Older age is an adverse prognostic factor in stage I, favorable histology Wilms' tumor treated with vincristine monochemotherapy: a study by the United Kingdom Children's Cancer Study Group, Wilm's Tumor Working Group.

PURPOSE: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms' tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. PATIENTS AND METHODS: During two consecutive trials of the United Kingdom Children's Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms' tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. RESULTS: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P =.001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P =.01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P =.66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). CONCLUSION: Treatment for stage I FH Wilms' tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms' tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.     

Nursing and motherhood constructions: implications for practice

The present paper addresses the relationship between community based child health nursing services and social constructions of motherhood within Australia during the 1920s. Following the First World War, child health nursing services (then generally known as infant welfare or child welfare services) were established in all Australian states. The focus of the paper is mainly upon the development of the Tasmanian child health service, with some reference to similar services in other states. Within two decades of their establishment, most child-bearing women in Tasmania were in contact with child health services and this apparent success meant that, thereafter, women in Tasmania cared for their children under the 'expert' guidance of nurses. As the 1920s progressed, child health nurses increasingly promoted one particular, and ultimately extremely influential, construction of motherhood, 'scientific motherhood', based upon the philosophy of Dr Truby King. I argue that an understanding of how nursing services have historically reinforced and promoted ideological constructions of motherhood enhances the practice of present day nurses working with women. This argument is supported by reference to present day nursing practice in relation to postnatal depression.     

Effects of 5-HT3 agonists on reproductive behaviors in rats

Activity at 5-HT₁ and 5-HT₂ receptor sites influences sexual behavior in male and female rats. 5-HT₃ antagonists reportedly have no effect on copulatory activity in rats of either sex although they influence a variety of other behaviors. The effects of 5-HT₃ agonists on sexual behavior are unknown. The following experiments were undertaken to assess the influence of the 5-HT₃ agonists 1-phenylbiguanide (PBG) and 2-methyl-serotonin (2-Me-5-HT) on sexual behavior, when administered intracerebroventricularly. Consistent with earlier reports indicating that 5-HT₁ and 5-HT₂ receptor activity influences reproductive activity in a sex-dependent manner, PBG was found to facilitate male, but not female, rat sexual behavior. 2-Me-5-HT, however, failed to modify either female or male rat sexual activity. Evidence that PBG, but not 2-Me-5-HT, induces carrier-mediated dopamine release suggests that the effect of PBG in male rats is due to dopaminergic mediation. Overall, the present data indicate that 5-HT₃ receptor activation has only slight effects on rat sexual behavior.     

Ethical issues in clinical neuroscience research: A patient’s perspective

A patient-centered paradigm for clinical research and medical care is presented as a solution to the problem of declining innovation and increasing costs and development time in the pipeline for new therapies. Fundamental differences in values and motivations among scientists, clinicians, industry sponsor, and patients in neurotherapeutics provide a framework for analysis of ethical conflicts and the loss of public confidence in medical research. Parkinson advocates’ views on clinical trial participation, perceived risks and benefits, placebo controls, and sham surgery are presented. These views reflect the sense of urgency and the unique perspective that comes from living with this progressive, debilitating condition full time. A patient-centered paradigm that includes authentic voices of patients as collaborators at every stage of development will help to resolve conflicts, build trust, recruit trial participants, and accelerate new therapies. Key elements are adaptive clinical trial methods and the development of information technology for the assessment of outcomes and surveillance of safety over the life cycle of a medical product. Supported by the Parkinson’s Disease Foundation, the Parkinson Pipeline Project is a grassroots group of Parkinson’s patients whose goal is to represent an authentic voice for patients in the treatment development process. This group promotes education and communication between members of the Parkinson’s community and active stakeholders in medical research, industry, and regulatory agencies. Its members are an example of a new breed of knowledgeable consumers, armed with first-hand access to research findings and reinforced by on-line connections to like-minded peers throughout the world.     

Cytochemical characteristics of neurons in the trigeminal mesencephalic nucleus of hatchling chicks

The goal of the present study was to identify cytochemical markers characteristic of muscle afferents in hatchling chicks. To this end, we stained neurons in the trigeminal mesencephalic nucleus with a variety of markers that label subsets of neurons in avian dorsal root ganglia. We found that trigeminal mesencephalic neurons are surprisingly heterogeneous in their cytochemical make-up, expressing, to varying degrees, substance P, cholecystokinin, carbonic anhydrase, calbindin D-28k, parvalbumin, and S-100β. Calbindin D28k and S-100β appeared to be expressed equally in medial and lateral divisions of the trigeminal mesencephalic nucleus. In contrast, substance P- and cholecystokinin-immunoreactive neurons were more abundant in the medial division, whereas carbonic anhydrase activity and parvalbumin immunoreactivity were stronger in the lateral division. We were unable to detect met-enkephalin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal peptide, somatostatin, γ-aminobutyric acid, or tyrosine hydroxylase in the trigeminal mesencephalic nucleus. Moreover, these neurons did not appear to bind the lectin Dolichos biflorus agglutinin. The heterogeneity of expression of markers among trigeminal mesencephalic nucleus neurons, especially between neurons in the medial and lateral divisions, suggests that these neurons are functionally diverse.     

Augmentation laser for proliferative diabetic retinopathy that fails to respond to initial panretinal photocoagulation.

PURPOSE: A study was performed to determine if diabetic subjects who fail to respond to initial panretinal photocoagulation with regression of retinopathy risk factors do better with supplemental panretinal photocoagulation. METHODS: Thirty-five patients with 3 or more retinopathy risk factors who failed to respond to panretinal photocoagulation with regression to less than 3 retinopathy risk factors by 3 weeks after initial panretinal photocoagulation were prospectively randomized to augmentation laser panretinal photocoagulation (MORE) or to no additional treatment (NOMORE). RESULTS: Six months after initial treatment, the MORE group (n = 16) had regressed a mean of -0.94 retinopathy risk factors (with 95% confidence interval [CI] -1.60 to -0.26), compared with -0.21 retinopathy risk factors (95% CI -0.69 to 0.27) in the NOMORE (n = 19) group (P = 0.055). However, by 1 year, there was no statistically significant difference in the amount of regression of retinopathy risk factors with a mean decrease of -1.12 (95% CI -2.0 to -0.24) versus -1.05 retinopathy risk factors (95% CI -1.80 to -0.28) in the 2 groups, respectively. Similarly, for visual acuity, there was no difference in outcome. For all study patients, the persistence of three or more retinopathy risk factors was associated with a poorer visual result than if there was regression to less than three retinopathy risk factors. CONCLUSION: This study shows that although augmentation panretinal photocoagulation achieved faster regression of retinopathy risk factors, by 1 year, there was no difference in either mean regression of retinopathy risk factors or visual acuity between eyes treated or not treated with augmentation panretinal photocoagulation. In addition, the study shows that the persistence of 3 or more retinopathy risk factors 1 year after treatment was associated with a poorer visual result. Because sample size limited the power of the study to find small differences between groups, and because in proliferative diabetic retinopathy small differences could be important clinically, the authors do not recommend changes in current clinical practice.