Investigation of aneuploidy induction in mouse oocytes following exposure to vinblastine-sulfate,pyrimethamine, diethylstilbestrol diphosphate,or chloral hydrate

The various causative and mechanistic phenomena associated with aneuploidy induction require considerable investigation to better understand the etiology of chromosome missegregation. We investigated the potential of vinblastine sulfate, pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate to induce numerical and structural chromosome changes in female mouse germ cells. Superovulated ICR mice were administered the compounds either by intraperitoneal injection or oral gavage, and oocytes were collected and processed for cytogenetic analysis 17 hr later. Vinblastine sulfate, administered i.p., induced a significant increase in the frequency of ovulated Ml oocytes and of hyperploid Mll oocytes compared to controls, but did not increase the frequency of structural aberrations. Pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate did not increase the frequency of numerical or structural chromosome changes in female mouse germ cells. © 1993 Wiley-Liss, Inc.     

A cluster of bacterial genes for anaerobic benzene ring biodegradation

A reductive benzoate pathway is the central conduit for the anaerobic biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction requires a large input of energy and this metabolic capability has, so far, been reported only in bacteria. To determine the molecular basis for this environmentally important process, we cloned and analyzed genes required for the anaerobic degradation of benzoate and related compounds from the phototrophic bacterium, Rhodopseudomonas palustris. A cluster of 24 genes was identified that includes twelve genes likely to be involved in anaerobic benzoate degradation and additional genes that convert the related compounds 4-hydroxybenzoate and cyclohexanecarboxylate to benzoyl-CoA. Genes encoding benzoyl-CoA reductase, a novel enzyme able to overcome the resonance stability of the aromatic ring, were identified by directed mutagenesis. The gene encoding the ring-cleavage enzyme, 2-ketocyclohexanecarboxyl-CoA hydrolase, was identified by assaying the enzymatic activity of the protein expressed in Escherichia coli. Physiological data and DNA sequence analyses indicate that the benzoate pathway consists of unusual enzymes for ring reduction and cleavage interposed among enzymes homologous to those catalyzing fatty acid degradation. The cloned genes should be useful as probes to identify benzoate degradation genes from other metabolically distinct groups of anaerobic bacteria, such as denitrifying bacteria and sulfate-reducing bacteria.     

Who among cytomegalovirus-seropositive liver transplant recipients is at risk for cytomegalovirus infection?

A vast majority of the transplant recipients are cytomegalovirus (CMV)-seropositive (R+). We sought to assess variables predictive of CMV infection, specifically in R+ liver transplant recipients. Study patients comprised 182 consecutive liver transplant recipients who survived at least 14 days after transplantation. Surveillance testing was used to detect CMV infection. Pre-emptive therapy was employed for the prevention of CMV disease, however, no antiviral prophylaxis was used for CMV infection. CMV infection developed in 32.5% (38 of 117) of R+ patients, 84.6% (33 of 39) of R-/D+, and 3.8% (1 of 26) of R-/D- patients. In R+ patients, Hispanic race (21.6% vs. 7.8%, P = 0.06), donor CMV seropositivity (73.7% vs. 45.6%, P = 0.005), and hepatocellular carcinoma (23.7% vs. 6.3%, P = 0.05) correlated with a higher risk of CMV infection. In a multivariate model, Hispanic race (OR: 3.5, 95% CI: 1.03-11.6, P = 0.045), donor CMV serostatus (OR: 4.0, 95% CI: 1.6-10.2, P = 0.003) and hepatocellular carcinoma (OR: 5.8, 95% CI: 1.6-20.5, P = 0.006) were all significant independent predictors of CMV infection. The aforementioned variables did not portend a higher risk of CMV infection in R-/D+ patients; donor CMV seropositivity overwhelmed all other risk factors in R- patients (P < 0.00001). In conclusion, CMV-seropositive liver transplant recipients at risk for CMV infection can be identified based on readily assessable variables. Preventive strategies may be selectively targeted toward these patients.     

Preparing faculty to use and develop computer-based instructional materials in nursing

This paper identifies the need for more specific guidelines in preparing faculty to use and develop computer-based instructional materials. Cory's model for faculty development is described and planning considerations are outlined. Finally, components of this multifaceted approach to faculty development—identifying available resources, emphasizing the current uses of computers, providing computer literacy/faculty awareness sessions, focusing on the instructional use of microcomputers, collaboration, and communication—are discussed.     

Nurse Migration from a Source Country Perspective: Philippine Country Case Study

Objectives. To describe nurse migration patterns in the Philippines and their benefits and costs.
Principal Findings. The Philippines is a job-scarce environment and, even for those with jobs in the health care sector, poor working conditions often motivate nurses to seek employment overseas. The country has also become dependent on labor migration to ease the tight domestic labor market. National opinion has generally focused on the improved quality of life for individual migrants and their families, and on the benefits of remittances to the nation. However, a shortage of highly skilled nurses and the massive retraining of physicians to become nurses elsewhere has created severe problems for the Filipino health system, including the closure of many hospitals. As a result, policy makers are debating the need for new policies to manage migration such that benefits are also returned to the educational institutions and hospitals that are producing the emigrant nurses.
Conclusions and Recommendations. There is new interest in the Philippines in identifying ways to mitigate the costs to the health system of nurse emigration. Many of the policy options being debated involve collaboration with those countries recruiting Filipino nurses. Bilateral agreements are essential for managing migration in such a way that both sending and receiving countries derive benefit from the exchange.     

Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome.

Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy. INTRODUCTION: Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD. MATERIALS AND METHODS: One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed. RESULTS: Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr. CONCLUSIONS: The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.     

Impact of smoking on cancer stage at diagnosis.

BACKGROUND: Studies evaluating the relationship between smoking and cancer spread are limited. METHODS: We studied the relationship between cancer stage at diagnosis (local, regional, or metastatic) and smoking history (current, previous, or nonsmoker). For lung cancer, patterns of spread were also studied. RESULTS: In a tumor registry for eastern North Dakota, northwestern Minnesota, and northern South Dakota, 11,716 cases were identified from 1986 to 2001. Current smokers (relative risk [RR], 2.11; 95% confidence interval, 1.93 to 2.32; P <.001) and previous smokers (RR, 1.56; 95% confidence interval, 1.42 to 1.72; P <.001) had an increased risk of metastatic disease at diagnosis. Current smokers (RR, 1.39; 95% confidence interval, 1.29 to 1.51; P <.001), but not previous smokers, also had an increased risk of regional disease. An increase in metastatic disease was most evident for prostate cancer (RR, 1.53; P =.003). An increase in regional disease was most evident for head and neck (RR, 3.53; P <.001), prostate (RR, 1.83; P =.030), and breast cancer (RR, 1.22; P =.005). Compared with previous smokers, current smokers with metastatic lung cancer were more likely to have involvement of the brain (33.6% v 23.0%; P =.004), bone marrow, adrenal gland, and pericardium (24.7% v 15.9%; P =.004). CONCLUSION: Previous or current smoking is a risk factor for increased cancer stage in a wide range of malignancies. Further study is required to determine whether this association is causal.