Experimental upper bound and theoretical expectations for parity-violating neutron spin rotation in 4He.

Neutron spin rotation is expected from quark-quark weak interactions in the standard model, which induce weak interactions among nucleons that violate parity. We present the results from an experiment searching for the effect of parity violation via the spin rotation of polarized neutrons in a liquid 4He medium. The value for the neutron spin rotation angle per unit length in 4He, d ϕ / d z = [ + 2.1 ± 8.3 (stat.) - 0.2 + 2.9 (sys.) ] × 10 - 7 rad/m, is consistent with zero. The result agrees with the best current theoretical estimates of the size of nucleon-nucleon weak amplitudes from other experiments and with the expectations from recent theoretical approaches to weak nucleon-nucleon interactions. In this paper we review the theoretical status of parity violation in the n → + 4He system and discuss details of the data analysis leading to the quoted result. Analysis tools are presented that quantify systematic uncertainties in this measurement and that are expected to be essential for future measurements.

A slow neutron polarimeter for the measurement of parity-odd neutron rotary power.

We present the design, description, calibration procedure, and an analysis of systematic effects for an apparatus designed to measure the rotation of the plane of polarization of a transversely polarized slow neutron beam as it passes through unpolarized matter. This device is the neutron optical equivalent of a crossed polarizer/analyzer pair familiar from light optics. This apparatus has been used to search for parity violation in the interaction of polarized slow neutrons in matter. Given the brightness of existing slow neutron sources, this apparatus is capable of measuring a neutron rotary power of dϕ/dz = 1 × 10(-7) rad/m.

Morinda citrifolia (Noni) as an Anti-Inflammatory Treatment in Women with Primary Dysmenorrhoea: A Randomised Double-Blind Placebo-Controlled Trial.

Introduction. Noni (Morinda citrifolia) has been used for many years as an anti-inflammatory agent. We tested the efficacy of Noni in women with dysmenorrhea. Method. We did a prospective randomized double-blind placebo-controlled trial in 100 university students of 18 years and older over three menstrual cycles. Patients were invited to participate and randomly assigned to receive 400 mg Noni capsules or placebo. They were assessed for baseline demographic variables such as age, parity, and BMI. They were also assessed before and after treatment, for pain, menstrual blood loss, and laboratory variables: ESR, hemoglobin, and packed cell volume. Results. Of the 1027 women screened, 100 eligible women were randomized. Of the women completing the study, 42 women were randomized to Noni and 38 to placebo. There were no significant differences in any of the variables at randomization. There were also no significant differences in mean bleeding score or pain score at randomization. Both bleeding and pain scores gradually improved in both groups as the women were observed over three menstrual cycles; however, the improvement was not significantly different in the Noni group when compared to the controls. Conclusion. Noni did not show a reduction in menstrual pain or bleeding when compared to placebo.

Acute pyelonephritis in pregnancy: a retrospective descriptive hospital based-study.

Introduction. Pyelonephritis is a common complication of pregnancy. It is also exacerbated by immunocompromised states and also the sickle cell gene. We reviewed this condition in Jamaican women. Method. We did a six year hospital database docket review. We found 102 confirmed cases. Results. Pyelonephritis was found in 0.7% of deliveries. The mean maternal age was 24 ± 5.83 years with 51% primiparity. Most (58.8%) occurred in the second trimester. The main symptoms were loin pain (96.2%) and abdominal pain (84.6%). It was more common on the right side in 67% of cases. On urinalysis, 81.4% had pyuria. The commonest organism was Escherichia coli, in 61% of cases. Patients given Antibiotics prior to admission had quicker resolution, P < 0.02. Haemoglobin S was found in 16% cases (general population 10%; P = 0.002). However diabetes was only found in 1.3% cases (1.5% expected). 61.3% had positive urine culture after treatment showed that 61.3% and 25% had recurrent pyelonephritis. Complications included 32% threatened preterm labour and 17% preterm delivery. About 6% of neonates had intrauterine growth restriction. There were no ICU admissions and no deaths. Conclusion. Early recognition and treatment of pyelonephritis result in good outcome. The condition is more prevalent in patients with the sickle cell gene and recurrence is high.

A first-in-human phase I trial of locally delivered human plasmin for hemodialysis graft occlusion.

BACKGROUND: Hemodialysis (HD) grafts often fail because of stenosis at the venous anastomosis and thrombotic occlusion. Percutaneous management relies on thrombolysis with plasminogen activators, mechanical removal of thrombus, and angioplasty of the stenotic lesion. OBJECTIVES: This report describes a phase I trial using Plasmin (Human) TAL 05-00018, a direct-acting fibrinolytic agent, to evaluate safety and, secondarily, to establish effective thrombolytic dosing. PATIENTS/METHODS: Six cohorts of five patients with acute HD graft occlusion documented by angiography were treated with escalating dosages of plasmin (1, 2, 4, 8, 12, and 24 mg) infused over 30 min via criss-crossed pulse-spray catheters within the graft. The primary efficacy endpoint was > or =50% thrombolysis, as determined by comparison of pre-plasmin and 30-min post-plasmin fistulograms. RESULTS: Of 31 subjects who received study drug (safety population), one withdrew and 30 completed the trial (evaluable for efficacy). There was no significant change in plasma alpha-2 antiplasmin or fibrinogen concentration, major bleeding did not occur, and there were no deaths. Serious adverse events in four patients were not related to the study drug. There was a dose-response relationship for the primary efficacy endpoint, all five subjects receiving 24 mg achieving >75% lysis. CONCLUSIONS: This first phase I study of Plasmin (Human) TAL 05-00018, infused into thrombosed HD grafts, documents safety at dosages of 1-24 mg and an effective thrombolytic dosage of 24 mg. The results establish a foundation for further clinical study of catheter-based plasmin administration in thrombotic disorders.

Topical analgesia for acute otitis media.

BACKGROUND: Acute otitis media (AOM) is a spontaneously remitting disease for which pain is the most distressing symptom. Antibiotics are now known to have less benefit than previously assumed. OBJECTIVES: To assess the effectiveness of topical analgesia for AOM. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to May Week 3 2006), EMBASE (1990 to December 2005) and LILACS (1982 to September 2005) without language restriction, and the reference lists of articles. We also contacted manufacturers and authors. SELECTION CRITERIA: Double-blind randomised or quasi-randomised controlled trials comparing an otic preparation with an analgesic effect (excluding antibiotics) versus placebo or an otic preparation with an analgesic effect (excluding antibiotics) versus any other otic preparation with an analgesic effect, in adults or children presenting at primary care settings with AOM without perforation. DATA COLLECTION AND ANALYSIS: Potential studies were screened independently and trial quality was assessed by three authors, and differences were resolved by discussion. Data was then independently extracted from the trials selected by two authors. We contacted the authors of three trials to acquire additional information not available in published articles. MAIN RESULTS: Our searches yielded 356 records; four trials met our criteria. One trial with 54 participants compared treatment with anaesthetic ear drops versus an olive oil placebo immediately at diagnosis. All patients were also given paracetamol. There was a statistically significant pain reduction of 25% in those receiving anaesthetic drops 30 minutes after instillation. Three trials (with one common co-author) compared anaesthetic ear drops with naturopathic herbal ear drops in 274 patients. One of these trials also used antibiotics in both groups. There were statistically significant differences at instillation of drops, or 15 or 30 minutes after the instillation (or both) on one to three days after diagnosis, always favouring the naturopathic group in each trial. AUTHORS' CONCLUSIONS: The evidence from these four randomised controlled trials, only one of which addresses the most relevant question of primary effectiveness, is insufficient to know whether ear drops are effective or not.

Haplotyping of the canine MHC without the need for DLA typing.

The genomic matching technique has proven useful in MHC haplotyping in humans. We have adopted a similar approach in Australian cattle dogs and report that genotyping can be achieved with a single assay.

Measurement of the Parity-Violating Neutron Spin Rotation in (4) He.

In the meson exchange model of weak nucleon-nucleon (NN) interactions, the exchange of virtual mesons between the nucleons is parameterized by a set of weak meson exchange amplitudes. The strengths of these amplitudes from theoretical calculations are not well known, and experimental measurements of parity-violating (PV) observables in different nuclear systems have not constrained their values. Transversely polarized cold neutrons traveling through liquid helium experience a PV spin rotation due to the weak interaction with an angle proportional to a linear combination of these weak meson exchange amplitudes. A measurement of the PV neutron spin rotation in helium (φ PV ( n ,α)) would provide information about the relative strengths of the weak meson exchange amplitudes, and with the longitudinal analyzing power measurement in the p + α system, allow the first comparison between isospin mirror systems in weak NN interaction. An earlier experiment performed at NIST obtained a result consistent with zero: φ PV ( n ,α) = (8.0 ±14(stat) ±2.2(syst)) ×10(-7) rad / m[1]. We describe a modified apparatus using a superfluid helium target to increase statistics and reduce systematic effects in an effort to reach a sensitivity goal of 10(-7) rad/m.

Hereditary sensory neuropathy type I: haplotype analysis shows founders in southern England and Europe.

Hereditary sensory neuropathy type I (HSN1) is the most common dominantly inherited degenerative disorder of sensory neurons. The gene mutation was mapped to chromosome 9 in a large Australian family, descended from an ancestor from southern England who was a convict. Dawkins et al. recently reported gene mutations in the SPTLC1 gene, in this and other families. The first description of hereditary sensory neuropathy, by Hicks, was in a family from London and Exeter. To determine if the families in the present study that have SPTLC1 mutations are related to English families with HSN1 and, possibly, to the family studied by Hicks, we performed haplotype analysis of four Australian families of English extraction, four English families, and one Austrian family. Three Australian families of English extraction and three English families (two of whom have been described elsewhere) had the 399T-->G SPTLC1 mutation, the same chromosome 9 haplotype, and the same phenotype. The Australian and English families may therefore have a common founder who, on the basis of historical information, has been determined to have lived in southern England prior to 1800. The sensorimotor neuropathy phenotype caused by the 399T-->G SPTLC1 mutation is the same as that reported by Campbell and Hoffman and, possibly, the same as that originally described by Hicks.

Regulation of caltrin mRNA expression by androgens in the murine prostate.

Testicular androgens induce the proliferation and differentiation of prostatic epithelial cells by regulating the expression of androgen target genes. The use of subtractive hybridization to isolate genes that are differentially expressed during the early phase of androgen-induced prostatic regrowth in castrated mice resulted in identification of the murine caltrin gene. Caltrin messenger RNA (mRNA) was highly expressed in the prostates of intact mice. Five weeks following castration of mice, steady state caltrin mRNA levels were reduced by 70%. Within 12 hours of administration of pharmacological doses of testosterone enanthate, steady state caltrin mRNA levels were elevated and increased to 90% of levels found in intact mice by 24 hours. Reverse transcriptase-polymerase chain reaction analysis of prostate tissue localized caltrin mRNA transcripts to the dorsal but not the ventral or lateral prostate. Within the dorsal prostate, in situ hybridization always localized caltrin mRNAs to the prostatic epithelial cells. Testosterone-induced increases in caltrin mRNA levels were detected prior to S-phase progression and initiation of proliferation in this cell population. Caltrin has been demonstrated previously to function as a calcium transport inhibitor at the plasma membrane. Findings of this study indicate that caltrin is highly expressed and androgen-regulated in the murine prostate, where it is associated with androgen-induced proliferation and differentiation of epithelial cells.

Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I.

Hereditary sensory neuropathy type I (HSN1) is the most common hereditary disorder of peripheral sensory neurons. HSN1 is an autosomal dominant progressive degeneration of dorsal root ganglia and motor neurons with onset in the second or third decades. Initial symptoms are sensory loss in the feet followed by distal muscle wasting and weakness. Loss of pain sensation leads to chronic skin ulcers and distal amputations. The HSN1 locus has been mapped to chromosome 9q22.1-22.3 (refs. 3,4). Here we map the gene SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, to this locus. Mutation screening revealed 3 different missense mutations resulting in changes to 2 amino acids in all affected members of 11 HSN1 families. We found two mutations to be located in exon 5 (C133Y and C133W) and one mutation to be located in exon 6 of SPTLC1 (V144D). All families showing definite or probable linkage to chromosome 9 had mutations in these two exons. These mutations are associated with increased de novo glucosyl ceramide synthesis in lymphoblast cell lines in affected individuals. Increased de novo ceramide synthesis triggers apoptosis and is associated with massive cell death during neural tube closure, raising the possibility that neural degeneration in HSN1 is due to ceramide-induced apoptotic cell death.

Exclusion of NFIL3 as the gene causing hereditary sensory neuropathy type I by mutation analysis.

Hereditary sensory neuropathy type I (HSN-I) is an autosomal dominant peripheral neuropathy affecting sensory and motor neurons. The disease involves distal sensory loss, distal muscle wasting and weakness, and variable neural deafness. The HSN1 locus has been mapped to a genetic interval of 3-4 cM on chromosome 9q22.1-q22.3 and is flanked by markers D9S1781 and FB19B7. This interval contains the gene NFIL3, a transcription factor that is regulated by the cytokine IL-3. Northern blot analysis of NFIL3 showed a ubiquitously expressed 2.2-kb mRNA. Expression was highest in the lung, with lower levels of expression in the brain and spinal cord. Mutation analysis by direct sequencing of reverse transcription/polymerase chain reaction products from HSN-I patients excluded the coding region of the NFIL3 from being involved in the pathogenesis of HSN-I.

A YAC-based transcript map of human chromosome 9q22.1-q22.3 encompassing the loci for hereditary sensory neuropathy type I and multiple self-healing squamous epithelioma.

Hereditary sensory neuropathy type I (HSN-I) is an autosomal dominant peripheral neuropathy, involving sensory and motor neurons. The disease involves distal sensory loss, distal muscle wasting and weakness, and variable neural deafness. The HSN-I locus has been mapped to a 3- to 4-cM genetic interval on chromosome 9q22.1-q22.3. As part of a positional cloning effort to identify the HSN-I gene, we have generated a YAC based transcript map that spans approximately 8 Mb between D9S318 and D9S1786. This transcript map encompasses both the HSN-I critical interval and the locus for multiple self-healing squamous epithelioma (MSSE, previously named ESS1). Forty two ESTs and six characterized genes have been localized across 10 YAC clones, within a framework of 19 genetic linkage markers. Three other characterized genes were localized immediately adjacent to this interval. We have accurately mapped two recently identified genes: NINJ1 was anchored to D9S12II, and the localization of the NOR1 gene was significantly refined. We have also investigated NOR1 and several other characterized genes that localize to chromosome 9q22 for a pathogenic role in HSN-I. This map provides candidate genes for HSN-I and MSSE and is an important step toward completing a functional map of this gene-rich interval.

Evidence for an X-linked genetic component in familial typical migraine.

Migraine is a common complex disorder that shows strong familial aggregation. There is a general increased prevalence of migraine in females compared with males, with recent studies indicating that migraine affects 18% of females compared with 6% of males. This preponderance of females among migraine sufferers coupled with evidence of an increased risk of migraine in first degree relatives of male probands but not in relatives of female probands suggests the possibility of an X-linked dominant gene. We report here the localization of a typical migraine susceptibility locus to the X chromosome. Of three large multigenerational migraine pedigrees two families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigrees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the localization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male probands and may be involved in the increased female prevalence of this disorder.

The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene.

Misalignment between the two elements of the CMT1A-REP binary repeat on chromosome 17p11.2-p12 causes two inherited peripheral neuropathies, Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies. This binary repeat contains repetitive DNA elements that include LINES, SINES, medium reiteration frequency repeats, and a transposon-like element. The COX10 gene has been mapped 10 kb centromeric to the distal CMT1A-REP element, and a portion of this gene is present in both the proximal and the distal CMT1A-REP elements. We report the isolation and characterization of a novel cDNA (C170RF1), which maps centromeric to and partially within the proximal CMT1A-REP element. Part of C170RF1 is transcribed from the opposite strand of the COX10 partial gene duplication present in the proximal CMT1A-REP element. This finding shows that C170RF1 and COX10 are being transcribed from opposite strands of identical DNA sequences that are separated by 1.5 Mb in the genome. RT-PCR analysis showed the proximal transcript was expressed in skeletal muscle. Sequence analysis identified an open reading frame encoding a 199-amino-acid protein. Zoo blot analysis showed that the transcript is conserved in nonhuman primates. The presence of a binary repeat contributes to the instability of this region of chromosome 17, yet two CMT1A-REP elements are present in the chimpanzee and all human populations. The presence of expressed sequences in both elements of the CMT1A-REP binary repeat could explain the maintenance of this repeat in humans.

Drug abuse in pregnancy: obstetric and neonatal problems. Ten years' experience.

Drug abuse is an increasing problem and approximately 80% of female drug abusers are of childbearing age. This retrospective case note study reviews 10 years' experience of the management of pregnant drug abusers (n = 57) in the obstetric hospital of a London teaching hospital. Surprisingly, in view of other reports of high morbidity, no significantly increased rates of obstetric and neonatal problems were found when this group was compared with case-matched controls. Thirty-nine per cent of drug abusers managed to reduce and stop their drug use. However, 56% of the infants of drug abusers had withdrawal symptoms. Concern for her unborn child can motivate the pregnant drug abuser to comply with treatment and thus improve the outcome of pregnancy.

Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1-->q22.3: exclusion of GAS1 and XPA.

The peripheral neuropathy, hereditary sensory neuropathy type I (HSN-I) is an autosomal dominant degenerative disorder of sensory and motor neurons. The disease leads to distal sensory loss, distal muscle wasting and weakness, and variable neural deafness. The HSN-I locus was recently mapped to a large genetic interval on chromosome 9q22 that includes the candidate genes GAS1 and XPA. XPA mutations have been shown to cause peripheral neuropathy, and GAS1 is related to the PMP22 gene, which is critical in the pathogenesis of two other peripheral neuropathies. By undertaking extensive genetic linkage analysis within the candidate region, we have refined the HSN-I locus to a critical interval of 3-4 cM. GAS1, XPA, and several other genes that map within the interval initially identified for the disease locus have been investigated and excluded from playing a pathogenic role in HSN-I.

Bullying, physical disability and the paediatric patient.

This study compared the rates and types of bullying in two groups of paediatric outpatients: those attending the Child Development Centre with conditions affecting their appearance or gait and a control group of those attending a general paediatric outpatient clinic with conditions not associated with visible abnormality. The children completed Olweus' self report bullying questionnaire anonymously. Using logistic regression analysis, the most important variables found to increase a child's chance of being bullied were having fewer friends, being alone at playtime, being male and requiring extra help in school. Significantly more of the group from the Child Development Centre were bullied during the term. However, there was no indication that the children attending the Child Development Centre with a visible disability were more likely to be victims than the control group once these four factors were taken into account.

The gene for hereditary sensory neuropathy type I (HSN-I) maps to chromosome 9q22.1-q22.3.

Hereditary sensory neuropathy type I (HSN-I, also known as hereditary sensory and autonomic neuropathy type I (HSAN-I), or hereditary sensory radicular neuropathy) is an autosomal dominant disorder that is the most common of a group of degenerative disorders of sensory neurons. HSN-I was initially recognized as a disease that produced mutilating ulceration leading to amputation of digits (Fig. 1). It was given names such as familial ulcers with mutilating lesions of the extremities and perforating ulcers with osseous atrophy. The disease involves a progressive degeneration of dorsal root ganglion and motor neurons, leading to distal sensory loss and later distal muscle wasting and weakness and variable neural deafness. Sensory deficits include loss of all modalities, particularly loss of sensation to pain and temperature. Skin injuries may lead to chronic skin ulcers, osteomyelitis, and extrusion of bone fragments, especially the metatarsals. Onset of symptoms is in the second or later decades. We undertook a genome screen using linkage analysis in four Australian HSN-I kindreds. We now show that the HSN1 gene maps to an 8-centiMorgan (cM) region flanked by D9S318 and D9S176 on chromosome 9q22.1-q22.3. Multipoint linkage analysis suggests a most likely location at D9S287, within a 4.9-cM confidence interval.