Late presentation of erythropoietic protoporphyria: case report and genetic analysis of family members.

Erythropoietic protoporphyria (EPP) is an inherited disorder of haem biosynthesis caused by decreased activity of the enzyme ferrochelatase (FECH), which catalyses the insertion of iron into protoporphyrin, the last step in haem biosynthesis. Development of clinically overt EPP usually requires inheritance of a severe FECH mutation trans to a low-expression FECH variant (FECH IVS3-48C), which is present in 13% of the U.K.

Gene dosage analysis identifies large deletions of the FECH gene in 10% of families with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria characterized by partial deficiency of ferrochelatase (FECH), accumulation of protoporphyrin IX in erythrocytes, skin, and liver, and acute photosensitivity. Genetic counseling in EPP requires identification of FECH mutations, but current sequencing-based procedures fail to detect mutations in about one in six families. We have used gene dosage analysis by quantitative PCR to identify large deletions of the FECH gene in 19 (58%) of 33 unrelated UK patients with EPP in whom mutations could not be detected by sequencing.

Interactions of primary neuroepithelial progenitor and brain endothelial cells: distinct effect on neural progenitor maintenance and differentiation by soluble factors and direct contact.

Neurovascular interactions are crucial for the normal development of the central nervous system. To study such interactions in primary cultures, we developed a procedure to simultaneously isolate neural progenitor and endothelial cell fractions from embryonic mouse brains. Depending on the culture conditions endothelial cells were found to favor maintenance of the neuroprogenitor phenotype through the production of soluble factors, or to promote neuronal differentiation of neural progenitors through direct contact.

Rurality and ethnicity in adolescent physical illness: are children of the growing rural Latino population at excess health risk?

Context And Purpose: This study's objectives are to: investigate potential additive and multiplicative influences of rurality and race/ethnicity on chronic physical illness in a nationally representative sample of youth; and examine intra-Latino processes using a Latino sub-sample. Specifically, we examine how rurality and individual psychosocial processes reflected by acculturation proxies (generational status and use of the English language at home) link to chronic physical illness of Latino youth. Finally, we examine whether these associations and the levels of chronic illness differ across Latino subgroups.

Elevated plasma cholesterol does not affect brain Abeta in mice lacking the low-density lipoprotein receptor.

Epidemiological studies support an association between vascular risk factors, including hypercholesterolemia, and Alzheimer's disease (AD). Recently, there has been much interest in the possibility that hypercholesterolemia might directly promote beta-amyloid (Abeta) production. Indeed, in vitro studies have shown that increasing cellular cholesterol levels enhances Abeta production.

Pepsin pretreatment allows collagen IV immunostaining of blood vessels in adult mouse brain.

While the brain vasculature can be imaged with many methods, immunohistochemistry has distinct advantages due to its simplicity and applicability to archival tissue. However, immunohistochemical staining of the murine brain vasculature in aldehyde fixed tissue has proven elusive and inconsistent using current protocols. Here we investigated whether antigen retrieval methods could improve vascular staining in the adult mouse brain.

European porphyria initiative (EPI): a platform to develop a common approach to the management of porphyrias and to promote research in the field.

Porphyrias are uncommon inherited diseases of haem biosynthesis for which the diagnosis and treatment varies in individual countries. Despite the existence of guidelines recommended by porphyria experts concerning the diagnosis and management of the acute porphyrias, and of specialist centres in most European countries, many clinicians still do not apply these guidelines. The European Porphyia Initiative (EPI) network was formed in 2001 in order to compare experience among countries to attempt to develop a common approach to the management of the porphyrias, particularly concerning recommendation of safe and unsafe drugs, and to facilitate international collaborative clinical and biological research.

Vitamin D levels, bone turnover and bone mineral density show seasonal variation in patients with chronic kidney disease stage 5.

Aim: Many patients with chronic kidney disease (CKD) have reduced levels of 25-hydroxyvitamin D (25(OH)D). Although renal conversion of 25(OH)D to calcitriol is reduced or absent in CKD stage 5 (GFR < 15 mL/min per 1.73 m(2) or on dialysis), 25(OH)D may have direct skeletal and non-skeletal paracrine actions.

Family medicine and the life course paradigm.

A unique characteristic of family physicians is that they seek to understand individual patients within the context of their families and larger social environments. Unfortunately, the intellectual development of family medicine is hampered by the reliance on epidemiologic, health service, and biomedical paradigms that are limited in their contextual perspectives on patients' lives. However, another paradigm, that of the life course, represents an interdisciplinary framework that views persons in context over time.

From marrow oedema to osteonecrosis: common paths in the development of post-transplant bone pain.

Osteonecrosis, the calcineurin-inhibitor-induced pain syndrome and transient marrow oedema may occur after renal transplantation, are generally painful and can be diagnosed by X-ray, radionuclide scan or magnetic resonance imaging. They share features of increased intraosseous pressure, compromised vascular supply, marrow oedema and the development of a 'bone compartment syndrome'. Glucocorticoid dosage is the most commonly implicated risk factor for osteonecrosis.

Research update: neurogenesis in adult brain and neuropsychiatric disorders.

Until recently neurogenesis in mammals was considered to occur only during the embryonic and early post-natal periods and to have no significant role in the adult nervous system. However, it is now accepted that neurogenesis occurs in two brain regions in adult mammals, namely, the hippocampus and olfactory bulb. In both regions new neurons arise from a resident population of neural progenitor cells that are maintained throughout adult life.

Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients.

Background: Calcimimetic agents have recently been evaluated in the treatment of secondary hyperparathyroidism (SHPT) as add-on therapy to calcitriol and vitamin D analogues and dietary phosphate binders.

Objectives: To evaluate the benefits and harms of calcimimetics for the prevention of secondary hyperparathyroid bone disease (including osteitis fibrosa cystica and adynamic bone disease) in dialysis patients with chronic kidney disease (CKD).

Search Strategy: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and conference proceedings were searched for randomised controlled trials (RCTs) evaluating any calcimimetic against placebo or another agent in pre-dialysis or dialysis patients with CKD.

25-Hydroxyvitamin D deficiency and diabetes predict reduced BMD in patients with chronic kidney disease.

Unlabelled: In this study of 242 patients with renal failure, women, patients with diabetes, and patients on peritoneal dialysis had the highest risk of 25-hydroxyvitamin D deficiency. Levels correlated positively to BMD Z scores, and hip BMD was inversely related to prevalent fracture. Increasing 25-hydroxyvitamin D levels may benefit these patients.

Racial self-categorization in adolescence: multiracial development and social pathways.

Research on multiracial individuals is often cross-sectional, obscuring the fluid nature of multiracial self-categorization across time. Pathways of racial self-identification are developed from a nationally representative sample of adolescents aged 14-18, measured again 5 years later. A significant proportion of multiracial adolescents change racial self-identification across time.

Erythropoietic protoporphyria in the U.K.: clinical features and effect on quality of life.

Background: Erythropoietic protoporphyria (EPP) is a rare inherited photodermatosis that causes lifelong painful photosensitivity. Neither its full clinical spectrum nor its impact on quality of life (QoL) has been investigated in a large cohort of patients.

Objectives: To document the clinical features of EPP and its impact on QoL in a high proportion of all patients with EPP resident in the U.

A randomized controlled equivalence trial of short-term complications and efficacy of tension-free vaginal tape and suprapubic urethral support sling for treating stress incontinence.

Objective: To establish the equivalence between the tension-free vaginal tape (TVT) and the suprapubic urethral support sling (SPARC). Approximately 35% of women have stress urinary incontinence (SUI), and although TVT is now perceived as the standard treatment, the SPARC is a very similar procedure and is thought to have fewer peri-operative complications.

Patients And Methods: Patients with clinical SUI were recruited from public and private urology/urogynaecology clinics, and participated in the trial of TVT vs SPARC.

The short-term and decade-long effects of divorce on women's midlife health.

We hypothesize that divorce immediately increases psychological distress and has long-term negative consequences for the physical health of divorced people. In addition, we hypothesize that divorce indirectly causes long-term increases in distress through stressful midlife events. The hypotheses are tested using data from 416 rural Iowa women who were interviewed repeatedly in the early 1990s when they were mothers of adolescent children; the women were interviewed again in 2001.

Relationships among sexual satisfaction, marital quality, and marital instability at midlife.

Sexual satisfaction, marital quality, and marital instability have been studied over the life course of couples in many previous studies, but less in relation to each other. On the basis of the longitudinal data from 283 married couples, the authors used autoregressive models in this study to examine the causal sequences among these 3 constructs for husbands and wives separately. Results of cross-lagged models, for both husbands and wives, provided support for the causal sequences that proceed from sexual satisfaction to marital quality, from sexual satisfaction to marital instability, and from marital quality to marital instability.

Meta-analysis of biochemical and patient-level effects of calcimimetic therapy.

Background: Many randomized trials have now evaluated the effects of calcimimetics in patients with chronic kidney disease and secondary hyperparathyroidism (SHPT) on standard therapy with vitamin D and/or phosphate binders. We conducted a meta-analysis to evaluate outcomes of therapy with these novel agents.

Methods: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and conference proceedings were searched for randomized controlled trials evaluating any calcimimetic against placebo or another agent in predialysis or dialysis patients with chronic kidney disease.

Changes in family financial circumstances and the physical health of married and recently divorced mothers.

This study investigates how divorce followed by single parenthood undermines the long-term physical health of rural mothers using four waves of survey data collected in Iowa, USA from 336 married and 80 divorced mothers during a 10-year period. Findings generally support the hypothesized pathways in that single-parenthood creates financial difficulties for rural mothers. Furthermore, this financial adversity is linked to self-assessed physical health trajectories that then contribute to change in morbidity.

Gendered trajectories of work control and health outcomes in the middle years: a perspective from the rural Midwest.

Objective: The objective was to investigate whether increasing health heterogeneity during the middle years is attributed, at least in part, to the influence of varying levels of, and changes in, work control of the current midlife cohort.

Method: The study used four waves of data collected from 372 employed rural women and 320 employed men of the midlife cohort during a 10-year period. Variables included self-reported work control, stressful nonwork life events, and mental and physical health.

Voluntary muscle activation is impaired by core temperature rather than local muscle temperature.

Fatigue during hyperthermia may be due in part to a failure of the central nervous system to fully activate the working muscles. We investigated the effects of passive hyperthermia on maximal plantar flexor isometric torque (maximal isometric voluntary contraction) and voluntary activation to determine the roles of local skin temperature, core temperature, and peripheral muscle temperature in fatigue. Nine healthy subjects were passively heated from 37.

Parathyroidectomy in the calcimimetic era.

With the introduction of the calcimimetic cinacalcet HCl, some patients who would previously have undergone parathyroidectomy are likely to remain on medical therapy. Data is available on complication rates and some important outcome measures of parathyroidectomy, but the efficacy of calcimimetics to influence patient-based endpoints such as cardiovascular mortality and renal osteodystrophy has not been established. Nevertheless, cinacalcet HCl has been demonstrated to improve levels of calcium, phosphate, the calcium phosphate product and parathyroid hormone (PTH).