Definition of an advanced nursing practice role in the NICU: the clinical nurse specialist/neonatal practitioner.

We surveyed 655 health professionals affiliated with tertiary level neonatal intensive care units in Canada and the United States to define an expanded role for nurses in neonatology and to determine the educational requirements for the role. The role, comprising advanced clinical practice, educational, research, and administrative responsibilities, is a blend of nurse practitioner and clinical nurse specialist activities. Based on survey findings, a neonatal stream within the existing Master of Health Sciences program at McMaster University was developed. To date, 15 clinical nurse specialists/neonatal practitioners (CNS/NPs) are employed in five neonatal intensive care units in Ontario and other related institutions. A randomized trial to evaluate these individuals is in progress.     

Aromatase and its inhibitors in breast cancer treatment — overview and perspective

Summary Estrogen has an important role in stimulating the growth of breast carcinomas. Inhibition of estrogen production is therefore a logical treatment strategy. A number of selective inhibitors have been developed against aromatase, a cytochrome P-450 enzyme which catalyzes the rate limiting step in the biosynthesis of estrogens. The mechanisms of the aromatase reaction, current knowledge of the enzyme, and regulation of its expression are discussed as the basis for inhibitor development. Two classes of aromatase inhibitors, steroidal and non-steroidal compounds, are now coming into use. Among the steroid substrate analogues, 4-hydroxyandrostenedione (4-OHA) has been shown to be effective in breast cancer patients with advanced disease and was recently approved for treatment in the United Kingdom. Several different classes of compounds which act as aromatase inhibitors are currently in clinical trials and should provide breast cancer patients with a number of treatment options. Among these are highly potent and selective non-steroidal inhibitors which have recently been found to suppress plasma and urinary estrogens over 95% in breast cancer patients. The potency of these newer aromatase inhibitors provides the opportunity to determine whether complete suppression of estrogen production and action will result in enhanced tumor regression.     

Biphasic effect of GABAA receptor agonists on prolactin secretion: evidence for two types of GABAA receptor complex on lactotrophes

The effects of GABA receptor agonists on prolactin secretion in vitro was examined using a rapid superfusion system. GABA and muscimol caused a biphasic effect on prolactin secretion, both components of which were antagonised by bicuculline methiodide, while baclofen had no effect on basal or stimulated secretion, demonstrating the GABAA receptor specificity of both components. Homocarnosine caused only inhibition of secretion, and a range of partly rigid GABA analogues were relatively poor at causing stimulation of secretion. Both effects of muscimol were antagonised by low-chloride medium and the anion channel blocker DIDS, but strychnine and picrotoxinin were both potent and selective antagonists of the stimulatory effect. These results demonstrate a novel biphasic effect of GABAA agonists or prolactin secretion, the two components of which appear to be independent and mediated by different types or states of GABAA receptor/chloride channel complex.     

Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis.

We have investigated the molecular basis of the marked elevation in erythrocyte adenosine deaminase (ADA) activity in a kindred with hereditary hemolytic anemia. Red cell ADA-specific activity was verified to be 70- to 100-fold normal levels. Western blots demonstrated a corresponding increase in erythrocyte ADA-specific immunoreactive protein. Analysis of genomic DNA revealed no evidence for amplification or major structural changes in the ADA gene. ADA-specific messenger RNA (mRNA) from proband reticulocytes was comparable in size and amount to mRNA from control reticulocytes. Translation of proband poly A+ reticulocyte mRNA in a rabbit reticulocyte lysate system and immunoprecipitation of 35S-labeled protein products with anti-ADA antibody yielded a band of approximately 42,000 apparent mol wt that was absent in translation products from control reticulocyte mRNAs. These data suggest that the increased ADA activity in red cells in this disorder results from the increased translation of an aberrant ADA mRNA.     

Caring for patients with traumatic injuries of the thoracic aorta.

Trauma is a major cause of mortality and morbidity in the United States, with blunt traumatic injuries of the thoracic aorta continuing to occur despite the increased use of seatbelts and airbags. Emerging from crash analysis are effective interventions and provides increased awareness of the occult nature of these types of injuries. This article describes those interventions that healthcare providers must embed throughout the continuum of care for patients experiencing thoracic aortic injuries. Outcomes will be dependent upon the healthcare provider's knowledge of the physics of the event and the urgency of the diagnosis, as well as the ability to assess and manage all the variables involved. Current procedural issues are delineated and case studies are used to illustrate the processes of care needed by these patients.     

A comparison of pregnancy outcome in overweight and normal weight women

From a population of singleton pregnancies, 152 overweight women (greater than 110% of standard) were matched with normal weight women (95-110%) for age, height, parity, race, and smoking habits. Comparisons were made of initial weight (weight at the first prenatal visit) and gestational weight gain and pregnancy outcome. Mean birth weights and gestational ages of infants of normal and overweight women were not significantly different. For normal weight women birth weight increased significantly as height, initial weight, and body mas index increased (p less than 0.01), but no such relationship existed for overweight women. The lack of effect of initial weight on birth weight in overweight women is attributable, in part, to the significantly less gestational weight gains of these mothers (6.3 kg vs 8.2 kg). When normal and overweight gravida had gestational weight gains of less than 7 kg, offspring of overweight mothers were significantly heavier. Gestational weight gain was positively correlated with birth weight for both normal (p less than 0.0001) and overweight women (p less than 0.001). Within the overweight and normal weight groups, smokers had lower initial weights and gestational weight gains than nonsmokers. Offspring of normal weight smokers had a mean birth weight 232 g less than that of nonsmokers (p less than 0.01). The difference in birth weight between overweight smokers and nonsmokers (135 g) was not statistically significant. While there is substantial data to support a weight gain of 10-12 kg in normal weight gravida, it would appear that a gain of approximately 7 kg in overweight middle class women does not impair fetal growth as measured by birth weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine and amine responses to D,L-fenfluramine in normal subjects.

To investigate indirectly the central neurotransmitter mechanisms of D,L-fenfluramine-induced hormone release, prolactin, adrenocorticotropic hormone, cortisol, growth hormone, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) responses to D,L-fenfluramine (60 mg, oral) were examined in a single-blind, placebo-controlled trial in 14 normal subjects. As compared with placebo, D,L-fenfluramine significantly increased both prolactin and cortisol. There was a significant correlation between the cortisol and prolactin responses. HVA levels were also significantly increased, but there were no changes in MHPG or 5HIAA. The elevation in HVA significantly correlated with increases in both prolactin and cortisol. These findings are consistent with recent animal studies suggesting that D,L-fenfluramine-induced prolactin and cortisol release may be mediated, at least in part, by catecholaminergic systems.     

Effects of improved contrast on lung-nodule detection. A clinical ROC study

We evaluated the effects of unsharp masking and highly efficient scatter rejection on film-screen chest radiographs of cancer patients. Unsharp masking significantly improved the detectability of lung nodules and visibility of anatomic structures in poorly penetrated areas of the chest. Highly efficient scatter rejection by an improved antiscatter grid provided only modest additional benefits. The study supports the conclusion that nodule detection in poorly penetrated areas on conventional chest radiographs is limited primarily by display contrast, whereas in the well-penetrated lung fields it is limited primarily by confusing background structures, rather than inadequate contrast. A method for analyzing clinical nodule detection data by transforming the FROC data to ROC coordinates also is demonstrated.     

Interactions Between Cytomegalovirus, Human Herpesvirus-6, and the Recurrence of Hepatitis C After Liver Transplantation

Recurrence of hepatitis C (HCV) following liver transplantation is common. Herpesvirus reactivation following transplant may have an immunomodulatory effect resulting in increased HCV replication. We studied whether cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) may be associated with HCV recurrence and viral load after transplant. We prospectively followed 66 HCV liver-transplant recipients with serial viral load testing for CMV and HHV-6. Infection and viral load were correlated with the development of biopsy-proven HCV recurrence and HCV viral loads. Histologic recurrence of HCV occurred in 41/66 (62.1%) patients. In the primary analysis, CMV infection and disease, and HHV-6 infection were not associated with HCV recurrence. Peak CMV and HHV-6 viral loads were not significantly different in patients with and without recurrence. No correlation was observed between HCV viral loads at 1 and 3 months post-transplant and peak HHV-6 or CMV viral loads. In a subgroup analysis, HHV-6 infection was associated with the development of more severe recurrence (hepatitis and/or fibrosis score > or = 2) (p = 0.01). Also, fibrosis scores at last follow up were higher in patients with CMV disease (1.67 vs. 0.56; p = 0.016) and in patients with HHV-6 infection (1.18 vs. 0.55; p = 0.031). In conclusion, HHV-6 and CMV infection and viral load were not associated with increased overall rates of HCV recurrence or HCV viral load after liver transplantation but may be associated with more severe forms of recurrence.