bluuebunny/crossref_metadata_2025 huggingface dataset:
From fish to modern humans – comparative anatomy, homologies and evolution of the pectoral and forelimb musculature
Authors: Diogo R. , Abdala V. , Aziz M. A. , Lonergan N. , Wood B. A.
Published: April 2009

In a recent study Diogo & Abdala [(2007) J Morphol 268, 504–517] reported the results of the first part of a research project on the comparative anatomy, homologies and evolution of the pectoral muscles of osteichthyans (bony fish and tetrapods). That report mainly focused on actinopterygian fish but also compared these fish with certain non‐mammalian sarcopterygians. This study, which reports the second part of the research project, focuses mainly on sarcopterygians and particularly on how the pectoral and forelimb muscles have evolved during the transitions from sarcopterygian fish and non‐mammalian tetrapods to monotreme and therian mammals and humans. The data obtained by our own dissections of all the pectoral and forelimb muscles of representative members of groups as diverse as sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals such as rodents, tree‐shrews, colugos and primates, including humans, are compared with the information available in the literature. Our observations and comparisons clearly stress that, with regard to the number of pectoral and forelimb muscles, the most striking transition within sarcopterygian evolutionary history was that leading to the origin of tetrapods. Whereas extant sarcopterygian fish have an abductor and adductor of the fin and a largely undifferentiated hypaxial and epaxial musculature, extant salamanders such as Ambystoma have more than 40 pectoral and forelimb muscles. There is no clear increase in the number of pectoral and forelimb muscles within the evolutionary transition that led to the origin of mammals and surely not to that leading to the origin of primates and humans.
Immunohistochemical localization of Clara cell secretory proteins (CC10‐CC26) and Annexin‐1 protein in rat major salivary glands
Authors: Cecchini Maria Paola , Merigo Flavia , Cristofoletti Mirko , Osculati Francesco , Sbarbati Andrea
Published: April 2009

The oral cavity is continuously bathed by saliva secreted by the major and minor salivary glands. Saliva is the first biological medium to confront external materials that are taken into the body as part of food or drink or inhaled volatile substances, and it contributes to the first line of oral defence. In humans, it has been shown that sputum and a variety of biological fluids contain Clara cell secretory proteins (CC10–CC26). Various studies of the respiratory apparatus have suggested their protective effect against inflammatory response and oxidative stress. Recently, CC10 deficiency has been related to the protein Annexin‐1 (ANXA1), which has immunomodulatory and anti‐inflammatory properties. Considering the defensive role of both Clara cell secretory proteins and ANXA1 in the respiratory apparatus, and the importance of salivary gland secretion in the first line of oral defence, we decided to evaluate the expression of CC10, CC26 and ANXA1 proteins in rat major salivary glands using immunohistochemistry. CC10 expression was found only in the ductal component of the sublingual gland. Parotid and submandibular glands consistently lacked CC10 immunoreactivity. In the parotid gland, both acinar and ductal cells were always CC26‐negative, whereas in the submandibular gland, immunostaining was localized in the ductal component and in the periodic acid Schiff (PAS)‐positive area. In the sublingual gland, ductal cells were always positive. Acinar cells were not immunostained at all. ANXA1 was expressed in ductal cells in all three major glands. In parotid and sublingual glands, acinar cells were negative. In submandibular glands, immunostaining was present in the mucous PAS‐positive portion, whereas serous acinar cells were consistently negative. The existence of some CC10‐CC26–ANXA1‐positive cells in rat salivary glandular tissue is an interesting preliminary finding which could support the hypothesis, suggested for airway tissue, that these proteins have a defensive and protective role. Protein expression heterogeneity in the different portions of the glands could be an important clue in further investigations of their role.
Invasive cervical cancer audit: a relative increase in interval cancers while coverage increased and incidence declined
Authors: Herbert A , Anshu  , Gregory M , Gupta SS , Singh N
Published: April 2009

Objective  To examine screening histories of women with invasive cervical cancer in a 12‐year period during the introduction of organised screening to assess its effectiveness.

Study Design  Screening histories were classified into six categories: no cytology record (1), previous cytology more than 5 years before diagnosis (2) and previous cytology within 5 years of diagnosis (3–6). Categories 3–6 were described as interval cancers and comprised previous negative cytology (3), previous repeats for low‐grade cytology (4), previous recommendations for investigation (5) and previous treatment (6).

Setting  Southampton and South West Hampshire (SSWH).

Population  Women resident in SSWH registered with invasive cervical carcinoma between 1985 and 1996.

Methods  Data were held for analysis on an anonymous spreadsheet.

Main outcome measures  Association of screening history categories with 3‐year time period, age group, type and stage of cancer and route to diagnosis; incidence per 100 000 women aged 25–64 years screened and not screened within 5 years in 1991–93 and 1994–96.

Results  Interval cancers increased as a proportion of all cancers from 31.5% in 1985–87 to 48.6% in 1994–96 (P= 0.002) and showed a peak in 1991–93. Their incidence decreased from 20.1 to 10.9 per 100 000 eligible women aged 25–64 years screened within 5 years (P= 0.008) between 1991–93 and 1994–96, while incidence in women not screened within 5 years was unchanged (44.2 and 40.4). Factors other than previous negative smears were recorded in 50.9% of interval cancers. Interval cancers were more likely to be low stage, screen detected and were diagnosed in younger women (P < 0.00001).

Conclusions  Interval cancers should be assessed as a proportion of eligible women screened within the same period of time and not as a proportion of all cancers. This audit demonstrates the importance of accurate cytology, appropriate follow up, prompt investigation and effective treatment of high‐grade precancerous lesions.
The effect of physical activity on pelvic organ prolapse
Authors: Ali‐Ross NS , Smith ARB , Hosker G
Published: April 2009

Objective  The objective of this study was to determine whether pelvic organ prolapse increases after physical activity.

Design  Prospective observational study.

Setting  St Mary’s Hospital, Manchester, UK.

Sample  Women undergoing surgery for pelvic organ prolapse.

Methods  Fifty‐four women were recruited to the study. Symptoms and POPQ findings were assessed after a period of prescribed activity and overnight bedrest.

Main outcome measures  Primary outcome was an increase in Pelvic Organ Prolapse Quantification (POPQ) measurements with activity. Secondary outcomes were association of symptoms or quality‐of‐life scores (Pelvic Floor Distress Inventory [PFDI] and Pelvic Floor Impact Questionnaire [PFIQ]) with an increase in POPQ measurements.

Results  There was a significant increase in POPQ stage and five vaginal parameters (Aa, Ba, C, Ap and Bp) with physical activity (P < 0.001). Reported symptoms, higher PFDI and PFIQ scores and higher individual symptom bother scores were not more common in the women with greater pelvic organ descent (measured by the POPQ system) following physical activity.

Conclusions  Greater pelvic organ prolapse was found on POPQ examination following physical activity, but this was not associated with worsening of symptoms and greater impairment of quality of life.
Balloon tamponade in the management of postpartum haemorrhage: a review
Authors: Georgiou C
Published: April 2009

Obstetric haemorrhage is a significant contributor to worldwide maternal morbidity and mortality. Guidelines for the management of postpartum haemorrhage (PPH) involve a stepwise escalation of pharmacological and eventual surgical approaches. The method of uterine tamponade using balloons has recently been added to the armamentarium for managing PPH. There are various balloons available including the Bakri, Foley, Sengstaken–Blakemore, Rusch and condom catheter. This paper reviews these uterine tamponade technologies in the management of PPH.
Long‐term mortality in women treated for cervical intraepithelial neoplasia
Authors: Jakobsson M , Gissler M , Paavonen J , Tapper A‐M
Published: April 2009

Objective  The objective of this study was to study whether women surgically treated for cervical intraepithelial neoplasia (CIN) have increased mortality later in life. We also wanted to study whether pregnancy beyond 22 weeks post‐treatment affects the risk.

Design  Register‐based retrospective cohort study from Finland.

Setting  National data of the Hospital Discharge Register and the Cause‐of‐Death Register during 1986–2003.

Population  A total of 25 827 women who had surgical treatment for CIN during 1986–2003.

Methods  We calculated standardised mortality ratios (SMRs) by dividing the numbers of observed deaths (until 31 December 2006) by the numbers of expected deaths.

Main outcome measures  SMRs for different causes‐of‐death groups.

Results  The overall mortality increased by 17% after treatment for CIN, including increased risk of dying from all diseases and medical conditions (SMR 1.13, 95% CI 1.01–1.26), cancers (SMR 1.09, 95% CI 0.91–1.27) and injury deaths (SMR 1.31, 95% CI 1.03–1.58). As expected, the mortality from cervical cancer was high (SMR 7.69, 95% CI 4.23–11.15). Women who had delivered post‐treatment tended to have decreased overall mortality (SMR 0.78, 95% CI 0.52–1.04) and decreased disease mortality (SMR 0.63, 95% CI 0.37–0.90). However, the mortality rate was significantly increased for women who had subsequent preterm delivery (SMR 2.51, 95% CI 1.24–3.78). In this subgroup, there was a tendency of increased mortality from diseases of the circulatory system, alcohol‐related causes and injury deaths.

Conclusions  Mortality rate was increased after surgical treatment for CIN. However, women who had delivered post‐treatment had decreased overall disease mortality rate. Subsequent preterm delivery may be a risk marker for increased long‐term mortality.
Results after conservative treatment of serous borderline tumours of the ovary with stromal microinvasion but without micropapillary pattern
Authors: Laurent I , Uzan C , Gouy S , Pautier P , Duvillard P , Morice P
Published: April 2009

The aim of this study was to assess the outcomes of women treated conservatively for a serous borderline ovarian tumour with stromal microinvasion (SBOT‐SMI) but without micropapillary pattern. Ten women treated conservatively for a stage I (n= 8) or stage IIIB (n= 2) tumour were followed up. With a median follow‐up duration of 62 months (range 7–117 months), five recurrences developed on the preserved ovary. All lesions were borderline recurrences (with noninvasive peritoneal implants in one). All women are currently disease free. Three women achieved a spontaneous pregnancy and three became pregnant after an in vitro fertilisation procedure. This study suggests that conservative treatment of SBOT‐SMI is safe.
A 2‐year study on cytomegalovirus infection during pregnancy in a French hospital
Authors: Picone O , Vauloup‐Fellous C , Cordier A‐G , Parent Du Châtelet I , Senat M‐V , Frydman R , Grangeot‐Keros L
Published: April 2009

Objectives To evaluate the proportion of pregnant women agreeing to cytomegalovirus (CMV) serologic screening. To collect data on CMV infection during pregnancy.

Design Prospective study.

Setting During two years, all pregnant women were informed on CMV infection. If the patient agreed, serological testing was performed around 12 weeks of gestation (WG) and, if negative, redone around 36 WG.

Population Four thousand two hundred and eighty‐seven pregnant women followed from 12 weeks to delivery.

Methods If the first CMV serologic test was negative, detailed hygiene information was given to the parents. Diagnosis of primary infection was based on the detection of CMV‐G, CMV‐M and low CMV‐G avidity index. When maternal infection was confirmed, diagnosis of CMV congenital infection was done in the newborns by urine culture within the three days following birth. Crude infection‐rate data consisted of the number of CMV infection cases and person‐time units for both exposed to hygiene CMV information (12 to 36 WG) and unexposed pregnant women (first 12 WG).

Main outcome measures Rate of CMV seropositive and seronegative women. Rate of women agreeing for screening. Rate of primary infection. Rate of seroconversion. Number of CMV‐infected newborns.

Results Among the 4287 women followed, 3792 were either seronegative or with an unknown immune status. 96.7% out of them agreed for screening. 53.2% were initially CMV‐specific IgG negative. Primary infection was detected in nine women between 0 and 12 WG (0.46%) and seroconversion was diagnosed in five women between 12 and 36 WG (0.26%) (midP = 0.02, 95% CI [1.07–13.6]).

Conclusions If clear information on CMV infection during pregnancy is given, patients frequently agree to screening. The rate of seroconversion after information, observed in this study, is low after counselling.
The management of epilepsy in pregnancy
Authors: Walker SP , Permezel M , Berkovic SF
Published: April 2009

While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre‐pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.
Cost‐effectiveness analysis of alternative first‐trimester pregnancy termination strategies in Mexico City
Authors: Hu D , Grossman D , Levin C , Blanchard K , Goldie SJ
Published: April 2009

Objective To assess the comparative health and economic outcomes associated with three alternative first‐trimester abortion techniques in Mexico City and to examine the policy implications of increasing access to safe abortion modalities within a restrictive setting.

Design Cost‐effectiveness analysis.

Setting Mexico City.

Population Reproductive‐aged women with unintended pregnancy seeking first‐trimester abortion.

Methods Synthesising the best available data, a computer‐based model simulates induced abortion and its potential complications and is used to assess the cost‐effectiveness of alternative safe modalities for first‐trimester pregnancy termination: (1) hospital‐based dilatation and curettage (D&C), (2) hospital‐based manual vacuum aspiration (MVA), (3) clinic‐based MVA and (4) medical abortion using vaginal misoprostol.

Main outcome measures Number of complications, lifetime costs, life expectancy, quality‐adjusted life expectancy.

Results In comparison to the magnitude of health gains associated with all safe abortion modalities, the relative differences between strategies were more pronounced in terms of their economic costs. Assuming all options were equally available, clinic‐based MVA was the least costly and most effective. Medical abortion with misoprostol provided comparable benefits to D&C, but cost substantially less. Enhanced access to safe abortion was always more influential than shifting between safe abortion modalities.

Conclusions This study demonstrates that the provision of safe abortion is cost‐effective and will result in reduced complications, decreased mortality and substantial cost savings compared with unsafe abortion. In Mexico City, shifting from a practice of hospital‐based D&C to clinic‐based MVA and enhancing access to medical abortion will have the best chance to minimise abortion‐related morbidity and mortality.
World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre‐eclampsia in populations of low nutritional status from developing countries
Authors: Villar J , Purwar M , Merialdi M , Zavaleta N , thi Nhu Ngoc N , Anthony J , De Greeff A , Poston L , Shennan A ,   on behalf of the WHO Vitamin C and Vitamin E trial group
Published: April 2009

Objective  To determine if vitamin C and E supplementation in high‐risk pregnant women with low nutritional status reduces pre‐eclampsia.

Design  Multicentred, randomised, controlled, double‐blinded trial.

Setting  Antenatal care clinics and Hospitals in four countries.

Population  Pregnant women between 14 and 22 weeks’ gestation.

Method  Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery.

Main outcome measures  Pre‐eclampsia, low birthweight, small for gestational age and perinatal death.

Results  Six hundred and eighty‐seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio‐economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre‐eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow‐up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre‐eclampsia (RR: 1.0; 95% CI: 0.9–1.3), eclampsia (RR: 1.5; 95% CI: 0.3–8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9–1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8–1.1), small for gestational age (RR: 0.9; 95% CI: 0.8–1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6–1.2) were also unaffected.

Conclusion  Vitamins C and E at the doses used did not prevent pre‐eclampsia in these high‐risk women.
Muscarinic toxins: tools for the study of the pharmacological and functional properties of muscarinic receptors
Authors: Servent Denis , Fruchart‐Gaillard Carole
Published: April 2009

Muscarinic receptors mediate metabotropic actions of acetylcholine in the CNS and PNS and autocrine functions of acetylcholine in non‐neuronal systems. Because of the lack of highly selective muscarinic ligands, the precise location, functional role, and roles in various diseases of the five muscarinic receptor subtypes remain unclear. Muscarinic toxins isolated from the venom ofDendroaspissnakes have a natural high affinity and selectivity, associated with roles as competitive antagonists, allosteric modulators, and potential agonists. These toxins may therefore be invaluable tools for studying muscarinic receptors. We review data on the structural and pharmacological characterization of the muscarinic toxins, focusing on recent structure–function studies on toxin–receptor interactions. We discuss the potential benefits of using these toxins for investigating muscarinic functionin vivo.
Variations in Help-Seeking, Battered Women's Relationship Course, Emotional Well-Being, and Experiences of Abuse Over Time
Authors: Bell Margret E. , Goodman Lisa A. , Dutton Mary Ann
Published: April 2009

Despite assumptions that leaving the batterer offers the best chance for improvement in battered women's lives, few studies provide conclusive data on this issue. Although many women eventually reunite with partners, also unexamined is the influence of relationship course over time. Five waves of data from 206 low-income, largely Black, help-seeking battered women revealed minimal differences in emotional well-being either initially or over time for women following different relationship trajectories during the course of 1 year. Consistency in relationship status (completely apart, completely together) tended to be associated with sharper drops in violence during the year; abuse tended to decrease most slowly among women who were in and out of their relationship over time. Findings suggest that the act of leaving is not necessarily associated with improvements for victims—how the process of leaving occurs may be more influential. Challenging common assumptions, women remaining with partners may sometimes fare better than women who leave.
College Women's Reactions to Sexual Assault Research Participation: Is it Distressing?
Authors: Edwards Katie M. , Kearns Megan C. , Calhoun Karen S. , Gidycz Christine A.
Published: April 2009

This study assessed college women's reactions to participating in sexual assault research. Women with sexual victimization histories reported more negative emotional reactions than nonvictimized women, but also greater benefits. Benefits to research participation outweighed costs for both women with and without sexual victimization histories. Women with and without sexual victimization histories evidenced significant improvements in several domains of mood over the course of the study, although victimized women improved less in several areas of mood. Participants' presurvey mood, assault severity, perpetrator aggression, self-blame, and perceived benefits to research participation all uniquely predicted participants' immediate negative emotional reactions to the research protocol. Descriptive analyses showed that only a small number of women reported negative emotional reactions to the research protocol.
p53/CEP‐1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress
Authors: Ventura Natascia , Rea Shane L. , Schiavi Alfonso , Torgovnick Alessandro , Testi Roberto , Johnson Thomas E.
Published: April 2009

Mitochondrial pathologies underlie a number of life‐shortening diseases in humans. In the nematode Caenorhabditis elegans, severely reduced expression of mitochondrial proteins involved in electron transport chain‐mediated energy production also leads to pathological phenotypes, including arrested development and/or shorter life; in sharp contrast, mild suppression of these same proteins extends lifespan. In this study, we show that the C. elegans p53 ortholog cep‐1 mediates these opposite effects. We found that cep‐1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin – the protein defective in patients with Friedreich’s Ataxia. Importantly, we show that cep‐1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. These findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial‐associated diseases.
Diminished contraction‐induced intracellular signaling towards mitochondrial biogenesis in aged skeletal muscle
Authors: Ljubicic Vladimir , Hood David A.
Published: April 2009

The intent of this study was to determine whether aging affects signaling pathways involved in mitochondrial biogenesis in response to a single bout of contractile activity. Acute stimulation (1 Hz, 5 min) of the tibialis anterior (TA) resulted in a greater rate of fatigue in old (36 month), compared to young (6 month) F344XBN rats, which was associated with reduced ATP synthesis and a lower mitochondrial volume. To investigate fiber type‐specific signaling, the TA was sectioned into red (RTA) and white (WTA) portions, possessing two‐ to 2.5‐fold differences in mitochondrial content. The expression and contraction‐mediated phosphorylation of p38, MKK3/6, CaMKII and AMPKα were assessed. Kinase protein expression tended to be higher in fiber sections with lower mitochondrial content, such as the WTA, relative to the RTA muscle, and this was exaggerated in tissues from senescent, compared to young animals. At rest, kinase activation was generally similar between young and old animals, despite the age‐related variations in mitochondrial volume. In response to contractile activity, age did not influence the signaling of these kinases in the high‐oxidative RTA muscle. However, in the low‐oxidative WTA muscle, contraction‐induced kinase activation was attenuated in old animals, despite the greater metabolic stress imposed by contractile activity in this muscle. Thus, the reduction of contraction‐evoked kinase phosphorylation in muscle from old animals is fiber type‐specific, and depends on factors which are, in part, independent of the metabolic milieu within the contracting fibers. These findings imply that the downstream consequences of kinase signaling are reduced in aging muscle.
Electoral behaviour behind the gates: partisanship and political participation among Canadian gated community residents
Authors: Walks R. Alan
Published: April 2009

Gated communities have been characterised as representing processes of ‘forting up’ and ‘civic secession’, in which their residents use gating as a strategy for withdrawing from political life and from taking collective responsibility for others. The assumption is that the residents of private gated communities should be less likely to participate in political life, and/or be more likely to support political parties on the right who advocate privatisation, reduced government expenditures and lower taxes. If the act of living in a gated community is associated with either greater support for parties and policies on the right of the political spectrum, or limited political participation, then the growth of such forms of privatised communities has potential implications for the future of urban politics and even for national political systems. However, despite surveys that have dealt with social attitudes ‘behind the gates’, insufficient attention has been paid to the politics of gated community residents. This paper fills this gap through a comparative analysis of electoral behaviour during the 2006 federal election at the level of the polling station. Electoral participation and partisanship in 27 gated communities in three Canadian metropolitan areas is compared against that of non‐gated residents. Regression analysis is conducted in order to determine whether gated community residents differ from their non‐gated counterparts in the way they vote and their levels of electoral turnout, after controlling for social composition. The potential implications of this research are then discussed.
Assessing Infection Control Measures for Pandemic Influenza
Authors: Wein Lawrence M. , Atkinson Michael P.
Published: April 2009

We construct a mathematical model of aerosol (i.e., droplet‐nuclei) transmission of influenza within a household containing one infected and embed it into an epidemic households model in which infecteds occasionally infect someone from another household; in a companion paper, we argue that the contribution from contact transmission is trivial for influenza and the contribution from droplet transmission is likely to be small. Our model predicts that the key infection control measure is the use of N95 respirators, and that the combination of respirators, humidifiers, and ventilation reduces the threshold parameter (which dictates whether or not an epidemic breaks out) by ≈20% if 70% of households comply, and by ≈40% if 70% of households and workplaces comply (≈28% reduction would have been required to control the 1918 pandemic). However, only ≈30% of the benefits in the household are achieved if these interventions are used only after the infected develops symptoms. It is also important for people to sleep in separate bedrooms throughout the pandemic, space permitting. Surgical masks with a device (e.g., nylon hosiery) to reduce face‐seal leakage are a reasonable alternative to N95 respirators if the latter are in short supply.
Almost 30 Years of Writing Research: Making Sense of it All with The Wrath of Khan
Authors: Graham Steve , Harris Karen R.
Published: April 2009

In this invited article, we present an ongoing research program in the area of writing. Although this program has focused on students with learning disabilities (LD) and other struggling writers, it has also concentrated more broadly on issues involving writing development and general writing instruction. One purpose of this review was to share our basic findings in each of these areas, as they have important implications for teaching writing to students with LD. Another purpose was to illustrate how an ongoing research program develops and grows over time. To make this process more concrete, we employed several different literacy devices, including drawing an analogy between the development of our research program and the development of the story line for Star Trek II: The Wrath of Khan. Our final purpose was to describe the research we plan to do in the near future.
Bisphosphonate‐related osteonecrosis: genetic and acquired risk factors
Authors: Sarasquete ME , González M , San Miguel JF , García‐Sanz R
Published: April 2009

The objectives of this study were to review epidemiological, clinical and biological aspects associated with the development of bisphosphonate‐related osteonecrosis of the jaw (BRONJ) in multiple myeloma (MM) patients, with special emphasis on the genetic aspects. A detailed review of previously described risk factors as well as recent genetic findings mostly comprises this work. The most recent meeting abstracts and relevant articles published in journals covered by the Science Citation Index and Medline are also examined. The review pays special attention to the genetic component of BRONJ. A total of 15 series and 14 guidelines or revisions were selected to fit the aims of the review. Gene variability was reviewed in depth to give a clinical illustration on the genetic aspects of BRONJ. Crude prevalence and 5‐year cumulative incidence were considered as the most important end points for predictive purposes. Several acquired factors were recognized as predictors for BRONJ in MM, especially intravenous bisphosphonates, dental trauma and advanced age. Among genetic factors, polymorphisms on CYP2C8 gene arise as a promising risk factor. Bisphosphonate‐related osteonecrosis of the jaw can be predicted with a conjunction of genetic and environmental risk factors.
Once daily dose gentamicin in neonates — is our dosing correct?
Authors: Serane Tiroumourougane V , Zengeya Stanley , Penford Gemma , Cooke Jane , Khanna Gitika , McGregor‐Colman Elle
Published: April 2009

Aim: The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates ≥32 weeks of gestation and ≤7 days of age.

Setting: Level II neonatal intensive care unit.

Subjects: Neonates ≥32 weeks of gestation and ≤7 days of age treated with gentamicin for presumed sepsis.

Methods: Gentamicin was administered by intravenous injection at 4 mg/kg/day once daily. Peak and trough gentamicin levels were measured at the third dose.

Results: In neonates with gestational age between 32 and 36 weeks, 14 out of 65 (22%) had trough serum concentration >2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty‐eight babies had audiometric evaluation which was normal.

Conclusion: A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two‐fifths of neonates between 32 and 36 ± 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32–36 weeks’ neonates.
Nutrient limitation along eutrophic rivers? Roles of N, P and K input in a species‐rich floodplain hay meadow
Authors: Loeb Roos , Kuijpers Lisa , Peters Roy C.J.H. , Lamers Leon P.M. , Roelofs Jan G.M.
Published: April 2009

Question: Is the growth of biodiverse floodplain plant communities along nutrient‐rich lowland rivers still limited by nutrients?

Location: Floodplains of the river Overijsselse Vecht, the Netherlands.

Methods: Soil characteristics and potential nutrient limitation of the vegetation types were studied in two hay meadows, both belonging to the Fritillario‐Alopecuretum, in the floodplain of the eutrophic river Overijsselse Vecht (the Netherlands). The meadows had different fertilization histories: one was a species‐rich hay meadow managed as a nature reserve, the other a newly created nature reserve that had been used as an agricultural pasture before. Sods collected from both locations were transferred to a glasshouse, fertilized weekly with NP, NK, PK, NPK or control solutions and harvested three times a year during two successive growing seasons.

Results: Biomass production of sods from both locations of this floodplain still appeared to be limited by N. Interestingly, the sods from the existing nature reserve were also limited by K, but only in the second year. Fertilization caused a shift in the relative abundance of the different plant families. Tissue nutrient concentrations were increased by fertilization with the nutrient in question, but decreased if biomass production was stimulated.

Conclusions: Even in eutrophic river areas, the nutrient concentrations of the surface water may still determine the development of potentially biodiverse floodplain vegetation.

Nomenclature: Van der Meijden (2005)
Effects of climate on occurrence and size of large fires in a northern hardwood landscape: historical trends, forecasts, and implications for climate change in Témiscamingue, Québec
Authors: Drever C. Ronnie , Bergeron Yves , Drever Mark C. , Flannigan Mike , Logan Travis , Messier Christian
Published: April 2009

Questions:What climate variables best explain fire occurrence and area burned in the Great Lakes‐St Lawrence forest of Canada? How will climate change influence these climate variables and thereby affect the occurrence of fire and area burned in a deciduous forest landscape in Témiscamingue, Québec, Canada?

Location:West central Québec and the Great Lakes‐St Lawrence forest of Canada.

Methods:We first used an information‐theoretic framework to evaluate the relative role of different weather variables in explaining occurrence and area burned of large fires (>200 ha, 1959‐1999) across the Great Lakes‐St Lawrence forest region. Second, we examined how these weather variables varied historically in Témiscamingue and, third, how they may change between the present and 2100 according to different scenarios of climate change based on two Global Circulation Models.

Results:Mean monthly temperature maxima during the fire season (Apr‐Oct) and weighted sequences of dry spells best explained fire occurrence and area burned. Between 1910 and 2004, mean monthly temperature maxima in Témiscamingue showed no apparent temporal trend, while dry spell sequences decreased in frequency and length. All future scenarios show an increase in mean monthly temperature maxima, and one model scenario forecasts an increase in dry spell sequences, resulting in a slight increase in forecasted annual area burned.

Conclusion:Despite the forecasted increase in fire activity, effects of climate change on fire will not likely affect forest structure and composition as much as natural succession or harvesting and other disturbances, principally because of the large relative difference in area affected by these processes.
Thiamin diphosphate in biological chemistry: analogues of thiamin diphosphate in studies of enzymes and riboswitches
Authors: Agyei‐Owusu Kwasi , Leeper Finian J.
Published: April 2009

The role of thiamin diphosphate (ThDP) as a cofactor for enzymes has been known for many decades. This minireview covers the progress made in understanding the catalytic mechanism of ThDP‐dependent enzymes through the use of ThDP analogues. Many such analogues have been synthesized and have provided information on the functional groups necessary for the binding and catalytic activity of the cofactor. Through these studies, the important role of hydrophobic interactions in stabilizing reaction intermediates in the catalytic cycle has been recognized. Stable analogues of intermediates in the ThDP‐catalysed reaction mechanism have also been synthesized and crystallographic studies using these analogues have allowed enzyme structures to be solved that represent snapshots of the reaction in progress. As well as providing mechanistic information about ThDP‐dependent enzymes, many analogues are potent inhibitors of these enzymes. The potential of these compounds as therapeutic targets and as important herbicidal agents is discussed. More recently, the way that ThDP regulates the genes for its own biosynthesis through the action of riboswitches has been discovered. This opens a new branch of thiamin research with the potential to provide new therapeutic targets in the fight against infection.
Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors
Authors: Bettendorff Lucien , Wins Pierre
Published: April 2009

Prokaryotes, yeasts and plants synthesize thiamin (vitamin B1) via complex pathways. Animal cells capture the vitamin through specific high‐affinity transporters essential for internal thiamin homeostasis. Inside the cells, thiamin is phosphorylated to higher phosphate derivatives. Thiamin diphosphate (ThDP) is the best‐known thiamin compound because of its role as an enzymatic cofactor. However, in addition to ThDP, at least three other thiamin phosphates occur naturally in most cells: thiamin monophosphate, thiamin triphosphate (ThTP) and the recently discovered adenosine thiamin triphosphate. It has been suggested that ThTP has a specific neurophysiological role, but recent data favor a much more basic metabolic function. During amino acid starvation, Escherichia coli accumulate ThTP, possibly acting as a signal involved in the adaptation of the bacteria to changing nutritional conditions. In animal cells, ThTP can phosphorylate some proteins, but the physiological significance of this mechanism remains unknown. Adenosine thiamin triphosphate, recently discovered in E. coli, accumulates during carbon starvation and might act as an alarmone. Among the proteins involved in thiamin metabolism, thiamin transporters, thiamin pyrophosphokinase and a soluble 25‐kDa thiamin triphosphatase have been characterized at the molecular level, in contrast to thiamin mono‐ and diphosphatases whose specificities remain to be proven. A soluble enzyme catalyzing the synthesis of adenosine thiamin triphosphate from ThDP and ADP or ATP has been partially characterized in E. coli, but the mechanism of ThTP synthesis remains elusive. The data reviewed here illustrate the complexity of thiamin biochemistry, which is not restricted to the cofactor role of ThDP.
Crystal structures of the regulatory subunit of Thr‐sensitive aspartate kinase from Thermus thermophilus
Authors: Yoshida Ayako , Tomita Takeo , Kono Hidetoshi , Fushinobu Shinya , Kuzuyama Tomohisa , Nishiyama Makoto
Published: April 2009

Crystal structures of the regulatory subunit of Thr‐sensitive aspartate kinase (AK; EC 2.7.2.4) from Thermus thermophilus (TtAKβ) were determined at 2.15 Å in the Thr‐bound form (TtAKβ‐Thr) and at 2.98 Å in the Thr‐free form (TtAKβ‐free). Although both forms are crystallized as dimers, the contact surface area of the dimer interface in TtAKβ‐free (3200 Å2) is smaller than that of TtAKβ‐Thr (3890 Å2). Sedimentation equilibrium analyzed by ultracentrifugation revealed that TtAKβ is present in equilibrium between a monomer and dimer, and that Thr binding shifts the equilibrium to dimer formation. In the absence of Thr, an outward shift of β‐strands near the Thr‐binding site (site 1) and a concomitant loss of the electron density of the loop region between β3 and β4 near the Thr‐binding site are observed. The mechanism of regulation by Thr is discussed on the basis of the crystal structures. TtAKβ has higher thermostability than the regulatory subunit of Corynebacterium glutamicum AK, with a difference in denaturation temperature (Tm) of 40 °C. Comparison of the crystal structures of TtAKβ and the regulatory subunit of C. glutamicum AK showed that the well‐packed hydrophobic core and high Pro content in loops contribute to the high thermostability of TtAKβ.
Delayed Complications of Gel Injection for Penile Girth Augmentation
Authors: Shaeer Osama , Shaeer Kamal
Published: April 2009

Introduction

Penile girth augmentation is a domain of extensive controversy and debate. A variety of methods is available for the choice of the surgeon including dermal-fat grafts and flaps. The need for a simple procedure with minimal donor site has lead to proposing injection therapy for penile augmentation, whether by fat or synthetic materials.

Aim

This work reports on a male patient suffering a deforming subcutaneous mass in the penis following penile girth augmentation by injection therapy using synthetic material, and describes its management, and pathologic analysis of the extracted tissue.

Methods

The mass was excised through a circumferential subcoronal incision while maintaining skin vascularity and integrity of the corpora. The excised tissue was microscopically examined.

Main Outcome Measures

Cosmetic and functional results of surgical correction.

Results

Cosmetic and functional outcome were acceptable. Pathology examination revealed features of foreign body granuloma.

Conclusion

Injection of fillers for girth augmentation of the penile shaft may result in delayed complications including migration, granulomatous reaction, and resorption that may occur beyond the follow-up span of the currently available study that recommends its use.
Patterns and Their Correlates of Seeking Treatment for Erectile Dysfunction in Type 2 Diabetic Patients
Authors: Jiann Bang-Ping , Lu Chih-Chen , Lam Hing-Chung , Chu Chih-Hsun , Sun Chun-Chin , Lee Jenn-Kuen
Published: April 2009

Introduction

Diabetic patients are at high risk of having erectile dysfunction (ED), but their doctors rarely pay attention to this association.

Aim

To evaluate the treatment-seeking patterns and their correlates for ED in type 2 diabetic patients.

Methods

A questionnaire containing Sexual Health Inventory for Men and questions inquiring treatment-seeking patterns was mailed or given to 4,040 subjects who had visited our endocrinology outpatient department for diabetes during January 2004 to May 2006.

Main Outcome Measures

The prevalence of being bothered and having interest in treatment, and the percentage having sought treatment in regard to ED and their correlates with age and ED severity.

Results

Of the subjects with questionnaire completed, 83.9% (708/844) had ED. Among the subjects with different severity of ED, the moderate group had the highest percentages regarding prevalence of being bothered (89.4%), having interest in treatment (78.5%), and having sought treatment (46.2%). Of all the subjects, only 14.2% had ever visited Western physicians, whereas embarrassment and misinformation about ED treatment were the leading reasons for never doing so. Over half (56.6%) of those with ED wished to discuss ED problem with their doctors, and of them 90.4% wished the doctors to initiate to broach this issue.

Conclusions

The prevalence of ED and the concerns about it were high in these diabetic patients. ED severity was the major determinant of their treatment-seeking decision, whereas only few of them had ever sought professional help. Routine screening of ED in diabetic patients is recommended.
Men’s Sexual Health: Evaluating the Effectiveness of Print- and PDA-Based CME
Authors: Broderick Gregory A. , Abdolrasulnia Maziar
Published: April 2009

Introduction

Personal digital assistant (PDA)-based continuing medical education (CME) activities have become widely available.

Aims

To evaluate the effectiveness of print- and PDA-based CME materials in erectile dysfunction (ED).

Methods

CME materials describing links between ED and comorbid medical conditions, effects of certain lifestyle modifications on ED, and treatment of ED with phosphodiesterase 5 (PDE5) inhibitors were distributed as a print supplement and as electronic modules, viewed with PDAs. We evaluated how effectively these materials improved evidence-based clinical choices, using survey questions about case vignettes and comparing responses of CME participants (N = 85) and matched nonparticipants (N = 94).

Main Outcome Measures

Effect size, measuring the difference in evidence-based clinical scores between participants and nonparticipants.

Results

CME certificates were awarded to 3,557 participants (459 print, 3,098 PDA). Among survey respondents, significantly more CME participants recognized that ED was associated with greater risk for myocardial infarction (61% participants; 34% nonparticipants; P ≤ 0.001) and was a strong marker for diabetes mellitus (37% participants; 9% nonparticipants; P ≤ 0.001). In contrast, participants and nonparticipants both displayed a good understanding of the relationships of smoking, obesity, and sedentary lifestyle with ED and of using PDE5 inhibitors to treat ED in patients with prostate cancer or benign prostatic hyperplasia; this likely reflects a good baseline understanding of these topics. Participants and nonparticipants each displayed a poor understanding of the recommendations regarding nonarteritic anterior ischemic optic neuropathy and PDE5 inhibitor use. Patient reluctance to discuss sexual concerns was perceived as the most significant barrier to optimal ED management.

Conclusions. 

Given patient reluctance to discuss sexual concerns, future CME activities should focus on educating health-care providers and patients that ED is a risk factor for cardiovascular disease and diabetes. Both print- and PDA-based CME on ED were effective; the large number of lesson completers suggests a trend toward on-demand, self-selected CME is positive.
Report of Two Cases of Bladder Perforation Caused by Reservoir of Inflatable Penile Prosthesis
Authors: Kramer Andrew C. , Chason Juddson , Kusakabe Alan
Published: April 2009

Introduction

Rupture of penile prosthesis reservoir into the bladder is an unusual and unexpected occurrence after prosthesis component replacement for malfunction. Scant literature exists describing a pathophysiology, diagnosis, and repair with device salvage.

Aim

Our goal is to describe an uncommon event in prosthetic surgery, and discuss the pathophysiology and ways to treat and perhaps avoid this occurrence.

Methods

Two patients presented with gross hematuria in the recovery room following repair of a cylinder to pump tubing break of their inflatable penile prostheses (IPPs). In each operation, the existing reservoir had been left in situ and refilled once placed in circuit with new cylinders and pump.

Results

The reservoirs had immediately ruptured into the bladder upon refilling, and were identified intravesically on cystoscopy and computed tomography scan. A one-step approach can be done to salvage the device, remove the eroded reservoir with bladder repair, and new reservoir placed directly into appropriate space.

Interpretation

During IPP revision, even when a reservoir is not manipulated simple tubing repair performed, gross hematuria in the recovery room likely signals bladder perforation. We include recommendations for reservoir management with implant revision, as well as surgical management and prevention of this complication.

Conclusions

Bladder perforation can be caused by penile implant revision even when the old reservoir is not manipulated. If this complication occurs, it can be surgically managed immediately. This can also potentially be avoided.