Deciding on Gender in Children with Intersex Conditions

Biologic factors such as genetic and hormonal influences contribute to gender identity, gender role behavior, and sexual orientation in humans, but this relationship is considerably modified by psychologic, social, and cultural factors. The recognition of biologically determined conditions leading to incongruity of genetically determined sex, somatic phenotype, and gender identity has led to growing interest in gender role development and gender identity in individuals with intersex conditions. Sex assignment of children with ambiguous genitalia remains a difficult decision for the families involved and subject to controversial discussion among professionals and self-help groups. Although systematic empirical data on outcomes of functioning and health-related quality of life are sparse, anecdotal evidence from case series and individual patients about their experiences in healthcare suggests traumatic experiences in some. This article reviews the earlier 'optimal gender policy' as well as the more recent 'full consent policy' and reviews published data on both surgical and psychosocial outcomes. The professional debate on deciding on sex assignment in children with intersex conditions is embedded in a much wider public discourse on gender as a social construction. Given that the empirical basis of our knowledge of the causes, treatment options, long-term outcomes, and patient preferences is insufficient, we suggest preliminary recommendations based on clinical experience, study of the literature, and interviews with affected individuals.     

Sensitivity and specificity of serology in determining recent acute Campylobacter infection

BACKGROUND: The measurement of serum antibodies to Campylobacter spp. has been used to investigate links between prior Campylobacter infections and the development of Guillain-Barre syndrome and its variants. Little is known of the serum antibody response to acute infections in the short- or long-term. AIMS: The aims of the present study were to investigate the normal serum response to an acute Campylobacter infection and the sensitivity and specificity of anti-Campylobacter antibodies in determining recent Campylobacter infection. METHODS: An enzyme-linked immunosorbent assay (ELISA) method was used to measure serum anti-Campylobacter immunoglobulin G (IgG), IgA and IgM antibodies. Controls consisted of 420 blood donors without recent gastroenteritis, 25 patients with other gastrointestinal infections, 24 patients with neurological conditions not affecting the peripheral nerves and 19 patients with autoimmune disorders. Three patient groups were assessed: 99 patients with acute Campylobacter infections, all of whom were tested 3 weeks post-infection; 69 of these patients tested 3-6 months later; and 74 additional patients tested >20 months post-infection. Western blot analysis was performed on controls and patients with high titre anti-Campylobacter antibodies to assess for cross-reactivity and specificity. RESULTS: Following acute infections, all antibody classes rose in the majority of but not in all patients, followed by decreasing titres that did not return to baseline levels. Sixteen per cent of enteritis cases did not demonstrate a rise in titres and 9% of cases had significant levels of antibodies >20 months post-infection. The ELISA used was shown to be highly specific for the detection of Campylobacter antibodies. CONCLUSION: The use of Campylobacter-specific antibody levels as the sole marker of prior infection is an unreliable method of determining the association between Campylobacter infection and neurological disease.     

Analyzing the time and value of housestaff inpatient work

OBJECTIVE: To determine time allocation and the perceived value to education and patient care of the weekday activities of internal medicine housestaff on inpatient rotations and to compare the work activities of interns and residents. DESIGN: An observational study. We classified activities along five dimensions (association, location, activity, time, and value), developed a computer-assisted self-interview survey, and demonstrated its face and content validity, internal consistency, and interrater reliability. Subjects were assigned survey computers for 5 consecutive weekdays over a 24-week period, into which they entered data when prompted several times a day. SETTING: The medical service of a university-affiliated Veterans Administration Medical Center. PARTICIPANTS: Sixty housestaff (36 interns, 24 residents) rotating on the inpatient wards. MEASUREMENTS AND MAIN RESULTS: We analyzed activities according to content (direct patient care, indirect patient care, education), association, and location. Likert-scale ratings of perceived value to education and patient care were also obtained. Housestaff provided complete responses to 3,812 (95%) of 3,992 prompts by a median of 11 seconds; 93% of responses were logically consistent across the measured dimensions. Housestaff spent more time in indirect patient care (56%) than in direct patient care (14%) or educational activities (45%). Formal educational activities had the highest educational value (66 on 0–100 scale), and direct care had the highest value to patient care (81). Over 30% of time was spent in administrative activities, which had low educational value (40). Compared with residents, interns allocated significantly less time to educational activities (38% vs 57%) and more time to lower-value activities such as documentation (19% vs 12%). CONCLUSIONS: Improved data collection methods demonstrate that housestaff in our program, particularly interns, spend much of their workday in activities that are low in educational and patient care value. Selective elimination or delegation of such activities would preserve higher-value experiences during reductions in overall inpatient training time. Planners can use automated random sampling to guide the rational redesign of housestaff work. Support for this work was provided by the Western Region of the Veterans Administration (Ambulatory Care and Education Initiative, 94–04), the Veterans Administration Center for the Study of Provider Behavior, and the RAND Graduate School. Dr. Bozzette is a Senior Research Associate of the HSR&D Service, Department of Veterans Affairs.     

Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease characterized by Lewy body formation and death of dopaminergic neurons. Mutations in alpha-synuclein and parkin cause familial forms of PD. Synphilin-1 was shown to interact with alpha-synuclein and to promote the formation of cytosolic inclusions. We now report that synphilin-1 interacts with the E3 ubiquitin-ligases SIAH-1 and SIAH-2. SIAH proteins ubiquitylate synphilin-1 both in vitro and in vivo, promoting its degradation by the ubiquitin-proteasome system. Inability of the proteasome to degrade synphilin-1/SIAH complex leads to a robust formation of ubiquitylated cytosolic inclusions. Ubiquitylation is required for inclusion formation, because a catalytically inactive mutant of SIAH-1, which still binds to synphilin-1, fails to promote inclusions. Like synphilin-1, alpha-synuclein associates with SIAH in intact cells, but the interaction with SIAH-2 was much stronger that with SIAH-1. In vitro experiments show that SIAH-2 monoubiquitylates alpha-synuclein. Further evidence that SIAH proteins may play a role in inclusion formation comes from the demonstration of SIAH immunoreactivity in Lewy bodies of PD patients.