bluuebunny/crossref_metadata_2025 huggingface dataset:
cAMP blocks MAPK activation and sclerotial development via Rap‐1 in a PKA‐independent manner in Sclerotinia sclerotiorum
Authors: Chen Changbin , Dickman Martin B.
Published: December 2004

Sclerotinia sclerotiorum is a filamentous ascomycete phytopathogen able to infect an extremely wide range of cultivated plants. Our previous studies have shown that increases in cAMP levels result in the impairment of the development of the sclerotium, a highly differentiated structure important in the disease cycle of this fungus. cAMP also inhibits the activation of a S. sclerotiorum mitogen‐activated protein kinase (MAPK), which we have previously shown to be required for sclerotial maturation; thus cAMP‐mediated sclerotial inhibition is modulated through MAPK. However, the mechanism(s) by which cAMP inhibits MAPK remains unclear. Here we demonstrate that a protein kinase A (PKA)‐independent signalling pathway probably mediates MAPK inhibition by cAMP. Expression of a dominant negative form of Ras, an upstream activator of the MAPK pathway, also inhibited sclerotial development and MAPK activation, suggesting that a conserved Ras/MAPK pathway is required for sclerotial development. Evidence from bacterial toxins that specifically inhibit the activity of small GTPases, suggested that Rap‐1 or Ras is involved in cAMP action. The Rap‐1 inhibitor, GGTI‐298, restored MAPK activation in the presence of cAMP, further suggesting that Rap‐1 is responsible for cAMP‐dependent MAPK inhibition. Importantly, inhibition of Rap‐1 is able to restore sclerotial development blocked by cAMP. Our results suggest a novel mechanism involving the requirement of Ras/MAPK pathway for sclerotial development that is negatively regulated by a PKA‐independent cAMP signalling pathway. Cross‐talk between these two pathways is mediated by Rap‐1.
A cis‐acting sequence involved in chromosome segregation in Escherichia coli
Authors: Fekete Richard A. , Chattoraj Dhruba K.
Published: December 2004

Eukaryotic chromosomes contain a locus, the centromere, at which force is applied to separate replicated chromosomes. A centromere analogue is also found in some bacterial plasmids and chromosomes, although not yet identified in the well‐studied Escherichia coli chromosome. We aimed to identify centromere‐like sequences in E. coli with the premise that such sequences would be the first to migrate towards the cell poles, away from the cell centre where DNA replication is believed to occur. We have labelled different loci on the chromosome by integrating arrays of binding sites for LacI–EYFP and phage λcI–ECFP and supplying these fusion proteins in trans. Comparison of such pairs of loci suggests the presence of a centromere‐like site close to the origin of replication. Polar migration of the site was dependent on migS, a locus recently implicated in chromosome migration, thus providing strong support for migS being the E. coli centromere.
The human malaria parasite Plasmodium falciparum possesses two distinct dihydrolipoamide dehydrogenases
Authors: McMillan Paul J. , Stimmler Luciana M. , Foth Bernardo J. , McFadden Geoffrey I. , Müller Sylke
Published: December 2004

The Plasmodium falciparum genome contains genes encoding three α‐ketoacid dehydrogenase multienzyme complexes (KADHs) that have central metabolic functions. The parasites possess two distinct genes encoding dihydrolipoamide dehydrogenases (LipDH), which are indispensable subunits of KADHs. This situation is reminiscent of that in plants, where two distinct LipDHs are found in mitochondria and chloroplasts, respectively, that are part of the organelle‐specific KADHs. In this study, we show by reverse transcription polymerase chain reaction (RT‐PCR) that the genes encoding subunits of all three KADHs, including both LipDHs, are transcribed during the erythrocytic development of P. falciparum. Protein expression of mitochondrial LipDH and mitochondrial branched chain α‐ketoacid dihydrolipoamide transacylase in these parasite stages was confirmed by Western blotting. The localization of the two LipDHs to the parasite's apicoplast and mitochondrion, respectively, was shown by expressing the LipDH N‐terminal presequences fused to green fluorescent protein in erythrocytic stages of P. falciparum and by immunofluorescent colocalization with organelle‐specific markers. Biochemical characterization of recombinantly expressed mitochondrial LipDH revealed that the protein has kinetic and physicochemical characteristics typical of these flavo disulphide oxidoreductases. We propose that the mitochondrial LipDH is part of the mitochondrial α‐ketoglutarate dehydrogenase and branched chain α‐ketoacid dehydrogenase complexes and that the apicoplast LipDH is an integral part of the pyruvate dehydrogenase complex which occurs only in the apicoplast in P. falciparum.
The malaria parasite Plasmodium falciparum has only one pyruvate dehydrogenase complex, which is located in the apicoplast
Authors: Foth Bernardo J. , Stimmler Luciana M. , Handman Emanuela , Crabb Brendan S. , Hodder Anthony N. , McFadden Geoffrey I.
Published: December 2004

The relict plastid (apicoplast) of apicomplexan parasites synthesizes fatty acids and is a promising drug target. In plant plastids, a pyruvate dehydrogenase complex (PDH) converts pyruvate into acetyl‐CoA, the major fatty acid precursor, whereas a second, distinct PDH fuels the tricarboxylic acid cycle in the mitochondria. In contrast, the presence of genes encoding PDH and related enzyme complexes in the genomes of five Plasmodium species and of Toxoplasma gondii indicate that these parasites contain only one single PDH. PDH complexes are comprised of four subunits (E1α, E1β, E2, E3), and we confirmed four genes encoding a complete PDH in Plasmodium falciparum through sequencing of cDNA clones. In apicomplexan parasites, many nuclear‐encoded proteins are targeted to the apicoplast courtesy of two‐part N‐terminal leader sequences, and the presence of such N‐terminal sequences on all four PDH subunits as well as phylogenetic analyses strongly suggest that the P. falciparum PDH is located in the apicoplast. Fusion of the two‐part leader sequences from the E1α and E2 genes to green fluorescent protein experimentally confirmed apicoplast targeting. Western blot analysis provided evidence for the expression of the E1α and E1β PDH subunits in blood‐stage malaria parasites. The recombinantly expressed catalytic domain of the PDH subunit E2 showed high enzymatic activity in vitro indicating that pyruvate is converted to acetyl‐CoA in the apicoplast, possibly for use in fatty acid biosynthesis.
Crustal structure of the southern Dabie ultrahigh‐pressure orogen and Yangtze foreland from deep seismic reflection profiling
Authors: Dong Shuwen , Gao Rui , Cong Bolin , Zhao Zhongyan , Liu Xiaochun , Li Sanzhong , Li Qiusheng , Huang Dongding
Published: December 2004

A new 140‐km‐long seismic reflection profile provides a high‐resolution crustal‐scale image of the southern Dabieshan high‐pressure (HP) metamorphic belt and the Yangtze foreland fold‐and‐thrust belt. The seismic image of the stacked section shows that the southern Dabieshan metamorphic terrane and Yangtze foreland belt are separated by a large north‐dipping fault. In the foreland the upper crust is dominated by a series of folds and thrusts formed during the collisional stage in the mid‐Triassic; it was reworked by crustal extension resulting in the formation of a late Jurassic and Cretaceous red‐bed basin. The southern Dabieshan profile shows stacked crustal slabs developed along the margin of the collisional orogenic belt. The Moho reflectors at 10–11 s (∼30–33 km) are seismically prominent and segmented by a number of south‐verging thrusts that were probably developed by foreland‐directed thrusting of the deeply subducted continental crust during exhumation. The seismic reflection profile suggests that structures related to the Triassic–Jurassic subduction and exhumation of the Yangtze plate are preserved despite the severe crustal extension superimposed during the late Mesozoic and Cenozoic.
Complete Tertiary exhumation history of the Menderes massif, western Turkey: an alternative working hypothesis
Authors: Seyitoǧlu Gürol , Işık Veysel , Çemen İbrahim
Published: December 2004

The main exhumation of the Menderes massif, western Turkey, occurred along an originally N‐dipping Datça–Kale main breakaway fault that controlled depositions in the Kale and the Gökova basins during the Oligocene – Early Miocene interval. The isostatically controlled upward bending of the main breakaway fault brings the lower plate rocks to the surface. In the Early Miocene, E–W‐trending N‐ and S‐dipping graben‐bounding faults fragmented the exhumed, dome‐shaped massif. The development of half grabens by rolling master fault hinges has allowed further exhumation of the central Menderes massif. After the Pliocene, high‐angle normal faults cut all of the previous structures. This model suggests that the Menderes massif is a single large metamorphic core complex that has experienced a two‐stage exhumation process.
A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length
Authors: Langbehn DR , Brinkman RR , Falush D , Paulsen JS , Hayden MR ,   on behalf of an International Huntington's Disease Collaborative Group
Published: December 2004

Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from “Will I get HD?” to “When will it manifest?” Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40‐year‐old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG‐related penetrance rates.
Proposal for molecular mechanism of thionins deduced from physico‐chemical studies of plant toxins
Authors: Stec B. , Markman O. , Rao U. , Heffron G. , Henderson S. , Vernon L.P. , Brumfeld V. , Teeter M.M.
Published: December 2004

Abstract:  We propose a molecular model for phospholipid membrane lysis by the ubiquitous plant toxins called thionins. Membrane lysis constitutes the first major effect exerted by these toxins that initiates a cascade of cytoplasmic events leading to cell death. X‐ray crystallography, solution nuclear magnetic resonance (NMR) studies, small angle X‐ray scattering and fluorescence spectroscopy provide evidence for the mechanism of membrane lysis. In the crystal structures of two thionins in the family, α1‐ and β‐purothionins (MW: approximately 4.8 kDa), a phosphate ion and a glycerol molecule are modeled bound to the protein. 31P NMR experiments on the desalted toxins confirm phosphate‐ion binding in solution. Evidence also comes from phospholipid partition experiments with radiolabeled toxins and with fluorescent phospholipids. This data permit a model of the phospholipid–protein complex to be built. Further, NMR experiments, one‐dimensional (1D)‐ and two‐dimensional (2D)‐total correlation spectroscopy (TOCSY), carried out on the model compounds glycerol‐3‐phosphate (G3P) and short chain phospholipids, supported the predicted mode of phospholipid binding. The toxins’ high positive charge, which renders them extremely soluble (>300 mg/mL), and the phospholipid‐binding specificity suggest the toxin–membrane interaction is mediated by binding to patches of negatively charged phospholipids [phosphatidic acid (PA) or phosphatidyl serine (PS)] and their subsequent withdrawal. The formation of proteolipid complexes causes solubilization of the membrane and its lysis. The model suggests that the oligomerization may play a role in toxin's activation process and provides insight into the structural principles of protein–membrane interactions.
An improved large‐scale synthesis of PEG‐peptides for gene delivery
Authors: Chen C.‐P. , Park Y. , Rice K.G.
Published: December 2004

Abstract:  Polyethylene glycol (PEG)‐peptides are under development as components of nonviral gene delivery systems. Several earlier reports have demonstrated that covalent attachment of PEG to the surface of peptide condensed DNA particles blocks non‐specific biodistribution during gene targeting. In this study, we report an improved large‐scale synthesis and purification of a DNA condensing PEG‐peptide used for gene delivery. The new method takes advantage of low‐pressure cation‐exchange chromatography to isolate dimeric Cys‐Trp‐Lys18. The dimeric peptide was reduced and directly conjugated with PEG‐maleimide resulting in PEG‐Cys‐Trp‐Lys18. The PEG‐peptide was purified by low‐pressure chromatography affording 50 μmol (400 mg) quantities of PEG‐peptide in >95% purity. The approach offers the advantage of avoiding preparative high‐performance liquid chromatography (HPLC) purifications of polylysine peptides to increase yield and capacity.
Value of reflux diagnostic questionnaire in the diagnosis of gastroesophageal reflux disease
Authors:   CHINESE GERD STUDY GROUP
Published: December 2004

OBJECTIVE:  To evaluate the value of the reflux diagnostic questionnaire (RDQ) in the diagnosis of gastroesophageal reflux disease (GERD).

METHODS:  One hundred and twenty‐eight patients with heartburn, substernal pain, acid reflux and regurgitation in 10 hospitals in China were assessed. Each symptom was scored according to severity and frequency (five scales). The highest score was 40. Upper gastrointestinal endoscopy and 24‐h esophageal pH monitoring were carried out in patients with symptom scores of more than six, and results were compared with the RDQ score to determine the critical value for diagnosis of GERD.

RESULTS:  The RDQ score correlated positively with the severity of reflux esophagitis. Esophageal pH monitoring showed that patients with abnormal RDQ had higher DeMeester scores compared with those with normal RDQ scores (20.18 vs 16.84). Taking 12 as the critical RDQ score for GERD, achieved a maximal Youden index. The area under the receiver operating characteristic curve was 0.71, the true positive diagnostic rate was 88.07%, and the true negative diagnostic rate was 68.42% with a sensitivity of 94.12% and specificity of 50%.

CONCLUSION:  The RDQ might be a useful screening test for GERD.
Risk factors for anastomotic leakage after anterior resection of the rectum
Authors: Matthiessen P. , Hallböök O. , Andersson M. , Rutegård J. , Sjödahl R.
Published: December 2004

Objective  Surgical technique and peri‐operative management of rectal carcinoma have developed substantially in the last decades. Despite this, morbidity and mortality after anterior resection of the rectum are still important problems. The aim of this study was to identify risk factors for anastomotic leakage in anterior resection and to assess the role of a temporary stoma and the need for urgent re‐operations in relation to anastomotic leakage.

Patients and methods  In a nine‐year period, from 1987 to 1995, a total of 6833 patients underwent elective anterior resection of the rectum in Sweden. A random sample of 432 of these patients was analysed (sample size 6.3%). The associations between death and 10 patient‐ and surgery‐related variables were studied by univariate and multivariate analysis. Data were obtained by review of the hospital files from all patients.

Results  The incidence of symptomatic clinically evident anastomotic leakage was 12% (53/432). The 30‐day mortality was 2.1% (140/6833). The rate of mortality associated with leakage was 7.5%. A temporary stoma was initially fashioned in 17% (72/432) of the patients, and 15% (11/72) with a temporary stoma had a clinical leakage, compared with 12% (42/360) without a temporary stoma, not significant. Multivariate analysis showed that low anastomosis (≤ 6 cm), pre‐operative radiation, presence of intra‐operative adverse events and male gender were independent risk factors for leakage. The risk for permanent stoma after leakage was 25%. Females with stoma leaked in 3% compared to men with stoma who leaked in 29%. The median hospital stay for patients without leakage was 10 days (range 5–61 days) and for patients with leakage 22 days (3–110 days).

Conclusion  In this population based study, 12% of the patients had symptomatic anastomotic leakage after anterior resection of the rectum. Postoperative 30‐day mortality was 2.1%. Low anastomosis, pre‐operative radiation, presence of intra‐operative adverse events and male gender were independent risk factors for symptomatic anastomotic leakage in the multivariate analysis. There was no difference in the use of temporary stoma in patients with or without anastomotic leakage.
Long strictureplasty is as safe and effective as short strictureplasty in small‐bowel Crohn's disease
Authors: Shatari T. , Clark M. A. , Yamamoto T. , Menon A. , Keh C. , Alexander‐Williams J. , Keighley M.
Published: December 2004

Background  For the past 20 years it has been shown that intestinal strictureplasty is safe and effective in the management of short strictureplasty. Long strictureplasty (> 20 cm) may be an alternative to resection in some patients, especially in diffuse disease or after previous extensive resections. We reviewed the outcome of long strictureplasty for Crohn's Disease, to examine safety and recurrence rates, compared with conventional short strictureplasty.

Methods  Sixty‐two patients have undergone single strictureplasty for jejunoileal Crohn's disease since 1974. Median follow‐up was 121 (range 7–253) months. Twenty‐one operations involved a single long strictureplasty, and 41 operations had a single short strictureplasty.

Results  No significant differences were identified between the groups. The postoperative complications in long strictureplasty included 2 abscesses only and after short strictureplasty there was one anastomotic leak and one postoperative abscess. The median hospital stay was 10 days after long strictureplasty and 9 days after short strictureplasty. Three‐, 5‐ and 10‐year disease‐free rates for long and short strictureplasty, respectively, were 3‐year 80.4% and 62.1%; 5‐year 55.2% and 49.8% and 10‐year 49.1% and 33.5% (NS).

Conclusions  These data indicate that long strictureplasty is safe and produces equivalent results to conventional (short) strictureplasty.
Shorter hospital stay associated with fastrack postoperative care pathways and laparoscopic intestinal resection are not associated with increased physical activity
Authors: Zutshi M. , Delaney C. P. , Senagore A. J. , Fazio V. W.
Published: December 2004

Objective  Recent prospective studies have shown that ‘fast track’ postoperative care protocols (FT) can reduce hospitalization after major intestinal surgery to 4.5 days, as compared to the 7–10 days with traditional management (TR) and 2.5 days after laparoscopic surgery (LC). We used computerized actigraphy (CA) to evaluate physical activity using TR, FT and LC approaches.

Methods  Fifteen patients undergoing intestinal resection by LC, TR and FT were recruited. CA devices were placed on the wrist and ankle of each patient from day1 until hospital discharge. Intra‐patient and intergroup analyses were performed using 24 h evaluations, and periods from 0800–2000h. Results are presented for, level of activity (LOA; activity counts per minute), activity index (AI;% epochs with activity) and acceleration index (ACI; change in activity rate during analysis period) for 0800–2000 h.

Results  Levels of activity measured by wrist and ankle CA devices for the three different care protocols were: LC, 6263 ± 8008 (wrist), 1640 ± 3795 (ankle); FT 7874 ± 8550 (wrist), 2153 ± 4838 (ankle); LC 8526 ± 9917 (wrist), 2326 ± 4905 (ankle). Length of hospital stay was significantly shorter in LC than FT and TR patients (P < 0.01). There was no significant increase in wrist or ankle LOA for FT or LC patients. Similarly, there was no difference in AI or ACI.

Conclusion  Although CA is an easily standardized method of evaluating physical activity after major abdominal surgery, no difference can be demonstrated between activity levels in patients managed by differing care pathways. Reductions in stay may be associated with factors other than a change in the level of physical activity after surgery.
Impact of national guidelines about the management of colorectal cancer on Australian surgeons' awareness of evidence: a pre/post survey
Authors: Cooney A. , Gattellari M. , Donnelly N. , Ward J.
Published: December 2004

Objective  To evaluate the immediate impact of national evidence‐based guidelines about colorectal cancer on Australian surgeons' self‐reported practice and their deficits in awareness of scientific evidence underpinning clinical management practices.

Design  Pre/post evaluation, comprising preguidelines survey (November 1998) and postguidelines survey (February 2001).

Methods  One hundred and fourteen Australian surgeons returned postguidelines surveys, of whom 103 (90%) agreed to matching of their pre‐ and postguidelines responses. National distribution of the CRC guidelines occurred in November 1999. Over the ensuing year, dissemination strategies included seminars, presentations at conferences and journal articles.

The main outcome measures used were changes in awareness of evidence for each of 23 clinical recommendations, changes in overall awareness score (maximum possible 23), changes in subscore for nine items for which evidence was compelling and predictors of change.

Results  Of those surgeons followed up, 95% were aware of the guidelines and 32% had read them in detail. Only 47% recalled the consumer version. The three most highly rated topics in the guidelines were: high–risk familial syndromes (45%); screening based on family history of colorectal cancer (40%); population screening for colorectal cancer (25%). Compared with baseline, there was a modest improvement in the mean overall awareness score (P = 0.02). Paired analyses of awareness of the evidence for each of 23 individual topics revealed significant improvement only in five. For two, awareness significantly decreased.

Conclusions  Our pre/post findings are not inconsistent with the expectation that dissemination of the CRC guidelines has had some short‐term impact. However, definitive evidence acquired through more rigorously designed controlled trials will be needed to determine first, whether surgical practice has changed and, second, whether implementation of the CRC guidelines or some other secular event caused such change.
Residual urine volume after total mesorectal excision: an indicator of pelvic autonomic nerve preservation? Results of a case‐control study
Authors: Kneist W. , Junginger T.
Published: December 2004

Objective  The rate of bladder dysfunctions after total mesorectal excision (TME) for rectal cancer can be decreased by bilateral pelvic autonomic nerve preservation (PANP). However, it is not clear yet, how often partial nerve impairment may lead to bladder dysfunction. It was the aim of a case‐control study, to examine the residual urine volume in patients before and after TME with and without complete PANP, in order to clarify, whether this parameter allows conclusions on the quality of PANP.

Patients and methods  Regarding bladder function, a case group (n = 26) without complete PANP was compared with a control group (n = 26) with complete identification and nerve preservation according to standadized intra‐operative documentation. Twenty‐six match pairs were established, identical regarding gender, wall infiltration depth, tumour site, operation procedure and operation extent. Rates of neoadjuvant therapy, R0‐classification, anastomotic leakage, wound and urinary tract infection were equally distributed for both the case‐ and control group (P > 0.05). Residual urine volume was pre‐ and post‐operatively determined by sonography.

Results  Pre‐operatively, residual urine volumes differed neither between the pairs nor between both groups with and without nerve preservation. In the case group with incomplete PANP there was a difference between pre‐ and post‐operative residual urine volume (median; quartil: 2.5 ml; 0.0–32.5 ml vs 130 ml; 0.0–317 ml; P = 0.001). In the control group there was no difference (median; quartile: 0.0 ml; 0.0–20 ml vs 15.5 ml; 0.0–62.0 ml; P = 0.07). The difference between the postoperatively measured volumes of the case and control group were significant (P = 0.001). With residual urine volume = 100 ml, the risk of incomplete PANP was 14 times higher (odds ratio).

Conclusions  Residual urine volume is an indicator of the completeness of PANP during TME. It should be determined pre‐ and post‐operatively, and besides the recording of the neurogenic bladder, serve as a quality control.
Are Child Developmental Outcomes Related to Before‐ and After‐School Care Arrangements? Results From the NICHD Study of Early Child Care
Authors:   National Institute of Child Health and Human Development Early Child Care Research Network
Published: December 2004

Data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care, a prospective, longitudinal study involving 933 children, were used to examine relations between cumulative participation in 5 types of out‐of‐school care (before‐ and after‐school programs, extracurricular activities, sitters, fathers, and nonadult care) and child developmental outcomes in the latter part of first grade (approximately age 7 years). Children who consistently participated in extracurricular activities during kindergarten and first grade obtained higher standardized test scores than children who did not consistently participate in these activities, controlling for child and family factors and children's prior functioning. Participation in other types of out‐of‐school care was not associated with child functioning in first grade when background factors were controlled.
American Academic Headache Specialists in Neurology: Practice Characteristics and Culture
Authors: Finkel AG
Published: December 2004

Headache diagnosis and treatment is the most important focus or concentration area for practising neurologists in America. The American Headache Society, formerly the American Association for the Study of Headache, is made up predominantly of neurologists. Recognition of the importance of the teaching and practice of headache medicine, especially migraine, is still incomplete at many academic teaching institutions. Suggestions that this results from inadequate academic hierarchies and education at graduate and post-graduate levels have been made. We therefore undertook a survey of academic practitioners of headache medicine in departments of neurology with membership of the American Headache Society. Subjects and addresses were identified using the 1999-2000 membership directory of the American Headache Society. Practice characteristics and time distribution were assessed. Teaching in undergraduate and resident programmes was also assessed. Fifty-five surveys from 46 institutions in 25 states were judged as adequate for this report. Academic neurologists with interest in headache medicine spent most of their time in clinic, with less than 25% spent doing either research or teaching. Medical schools had an average of 1 h of preclinical and 2 h of clinical teaching in headache. Neurology residents received an average of 3 h of didactic instruction in headache. This report is the first of its kind to review the practice characteristics and culture of headache medicine in the setting of academic departments of neurology. It describes a clinical practice similar to those of other non-academic American neurologists.
Familial Hemiplegic Migraine: Follow-up Findings of Diffusion-Weighted Magnetic Resonance Imaging (MRI), Perfusion-MRI and [99mTc] HMPAO-SPECT in a Patient with Prolonged Hemiplegic Aura
Authors: Oberndorfer S , Wöber C , Nasel C , Asenbaum S , Lahrmann H , Fueger B , Grisold W
Published: December 2004

Familial hemiplegic migraine (FHM) is a rare inherited autosomal dominant disorder. Migraine aura may last up to several weeks and then resolve without sequel. We report a 21-year-old male with FHM since the age of 3 years. Diffusion-weighted magnetic resonance imaging (DWI), perfusion-MR imaging (P-MRI) and [99mTc] hexamethyl-propyleneamine-oxime-single photon emission tomography (HMPAO-SPECT) were performed on day 2, when he was somnolent with right-sided hemiplegia, on day 9 when a mild hemiparesis was still present and on day 24 after recovery. The right central region showed normal findings in DWI, whereas P-MRI and SPECT revealed hyperperfusion on day 2, less marked on day 9, and normal findings on day 24. In conclusion, this case report indicates for the first time, by means of SPECT, P-MRI and DWI studies, that even extremely long-lasting migraine aura is not associated with cerebral ischaemia. Therefore, it supports the revised International Headache Society criteria where the term ‘persistent’ aura is proposed.
The Sumatriptan/Naratriptan Aggregated Patient (SNAP) Database: Aggregation, Validation and Application
Authors: Barrows C , Saunders W , Austin R , Putnam G , Mansbach H ,   for the SNAP Study Group∗
Published: December 2004

Pooled data from multiple clinical trials can provide information for medical decision-making that typically cannot be derived from a single clinical trial. By increasing the sample size beyond that achievable in a single clinical trial, pooling individual-patient data from multiple trials provides additional statistical power to detect possible effects of study medication, confers the ability to detect rare outcomes, and facilitates evaluation of effects among subsets of patients. Data from pharmaceutical company-sponsored clinical trials lend themselves to data-pooling, meta-analysis, and data mining initiatives. Pharmaceutical company-sponsored clinical trials are arguably among the most rigorously designed and conducted of studies involving human subjects as a result of multidisciplinary collaboration involving clinical, academic and/or governmental investigators as well as the input and review of medical institutional bodies and regulatory authorities. This paper describes the aggregation, validation and initial analysis of data from the sumatriptan/naratriptan aggregate patient (SNAP) database, which to date comprises pooled individual-patient data from 128 clinical trials conducted from 1987 to 1998 with the migraine medications sumatriptan and naratriptan. With an extremely large sample size (>28000 migraineurs, >140000 treated migraine attacks), the SNAP database allows exploration of questions about migraine and the efficacy and safety of migraine medications that cannot be answered in single clinical trials enrolling smaller numbers of patients. Besides providing the adequate sample size to address specific questions, the SNAP database allows for subgroup analyses that are not possible in individual trial analyses due to small sample size. The SNAP database exemplifies how the wealth of data from pharmaceutical company-sponsored clinical trials can be re-used to continue to provide benefit.
Comparison of Rizatriptan 5 mg and 10 mg Tablets and Sumatriptan 25 mg and 50 mg Tablets
Authors: Kolodny A , Polis A , Battisti WP , Johnson-Pratt L , Skobieranda F ,   Rizatriptan Protocol 052 Study Group∗
Published: December 2004

This randomized, double-blind, two-attack, placebo-controlled, crossover study explored the efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 50 mg as well as rizatriptan 5 mg compared with sumatriptan 25 mg in the acute treatment of migraine. Following randomization to one of six possible treatment sequences, patients ( n = 1447) treated two sequential attacks, of moderate or severe intensity, separated by at least 5 days. Patients assessed pain severity, migraine-associated symptoms, and functional disability at 0.5, 1, 1.5, and 2 h post treatment. Compared with placebo, all treatments were effective. On the primary endpoint of time to pain relief, rizatriptan 10 mg was not statistically different from sumatriptan 50 mg [odds ratio (OR) 1.10, P = 0.161], and rizatriptan 5 mg was statistically superior to sumatriptan 25 mg (OR 1.22, P = 0.007). In general, rizatriptan 10 mg and 5 mg treatment resulted in improvement compared with the corresponding doses of sumatriptan on measures of pain severity, migraine symptoms, and functional disability and the 5-mg dose reached statistical significance on almost all measures. All treatments were generally well tolerated.
Lowering the doses of mifepristone and gemeprost for early abortion: a randomised controlled trial
Authors:   World Health Organization Task Force on Post‐ovulatory Methods for Fertility Regulation,   Participants are listed on page 742
Published: December 2004

Objective To test the efficacy of lower doses of mifepristone and gemeprost for medical induction of early abortion.

Design Randomised controlled trial. Participants were blinded as to the therapy and physicians to the dose of mifepristone.

Setting Thirteen hospital gynaecological units in different continents.

Participants 1224 healthy pregnant women requesting medical abortion at <57 days from last menses.

Intervention Random allocation to one of four regimens: mifepristone 50 mg by mouth followed by either 0.5 mg or 1.0 mg gemeprost vaginally on day 3; mifepristone 200 mg by mouth followed by either 0.5 mg or 1.0 mg gemeprost vaginally. We concealed the allocation sequence from clinicians enrolling participants, and maintained double blinding throughout.

Main outcome measures Incidence of complete abortion; subordinate outcome measures included side effects such as vomiting and fall in haemoglobin, as well as the need for emergency curettage and blood transfusion.

Results The success rate was significantly related to the dose of mifepristone. The relative risk of failure to have a complete abortion with the lower dose of mifepristone was 1.6 (95% CI: 1.1‐2.3) times that with the higher dose. The relative risk of failure with the lower dose of gemeprost (1.3; 95% CI: 0.9‐1.8) did not reach statistical significance.

Conclusions A single dose of mifepristone 50 mg followed by gemeprost is inadequate for early medical abortion. There was no significant difference in side effects between the four treatment groups.
Spousal physical violence against women during pregnancy
Authors: Peedicayil Abraham , Sadowski Laura S. , Jeyaseelan Lakshman , Shankar Viswanathan , Jain Dipty , Suresh Saradha , Bangdiwala Shrikant I. ,   the IndiaSAFE Group
Published: December 2004

Objective  To determine the prevalence of physical violence during pregnancy and the factors associated with it.

Design  A population‐based, multicentre, cross sectional household survey.

Setting  Rural, slum and urban non‐slum areas of Bhopal, Chennai, Delhi, Lucknow, Nagpur, Trivandrum and Vellore, in India.

Participants  A total of 9938 women who were 15 to 49 years of age and living with a child younger than 18 years old.

Methods  Probability proportionate to size sampling of households was performed in three strata. Trained field workers administered a structured questionnaire. Women who reported domestic violence were asked about violence during pregnancy. Outcome variables included six violent behaviours: slap, hit, kick, beat, use of weapon and harm in any other way. Moderate to severe violence was defined as experience of any one or more of the following behaviours: hit, beat or kick. Odds ratios were calculated for risk and protective factors of violence during pregnancy using logistic regression.

Main outcome measures  Physical spousal violence.

Results  The lifetime experience, during pregnancy, of being slapped was 16%, hit 10%, beat 10%, kicked 9%, use of weapon 5% and harmed in any other way 6%. Eighteen percent of women experienced at least one of these behaviours and 3% experienced all six. The overall prevalence of moderate to severe violence during pregnancy was 13%. Logistic regression showed that the factors determining whether a woman experienced moderate to severe violence during pregnancy were: husband accusing wife of an affair (OR 7.1; 95% CI 5.1 to 9.8), dowry harassment (OR 4.1; 95% CI 2.8 to 6.1), husband having an affair (OR 3.7; 95% CI 2.8 to 4.8), husband being regularly drunk (OR 3.2; 95% CI 2.6 to 4.1), low education of husband (OR 2.8; 95% CI 1.4 to 5.6), substance abuse by husband (OR 2.6; 95% CI 1.3 to 5.5), no social support (OR 1.8; 95% CI 1.1 to 3.0), three or more children (OR 1.6; 95% CI 1.2 to 2.1) and household crowding (OR 1.1; 95% CI 1.0 to 1.2).

Conclusion  In this study, 12.9% of women experienced moderate to severe physical violence during pregnancy. Suspicion of infidelity, dowry harassment, husband being regularly drunk and low education of husband were the main risk factors for violence during pregnancy.
Caesarean section is protective against stress urinary incontinence: an analysis of women with multiple deliveries
Authors: Chaliha Charlotte , Digesu Alex , Hutchings Anna , Soligo Marco , Khullar Vik
Published: December 2004

All women who had three elective caesarean sections were selected from a database of 40,000 women delivering between 1977 and 1998, and age‐matched with women having three vaginal births. They all completed a (validated) urinary and bowel symptom questionnaire. Women who had vaginal births had a significantly higher prevalence of stress incontinence but not other urinary or faecal symptoms compared with those delivered by caesarean section. The prevalence of faecal incontinence was lower than the prevalence of urinary incontinence. Although the prevalence of faecal incontinence was lower after caesarean delivery, this was not statistically different. These data have shown that caesarean section was associated with a lower risk of urinary incontinence, although a protective effect on development of faecal symptoms was not seen.
Evaluation of the effect of uterine artery embolisation on menstrual blood loss and uterine volume
Authors: Khaund A. , Moss J.G. , McMillan N. , Lumsden M.A.
Published: December 2004

Objective  To evaluate the effect of uterine artery embolisation (UAE) on menstrual blood loss (MBL) and uterine volume in women with symptomatic uterine fibroids.

Design  Prospective observational study.

Setting  West of Scotland gynaecology and radiology departments.

Population  Fifty women (mean age 43 years) with symptomatic fibroids undergoing UAE between January 1999 and June 2003.

Methods  Women collected sanitary protection from one menses pre‐embolisation and at regular intervals thereafter. This allowed objective measurement of MBL using the alkaline haematin technique. Uterine volume was calculated using magnetic resonance imaging (MRI) before and six months following embolisation. Interventional radiologists performed bilateral UAE. The Wilcoxon's signed rank test was used for statistical analysis of data.

Main outcome measures  Post‐embolisation MBL and uterine volume changes.

Results  Median pretreatment MBL was 162 mL (mean 234, range 9–1339). The median MBL decreased to 60 mL at 3 months (n= 34, range 0–767, P < 0.001), 70 mL at 6–9 months (n= 34, range 0–1283, P < 0.001), 37 mL at 12–24 months (n= 25, range 0–265, P < 0.001), 18 mL at 24–36 months (n= 17, range 0–205, P < 0.001) and 41 mL at 36–48 months (n= 6, range 0–66, P < 0.05). The median reduction in uterine volume was 40% (n= 46, 95% CI 33.0–49.7, P < 0.001).

Conclusions  UAE causes a statistically significant reduction in objectively measured MBL. UAE is also associated with a statistically significant reduction in uterine volume at six months. There was no relationship between the changes in uterine volume and MBL.
Preventing ectopic pregnancies: how often does transperitoneal transmigration of sperm occur in effecting human pregnancy?
Authors: Nahum Gerard G. , Stanislaw Harold , McMahon Connette
Published: December 2004

Objective  Transperitoneal transmigration of sperm constitutes the mechanism by which ectopic pregnancies occur in unilaterally obstructed fallopian tubes. This study was undertaken to determine how often sperm transmigrate across the peritoneal cavity to effect human pregnancy.

Design  In women with non‐communicating rudimentary uterine horn pregnancies, the ratio of total uterine horn pregnancies to prior contralateral hemi‐uterine pregnancies was calculated to infer the overall transperitoneal sperm transmigration rate. The prior parity frequency distribution was also determined to calculate the best‐fit per‐pregnancy probability of attaining a rudimentary horn pregnancy with each subsequent gestation using maximum likelihood estimation.

Setting  20th century.

Sample  Non‐communicating rudimentary uterine horn pregnancies reported from 40 countries.

Methods  Two hundred and seventy‐two cases were identified using manual and computerised searches of Index Medicus, Excerpta Medica, the Index‐Catalogue of the Library of the Surgeon‐General's Office and standard reference tracing.

Main outcome measures  The ratio of total prior non‐rudimentary uterine horn pregnancies to rudimentary uterine horn pregnancies and the frequency distribution of prior maternal parities.

Results  Prior to the incident 272 uterine horn pregnancies, the number of observed pregnancies was 292 (ratio = 0.93), implying an aggregate sperm transmigration rate of 0.48. Using the prior parity frequency distribution, the best‐fit probability of attaining a rudimentary horn gestation per‐pregnancy was 0.51 (95% CI 0.48–0.56).

Conclusions  Intraperitoneal sperm transmigration occurs approximately half the time in effecting spontaneous human pregnancies. To minimise the risk of ectopic tubal pregnancy in woman with unilaterally damaged fallopian tubes, salpingectomy should be the preferred surgical treatment, rather than attempting tubal salvage and repair.
Myo‐inositol, glucose and zinc status as risk factors for non‐syndromic cleft lip with or without cleft palate in offspring: a case–control study
Authors: Krapels Ingrid P.C. , van Rooij Iris A.L.M. , Wevers Ron A. , Zielhuis Gerhard A. , Spauwen Paul H.M. , Brussel Wim , Steegers‐Theunissen Régine P.M.
Published: December 2004

Objective  To investigate myo‐inositol, glucose and zinc status in mothers and their infants on cleft lip with or without cleft palate risk (CLP).

Design  Case–control study.

Setting  University Medical Centre Nijmegen, the Netherlands.

Population  Eighty‐four mothers and their CLP child and 102 mothers and their healthy child.

Methods  Venous blood samples were obtained to determine serum myo‐inositol and glucose and red blood cell zinc concentrations in mothers and children. Geometric means were calculated and compared between the groups. The blood parameters were dichotomised with cutoff points based on control values, P90 for glucose concentrations.

Main outcome measures  Geometric means (P5–P95) and odds ratios (95% confidence intervals).

Results  The CLP children (P= 0.003) and their mothers (P= 0.02) had significantly lower red blood cell zinc concentrations than controls. A low maternal serum myo‐inositol concentration (<13.5 μmol/L) and a low red blood cell zinc concentration (<189 μmol/L) increased CLP risk [odds ratio 3.0 (95% CI 1.2–7.4) and 2.0 (95% CI 0.8–4.8), respectively]. Children with low myo‐inositol (<21.5 μmol/L ) or low red blood cell zinc concentrations (<118 μmol/L) were more likely to have CLP [odds ratio 3.4 (95% CI 1.3–8.6) and 3.3 (95% CI 1.3–8.0), respectively]. Glucose was not a risk factor for CLP in mothers and children. Maternal and child myo‐inositol as well as zinc concentrations were slightly, albeit significantly correlated, rPearson= 0.33 (P= 0.0006) and rPearson= 0.23 (P= 0.01), respectively.

Conclusion  This study demonstrates for the first time that zinc and myo‐inositol are important in the aetiology of CLP.
Severe complications of hysterectomy: the VALUE study
Authors: McPherson K. , Metcalfe M.A. , Herbert A. , Maresh M. , Casbard A. , Hargreaves J. , Bridgman S. , Clarke A.
Published: December 2004

Objectives  To model the determinants of serious operative and post‐operative complications of hysterectomy and their potential risk factors.

Design  A prospective cohort of women undergoing hysterectomies for benign indications in 1994/1995, with a six‐week postsurgery follow up.

Population and setting  A total of 37,512 women from 276 NHS and 145 private hospitals in England, Wales and Northern Ireland, originally recruited to compare the outcomes of endometrial destruction with those of hysterectomy.

Methods  Gynaecologists reported hysterectomies for non‐malignant indications carried out during a 12‐month period beginning in October 1994 and follow up data were obtained at outpatient follow up six weeks postsurgery. Odds ratios of severe complications by indication and method, adjusting for measured intrinsic risk factors, were calculated.

Main outcome measures  Severe operative and post‐operative complications.

Results  Severe operative complications occurred in 3%. The risk decreased with age and increased with greater parity and history of serious illness. Women with symptomatic fibroids (4.4%, 95% CI 3.9–4.9) experienced more complications than women with dysfunctional uterine bleeding (3.6%, 3.2–3.8), adjusted odds ratio (OR) = 1.3 (95% CI 1.1–1.6). Laparoscopic procedures (6.1%) doubled the risk of operative complications of abdominal hysterectomy (3.6%) (adjusted OR = 1.9, 1.5–2.5). Post‐operative complications occurred in around 1% of women, with a slight decrease with increasing age, and the strongest risk factor was a history of operative complications. Relative to dysfunctional uterine bleeding (1.0%), a higher risk for fibroids (1.2%) persisted after adjustments (RR = 1.5, 1.1–2.0). Both vaginal (1.2%) and laparoscopic (1.7%) techniques had significantly higher adjusted risks than abdominal operations (0.9%), RR = 1.4 (1.0–1.9) and RR = 1.6 (1.0–2.7). There were no operative deaths; 14 women died within the six‐week postsurgery (a crude mortality rate of 3.8/1000, 2.5–6.4).

Conclusions  Hysterectomy is a common, routine surgery with comparatively rare serious complications. However, younger women, women with more vascular pelvises, who undergo hysterectomy, especially laparoscopically assisted vaginal surgery for symptomatic fibroids, are at most risk of experiencing severe complications both operatively and post‐operatively. Therefore, a less invasive alternative treatment for symptomatic fibroids could particularly benefit this group of women, while less invasive treatments for dysfunctional uterine bleeding, such as various methods of endometrial ablations or resections, would need to meet the current low levels of clinical complications in order to replace hysterectomy.