bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot study of the eccentric decline squat in the management of painful chronic patellar tendinopathy
Authors: Purdam C R , Jonsson P , Alfredson H , Lorentzon R , Cook J L , Khan K M
Published: July 2004

Objectives:This non-randomised pilot study investigated the effect of eccentric quadriceps training on 17 patients (22 tendons) with painful chronic patellar tendinopathy.

Methods:Two different eccentric exercise regimens were used by subjects with a long duration of pain with activity (more than six months). (a) Nine consecutive patients (10 tendons; eight men, one woman; mean age 22 years) performed eccentric exercise with the ankle joint in a standard (foot flat) position. (b) Eight patients (12 tendons; five men, three women; mean age 28 years) performed eccentric training standing on a 25° decline board, designed to increase load on the knee extensor mechanism. The eccentric training was performed twice daily, with three sets of 15 repetitions, for 12 weeks. Primary outcome measures were (a) 100 mm visual analogue scale (VAS), where the subject recorded the amount of pain during activity, and (b) return to previous activity. Follow up was at 12 weeks, with a further limited follow up at 15 months.

Results:Good clinical results were obtained in the group who trained on the decline board, with six patients (nine tendons) returning to sport and showing a significantly reduced amount of pain over the 12 week period. Mean VAS scores fell from 74.2 to 28.5 (p  =  0.004). At 15 months, four patients (five tendons) reported satisfactory results (mean VAS 26.2). In the standard squat group the results were poor, with only one athlete returning to previous activity. Mean VAS scores in this group were 79.0 at baseline and 72.3 at 12 weeks (p  =  0.144).

Conclusion:In a small group of patients with patellar tendinopathy, eccentric squats on a decline board produced encouraging results in terms of pain reduction and return to function in the short term. Eccentric exercise using standard single leg squats in a similar sized group appeared to be a less effective form of rehabilitation in reducing pain and returning subjects to previous levels of activity.
Does generalised ligamentous laxity increase seasonal incidence of injuries in male first division club rugby players?
Authors: Stewart D R , Burden S B
Published: July 2004

Objectives:To investigate if ligamentous laxity increases seasonal incidence of injury in male first division club rugby players, and to determine if strength protects against injury in hypermobile and tight players.

Methods:Fifty one male first division club rugby players were examined for ligamentous laxity using the Beighton-Horan assessment and graded with an overall laxity score ranging from 0 (tight) to 9 (hyperlax). Each participant was classified into a group determined by their laxity score: tight (0–3), hypermobile (4–6), or excessively hypermobile (7–9). The incidence of joint injuries was recorded prospectively throughout the rugby season and correlated with laxity score. Differences between the groups were analysed.

Results:The overall prevalence of generalised joint hypermobility was 24% (12/51). The incidence of injuries was significantly higher in hypermobile (116.7 per 1000 hours) than tight (43.6 per 1000 hours) players (p  =  0.034). There were no significant differences in peak strength between the hypermobile and tight groups.

Conclusions:The laxity of the players may explain the differences in injury rates between these groups. Peak strength does not protect the hypermobile joint against injury. It appears that hypermobility may cause an increase in the injury rate of male first division club rugby players.
Hip fracture-dislocation in football: a report of two cases and review of the literature
Authors: Giza E , Mithöfer K , Matthews H , Vrahas M
Published: July 2004

Soccer is the world’s most popular sport, with over 200 million participants world wide. Fractures account for only 4–9% of acute injuries, and hip fracture-dislocation is extremely uncommon. The potentially serious long term sequelae require that team physicians have an awareness of this injury. Two cases of traumatic hip fracture-dislocation are here reported in recreational soccer players sustained by low energy mechanisms. Prompt reduction and fixation are important to produce a stable and congruent joint.
A one season prospective cohort study of volleyball injuries
Authors: Verhagen E A L M , Van der Beek A J , Bouter L M , Bahr R M , Mechelen W Van
Published: July 2004

Objective:To estimate the overall incidence of acute and overuse volleyball injuries, and to describe factors associated with ankle sprains.

Methods:486 players from the second and third Dutch national volleyball divisions participated in the study and were followed prospectively during a whole season. Three measurements were made during the season (baseline, follow up 1, and follow up 2), where all players completed a questionnaire on demographic variables (only at baseline), sports participation, use of preventive measures, and previous injuries. Volleyball exposure during training and matches was recorded for each individual player by the coach on a weekly exposure form. In case of injury the coach provided the injured player with an injury registration form, which had to be completed within one week after the onset of injury.

Results:100 injuries were reported, resulting in an overall injury incidence of 2.6 injuries/1000 hours. The incidence of acute injuries was 2.0/1000 hours. Ankle sprains (n = 41) accounted for most of the acute injuries, and 31 (75%) of all players with an ankle sprain reported a previous ankle sprain. Twenty five overuse injuries were reported. The overall incidence of overuse injuries was 0.6/1000 hours; the back and the shoulder were the most common sites.

Conclusions:Ankle sprain is the most common injury in volleyball, accounting for 41% of all volleyball related injuries. Previous injury seems to be an important risk factor for an ankle sprain. Injury prevention programmes should focus on ankle sprains and concentrate on players with previous ankle sprains.
Upper airway obstruction masquerading as exercise induced bronchospasm in an elite road cyclist
Authors: Fallon K E
Published: July 2004

This case concerns an elite road cyclist who complained of occasional dyspnoea and inspiratory difficulty during intense exercise. Clinical examination was normal and the final diagnosis was vocal cord dysfunction, a paradoxical closure of the vocal cords during inspiration which is highly associated with inspiratory stridor at high rates of ventilation. Awareness by the sports physician of this not uncommon condition is important to avoid misdiagnosis.
Avulsion fracture of peroneus longus at the first metatarsal insertion: a case report
Authors: Murakami T , Okamura K , Harada S , Setojima M , Ikushiba Y , Miyamoto Y , Li S , Yamada M
Published: July 2004

Reports of isolated avulsion fracture at the planter lateral base of the first metatarsal without injury of the tarsometatarsal joint are very rare. A 24 year old man sustained an avulsion fracture at the plantar lateral base of the first metatarsal. Normal alignment of metatarsal bones and tarsometatarsal joint was maintained. In this paper, we describe internal fixation of the displaced fragment usingxray and minimally invasive surgery with good results.
Little league shoulder syndrome in an adolescent cricket player: Figure 1
Authors: Drescher W R , Falliner A , Zantop T , Oehlert K , Petersen W , Hassenpflug J
Published: July 2004

The first case of little league shoulder syndrome in a cricket player is reported. The condition has been reported in baseball pitchers and is characterised by a proximal humeral epiphyseolysis.
From catastrophe to complexity: a novel model of integrative central neural regulation of effort and fatigue during exercise in humans
Authors: Noakes T D , St Clair Gibson A , Lambert E V
Published: July 2004

It is a popular belief that exercise performance is limited by metabolic changes in the exercising muscles, so called peripheral fatigue. Exercise terminates when there is a catastrophic failure of homoeostasis in the exercising muscles. A revolutionary theory is presented that proposes that exercise performance is regulated by the central nervous system specifically to ensure that catastrophic physiological failure does not occur during normal exercise in humans.
LOW-NOISE SILICON-ON-INSULATOR HALL DEVICES
Authors: HADDAB Y. , MOSSER V. , LYSOWEC M. , SUSKI J. , DEMEUS L. , RENAUX C. , ADRIAENSEN S. , FLANDRE D.
Published: July 2004

Hall sensors are used in a very wide range of applications. A very demanding one is electrical current measurement for metering purposes. In addition to high precision and stability, a sufficiently low noise level is required. Cost reduction through sensor integration with low-voltage/low-power electronics is also desirable. The purpose of this work is to investigate the possible use of SOI (Silicon On Insulator) technology for this integration. We have fabricated SOI Hall devices exploring the useful range of silicon layer thickness and doping level. We show that noise is influenced by the presence of LOCOS and p-n depletion zones near the edges of the active zones of the devices. A proper choice of SOI technological parameters and process flow leads to up to 18 dB reduction in Hall sensor noise level. This result can be extended to many categories of devices fabricated using SOI technology.
Response of hepatic proteins to the lowering of habitual dietary protein to the recommended safe level of intake
Authors: Afolabi Paul R. , Jahoor Farook , Gibson Neil R. , Jackson Alan A.
Published: July 2004

The plasma concentrations of albumin, HDL apolipoprotein A1 (apoA1), retinol-binding protein (RBP), transthyretin (TTR), haptoglobulin, and fibrinogen were measured, and a stable isotope infusion protocol was used to determine the fractional and absolute synthesis rates of RBP, TTR, and fibrinogen in 12 young adults on three occasions during a reduction of their habitual protein intake from 1.13 to 0.75 g·kg−1·day−1for 10 days. This study was performed to determine whether healthy adults could maintain the rates of synthesis of selected nutrient transport and positive acute-phase proteins when consuming a protein intake of 0.75 g·kg−1·day−1. During the lower protein intake, the plasma concentration of all the proteins, other than HDL-apoA1, remained unchanged. HDL-apoA1 concentration was significantly reduced ( P < 0.05) after 3 days of the lower protein intake, but not at 10 days. The rates of synthesis of RBP and TTR declined significantly ( P < 0.05), whereas the rate of synthesis of fibrinogen remained unchanged. The results indicate that, when normal adults consume the recommended safe level of protein, 0.75 g·kg−1·day−1, there is a slower rate of turnover of nutrient transport proteins than on their habitual diet. Hence, healthy individuals consuming this amount of protein may be less able to mount an adequate metabolic response to a stressful stimulus.
Components of a platelet-activating factor-signaling loop are assembled in the ovine endometrium late in the estrous cycle
Authors: Chami O. , Evans G. , O'Neill C.
Published: July 2004

Pulsatile release of uterine prostaglandin F2α(PGF2α) induces luteolysis in ruminants. Exogenous PAF is well known to cause PGF2αrelease from the ovine uterus. This study examines whether the components of a PAF-signaling loop exist in sheep at the time luteolysis is normally initiated. Day 14 of the cycle was the first day the uterus responded to an infusion of PAF, inducing a significant short-term increase in circulating levels of the PGF2αmetabolite. There was a significant increase of PAF concentration ( P < 0.001) in the endometrium and PAF release by tissue explants ( P < 0.001) from day 10 to day 16 of the cycle. Endometrial tissue PAF receptor mRNA expression was induced ( P < 0.01) by estradiol and progesterone treatment of animals, and transcripts were present between days 10 and 16 of the estrous cycle. Western analysis of endometrial tissue showed marked upregulation of PAF receptor protein expression from day 14 of the cycle, and immunolocalization studies showed that the receptor expression was predominantly around the endometrial glands. PAF:acetylhydrolase was primarily located within the lumen of the endometrial glands. The study shows that a PAF-signaling loop was assembled within the ovine endometrium at the time that PGF2αpulsatility was first observed.
Dynamical effects of diffusive cell coupling on cardiac excitation and propagation: a simulation study
Authors: Qu Zhilin
Published: July 2004

Cell coupling is considered to be important for cardiac action potential propagation and arrhythmogenesis. We carried out computer simulations to investigate the effects of stimulation strength and cell-to-cell coupling on action potential duration (APD) restitution, APD alternans, and stability of reentry in models of isolated cell, one-dimensional cable, and two-dimensional tissue. Phase I formulation of the Luo and Rudy action potential model was used. We found that stronger stimulation resulted in a shallower APD restitution curve and onset of APD alternans at a faster pacing rate. Reducing diffusive coupling between cells prolonged APD. Weaker diffusive currents along the direction of propagation steepened APD restitution and caused APD alternans to occur at a slower pacing rate in tissue. Diffusive current due to curvature changed APD but had little effect on APD restitution slope and onset of instability. Heterogeneous cell coupling caused APD inhomogeneities in space. Reduction in coupling strength either uniformly or randomly had little effect on the rotation period and stability of a reentry, but random cell decoupling slowed the rotation period and, thus, stabilized the reentry, preventing it from breaking up into multiple waves. Therefore, in addition to its effects on action potential conduction velocity, diffusive cell coupling also affects APD in a rate-dependent manner, causes electrophysiological heterogeneities, and thus modulates the dynamics of cardiac excitation. These effects are brought about by the modulation of ionic current activation and inactivation.
cAMP modulates cGMP-mediated cerebral arteriolar relaxation in vivo
Authors: Xu Hao-Liang , Wolde Hailemariam M. , Gavrilyuk Vitaliy , Baughman Verna L. , Pelligrino Dale A.
Published: July 2004

No studies have specifically addressed whether cAMP can influence nitric oxide (NO)/cGMP-induced cerebral vasodilation. In this study, we examined whether cAMP can enhance or reduce NO-induced cerebral vasodilation in vivo via interfering with cGMP efflux or through potentiating phosphodiesterase 5 (PDE5)-mediated cGMP breakdown, respectively, in cerebral vascular smooth muscle cells (CVSMCs). To that end, we evaluated, in male rats, the effects of knockdown [via antisense oligodeoxynucleotide (ODN) applications] of the cGMP efflux protein multidrug resistance protein 5 (MRP5) and PDE5 inhibition on pial arteriolar NO donor [ S-nitroso- N-acetyl penicillamine (SNAP)]-induced dilations in the absence and presence of cAMP elevations via forskolin. Pial arteriolar diameter changes were measured using well-established protocols in anesthetized rats. In control (missense ODN treated) rats, forskolin elicited a leftward shift in the SNAP dose-response curves (∼50% reduction in SNAP EC50). However, in MRP5 knockdown rats, cAMP increases were associated with a substantial reduction in SNAP-induced vasodilations (reflected as a significant 35–50% lower maximal response). In the presence of the PDE5 inhibitor MY-5445, the repression of the NO donor response accompanying forskolin was prevented. These findings suggest that cAMP has opposing effects on NO-stimulated cGMP increases. On the one hand, cAMP limits CVSMC cGMP loss by restricting cGMP efflux. On the other, cAMP appears to enhance PDE5-mediated cGMP breakdown. However, because increased endogenous cAMP seems to potentiate NO/cGMP-induced arteriolar relaxation when MRP5 expression is normal, the effect of cAMP to reduce cGMP efflux appears to predominate over cAMP stimulation of cGMP hydrolysis.
LDL receptor-related protein LRP6 regulates proliferation and survival through the Wnt cascade in vascular smooth muscle cells
Authors: Wang Xiaohong , Adhikari Neeta , Li Qinglu , Hall Jennifer L.
Published: July 2004

Initial studies have established expression of low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) in vascular smooth muscle cells (VSMCs). We hypothesized that LRP6 is a critical mediator governing the regulation of the canonical Wnt/β-catenin/T cell factor 4 (Tcf-4) cascade in the vasculature. This hypothesis was based on our previous work demonstrating a role for the β-catenin/Tcf-4 pathway in vascular remodeling as well as work in other cell systems establishing a role for LRP family members in the Wnt cascade. In line with our hypothesis, LRP6 upregulation significantly increased Wnt-1-induced Tcf activation. Moreover, a dominant interfering LRP6 mutant lacking the carboxyl intracellular domain (LRP6ΔC) abolished Tcf activity. LRP6-induced stimulation of Tcf was blocked in VSMCs harboring constitutive expression of a dominant negative Tcf-4 transgene lacking the β-catenin binding domain, suggesting that LRP6-induced activation of Tcf was mediated through a β-catenin-dependent signal. Expression of the dominant interfering LRP6ΔC transgene was sufficient to abolish the Wnt-induced survival as well as cyclin D1 activity and cell cycle progression. In conclusion, these findings provide the first evidence of a role for an LDL receptor-related protein in the regulation of VSMC proliferation and survival through the evolutionary conserved Wnt signaling cascade.
Estimation of paracellular conductance of primary rat alveolar epithelial cell monolayers
Authors: Kim Kwang-Jin , Borok Zea , Ehrhardt Carsten , Willis Brigham C. , Lehr Claus-Michael , Crandall Edward D.
Published: July 2004

Freshly isolated rat type II pneumocytes, when grown on permeable tissue culture-treated polycarbonate filters, form confluent alveolar epithelial cell monolayers (RAECM). Cells in RAECM undergo transdifferentiation, exhibiting over time morphological and phenotypic characteristics of type I pneumocytes in vivo. We recently reported that transforming growth factor-β1 (TGF-β1) decreases overall monolayer resistance ( Rte) and stimulates short-circuit current in a dose-dependent manner. In this study, we investigated the effects of TGF-β1 (50 pM) or 10% newborn bovine serum (NBS) on modulation of paracellular passive ion conductance and its contribution to total passive ion conductance across RAECM. On days 5–7 in culture, tight-junctional resistance ( Rtj, kΩcm2) of RAECM, cultured in minimally defined serum-free medium (MDSF) with or without TGF-β1 or NBS, was estimated from the relationship between observed transmonolayer voltage and resistance after addition of gramicidin D to apical potassium isethionate Ringer solution under open-circuit conditions. NaCl Ringer solution bathed the basolateral side throughout the experimental period. Results showed that transmonolayer conductance (1/ Rte) and tight-junctional conductance (1/ Rtj) are 0.59 and 0.14 mS/cm2 for control monolayers in MDSF, 1.59 and 0.38 mS/cm2 for monolayers exposed to TGF-β1, and 0.38 and 0.18 mS/cm2 for monolayers grown in the presence of NBS. The contributions to total transepithelial ion conductance by the paracellular pathway are estimated to be 23, 23, and 47% for control, TGF-β1-exposed, and newborn bovine serum (NBS)-treated RAECM, respectively.
Chronic fluoxetine microdialysis into the medullary raphe nuclei of the rat, but not systemic administration, increases the ventilatory response to CO2
Authors: Taylor Natalie C. , Li Aihua , Green Adam , Kinney Hannah C. , Nattie Eugene E.
Published: July 2004

In conscious rats, focal CO2 stimulation of the medullary raphe increases ventilation, whereas interference with serotonergic function here decreases the ventilatory response to systemic hypercapnia. We sought to determine whether repeated administration of a selective serotonin reuptake inhibitor in this region would increase the ventilatory response to hypercapnia in unanesthetized rats. In rats instrumented with electroencephalogram-electromyogram electrodes, 250 or 500 μM fluoxetine or artificial cerebrospinal fluid (aCSF) was microdialyzed into the medullary raphe for 30 min daily over 15 days. To compare focal and systemic treatment, two additional groups of rats received 10 mg·kg−1·day−1 fluoxetine or vehicle systemically. Ventilation was measured in normocapnia and in 7% CO2 before treatment ( day 0), acutely ( days 1 or 3), on day 7, and on day 15. There was no change in normocapnic ventilation in any treatment group. Rats that received 250 μM fluoxetine microdialysis showed a significant 13% increase in ventilation in wakefulness during hypercapnia on day 7, due to an increase in tidal volume. In rats microdialyzed with 500 μM fluoxetine, there were 16 and 32% increases in minute ventilation during hypercapnia in wakefulness and sleep on day 7, and 20 and 28% increases on day 15, respectively, again due to increased tidal volume. There was no change in the ventilatory response to CO2 in rats microdialyzed with aCSF or in systemically treated rats. Chronic fluoxetine treatment in the medullary raphe increases the ventilatory response to hypercapnia in an unanesthetized rat model, an effect that may be due to facilitation of chemosensitive serotonergic neurons.
Ventilatory responses to carbon dioxide at low and high levels of oxygen are elevated after episodic hypoxia in men compared with women
Authors: Morelli Chris , Badr M. Safwan , Mateika Jason H.
Published: July 2004

We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 ± 0.82 vs. women, 4.70 ± 0.77 l·min−1·Torr−1; 150 Torr: men, 4.33 ± 1.15 vs. women, 3.21 ± 0.58 l·min−1·Torr−1). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 ± 1.40 vs. women, 5.97 ± 0.71 l·min−1·Torr−1; 150 Torr: men, 5.73 ± 0.81 vs. women, 3.83 ± 0.56 l·min−1·Torr−1). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.
Why Trypanosomes Cause Sleeping Sickness
Authors: Lundkvist Gabriella B. , Kristensson Krister , Bentivoglio Marina
Published: July 2004

African trypanosomiasis or sleeping sickness is hallmarked by sleep and wakefulness disturbances. In contrast to other infections, there is no hypersomnia, but the sleep pattern is fragmented. This overview discusses that the causative agents, the parasites Trypanosoma brucei, target circumventricular organs in the brain, causing inflammatory responses in hypothalamic structures that may lead to dysfunctions in the circadian-timing and sleep-regulatory systems.
KSHV viral cyclin binds to p27KIP1 in primary effusion lymphomas
Authors: Järviluoma Annika , Koopal Sonja , Räsänen Susanna , Mäkelä Tomi P. , Ojala Päivi M.
Published: July 2004

Primary effusion lymphomas (PELs) represent a unique non-Hodgkin lymphoma that is consistently infected by Kaposi sarcoma herpesvirus (KSHV). PEL cells express high levels of the cell cycle inhibitor p27KIP1 and yet proliferate actively. KSHV genome encodes a viral cyclin homolog, v-cyclin, which has previously been implicated in down-regulation of p27KIP1 levels. To address how PEL cells can tolerate high p27KIP1 levels, we investigated functional interactions between v-cyclin and p27KIP1 using PEL-derived cell lines as a model system. Here we demonstrate that v-cyclin and p27KIP1 stably associate in PEL cells in vivo suggesting an attractive model by which p27KIP1 is inactivated in the actively proliferating PEL cells. Moreover, we show that v-cyclin and cyclin-dependent kinase 6 (CDK6) form an active kinase without p27KIP1 and that CDK6 is the in vivo catalytic subunit of v-cyclin in PEL cells. These findings suggest that KSHV may promote oncogenesis in PEL by expressing v-cyclin, which both overrides negative cell cycle controls present in the PEL precursor cells and induces a strong proliferative signal via CDK6 kinase activity. (Blood. 2004;104:3349-3354)
Early endothelial dysfunction in cholesterol-fed rabbits: a non-invasive in vivo ultrasound study.
Authors: Drolet Marie-Claude , Plante Éric , Battistini Bruno , Couet Jacques , Arsenault Marie
Published: July 2004

Background

Endothelial function in hypercholesterolemic rabbits is usually evaluated ex vivo on isolated aortic rings. In vivo evaluation requires invasive imaging procedures that cannot be repeated serially.

Aim

We evaluated a non-invasive ultrasound technique to assess early endothelial function in rabbits and compare data with ex vivo measurements.

Methods

Twenty-four rabbits (fed with a cholesterol diet (0.5%) for 2 to 8 weeks) were given progressive infusions of acetylcholine (0.05–0.5 μg/kg/min) and their endothelial function was assessed in vivo by transcutaneous vascular ultrasound of the abdominal aorta. Ex vivo endothelial function was evaluated on isolated aortic rings and compared to in vivo data.

Results

Significant endothelial dysfunction was demonstrated in hypercholesterolemic animals as early as 2 weeks after beginning the cholesterol diet (aortic cross-sectional area variation: -2.9% vs. +4% for controls, p < 0.05). Unexpectedly, response to acetylcholine at 8 weeks was more variable. Endothelial function improved in 5 rabbits while 2 rabbits regained a normal endothelial function. These data corroborated well with ex vivo results.

Conclusion

Endothelial function can be evaluated non-invasively in vivo by transcutaneous vascular ultrasound of the abdominal aorta in the rabbit and results correlate well with ex vivo data.
Echocardiographic assessment and percutaneous closure of multiple atrial septal defects
Authors: Mitchell Andrew RJ , Roberts Philip , Eichhöfer Jonas , Timperley Jonathan , Ormerod Oliver JM
Published: July 2004

Atrial septal defect closure is now routinely performed using a percutaneous approach under echocardiographic guidance. Centrally located, secundum defects are ideal for device closure but there is considerable morphological variation in size and location of the defects. A small proportion of atrial septal defects may have multiple fenestrations and these are often considered unsuitable for device closure. We report three cases of multiple atrial septal defects successfully closed with two Amplatzer septal occluders.
Cancer of the endometrium: current aspects of diagnostics and treatment
Authors: Münstedt Karsten , Grant Phillip , Woenckhaus Joachim , Roth Gabriele , Tinneberg Hans-Rudolf
Published: July 2004

Background

Endometrial cancer represents a tumor entity with a great variation in its incidence throughout the world (range 1 to 25). This suggests enormous possibilities of cancer prevention due to the fact that the incidence is very much endocrine-related, chiefly with obesity, and thus most frequent in the developed world. As far as treatment is concerned, it is generally accepted that surgery represents the first choice of treatment. However, several recommendations seem reasonable especially with lymphadenectomy, even though they are not based on evidence. All high-risk cases are generally recommended for radiotherapy.

Methods

A literature search of the Medline was carried out for all articles on endometrial carcinoma related to diagnosis and treatment. The articles were systematically reviewed and were categorized into incidence, etiology, precancerosis, early diagnosis, classification, staging, prevention, and treatment. The article is organized into several similar subheadings.

Conclusions

In spite of the overall good prognosis during the early stages of the disease, the survival is poor in advanced stages or recurrences. Diagnostic measures are very well able to detect asymptomatic recurrences. These only seem justified if patients' chances are likely to improve, otherwise such measures increases costs as well as decrease the patients' quality of life. To date neither current nor improved concepts of endocrine treatment or chemotherapy have been able to substantially increase patients' chances of survival. Therefore, newer concepts into the use of antibodies e.g. trastuzumab in HER2-overexpressing tumors and the newer endocrine compounds will need to be investigated. Furthermore, it would seem highly desirable if future studies were to identify valid criteria for an individualized management, thereby maximizing the benefits and minimizing the risks.
Both U2 snRNA and U12 snRNA are required for accurate splicing of exon 5 of the rat calcitonin/CGRP gene
Authors: ROESSER JAMES R.
Published: July 2004

Two classes of spliceosome are present in eukaryotic cells. Most introns in nuclear pre-mRNAs are removed by a spliceosome that requires U1, U2, U4, U5, and U6 small nuclear ribonucleoprotein particles (snRNPs). A minor class of introns are removed by a spliceosome containing U11, U12, U5, U4atac, and U6 atac snRNPs. We describe experiments that demonstrate that splicing of exon 5 of the rat calcitonin/CGRP gene requires both U2 snRNA and U12 snRNA. In vitro, splicing to calcitonin/ CGRP exon 5 RNA was dependent on U2 snRNA, as preincubation of nuclear extract with an oligonucleotide complementary to U2 snRNA abolished exon 5 splicing. Addition of an oligonucleotide complementary to U12 snRNA increased splicing at a cryptic splice site in exon 5 from <5% to 50% of total spliced RNA. Point mutations in a candidate U12 branch sequence in calcitonin/CGRP intron 4, predicted to decrease U12-pre-mRNA base-pairing, also significantly increased cryptic splicing in vitro. Calcitonin/CGRP genes containing base changes disrupting the U12 branch sequence expressed significantly decreased CGRP mRNA levels when expressed in cultured cells. Coexpression of U12 snRNAs containing base changes predicted to restore U12-pre-mRNA base pairing increased CGRP mRNA synthesis to the level of the wild-type gene. These observations indicate that accurate, efficient splicing of calcitonin/CGRP exon 5 is dependent upon both U2 and U12 snRNAs.
RNA editing of a miRNA precursor: FIGURE 1.
Authors: LUCIANO DANIEL J. , MIRSKY HENRY , VENDETTI NICHOLAS J. , MAAS STEFAN
Published: July 2004

Micro RNAs comprise a large family of small, functional RNAs with important roles in the regulation of protein coding genes in animals and plants. Here we show that human and mouse miRNA22 precursor molecules are subject to posttranscriptional modification by A-to-I RNA editing in vivo. The observed editing events are predicted to have significant implications for the biogenesis and function of miRNA22 and might point toward a more general role for RNA editing in the regulation of miRNA gene expression.
Eino and Elisa
Authors: Kjellberg Seppo
Published: July 2004

In a recent Finnish qualitative study on urban sustainability it became evident that two devoted lay Christians held totally opposite opinions on the subject. One defended an anthropocentric viewpoint on the basis of the Hebrew Bible idea of humans being made in the image of God, while the other used the same text to defend an ecocentric view of environmentally responsible humans. Within the context of the Finnish State Church, both views can—without attracting attention—live side by side as Christian answers to the demand for sustainable city planning. However, a paradigm transition towards a more holistic view of the environment seems to be forthcoming. I would suggest that a culture of dialogue, both between Christians themselves and between Christians and people holding a different world-view, would lead to better self-understanding and to an ability to use the best of the Christian heritage for the development of a holistically understood ecological city. In order to be a truly liberating theology, urban ecotheology has to be openly discursive. To understand this, the alternative models for a contextual theology espoused by Sallie McFague are especially helpful.
Re-envisioning Ecotheology and the Divine from the Margins
Authors: Rieger Joerg
Published: July 2004

While concerns for the environment and concerns for oppression along the lines of class, race, and gender have developed on different tracks, there are an increasing number of proposals for bringing them together. Feminist and liberation theologians have led the way. In the process, the various perspectives have begun to reshape each other. At a time when ecological concerns seem to become more and more ‘wedded to the dominant world view’, a perspective which re-envisions humanity, the divine, and ecology from the margins might help to develop new horizons. The result is a more constructive ecotheological perspective which will lead us beyond the hegemonic tendencies of romantic or ‘purely factual’ views of the environment.
Economic Analysis of Intravenous Plus Oral Amiodarone, Atrial Septal Pacing, and Both Strategies to Prevent Atrial Fibrillation After Open Heart Surgery
Authors: Reddy Prabashni , Kalus James S. , Caron Michael F. , Horowitz Sheryl , Karapanos Angiliki , Coleman Craig I. , Kluger Jeffrey , White C. Michael
Published: July 2004

Study Objectives. To compare the cost‐effectiveness of intravenous plus oral amiodarone, atrial septal pacing, and both strategies combined to prevent atrial fibrillation after open heart surgery. Secondary objectives were to compare the cost‐effectiveness of amiodarone versus no amiodarone and of pacing versus no pacing, and to compare hospitalization costs of the various strategies.

Design. Piggyback cost analysis of a randomized, 2 times 2 factorial trial.

Setting. Urban academic hospital.

Patients. One hundred and sixty patients with coronary artery and/or valvular disease.

Intervention. Patients were randomized to receive amiodarone or matching placebo and then further randomized to receive atrial septal pacing or no pacing.

Measurements and Main Results. The economic analysis was conducted from a hospital perspective. Charges were converted to costs using cost: charge ratios. For the cost‐effectiveness analysis, a joint distribution of costs and effectiveness was performed using the nonparametric bootstrap method. Amiodarone plus pacing significantly decreased the frequency of atrial fibrillation after open heart surgery, compared with amiodarone alone, pacing alone, and placebo. Total costs (mean ± SD) were $27,026 ± 30,226 for the placebo group, $22,725 ± 17,661 for the amiodarone group, $33,868 ± 60,309 for the pacing group, and $18,697 ± 8174 for the amiodarone plus pacing group (p=0.27). In the joint distribution cost‐effectiveness analysis, when compared with placebo, the probability of lower cost but higher effect (superiority) was 67% for amiodarone, 15% for pacing, and 97% for amiodarone plus pacing. In the multivariate analysis, preoperative β‐blockers and amiodarone were negatively associated with hospital costs (p<0.05).

Conclusions. Data suggest that both amiodarone alone and the combination of amiodarone plus pacing are cost‐effective compared with placebo. Additional comparative studies of these strategies are warranted to confirm these findings.
Atomoxetine, a Novel Treatment for Attention‐Deficit—Hyperactivity Disorder
Authors: Christman Alisa K. , Fermo Joli D. , Markowitz John S.
Published: July 2004

Atomoxetine is the first nonstimulant drug approved by the United States Food and Drug Administration (FDA) for the treatment of attention‐deficit–hyperactivity disorder (ADHD), and the only agent approved by the FDA for the treatment of ADHD in adults. Atomoxetine is a norepinephrine transport inhibitor that acts almost exclusively on the noradrenergic pathway. Its mechanism of action in the control and maintenance of ADHD symptoms is thought to be through the highly specific presynaptic inhibition of norepinephrine. Clinical trials to evaluate the short‐term effects of atomoxetine in children and adults have shown that atomoxetine is effective in maintaining control of ADHD. Likewise, long‐term trials have determined that atomoxetine is effective in preventing relapse of ADHD symptoms without an increase in adverse effects. A comparative trial of atomoxetine with methylphenidate in school‐aged children indicated similar safety and efficacy without the abuse liability associated with some psychostimulants. The most commonly reported adverse effects in children and adolescents are dyspepsia, nausea, vomiting, decreased appetite, and weight loss. The rates of adverse events in the trials were similar for both the once‐ and twice‐daily dosing regimens. The discontinuation rate was 3.5% in patients treated with atomoxetine versus 1.4% for placebo and appeared to be dose dependent, with a higher percentage of discontinuation at dosages greater than 1.5 mg/kg/day. In clinical trials involving adults, the emergence of clinically significant or intolerable adverse events was low. The most common adverse events in adults were dry mouth, insomnia, nausea, decreased appetite, constipation, urinary retention or difficulties with micturition, erectile disturbance, dysmenorrhea, dizziness, and decreased libido. Sexual dysfunction occurred in approximately 2% of patients treated with atomoxetine. Atomoxetine should be used with caution in patients who have hypertension or any significant cardiovascular disorder. Overall, atomoxetine therapy in patients with ADHD appears to be effective in controlling symptoms and maintaining remission, with the advantages being comparable efficacy with that of methylphenidate, a favorable safety profile, and non–controlled substance status. Additional long‐term studies are needed to determine its continued efficacy for those who require lifelong treatment, and comparative trials against other stimulant and nonstimulant agents.
Angiotensin‐Converting Enzyme Inhibitors and Stroke Risk: Benefit Beyond Blood Pressure Reduction?
Authors: Hilleman Daniel E. , Lucas B. Daniel
Published: July 2004

Hypertension, a leading cause of morbidity and mortality, accounts for 25–49% of all strokes. Randomized placebo‐controlled trials primarily with diuretics and β‐blockers administered in patients with hypertension have demonstrated a 38% reduction in primary stroke. Placebo‐controlled trials with angiotensin‐converting enzyme (ACE) inhibitors have not been conducted in patients with hypertension. However, in a meta‐analysis of four placebo‐controlled trials of ACE inhibitors in patients with coronary heart disease and/or diabetes mellitus, the overall risk of primary stroke was significantly reduced. Results of the Heart Outcomes Prevention Evaluation trial, which produced a substantial reduction in stroke with an apparently small reduction in blood pressure, suggest that the benefit of ACE inhibitors may be related to their effects on the renin‐angiotensin‐aldosterone system more than on blood pressure reduction. In active‐control comparisons in patients with hypertension, ACE inhibitors have demonstrated reductions in primary stroke risk similar to reductions with diuretics, β‐blockers, and calcium channel blockers. The data suggest that for primary prevention of stroke antihypertensive therapy should be individualized in patients. Relatively few data are available concerning the benefit of antihypertensive therapy in the secondary prevention of stroke. In patients who had experienced a stroke or transient ischemic attack, therapy with a diuretic or a combination of a diuretic plus an ACE inhibitor could be recommended based on available outcome studies conducted in this patient population. It is premature to conclude that the benefit of ACE inhibitor therapy in primary or secondary prevention of stroke is an effect independent of blood pressure reduction. Hypertension detection, treatment, and control in patients still must be the principal focus of clinicians for both primary and secondary prevention of stroke.
Cost of a Pharmacist‐Directed Intervention to Increase Treatment of Hypercholesterolemia
Authors: Hilleman Daniel E. , Faulkner Michele A. , Monaghan Michael S.
Published: July 2004

Study Objective. To evaluate the cost of a pharmacist‐directed intervention that prompts physicians to treat hypercholesterolemia more aggressively in patients with coronary heart disease (CHD).

Methods. Health care resource use and CHD outcomes were evaluated for 612 patients with CHD followed for 2 years after an index hospitalization for an ischemic event. After discharge, the physicians of 309 patients who had been admitted from January 1–March 31, 1999, were contacted by telephone and mail concerning lipid profiles and statin therapy. These patients were the intervention group. Controls were 303 patients admitted from October 1–December 31, 1998; their physicians were not contacted. Costs of the physician‐prompting intervention, clinic visits, laboratory tests, statin drugs, and CHD outcomes were compared between these two patient groups.

Results. The number of clinic visits, laboratory tests, and statins prescribed was significantly greater for the intervention group versus the controls. A significantly higher percentage of patients in the intervention group (55%) than in the control group (18%) achieved their National Cholesterol Education Program target low‐density lipoprotein cholesterol level and had significantly better CHD outcomes. The cost of the physician‐prompting intervention (pharmacist salaries, postage, telephone calls) was $102,941. For patients in the intervention and control groups, respectively, the cost of statin therapy was $352,365 and $200,087, the cost of clinic visits and laboratory tests $48,097 and $27,367, and the cost of coronary heart disease outcomes, such as myocardial infarction, coronary artery bypass graft, percutaneous transluminal and coronary angioplasty, $1,073,495 and $1,741,220. The total cost was $1,576,898 and $1,968,674, respectively, for patients in the intervention and control groups. Net savings was $1394/patient over the 2‐year period.

Conclusion. A relatively simple physician‐prompting intervention involving patients with CHD significantly improved the use of lipid testing and statin therapy. Improved use of statins was associated with better CHD outcomes. As a result, the physician‐prompting intervention was associated with cost savings. This intervention should be implemented for patients with CHD discharged after hospitalization for an ischemic event.
Fatal Lactic Acidosis Associated with Coadministration of Didanosine and Tenofovir Disoproxil Fumarate
Authors: Guo Yi , Fung Horatio B.
Published: July 2004

Lactic acidosis is an uncommon but potentially life‐threatening adverse effect of didanosine. When given concomitantly with tenofovir disoproxil fumarate (DF), the area under the concentration‐time curve of didanosine is increased by 48–60%. A 63‐year‐old man with human immunodeficiency virus (HIV) infection tolerated several didanosine‐containing antiretroviral regimens. He developed generalized weakness, loss of appetite, weight loss, nausea, and vomiting 1.5 years after tenofovir DF was added to his didanosine‐containing regimen. He was diagnosed with lactic acidosis and died after a 13‐day hospital stay, when his lactate level increased to 189.7 mg/dl and his arterial blood gas pH value fell to 6.75. Health care providers should maintain a high index of suspicion for lactic acidosis in patients with HIV infection who receive didanosine and tenofovir DF concurrently. For patients receiving antiretroviral regimens containing this drug combination, it would be prudent to monitor lactate levels periodically. This is especially important when patients experience symptoms suggestive of lactic acidosis, such as weakness, abdominal pain, weight loss, nausea and vomiting, and shortness of breath.
Elevated Defibrillation Threshold with Venlafaxine Therapy
Authors: Carnes Cynthia A. , Pickworth Kerry K. , Votolato Nicholas A. , Raman Subha V.
Published: July 2004

Depression is a common comorbidity in patients with heart failure or implantable cardioverter‐defibrillators (ICDs). A 35‐year‐old woman with depression, nonischemic cardiomyopathy, and a history of cardiac arrest had an ICD implanted. During initial testing, the device failed to internally defibrillate the patient. Venlafaxine, an antidepressant with cardiac sodium channel blocking activity, was identified as a potential contributor to her elevated defibrillation threshold. After the venlafaxine was discontinued, the ICD was able to successfully internally defibrillate the patient. Clinicians should be aware of this potential adverse drug‐device interaction. Further studies are needed to determine the clinical significance of venlafaxine therapy in patients with ICDs.
Pharmacoepidemiology I: A Review of Pharmacoepidemiologic Study Designs
Authors: Etminan Mahyar , Samii Ali
Published: July 2004

This article is the first of two parts on pharmacoepidemiology, a relatively new science that explores drug efficacy or toxicity using large observational study designs. The number of pharmacoepidemiologic studies published in medical journals has increased, as these studies have explored drug‐related questions that at times cannot be answered in randomized clinical trials. Four pharmacoepidemiologic study designs will be discussed that explore the association between a specific pharmacologic agent and a disease of interest: cohort studies, case‐control studies, case‐crossover studies, and case‐time‐control studies.