Developmental influences on fertility decisions by women: an evolutionary perspective.

Developmental environments are crucial for shaping our life course. Elements of the early social and biological environments have been consistently associated with reproduction in humans. To date, a strong focus has been on the relationship between early stress, earlier menarche and first child birth in women. These associations, found predominately in high-income countries, have been usefully interpreted within life-history theory frameworks. Fertility, on the other hand--a missing link between an individual's early environment, reproductive strategy and fitness--has received little attention. Here, we synthesize this literature by examining the associations between early adversity, age at menarche and fertility and fecundity in women. We examine the evidence that potential mechanisms such as birth weight, childhood body composition, risky health behaviours and developmental influences on attractiveness link the early environment and fecundity and fertility. The evidence that menarche is associated with fertility and fecundity is good. Currently, owing to the small number of correlational studies and mixed methodologies, the evidence that early adversity predicts fecundity and fertility is not conclusive. This area of research is in its infancy; studies examining early adversity and adult fertility decisions that can also examine likely biological, social and psychological pathways present opportunities for future fertility research.

The influence of motivation in recruitment and retention of rural and remote allied health professionals: a literature review.

INTRODUCTION: Recruitment and retention of allied health professionals (AHPs) to remote and rural Australia is challenging and correlates with poorer health status of remote and rural residents. While much has been written about the recruitment and retention problem, this study took a new approach by reviewing the literature describing the motivation of AHPs to work in remote and rural areas and then analyzing the findings from the perspective of motivation theory using Herzberg's extrinsic and intrinsic classification. Intrinsic motivation incentives are known to contribute to job satisfaction and come from within the individual, for example the pleasure derived from autonomy or challenge at work. In contrast, extrinsic motivation incentives are provided by the job and include such factors as salary and professional development provisions. Extrinsic incentives are important because they prevent job dissatisfaction. Job satisfaction has been shown to be linked with increased retention. METHOD: Thirty-five articles, including 26 from Australia, met the inclusion criteria. The key findings related to motivation from each article are outlined and the results classified into the extrinsic-intrinsic framework. The incentives are then further analyzed as having a positive or a negative influence. RESULTS: In total, 38 different incentives were described a total of 246 times. Of the total, almost half (n=115) comprised extrinsic incentives with a negative influence, with poor access to professional development, professional isolation and insufficient supervision the most frequently reported. Rural lifestyle and diverse caseloads were the most frequently mentioned positive extrinsic incentives, while autonomy and community connectedness were the most cited positive intrinsic incentives. Negative intrinsic incentives were mentioned least frequently (n=18); however, of these, feeling overwhelmed and that your work was not valued by the community were the most commonly reported. CONCLUSIONS: The results demonstrate the significant burden of extrinsic incentives with a negative influence that are perceived by AHPs in remote and rural areas. The high turnover rate of AHPs in remote and rural areas is likely to be, in part, due to the job dissatisfaction from these disincentives. More positive intrinsic incentives were reported than negative. This suggests the potential for intrinsic incentives, known to contribute to job satisfaction, to be mediating the extrinsic disincentives. The policy implications of this work include the importance of addressing extrinsic disincentives. Simultaneously, the existing intrinsic incentives need to be nurtured and developed. Organizations that implement strategies to enhance both extrinsic and intrinsic motivation incentives are more likely to successfully address their AHP workforce shortage.

Bacillus circulans endophthalmitis.

An 80-year-old woman presented with right endophthalmitis, characterized by chalky white deposits covering her posterior capsule. This occurred 17 months after uncomplicated right cataract surgery. A three-port pars plana vitrectomy and partial posterior capsulectomy isolated Bacillus circulans, and the patient made a rapid and full recovery on topical cephalothin and prednisolone acetate 1%. The case demonstrates that, unlike endophthalmitis due to other Bacillus spp., B. circulans endophthalmitis does not necessarily follow a fulminant course. It is the first report describing a subacute presentation, and response to posterior capsulectomy and simple antibiotic therapy It is also the first description of B. circulans causing white plaques in the posterior capsule, a finding characteristic of chronic endophthalmitis and previously considered pathognomonic of Proprionibacterium acnes endophthalmitis.

Mentoring benefits and issues for public health nurses.

New public health nurses (PHNs) move from novice to expert status with enormous expectations from their organization, their peers, and themselves. These expectations lead to stress that may be beyond the level of endurance. Mentoring is an important answer to this problem. Mentoring is the greatest gift PHNs can give to each other, especially for PHNs who self-identified themselves as minority cultural group members. This article describes definitions, roles, benefits, and responsibilities of mentors and mentees and includes mentoring concerns, current and proposed mentoring programs, and mentoring issues for gender and race. Organizational mentoring programs can be created that will facilitate the development of mentoring relationships. These programs help experienced PHNs bridge the gap between the theory and reality of nursing for themselves and inexperienced colleagues.

Single-nucleotide polymorphism genotyping using microarrays.

This unit provides a set of protocols for high throughput SNP genotyping using oligonucleotide microarrays. The basic protocol utilizes allele-specific hybridization in which the microarray provides both the allele discrimination and read-out. In the alternate approach, the allele discrimination is accomplished in solution and then the array is used to provide the read-out of the genotyping reaction. Single nucleotide polymorphisms (SNPs) offer several advantages over other genetic markers including their high density in the.

Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma.

OBJECTIVE: Patients with non-acquired immunodeficiency syndrome-related primary central nervous system lymphomas have the potential to achieve durable complete responses without radiotherapy, with treatment using enhanced chemotherapy delivery with blood-brain barrier disruption (BBBD). Reported 5-year survival rates with combined chemotherapy and radiotherapy were generally only 9 to 22% and were associated, in one study, with an overall 32% incidence of overt dementia and ataxia, which are dramatically increased among patients more than 60 years of age. METHODS: At the Oregon Health Sciences University, 111 consecutive patients with non-acquired immunodeficiency syndrome-related central nervous system lymphomas were prospectively treated with methotrexate-based, BBBD-enhanced chemotherapy and underwent formal neuropsychological evaluations. Of those, 74 patients had no systemic lymphoma and had received no prior irradiation; those 74 patients are described in this report. RESULTS: The estimated 5-year survival rate for this group was 42%, and the median survival time was 40.7 months. Overall, 48 patients (65%) exhibited complete responses and 36 patients continued to exhibit complete responses after 1 year of BBBD-enhanced chemotherapy. Of those 36 patients, none demonstrated evidence of cognitive loss in neuropsychological tests and/or clinical examinations. CONCLUSION: BBBD-enhanced chemotherapy delivery, without subsequent radiotherapy, resulted in favorable survival and cognitive outcomes for patients with primary central nervous system lymphomas who had not previously undergone irradiation. A cooperative multicenter study of intravenous chemotherapy without radiotherapy versus BBBD-enhanced chemotherapy would address the feasibility and necessity of performing a Phase III study for these rare central nervous system malignancies.

Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors.

BACKGROUND: The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood-brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers. METHODS: Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures). RESULTS: Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11 of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment. CONCLUSIONS: Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy-sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers.

Unusual cervical spinal cord toxicity associated with intra-arterial carboplatin, intra-arterial or intravenous etoposide phosphate, and intravenous cyclophosphamide in conjunction with osmotic blood brain-barrier disruption in the vertebral artery.

BACKGROUND AND PURPOSE: When the clinical and radiologic characteristics of an unusual cervical spinal cord complication of intra-arterial (IA) chemotherapy with blood brain-barrier (BBB) disruption in the vertebral circulation are documented. Seven cases are reported and analyzed in search of a pathophysiologic explanation. METHODS: We retrospectively identified 94 patients who received a total of 380 standardized regimens of IA carboplatin, IA or IV etoposide phosphate, and IV cyclophosphamide infusion in conjunction with osmotic BBB disruption of the vertebral artery. We describe seven of those patients in whom unexpected neck pain developed followed by neurologic symptoms primarily in the upper extremities. RESULTS: The symptoms correlated with MR abnormalities (T1 hypointensity, T2 hyperintensity, and unusual contrast enhancement) in the cervical spinal cord, usually involving the gray matter. The neurologic deficits and MR changes were generally transient. One patient who received a flu vaccination 48 hours before the chemotherapy incurred progressive myelitis and expired. CONCLUSION: The pathophysiology of this complication is probably multifactorial but may be related to vascular streaming and an atypical inflammatory toxic reaction to carboplatin and etoposide. The complication has not recurred during a 6-month period following modification of the protocol.

Effects of cutaneous aspirin on the human stomach and duodenum.

Oral aspirin blocks cyclooxygenase in platelets, lowering serum thromboxane concentrations. Oral aspirin also blocks cyclooxygenase in the gastrointestinal mucosa, lowering prostaglandin production and increasing the risk of gastrointestinal ulceration and bleeding. Aspirin placed on the skin also inhibits cyclooxygenase in platelets, but aspirin absorption through skin is slow, which may minimize the gastrointestinal effects. Our objectives in this study were 1) to compare the pharmacokinetic and pharmacodynamic effects of cutaneous and oral aspirin in healthy volunteers and 2) to compare the effects of cutaneous aspirin on gastroduodenal mucosal prostaglandin E2 and F2 alpha content and on mucosal damage, using endoscopy. The bioavailability of cutaneous aspirin was 4%-8% that of oral aspirin. Cutaneous aspirin (750 mg/day for 10 days) significantly lowered serum thromboxane (by 85%) and gastric and duodenal prostaglandins (by 49%-71%); placebo had no effect. Moreover, cutaneous aspirin, but not placebo, resulted in significant gastric mucosal injury. These findings demonstrate that even tiny amounts of aspirin in the blood (2 microM) have inhibitory effects on prostaglandin production in the human stomach and duodenum that result in gastric mucosal damage, even without direct exposure of the stomach to aspirin.

Enrichment for loci identical-by-descent between pairs of mouse or human genomes by genomic mismatch scanning.

Mapping genes that underlie complex genetic traits, including genes that determine susceptibility to common diseases, requires an efficient method for high-resolution genotyping. Single-nucleotide differences between pairs of allelic sequences from unrelated individuals occur approximately once in every kilobase. Genomic mismatch scanning (GMS), by analyzing numerous single-nucleotide polymorphisms in a single genome-wide step, offers a potentially powerful and efficient approach to linkage analysis. GMS, originally developed in a yeast system, is shown here to be applicable to the more complex mouse and human genomes.

Rural attachments for students in the health professions: are they worthwhile?

In the period 1991-96, 156 undergraduates from 14 health disciplines at the University of Sydney completed rural attachments in rural and remote areas of Australia as part of the Rural Careers Project. On return from their attachment, students were encouraged to write a brief report of their experiences. Ninety-two available reports were analysed as one means of assessing the success of the attachments with respect to informing students about rural health issues and stimulating their interest in rural careers after graduation. A content analysis of the students' written comments about their perceptions and experiences was completed. Students were extremely positive about the value of the attachments and expressed more positive than negative comments regarding their perceptions of rural life and work. The results show that rural attachments are indeed worthwhile learning opportunities.

Allogeneic bone marrow transplant for chronic myelogenous leukemia in a patient with multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which immune mechanisms appear to be an important component of the pathophysiology. Although the clinical manifestations are variable, a subset of patients develops a progressive clinical course associated with marked neurologic impairment and significant morbidity. BMT has been proposed as treatment for such patients based on preclinical data as well as clinical observations in other autoimmune diseases. We report clinical and MRI findings in an MS patient, later diagnosed with CML, and treated with an allogeneic BMT.

Phase II study of paclitaxel in patients with recurrent malignant glioma.

PURPOSE: To assess the efficacy and toxicity of paclitaxel administered as a 3-hour infusion to patients with recurrent malignant glioma. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma following radiation therapy, who had received no more than one prior chemotherapy regimen and who had a Karnofsky performance status (KPS) > or = 60, were treated with a 3-hour infusion of paclitaxel every 3 weeks. The initial dose was 210 mg/m2; dose escalation to 240 mg/m2 was allowed. Tumor response was assessed at 6-week intervals using radiographic and clinical criteria. Treatment was continued until documented tumor progression or a total of 12 paclitaxel infusions. RESULTS: Of 41 eligible patients, all were assessable for treatment toxicity and 40 (98%) were assessable for response. The response rate (disease stabilization or better) was 35%. Twenty-nine patients (71%) underwent dose escalation to 240 mg/m2 without the use of growth factors. Toxicities included alopecia (98%), nausea (22%), arthralgias (32%), CNS toxicity (24%), peripheral neuropathy (15%), cardiac toxicity (7%), and myelosuppression (10% grade 3 or 4 hematologic toxicity). No patient developed febrile neutropenia. There was one allergic reaction (2%). CONCLUSION: Paclitaxel is well tolerated at this dose schedule in patients with recurrent malignant glioma, and affords a modest response rate. Because minimal myelotoxicity was encountered in our patients, a dose-escalating phase I/II study of paclitaxel is planned to determine the maximal-tolerated dose (MTD).

Public opinion on tobacco use, its taxes and public policy.

Public opinion is an important vehicle in shaping legislative efforts and public policy related to tobacco use and related taxes. This study examined public opinion about policy related to tobacco use and raising tobacco taxes in a Midwestern state. The American Lung Association of Indiana provided a grant to sponsor this project. A structured questionnaire was developed, field tested and revised for the final data collection procedure. A sample of 800 adult subjects was randomly selected and telephone interviewed by the Indiana University Center for Survey Research. The collected data were subjected to descriptive and inferential statistics. The data revealed a good representative sample of adult males and females for various age groups and socioeconomic backgrounds. Among other findings, 29% were currently smokers, 23% were former smokers, and 47.5% never smoked. More than 90% support a requirement that public places have nonsmoking areas. About 85% favor an increase in cigarette taxes to pay for health education and tobacco-related research. The relationship of the subjects' gender, education and income to their opinion about the various aspects of tobacco, taxes and related policies were examined.

Identifying protein kinases in crude extracts that phosphorylate cyclic GMP-binding cyclic-GMP specific phosphodiesterase.

The main protein kinase that phosphorylates cyclic GMP-binding cyclic GMP-specific phosphodiesterase (cG-BPDE) in crude extracts of bovine lung is cyclic GMP-dependent protein kinase. This can be shown by the use of either exogenous or endogenous cG-BPDE as substrate for endogenous cyclic GMP-dependent protein kinase. The characteristics of this phosphorylation suggest a physiological significance.

Speech and language outcomes 3 years after neonatal intensive care.

Although major handicap rates have been documented in children who required neonatal intensive care, minor handicap rates, including speech and language problems, have received less attention. This paper reports the first stage of a longitudinal study of 118 children, which investigated the speech and language outcomes at 3 years of age. Differences from the normal population were found for the articulation measure, but not for the language comprehension and expression measures used. A major overall communication problem was determined to exist in 13% of the children. The impact of perinatal, medical and environmental variables was investigated. Variables such as low birthweight, short gestational age and mechanical ventilation, found to be important in other studies, had no significant impact on the speech and language outcomes of this cohort of 3 years old. However, for children who had experienced respiratory distress syndrome, there was an effect on articulation and language expression. Paediatric complications and maternal education level had the largest effects on language comprehension and expression, suggesting they were the persistent variables which most contributed to speech and language outcomes at 3 years of age.

Speech and language outcomes in preschool-aged survivors of neonatal intensive care.

This paper reports on the second stage of a longitudinal follow-up of the speech and language outcomes in a cohort of children who required neonatal intensive care. From 3 years of age, when the first stage was completed, to preschool age, the rate for major overall communication problems rose from 13% to 17%. However, when children with frank neurological or intellectual problems were excluded, this figure dropped to 8%. The impact of perinatal, medical and environmental variables on speech and language outcomes was again investigated. Differences were found between those that were important at 3 years of age and those that were important at preschool age. New variables emerged as contributing to language expression, including gender and the perinatal variables, gestational age and respiratory distress syndrome. Maternal education level was even more important to language comprehension at preschool age than at 3 years of age. Factors that might explain improvement, or lack of improvement, in speech and language skills are discussed.

Peer learning in clinical education.

The purpose of this paper is to raise awareness of peer learning as a process that is potentially beneficial to clinical education. Peer learning is a well documented learning strategy in paediatric educational literature. Many allied health clinical education programs purport to utilize it as a learning technique. Do we really know what peer learning is, how to promote it and why it is beneficial to facilitate it? This paper addresses these questions by considering terminology and definitions of peer learning and briefly outlining theoretical justification for its use in clinical education. Literature regarding the application of peer learning in clinical education is reviewed and the reported and purported benefits of peer learning are discussed.

A phenylalanine in peptide substrates provides for selectivity between cGMP- and cAMP-dependent protein kinases.

Bovine lung cGMP-binding cGMP-specific phosphodiesterase (cG-BPDE) is a potent and relatively specific substrate for cGMP-dependent protein kinase (cGK) as compared to cAMP-dependent protein kinase (cAK) (Thomas, M. K., Francis, S. H., and Corbin, J. D. (1990) J. Biol. Chem. 265, 14971-14978). A synthetic peptide, RKISASEFDRPLR (BPDEtide), was synthesized corresponding to the sequence surrounding the phosphorylation site in cG-BPDE. BPDEtide retained the cGK/cAK kinase specificity demonstrated by native cG-BPDE: the apparent Km of BPDEtide for cGK was 5-fold lower than that for cAK (Km = 68 and 320 microM, respectively). Vmax values were 11 mumol/min/mg for cGK and 3.2 mumol/min/mg for cAK. The peptide was not phosphorylated to a measurable extent by protein kinase C or by calcium/calmodulin-dependent protein kinase II. Thus, the primary amino acid sequence of the peptide substrate was sufficient to confer kinase specificity. Studies in crude tissue extracts indicated that BPDEtide was the most selective peptide substrate documented for measuring cGK activity. Peptide analogs of BPDEtide were synthesized to determine the contribution of specific residues to cGK or cAK substrate specificity. Substitution of a Lys for the amino-terminal Arg did not reduce cGK/cAK specificity; neither did the exchange of an Ala for the non-phosphorylated Ser nor the removal of the 3 carboxyl-terminal residues. A truncated BPDEtide (RKISASE) served equally well as substrate (Km approximately 90 microM) for both kinases. However, restoration of the Phe, to yield RKISASEF, reproduced the original cGK/cAK specificity for BPDEtide (Km = 120 and 480 microM, respectively), primarily by decreasing the affinity of cAK. Addition of a carboxyl-terminal Phe to the peptide RKRSRAE (derived from the sequence of the cGK phosphorylation site in histone H2B) or to the peptide LRRASLG (derived from the sequence of the cAK phosphorylation site in pyruvate kinase) also improved the cGK/cAK specificity by decreasing the affinity of cAK. These data suggested that the Phe in each substrate tested is a negative determinant for cAK.