Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations.

Objectives: Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms.

Methods: Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues.

Thrombosis with erythropoietic stimulating agents-does iron-deficient erythropoiesis play a role?

Thrombocytosis is common in iron deficiency and resolves following iron repletion. Increased platelet number, whether from iron deficiency or from other causes, may increase the risk of thrombovascular events. One mechanism thought to mediate iron deficiency-induced thrombocytosis is increased erythropoietin production.

Femtosecond photolysis of aqueous formamide.

In this work, we investigate the primary photodynamics of aqueous formamide. The formamide was photolyzed using 200 nm femtosecond pulses, and formation of products and their relaxation was followed with approximately 300 fs time resolution using probe pulses covering the range from 193 to 700 nm. Following excitation, the majority of formamide molecules (approximately 80%) converts the electronic excitation energy to vibrational excitation, which effectively is dissipated to the solvent through vibrational relaxation in just a few picoseconds.

Familial osteochondritis dissecans associated with early osteoarthritis and disproportionate short stature.

Objective: Familial osteochondritis dissecans (OCD) is a rare disorder characterised by disturbed chondro-skeletal development, disproportionate growth and deformation of the skeleton.

Design: We identified a five-generation family with 15 living affected members from Northern Sweden. The disorder was diagnosed with a case definition of OCD in at least one joint.

Ferric gluconate reduces epoetin requirements in hemodialysis patients with elevated ferritin.

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated.

Effects of oxybutynin transdermal system on health-related quality of life and safety in men with overactive bladder and prostate conditions.

Aims: Overactive bladder (OAB) is common in men and may exist concomitantly with benign prostatic hyperplasia (BPH) and obstruction. We present a subanalysis of results from men with OAB in a 6-month, open-label study of treatment with the oxybutynin transdermal system (OXY-TDS). Broad entry criteria were incorporated to yield a clinically representative population.

Alpha-cardiac actin mutations produce atrial septal defects.

Atrial septal defect (ASD) is one of the most frequent congenital heart defects (CHDs) with a variable phenotypic effect depending on the size of the septal shunt. We identified two pedigrees comprising 20 members segregating isolated autosomal dominant secundum ASD. By genetic mapping, we identified the gene-encoding alpha-cardiac actin (ACTC1), which is essential for cardiac contraction, as the likely candidate.

Single-dosage pharmacokinetics of sodium ferric gluconate complex in iron-deficient pediatric hemodialysis patients.

Background And Objectives: The clinical use of sodium ferric gluconate complex in iron-deficient pediatric patients receiving hemodialysis was recently approved. This study was designed to describe the pharmacokinetic parameters of the medication.

Design, Setting, Participants, & Measurements: Iron-deficient pediatric (< or = 15 yr) hemodialysis patients were randomly assigned to two doses (1.

Evidence of altered epidermal nerve fiber morphology in adults with self-injurious behavior and neurodevelopmental disorders.

The purpose of this preliminary study was to examine the morphology and neuropeptide density of epidermal nerve fibers quantified through skin biopsy samples from three adults with neurodevelopmental disorders and chronic self-injurious behavior (SIB) secondary to mental retardation compared with non-SIB normal IQ controls. A cross-sectional design was used with 3mm punch skin biopsies collected from each participant from non-self-injurious body sites and compared with site-matched existing normal control skin samples. The study was conducted at an outpatient clinic.

Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis.

Background: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin disorders. Several mutant genes have been identified in ARCI, but the association between genotype and phenotype is poorly understood.

Methods: To investigate genotype-phenotype correlations in ARCI, we selected 27 patients from 18 families with specific ultrastructural features of the epidermis.

Kostmann syndrome or infantile genetic agranulocytosis, part two: Understanding the underlying genetic defects in severe congenital neutropenia.

Unlabelled: Congenital neutropenia in man was first reported 50 years ago by the Swedish paediatrician Rolf Kostmann. He coined the term 'infantile genetic agranulocytosis' for this condition, which is now known as Kostmann syndrome. Recent studies have revealed mutations in ELA-2, encoding the neutrophil granule protease, neutrophil elastase, in autosomal dominant neutropenia, and mutations in HAX-1, encoding an anti-apoptotic protein, in autosomal recessive neutropenia.

A longitudinal study of LH, gonadal and adrenal steroids in four intact Asian bull elephants (Elephas maximus) and one castrate African bull (Loxodonta africana) during musth and non-musth periods.

During their annual musth cycle, adult African and Asian bull elephants have increased gonadal androgens (testosterone [T], dihydrotestosterone [DHT], androstenedione [A4]). Because musth is a physiologically and psychologically stressful time, this study was conducted to investigate whether the adrenal glands (stimulated by stress) increase production of both glucocorticoids and androgens during musth. Weekly serum samples were taken for 11-15 months from four intact adult Asian bull elephants, and from a castrate African bull elephant who exhibits musth.

Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy.

Purpose: To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa.

Patients And Methods: In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin > or =100 ng/ml or transferrin saturation > or =15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal.

Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study.

Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation (TSAT). The Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) trial was designed to evaluate the efficacy of intravenous ferric gluconate in such patients. Inclusion criteria were hemoglobin or=225 IU/kg per wk or >or=22,500 IU/wk.

FGF10 missense mutations in aplasia of lacrimal and salivary glands (ALSG).

Aplasia of lacrimal and salivary glands (ALSG) is an autosomal dominant congenital anomaly characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems. Affected individuals present with irritable eyes and dryness of the mouth with variable expressivity. Mutations in FGF10 were recently described in ALSG and in lacrimo-auriculo-dento-digital (LADD) syndrome which are overlapping clinical entities.

Assignment of the gene locus for severe congenital neutropenia to chromosome 1q22 in the original Kostmann family from Northern Sweden.

Autosomal recessive severe congenital neutropenia (SCN) or Kostmann syndrome is characterised by reduced neutrophil counts and subsequent recurrent bacterial infections. The disease was originally described in a large consanguineous pedigree from Northern Sweden. A genome-wide autozygosity scan was initiated on samples from four individuals in the original pedigree using high density single nucleotide polymorphism (SNP) genotyping arrays in order to map the disease locus.

Oxybutynin transdermal system improves the quality of life in adults with overactive bladder: a multicentre, community-based, randomized study.

Objective: To assess health-related quality-of-life (HRQoL) and safety with the oxybutynin transdermal system (OXY-TDS) (Oxytrol), Watson Pharma, Corona, CA, USA) in the Multicentre Assessment of Transdermal Therapy in Overactive Bladder With Oxybutynin (MATRIX) study, as HRQoL measurements are increasingly important in evaluating pharmacotherapy for overactive bladder (OAB).

Patients And Methods: This randomized, open-label, community-based study enrolled 2878 participants aged >/=18 years who had been given a diagnosis of OAB. The 327 study sites were representative of various practice types.

HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease).

Autosomal recessive severe congenital neutropenia (SCN) constitutes a primary immunodeficiency syndrome associated with increased apoptosis in myeloid cells, yet the underlying genetic defect remains unknown. Using a positional cloning approach and candidate gene evaluation, we identified a recurrent homozygous germline mutation in HAX1 in three pedigrees. After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann.

The impact of the overactive bladder syndrome on sexual function: a preliminary report from the Multicenter Assessment of Transdermal Therapy in Overactive Bladder with Oxybutynin trial.

Objective: The objective of the study was to determine the impact of overactive bladder on sexual function from a preliminary analysis of the Multicenter Assessment of Transdermal Therapy in Overactive Bladder with Oxybutynin study.

Study Design: The Multicenter Assessment of Transdermal Therapy in Overactive Bladder with Oxybutynin study was an open-label, prospective trial of 2878 subjects with overactive bladder, treated with transdermal oxybutynin for 6 months or less. The impact of overactive bladder on sexual function before and after treatment was assessed via item responses from the King's Health Questionnaire and Beck Depression Inventory-II (kappa-test).

Constitutional downregulation of SEMA5A expression in autism.

There is strong evidence for the importance of genetic factors in idiopathic autism. The results from independent twin and family studies suggest that the disorder is caused by the action of several genes, possibly acting epistatically. We have used cDNA microarray technology for the identification of constitutional changes in the gene expression profile associated with idiopathic autism.

A founder mutation for ichthyosis prematurity syndrome restricted to 76 kb by haplotype association.

Autosomal recessive congenital ichthyosis (ARCI) is a group of keratinisation disorders that includes the ichthyosis prematurity syndrome (IPS). IPS is rare and almost exclusively present in a restricted region in the middle of Norway and Sweden, which indicates a founder effect for the disorder. We recently reported linkage of IPS to chromosome 9q34, and we present here the subsequent fine-mapping of this region with known and novel microsatellite markers as well as single nucleotide polymorphisms (SNPs).

Familial Ménière's disease in five generations.

Objective: Clinical characterization of a Swedish family followed for five generations. Several members of each generation had Ménière's disease (MD). Possible modes of genetic transmission were assessed.

Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23.

Autosomal dominant leukodystrophy (ADLD) with autonomic symptoms is a slowly progressive leukodystrophy with an onset in the 4th to 6th decade of life. Early symptoms are derived from the autonomic nervous system with bladder dysfunction in the majority of patients. The disease progresses slowly with loss of fine motor skills, ataxia, and affected individuals may survive for two decades after onset of symptoms.

Variant phenotype of Best vitelliform macular dystrophy associated with compound heterozygous mutations in VMD2.

Purpose: To characterize the phenotype of members of a Swedish family with Best macular dystrophy and two distinct mutations in VMD2.

Methods: Venous blood samples were obtained from six family members and screened for mutations in VMD2. Six individuals were examined clinically, four of whom were further investigated with full-field electroretinography (ERG), electro-oculography (EOG), multifocal electroretinography (mfERG), and optical coherence tomography (OCT).

A Meniere's disease gene linked to chromosome 12p12.3.

Meniere's disease (MD) is characterized by spontaneous attacks of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The majority of patients with MD appear sporadic but 5%-13% of the cases have a family history for the disease. The cause of both the sporadic and inherited forms of MD remains unclear despite a number of candidate genes defined from their association with hearing loss.