Myometrial Defect in a Subsequent Pregnancy After Uterine Artery Embolization for Postpartum Hemorrhage, in the Absence of Leiomyomas or Previous Uterine Surgery.

BACKGROUND: Pregnancy occurring after uterine artery embolization are often complicated by adverse fetal and obstetric outcomes. CASE: This report describes the case of a myometrial defect in a subsequent pregnancy after uterine artery embolization for postpartum hemorrhage. A 26-year-old G2, P2 woman had a vaginal delivery of twins 2 years earlier that required uterine artery embolization for postpartum hemorrhage. In this case, she presented at 183 weeks gestation with pelvic pain and an ultrasound scan revealing an area of myometrium measuring 3.2 mm. The myometrium progressively thinned to 0.7 mm at 32 weeks. After cesarean hysterectomy, pathologic examination revealed large myometrial defects separate from the placenta increta. CONCLUSION: Given the myometrial defects and placenta increta observed in a pregnancy after uterine artery embolization without documented fibroids or uterine surgery, consideration should be given to antenatal myometrial thickness surveillance.

Robotic-assisted vesicovaginal fistula repair using an extravesical approach without interposition grafting.

BACKGROUND: Post-hysterectomy vesicovaginal fistula (VVF) is rare. In addition to conventional abdominal and vaginal approaches, robotic-assisted VVF repairs have recently been described. We present a case of an extravesical, robotic-assisted VVF repair, without placement of an interposition graft performed in a Canadian teaching center. CASE: A 51-year-old woman presented with urinary incontinence 5 days after laparoscopic hysterectomy. Computed tomography cystogram, cystoscopy, and methylene blue dye test, confirmed a VVF above the bladder trigone. The patient underwent a robotic-assisted VVF repair 3 months after presentation, without complication. An abdominal, extravesical approach was used. Operative time was 116 min and repeat CT cystogram showed no evidence of persistent. CONCLUSION: We have demonstrated that a VVF repair, using a robotic-assisted, extravesical approach without interposition graft placement, can be safe, less invasive and have a successful outcome at 1 year of follow-up.

To fast or feed: an alternative life history for anadromous brook trout Salvelinus fontinalis overwintering within a harbour.

The seasonal feeding pattern of sea-run brook trout Salvelinus fontinalis was studied from November to May 2010-2012 in Antigonish Harbour, Nova Scotia, Canada (45° 38' N; 61° 55' W). Sixty-three S. fontinalis (mean ± s.d. fork length = 330 ± 70 mm and mass = 536 ± 351 g) captured had fed predominantly on fishes (Fundulidae and Gasterosteidae). Percentage of empty stomachs was highest during autumn (18%) and winter (22%) and lowest in spring (7%). Stomach fullness increased from autumn to a maximum during winter, relating to near-zero body temperatures which may have effectively stopped gastric evacuation. Although feeding occurred during winter (December to March), consumption rates were calculated as negative values, and subsequently returned to positive values in spring (April to May). The over-winter life-history strategy of this sea-run S. fontinalis population appears to be a feeding marine migration in which fish continually increase body condition, representing an alternative to the more common overwintering strategy of starvation in fresh water until spring.

Confirmation that Xq27 and Xq28 are susceptibility loci for migraine in independent pedigrees and a case-control cohort.

Investigations into migraine genetics have suggested that susceptibility loci exist on the X chromosome. These reports are supported by evidence that demonstrates male probands as having a higher proportion of affected first-degree relatives as well as the female preponderance of 3:1 that the disorder displays. We have previously implicated the Xq24-28 locus in migraine using two independent multigenerational Australian pedigrees that demonstrated excess allele sharing at the Xq24, Xq27 and Xq28 loci. Here, we expand this work to investigate a further six independent migraine pedigrees using 11 microsatellite markers spanning the Xq27­28 region. Furthermore, 11 candidate genes are investigated in an Australian case-control cohort consisting of 500 cases and 500 controls. Microsatellite analysis showed evidence of excess allele sharing to the Xq27 marker DXS8043 (LOD* 1.38 P00.005) in MF879 whilst a second independent pedigree showed excess allele sharing to DXS8061 at Xq28 (LOD* 1.5 P00.004). Furthermore, analysis of these key markers in a case control cohort showed significant association to migraine in females at the DXS8043 marker (T1 P00.009) and association with MO at DXS8061 (T1 P00.05). Further analysis of 11 key genes across these regions showed significant association of a three-marker risk haplotype in the NSDHL gene at Xq28 (P00.0082). The results of this study add further support to the presence of migraine susceptibility loci on chromosome Xq27 and Xq28 as well as point to potential candidate genes in the regions that warrant further investigation.

Association study of calcitonin gene-related polypeptide-alpha (CALCA) gene polymorphism with migraine.

Migraine is a neurological disorder that is associated with increased levels of calcitonin gene-related peptide (CGRP) in plasma. CGRP, being one of the mediators of neurogenic inflammation and a phenomenon implicated in the pathogenesis of migraine headache, is thus suggested to have an important role in migraine pathophysiology. Polymorphisms of the CALCA gene have been linked to Parkinson's disease, ovarian cancer and essential hypertension, suggesting a functional role for these polymorphisms. Given the strong evidence linking CGRP and migraine, it is hypothesised that polymorphisms in the CALCA gene may play a role in migraine pathogenesis. Seemingly non functional intronic polymorphisms are capable of disrupting normal RNA processing or introducing a splice site in the transcript. A 16bp deletion in the first intron of the CALCA gene has been reported to be a good match for the binding site for a transcription factor expressed strongly in neural crest derived cells, AP-2. This deletion also eliminates an intron splicing enhancer (ISE) that may potentially cause exon skipping. This study investigated the role of the 16bp intronic deletion in the CALCA gene in migraineurs and matched control individuals. Six hundred individuals were genotyped for the deletion by polymerase chain reaction followed by fragment analysis on the 3130 Genetic Analyser. The results of this study showed no significant association between the intronic 16bp deletion in the CALCA gene and migraine in the tested Australian Caucasian population. However, given the evidence linking CGRP and migraine, further investigation of variants with this gene may be warranted.

Association of a Notch 3 gene polymorphism with migraine susceptibility.

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) shares common symptoms with migraine. Most CADASIL causative mutations occur in exons 3 and 4 of the Notch 3 gene. This study investigated the role of C381T (rs 3815188) and G684A (rs 1043994) single nucleotide polymorphisms (SNP) in exons 3 and 4, respectively, of the Notch 3 gene in migraine. RESULTS: The first part of the study, in a population of 275 migraineurs and 275 control individuals, found a significant association between the C381T variant and migraine, specifically in migraine without aura (MO) sufferers. The G684A variant was also found to be significantly associated with migraine, specifically in migraine with aura (MA) sufferers. A follow-up study in 300 migraineurs and 300 control individuals did not show replicated association of the C381T variant with migraineurs. However, the G684A variant was again shown to be significantly associated with migraine, specifically with MA. CONCLUSION: Further investigation of the G684A variant and the Notch 3 gene is warranted to understand their role in migraine.

Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk.

BACKGROUND: The nature of the relationship between duration of the pre-diagnostic interval in schizophrenia and better outcomes remains unclear. AIMS: To re-examine data from one of the earliest studies suggesting an association between long pre-treatment interval and compromised outcome, assessing the relationship between symptomatic and social variables and increased relapse risk at 1 year. METHOD: Symptomatic, social and demographic data from participants in the Northwick Park Study of First Episodes who completed 12-month follow-up (n = 101) were re-analysed in the context of duration of untreated illness (DUI). RESULTS: At admission, those with long DUI were more likely to have lower scores on tension derived from the Present State Examination, exhibited more behaviour threatening to others and more bizarre behaviour, were more likely to be single, to live alone or dependently, to be unemployed and to have experienced more adverse life events prior to admission. Logistic regression showed that diminished tension, bizarre behaviour and unemployed status independently increased the risk of relapse, bizarre behaviour making the single biggest contribution. Tension did not remain significant with log-transformation of data. CONCLUSIONS: Findings are consistent with the conclusion that long DUI can reflect characteristics of the psychosis itself rather than delay in treatment.

Association between migraine and a functional polymorphism at the dopamine beta-hydroxylase locus.

Migraine is a common neurological disorder with a significant genetic component. Although a number of linkage and association studies have been undertaken, the number and identity of all migraine susceptibility genes has yet to be defined. The existence of dopaminergic hypersensitivity in migraine has been recognised on a pharmacological basis and some studies have reported genetic association between migraine and dopamine-related gene variants. Our laboratory has previously reported association of migraine with a promoter STR marker in the dopamine beta hydroxylase (DBH) gene. In the present study, we analysed two additional DBH markers in two independent migraine case-control cohorts. These two markers are putative functional SNPs, one within the promoter (-1021C-->T) and another SNP (+1603C-->T) in exon 11 of the DBH gene. The results showed a significant association for allelic and genotypic frequency distribution between the DBH marker in the promoter and migraine in the first (P = 0.004 and P = 0.012, respectively) and the second (P = 0.013 and P = 0.031, respectively) tested cohorts. There was no association observed between either genotype and/or allelic frequencies for the DBH marker located in exon 11 and migraine (P > or = 0.05). The promoter DBH marker, reported associated with migraine in this study, has been shown to affect up to 52% of plasma DBH activity. Varying DBH activity levels have been postulated to be involved in migraine process with an increase of dopamine, resulting from a lower DBH activity shown positively correlated with migraine severity. It is plausible that the functional promoter variant of DBH may play a role in the migraine disorder.

Effects of SCA1, MJD, and DPRLA triplet repeat polymorphisms on cognitive phenotypes in a normal population of adolescent twins.

The expansion of unstable trinucleotide CAG repeat polymorphisms of a number of genes causes several neurodegenerative disorders with decreased cognitive function, the severity of the disorder being related to allele length at the triplet repeat locus. While the effects of repeat length have been well studied in clinical samples, there has been little investigation of the effects of triplet repeat variation in the normal range for these genes. We have, therefore, examined linkage and association for three CAG triplet repeat markers (Spinocerebellar Ataxia Type 1, SCA1; Machado-Joseph Disease, MJD; Dentatorubro-pallidoluysian Atrophy, DRPLA) to assess their contribution to variation in cognitive ability (IQ, reading ability, processing speed) in a normal, unselected sample of adolescent twins (248 dizygotic (DZ) sibling pairs, aged 16 years). Association tests, performed in Mx and QTDT, showed a consistent positive association of SCA1 with Arithmetic (P = 0.04). While association was supported between SCA1 and Cambridge reading scores and between DRPLA and inspection time, results were inconsistent across software packages. Given the number of statistical tests performed, it is unlikely that trinucleotide repeat variation in the normal range for these genes influences variation in normal cognition.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility.

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5' and 3' regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5' region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5' repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5' and 3' genetic variants were investigated.

Analysis of chromosome 1 microsatellite markers and the FHM2-ATP1A2 gene mutations in migraine pedigrees.

OBJECTIVES: The aims of the study were: (i) to extend our linkage analysis of chromosome 1q microsatellite markers in predominantly migraine with aura pedigrees and (ii) to test the novel FHM-2 ATP1A2 gene for involvement in these migraine affected pedigrees and a previous pedigree (MF14) showing evidence of linkage of markers to C1q31. METHODS: A chromosome 1 scan (31 markers) was performed in 21 multiplex pedigrees affected predominantly with migraine with aura (MA). The known FHM-2 ATP1A2 gene mutations were tested, by sequencing, for the involvement in MA and migraine without aura (MO) in these pedigrees. Sequencing was performed in the coding areas of the ATP1A2 gene through three MA individuals from MF14. RESULTS: Evidence for linkage was obtained at C1q23 to markers spanning the ATP1A2 gene. However, testing of the known ATP1A2 gene mutations (for FHM) in common migraine probands of pedigrees showing excess allele sharing was negative. Sequencing of the entire coding areas of the gene through all the three MA affected from MF14 was also negative for mutations. DISCUSSION: Microsatellite markers on chromosome 1q23 show evidence of excess allele sharing in MA and some MO pedigrees, suggesting linkage to the common forms of migraine and the presence of a susceptibility gene in this region. The FHM-2 (ATP1A2 gene) does not seem to be involved in the common types of migraine. Despite certain clinical characteristics, the genetic correlation between FHM and familial typical migraine remains unclear. Several candidate genes lie within the C1q23 and C1q31 cytogenetic regions; therefore, further studies are needed.

Serum TGF-beta 1 and TNF-alpha levels and cardiac fibrosis in experimental chronic renal failure.

OBJECTIVES: To characterize dynamics of changes of serum levels of TGF-beta1 and TNF-alpha in rats with cardiac fibrosis (CF) occurring during chronic renal failure (CRF), and to reveal the character pf correlations of these factors with amounts of cardiac collagen. DESIGN AND METHODS: CRF was induced by unilateral nephrectomy and by electrocoagulation of 25% of the cortex of remnant kidney. Post-operative checkpoints were 2, 4, and 6 months. Serum TGF-beta1 and TNF-alpha levels were measured by ELISA. RESULTS: CF became pronounced only at 6 months of CRF, while serum TGF-beta1 concentrations reached maximum at 4 months, i.e., at the checkpoint preceding the development of CF. Multiple regression showed cardiac collagen to correlate with both serum TGF-beta1 levels and time from the onset of CRF. Sensitivity and specificity of TGF-beta1 as serum marker of CF were 86% and 75%.

A genome-wide scan provides evidence for loci influencing a severe heritable form of common migraine.

Migraine is a prevalent neurovascular disease with a significant genetic component. Linkage studies have so far identified migraine susceptibility loci on chromosomes 1, 4, 6, 11, 14, 19 and X. We performed a genome-wide scan of 92 Australian pedigrees phenotyped for migraine with and without aura and for a more heritable form of "severe" migraine. Multipoint non-parametric linkage analysis revealed suggestive linkage on chromosome 18p11 for the severe migraine phenotype (LOD*=2.32, P=0.0006) and chromosome 3q (LOD*=2.28, P=0.0006). Excess allele sharing was also observed at multiple different chromosomal regions, some of which overlap with, or are directly adjacent to, previously implicated migraine susceptibility regions. We have provided evidence for two loci involved in severe migraine susceptibility and conclude that dissection of the "migraine" phenotype may be helpful for identifying susceptibility genes that influence the more heritable clinical (symptom) profiles in affected pedigrees. Also, we concluded that the genetic aetiology of the common (International Headache Society) forms of the disease is probably comprised of a number of low to moderate effect susceptibility genes, perhaps acting synergistically, and this effect is not easily detected by traditional single-locus linkage analyses of large samples of affected pedigrees.

RETIRED: Choice of surgery for stress incontinence.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Investigation of the low-density lipoprotein receptor gene and cholesterol as a risk factor for migraine.

The Low-Density Lipoprotein Receptor (LDLR) gene is a cell surface receptor that plays an important role in cholesterol homeostasis. We investigated the (TA)n polymorphism in exon 18 of the LDLR gene on chromosome 19p13.2 performing an association analysis in 244 typical migraine-affected patients, 151 suffering from migraine with aura (MA), 96 with migraine without aura (MO) and 244 unaffected controls. The populations consisted of Caucasians only, and controls were age- and sex-matched. The results showed no significant difference between groups for allele frequency distributions of the (TA)n polymorphism even after separation of the migraine-affected individuals into subgroups of MA and MO affected patients. This is in contradiction to Mochi et al. who found a positive association of this variant with MO. Our study discusses possible differences between the two studies and extends this research by investigating circulating cholesterol levels in a migraine-affected population.

Adult onset Krabbe disease may mimic motor neurone disease.

Krabbe's disease (galactocerebrosidase deficiency) rarely presents in adults, usually with predominantly upper motor neurone clinical features. We report a case in whom the clinical features were similar to motor neurone disease. Nerve conduction studies and neuroimaging were important in leading to the correct diagnosis. Differences in adult-onset presentations are described.

RETIRED: Tension-free vaginal tape (TVT) procedure.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim.

This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34(+) yield 0.5-1.9 x 10(6)/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20 microg/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20 microg/kg/day plus filgrastim 5-10 microg/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of >or=3 x 10(6) CD34(+) cells/kg. In both groups, CD34(+) yield (x 10(6)/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 10(6)/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 10(6)/kg BW in the prior mobilization as in those with 0.76-1.99 x 10(6)/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34(+) cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.

Telemedicine and clinical genetics: establishing a successful service.

There is a surprising lack of published experience on the use of videoconferencing in clinical genetics. Patients were randomly allocated to either a telegenetic (cases) or face-to-face (control) conventional clinic. The telegenetic consultation was done by videoconferencing, using ISDN lines at 384 kbit/s. Evaluation by the doctor and counsellor took place immediately after each appointment. The patient was asked to evaluate the appointment by telephone questionnaire about four weeks after the event. Forty-two patients were invited to participate and 33 (79%) returned their consent forms. Four patients declined to participate and were seen in ordinary face-to-face clinics. Preliminary results showed that the assessment of the telegenetics consultations by doctors, counsellors and patients was very favourable, and they responded positively when asked if they would be happy to use telemedicine in the future. For use in selected consultations, videoconferencing does appear to fulfil a useful role in clinical genetics.