated with outcomes of surgery, including resectability and survival. RESULTS: Seventy-seven patients with operable pancreatic carcinoma were evaluated before operation. With the Memorial Pain Assessment Card and a demographic questionnaire, an analysis of analgesic use and pain prevalence and intensity were quantitated. Twenty-two (29%) of 77 patients reported no pain. Fifty-five had mild to severe pain. Moderately severe or greater pain (Memorial Pain Assessment Card Tursky scores of 5 or greater or visual analogue self-assessment pain intensity scores greater than 30) was found in 20 patients. Twenty-six (34%) patients had resectable disease. Of the 51 patients who did not have resections, 35 had metastatic disease. Locoregional unresectable disease without metastases was found in 16 patients. Resectability was correlated with the presence of pain (p = 0.04). The median survival for all patients was 6.7 months. Not surprisingly, patients undergoing resection had a significantly better median survival than did those whose disease was unresectable (5.5 versus 15.1 months). Pain before operation significantly predicted survival (median survival for those with pain, 5.7 months; for those without pain, 15 months; p = 0.003). Even among patients who underwent resection, the presence of pain was associated with a worse survival (21.9 months versus 9.2 months; p = 0.045). In a multivariate analysis the two significant variables were inability to undergo resection and presence of any pain. CONCLUSIONS: The presence of pain in newly diagnosed patients with potentially operable pancreatic cancer is an ominous predictor of resectability and of survival. Even if the patient can undergo resection, the presence of preoperative pain is associated with a poor prognosis. Patients with operable pancreatic cancer who present with pain, even those whose evaluation shows a likelihood of resectability, are at high risk for recurrence with an impaired survival compared with those patients without pain.

Adenocarcinoma↗

CD34 counts to predict the adequate collection of peripheral blood progenitor cells.

An essential prerequisite for successful procurement of sufficient autologous peripheral blood progenitor cells (PBPC) for engraftment is the optimal timing of collection. A number of surrogate markers of peripheral blood progenitor cells were analysed to identify a single test which could predict the optimum time to harvest, providing at least 2 x 10(6) CD34+ cells/kg patient body weight. The study comprised 95 patients undergoing varied mobilisation regimens with chemotherapy and G-CSF for both solid tumours and haematological malignancies. One hundred and fifty-seven PBPC harvests were collected. Full blood counts (FBC) and CD34+ cell enumeration was performed on blood samples taken during the mobilisation period and immediately prior to leucapheresis (pre-harvest). All PBPC collections were assayed for colony-forming cells and CD34+ cells in addition to a FBC. The white cell count on the day of harvest showed only weak correlation with the total number of CD34+ cells in the collection (r = 0.30). In contrast, the absolute number of circulating CD34+ cells strongly correlated with the CD34+ cell and CFU-GM yield of the corresponding apheresis product. Provided the mobilisation sample contained > or =20 x 10(6) CD34+ cells/ml, 94% of single collections, performed the following day, contained > or =2 x 10(6) CD34+ cells/kg.

Adolescent↗

A concept analysis of consent.

This paper considers the meaning of consent for nursing. Consent had traditionally been looked at in relation to the medical profession. The paper argues for patient advocacy and discusses issues of competency and advocacy and implications for practice. The paper then goes on to critique the process of concept analysis and suggests ways of proceeding with this vital development for nursing.

Ethics, Nursing↗

Comparison of in vivo red cell survival of donations collected by Haemonetics MCS versus conventional collection.

The Haemonetics Multicomponents System (MCS) cell separator allows concurrent donation of red cells in addition to platelets and/or plasma, thus increasing the versatility of apheresis donations. In vivo survival of autologous red cells obtained by MCS was compared with red cells collected conventionally. In this cross-over controlled study, five male volunteers donated one unit of red cells by MCS and one unit of whole blood by the conventional manual method, 3 months apart. After storing donations in SAG-M for 35 days under standard conditions, radioactive (51Cr)-labelled autologous red cells were injected into each donor. The post-transfusion recovery (PTR) of red cells at 24 and 48 h did not show any significant difference between red cells obtained manually and by MCS, indicating that processing differences have no detrimental effects on red cell survival.

Blood Donors↗