On the presence and immunoregulatory functions of extracellular microRNAs in the trematode Fasciola hepatica.

Liver flukes represent a paraphyletic group of endoparasitic flatworms that significantly affect man either indirectly due to economic damage on livestock or directly as pathogens. A range of studies have focussed on how these macroscopic organisms can evade the immune system and live inside a hostile environment such as the mammalian liver and bile ducts. Recently, microRNAs, a class of short noncoding gene regulators, have been proposed as likely candidates to play roles in this scenario. MicroRNAs (miRNAs) are key players in development and pathogenicity and are highly conserved between metazoans: identical miRNAs can be found in flatworms and mammalians. Interestingly, miRNAs are enriched in extracellular vesicles (EVs) which are secreted by most cells. EVs constitute an important mode of parasite/host interaction, and recent data illustrate that miRNAs play a vital part. We have demonstrated the presence of miRNAs in the EVs of the trematode species Dicrocoelium dendriticum and Fasciola hepatica (Fhe) and identified potential immune-regulatory miRNAs with targets in the host. After our initial identification of miRNAs expressed by F. hepatica, an assembled genome and additional miRNA data became available. This has enabled us to update the known complement of miRNAs in EVs and speculate on potential immune-regulatory functions that we review here.

T wave "humps" as a potential electrocardiographic marker of the long QT syndrome.

OBJECTIVES: This study attempted to determine the prevalence and electrocardiographic (ECG) lead distribution of T wave "humps" (T2, after an initial T wave peak, T1) among families with long QT syndrome and control subjects. BACKGROUND: T wave abnormalities have been suggested as another facet of familial long QT syndrome, in addition to prolongation of the rate-corrected QT interval (QTc), that might aid in the diagnosis of affected subjects. METHODS: The ECGs from 254 members of 13 families with long QT syndrome (each with two to four generations of affected members) and from 2,948 healthy control subjects (age > or = 16 years, QTc interval 0.39 to 0.46 s) were collected and analyzed. Tracings from families with long QT syndrome were read without knowledge of QTc interval or family member status (210 blood relatives and 44 spouses). RESULTS: We found that T2 was present in 53%, 27% and 5% of blood relatives with a "prolonged" (> or = 0.47 s, "borderline" (0.42 to 0.46 s) and "normal" (< or = 0.41 s) QTc interval, respectively (p < 0.0001), but in only 5% and 0% of spouses with a borderline and normal QTc interval, respectively (p = 0.06 vs. blood relatives). Among blood relatives with T2, the mean [+/- SD] maximal T1T2 interval was 0.10 +/- 0.03 s and correlated with the QTc interval (p < 0.01); a completely distinct U wave was seen in 23%. T2 was confined to leads V2 and V3 in 10%, whereas V4, V5, V6 or a limb lead was involved in 90% of blood relatives with T2. Among blood relatives with a borderline QTc interval, 50% of those with versus 20% of those without major symptoms manifested T2 in at least one left precordial or limb lead (p = 0.05). A T2 amplitude > 1 mm (grade III) was observed, respectively, in 19%, 6% and 0% of blood relatives with a prolonged, borderline and normal QTc interval with T2 in at least one left precordial or limb lead. Among the 2,948 control subjects, 0.6% exhibited T2 confined to leads V2 and V3, and 0.9% had T2 involving one or more left precordial lead (but none of the limb leads). Among 37 asymptomatic adult blood relatives with QTc intervals 0.42 to 0.46 s, T2 was found in left precordial or limb leads in 9 (24%; 5 with limb lead involvement) versus only 1.9% of control subjects with a borderline QTc interval (p < 0.0001). CONCLUSIONS: These findings are consistent with the hypothesis that in families with long QT syndrome, T wave humps involving left precordial or (especially) limb leads, even among asymptomatic blood relatives with a borderline QTc interval, suggest the presence of the long QT syndrome trait.

Percutaneous coronary laser balloon angioplasty: initial results of a multicenter experience.

A multicenter clinical trial was initiated to test the potential safety and short-term efficacy of a percutaneous coronary application of laser balloon angioplasty, which has been shown experimentally to alleviate the common causes (dissection, recoil, thrombus) of suboptimal luminal results of conventional balloon angioplasty. Fifty-five patients, the majority (62%) of whom had relatively high risk lesions, were treated in 10 centers with a laser balloon that was identical in size (3 x 20 mm) to a balloon used for conventional balloon angioplasty performed on the same lesion immediately before laser balloon angioplasty. One or more neodymium:yttrium aluminum garnet (Nd:YAG) (1,060 nm) laser doses of 250 to 450 J were each delivered over a 20 s duration per exposure. Immediately and 1 day after laser balloon angioplasty no significant adverse effects on the arterial lumen were noted in any patient. By computerized image analysis of cineangiograms initial conventional balloon angioplasty failed to achieve a minimal luminal diameter greater than 1.5 mm in 14 patients (25%), including 3 patients with acute closure. However, after subsequent laser balloon angioplasty, minimal luminal diameter exceeded this value in all patients including this subgroup. Overall, minimal luminal diameter increased from 1.74 +/- 0.46 mm after conventional balloon angioplasty to 2.32 +/- 0.31 mm after laser balloon angioplasty (p less than 0.001) with no change found on 1 day and 1 month follow-up angiograms. Thus, laser balloon angioplasty is a safe, effective procedure for improving luminal dimensions after conventional balloon angioplasty.

Age-gender influence on the rate-corrected QT interval and the QT-heart rate relation in families with genotypically characterized long QT syndrome.

OBJECTIVES: We sought to analyze age-gender differences in the rate-corrected QT (QTc) interval in the presence of a QT-prolonging gene. BACKGROUND: Compared with men, women exhibit a longer QTc interval and an increased propensity toward torsade de pointes. In normal subjects, the QTc gender difference reflects QTc interval shortening in men during adolescence. METHODS: QTc intervals were analyzed according to age (< 16 or > or = 16 years) and gender in 460 genotyped blood relatives from families with long QT syndrome linked to chromosome 11p (KVLQT1; n = 199), 7q (HERG; n = 208) or 3p (SCN5A; n = 53). RESULTS: The mean QTc interval in genotype-negative blood relatives (n = 240) was shortest in men, but similar among women, boys and girls. For genotype-positive blood relatives, men exhibited the shortest mean QTc interval in chromosome 7q- and 11p-linked blood relatives (n = 194), but not in the smaller 3p-linked group (n = 26). Among pooled 7q- and 11p-linked blood relatives, multiple regression analysis identified both genotype (p < 0.001) and age-gender group (men vs. women/children; p < 0.001) as significant predictors of the QTc interval; and heart rate (p < 0.001), genotype (p < 0.001) and age-gender group (p = 0.01) as significant predictors of the absolute QT interval. A shorter mean QT interval in men was most evident for heart rates < 60 beats/min. CONCLUSIONS: In familial long QT syndrome linked to either chromosome 7q or 11p, men exhibit shorter mean QTc values than both women and children, for both genotype-positive and -negative blood relatives. Thus, adult gender differences in propensity toward torsade de pointes may reflect the relatively greater presence in men of a factor that blunts QT prolongation responses, especially at slow heart rates.

Unrecognized paroxysmal supraventricular tachycardia. Potential for misdiagnosis as panic disorder.

BACKGROUND: The diagnostic criteria for panic disorder include symptoms commonly experienced by patients with paroxysmal supraventricular tachycardia (PSVT). Since electrocardiographic documentation of PSVT can be elusive, symptoms may be ascribed to other conditions. OBJECTIVE: To systematically evaluate the potential for PSVT to simulate panic disorder. METHODS: A retrospective survey of 107 consecutive patients with reentrant PSVT was conducted. Objective and subjective assessments of PSVT symptomatology were made, including the application of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), panic disorder criteria. RESULTS: The criteria for panic disorder according to DSM-IV were fulfilled by 67% of patients. Paroxysmal supraventricular tachycardia was unrecognized after initial medical evaluation in 59 patients (55%), including 13 (41%) of 32 patients with ventricular preexcitation by electrocardiogram, and remained unrecognized for a median of 3.3 years. Prior to eventual identification of PSVT, physicians (nonpsychiatrists) attributed symptoms to panic, anxiety, or stress in 32 (54%) of the 59 patients. When PSVT was unrecognized, women were more likely than men to have symptoms ascribed to psychiatric origins (65% vs 32%, respectively; P < .04). Paroxysmal supraventricular tachycardia was detected in only 6 (9%) of 64 patients undergoing Holter monitoring vs 8 (47%) of 17 patients who wore an event monitor (P < .001). During a 20-month median follow-up, electrophysiologically guided therapy (ablation in 81% of patients) resolved symptoms in 86% of patients; only 4% continued to meet DSM-IV panic disorder criteria without evidence of PSVT recurrence. CONCLUSIONS: The clinical characteristics of patients with PSVT referred for electrophysiologically guided therapy can mimic panic disorder. Diagnosis of PSVT is often delayed by inappropriate rhythm detection techniques (Holter instead of event monitoring) and failure to recognize ventricular preexcitation on the sinus electrocardiogram; symptoms due to unrecognized PSVT are often ascribed to psychiatric conditions.

The revised microRNA complement of Fasciola hepatica reveals a plethora of overlooked microRNAs and evidence for enrichment of immuno-regulatory microRNAs in extracellular vesicles.

MicroRNAs (miRNAs) are gene regulators that have recently been shown to down-regulate the immune response via extracellular vesicles in the mammalian host of helminthic parasites. Using the miRNA prediction pipeline miRCandRef, we expanded the current miRNA set of the liver fluke Fasciola hepatica (Platyhelminthes, Trematoda) from 16 to 54 miRNAs (42 conserved and 13 novel). Comparing the cellular expression levels with extracellular vesicles, we found all miRNAs expressed and enriched for miRNAs with immuno-regulatory function, tissue growth and cancer. Our findings support the hypothesis that miRNAs are the molecular mediators of the previously demonstrated immune modulatory function of extracellular vesicles.

Risk of respiratory distress syndrome after prenatal dexamethasone treatment.

A prospective double-blind randomized clinical trial was carried out to determine whether glucocorticoid treatment reduces the risk of respiratory distress syndrome (RDS) in prematurely born infants. There were 127 infants born to 122 mothers who received either steroid (dexamethasone phosphate) or placebo. No differences between groups occurred in risk factors for RDS (eg, prepartum asphyxia, male sex, cesarean section). When those who received a full course of dexamethasone therapy were compared with those who received placebo, a significant reduction was found in risk, severity, and deaths due to RDS. An increased incidence of infection in mothers treated with steroid was evident, particularly after premature rupture of membranes. We conclude that steroids are effective in reducing risk of RDS, but safer and more efficacious approaches for the prevention of RDS should be sought.

Outcome with implantable cardioverter-defibrillator therapy for survivors of ventricular fibrillation secondary to idiopathic dilated cardiomyopathy or coronary artery disease without myocardial infarction.

Patients with idiopathic dilated cardiomyopathy (IDC) constitute a minority among implantable cardioverter-defibrillator (ICD) recipients; how these patients fare versus those with coronary artery disease (CAD) is not well defined, nor is the mechanism of cardiac arrest recurrence, which may involve a more significant role of bradyarrhythmias. A retrospective multicenter study regarding outcome of ICD therapy was conducted in 224 patients with either IDC (n = 69; 31%) or CAD (n = 155; 69%) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Patients with IDC were significantly younger (mean age 57 vs 61 years in patients with CAD, p < 0.04) and less male predominant (64 vs 79% in patients with CAD, p < 0.02). There was no significant difference in mean left ventricular ejection fraction (0.27 in IDC patients vs 0.29 in CAD patients), but sustained ventricular tachycardia was induced less often in patients with IDC (21 vs 58% in CAD patients, p < 0.001). Bradycardia pacing, either by an ICD with bradycardia pacing ability or a separate bradycardia pacemaker, was available in only 15% of ICD implantees. During a median follow-up duration of 1.7 years for patients with IDC and 1.9 years for patients with CAD, estimated cumulative event rates were similar for any type shock (2-year incidence of 74% in IDC patients, 69% in CAD patients) as well as for appropriate shock (2-year incidence of 46% in IDC patients, 40% in CAD patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term survival of patients with coronary artery disease and left ventricular dysfunction: implications for the role of myocardial viability assessment in management decisions.

OBJECTIVES: Our purpose was to evaluate the long-term benefit of myocardial viability assessment for stratifying risk and selecting patients with low ejection fraction for coronary artery bypass grafting and to determine the relation between the severity of anginal symptoms, the amount of ischemic myocardium, and clinical outcome. METHODS: We studied 93 consecutive patients with severe coronary artery disease and low ejection fraction (median, 25%) who underwent positron emission tomography to delineate the extent of perfusion-metabolism mismatch (reflecting hibernating myocardium) for potential myocardial revascularization. Median follow-up was 4 years (range, 0 to 6.2 years). RESULTS: Fifty patients received medical therapy, and 43 patients underwent bypass grafting. In Cox survival models, heart failure class, prior myocardial infarction, and positron emission tomographic mismatch were the best predictors of survival. Patients with positron emission tomographic mismatch receiving bypass grafting had improved 4-year survival compared with those on medical therapy (75% versus 30%; P =.007) and a significant improvement in angina and heart failure symptoms. In patients without positron emission tomographic mismatch, bypass grafting tended to improve survival and symptoms only in those patients with severe angina (100% versus 60%; P =.085), whereas no survival advantage was apparent in patients with minimal or no anginal symptoms (63% versus 52%; P =.462). CONCLUSIONS: Patients with low ejection fraction and evidence of viable myocardium by positron emission tomography have improved survival and symptoms with coronary bypass grafting compared with medical therapy. In patients without evidence of viability, survival and symptom improvement with bypass grafting are apparent only among those patients with severe angina.

Computer-generated fiscal reports for food cost accounting.

To optimize resource utilization for the provision of health-care services, well designed food cost accounting systems should facilitate effective decision-making. Fiscal reports reflecting the financial status of an organization at a given time must be current and representative so that managers have adequate data for planning and controlling. The computer-assisted food cost accounting discussed in this article can be integrated with other sub-systems and operations management techniques to provide the information needed to make decisions regarding revenues and expenses. Management information systems must be routinely evaluated and updated to meet the current needs of administrators. Further improvements in the food cost accounting system will be desirable whenever substantial changes occur within the foodservice operation at the University of Missouri-Columbia Medical Center or when advancements in computer technology provide more efficient methods for manipulating data and generating reports. Development of new systems and better applications of present systems could contribute significantly to the efficiency of operations in both health care and commercial foodservices. The computer-assisted food cost accounting system reported here might serve s a prototype for other management cost information systems.

A computer-assisted management information system for nutrition services.

A computer-assisted management information system was created to facilitate effective management of clinical nutrition services and labor resources in a 330-bed teaching and research hospital. Standards were developed for the quality and quantity of nutrition care, time required to provide nutrition care, and utilization of dietitians' time. Computer software was developed to report the volume of services provided, the need for services, and the utilization of labor hours. Data were evaluated to determine whether services were consistent with standards and to calculate a recommended number of clinical dietitian full-time equivalents for the hospital. Furthermore, the management information system was instrumental in developing a fee-for-service structure, for evenly distributing work loads among dietitians, and for monitoring adherence to standards of care.

A new operation for the prevention and treatment of amputation neuromas.

A stump neuroma is caused by the disorganised growth of axon cylinders into proliferating granulation tissue, but this is stopped by an undamaged epineural sleeve. We report experiments in the rat in which the epineural sleeve of the stump of the sciatic nerve was freed from nerve fascicles for about 5 mm and then sealed with a synthetic tissue adhesive. Neuroma formation was largely prevented in comparison with the results of other methods. This new technique has been used to treat 68 painful neuromas in 36 patients. All but three of the patients were cured or improved and none were made worse.

Aortography in children with myelomeningocele and lumbar kyphosis.

In 21 children with myelomeningocele who underwent kyphectomy for congenital kyphosis of the lumbar spine, aortography revealed no case in which the aorta followed the spinal curvature. Many anomalies of the intercostal and segmental arteries were demonstrated which were only in part associated with deformities of the respective vertebral bodies. The kidneys, which were frequently malformed, often lay within the kyphosis and were therefore at risk of operative damage. We conclude that the aorta is not at risk and that aortography is not usually necessary before kyphectomy, except in patients who have undergone prior abdominal surgery. Non-invasive methods (ultrasound, CT or MRI) should be used to detect malpositions and malformations of the kidneys.

Effect of oral captopril on premature ventricular complexes in patients with preserved left ventricular systolic function: a randomized clinical trial.

Some studies have suggested that angiotensin-converting enzyme (ACE) inhibition in patients with heart failure is associated with a decrease in frequency of spontaneous premature ventricular complexes (PVCs). It is not clear whether such a finding represents a primary effect of ACE inhibition or, instead, a secondary result of treatment of heart failure. For a primary drug effect to be present, PVC suppression during ACE inhibition should also occur in patients with preserved left ventricular systolic function. We therefore undertook a randomized double-blind placebo-controlled crossover clinical trial to assess the effect of oral captopril (50 mg. b.i.d.) on ventricular arrhythmia frequency in 11 patients with > 30 PVCs/h (during a 48-h ambulatory recording) and a left ventricular ejection fraction of > or = 45% (measured by radionuclide multigated acquisition scan). Pharmacologic activity of the administered drug was evidenced by an increase in median plasma renin activity to 2.4 ng/AI/ml/h from a value of 1.1 ng/AI/ml/h during placebo (p = 0.001) and an 8.5 +/- 10.3 drop in mean diastolic blood pressure during captopril versus placebo (p < 0.03). During captopril treatment, a mean of 491 +/- 378 PVCs/h were observed compared with 389 +/- 169 PVCs/h during placebo, a nonsignificant difference. There was also no significant change in left ventricular ejection fraction, plasma catecholamines, or serum potassium during captopril treatment. Thus, ACE inhibition in patients with preserved left ventricular systolic function fails to suppress ventricular ectopic activity. Extrapolated to patients with heart failure, our observations argue against a primary PVC suppressive action of ACE inhibitors but do not rule out possible secondary antiarrhythmic effects of these agents.

Routine withholding of digitalis for heart rate below 60 beats per minute: widespread nursing misconceptions.

OBJECTIVE: To describe the nursing practice of withholding digitalis solely on the basis of a heart rate less than 60 beats/min and to determine the rationale for this practice. DESIGN: Non-randomized survey. SETTING: Five hospitals in a midwestern metropolitan area, ranging from affiliates of a university medical center to a private community-based hospital. SUBJECTS: Two hundred twelve nurses, 53% from critical care units, 19% from step-down units, and 28% from nonmonitored units). RESULTS: Eighty-one percent of respondents either withheld digitalis unnecessarily or administered the drug without correctly indicating why they did so. Nurses with CCRN certification were more likely to answer correctly than those who were not certified (p = 0.0001). Categories for incorrect rationale were (1) incorrect understanding of the drug's mechanism of action (46%), (2) deference to physician's decision-making (28%), (3) adherence to hospital policy (18%), and (4) adherence to guidelines taught in nursing school (6%). CONCLUSIONS: The results document the need to correct widespread misconceptions regarding the mechanism of action for digitalis and subsequent nursing practice.

A family practice residency curriculum in critical appraisal of the medical literature.

This paper reports a five-year experience with a comprehensive curriculum for teaching critical appraisal and practical research skills to family practice residents. The curriculum includes a seminar series in research and medical practice and simulated research projects. Rationale, methods, format, and evaluations of the curriculum are presented. The curriculum prepared graduates to critically review research studies in the professional literature and translate valid conclusions into medical practice. Residents were able to identify potential areas of research interest and acquired additional skills that encouraged continuing education and professional growth.

Osteoid osteoma of the radial styloid mimicking stenosing tenosynovitis. A case report.

An osteoid osteoma of the styloid process of the radius mimicking de Quervain's tenovaginitis in a 28-year-old man is reported. As the clinical presentation and X-rays of the wrist were not typical of an osteoid osteoma, only the histological examination led to the correct diagnosis.

[Secondary arthrosis of the wrist joint in malposition of healed and uncorrected distal radius fracture]. / Die sekundäre Arthrose des Handgelenkes bei in Fehlstellung verheilter und nicht korrigierter distaler Radiusfraktur.

The authors report on long-term results of thirty-five unreduced distal radius fractures with malunion. The mean observation period was 11.5 years (5 to 45 years). It was found malalignment of the carpal articular surface of the radius with a resulting decrease in range of motion of the wrist, well tolerated by the patients and apparently not very painful. Much more evident was pain and decreased motion in the distal radio-ulnar joint for pronation and supination, which paralleled the extent of osteoarthrosis of this joint. This reduced forearm rotation was due to shortening of the radius, leading to incongruency and even dislocation of the distal radio-ulnar joint.

[The Freehand System: an implantable neuroprosthesis for functional electrostimulation of the upper extremity]. / Das Freehand-System: Eine implantierbare Neuroprothese zur funktionellen Elektrostimulation der oberen Extremität.

We report on the first experience with the Freehand system in German-speaking countries, an implantable neuroprosthesis developed for the functional electrical stimulation of the upper extremity. Indications for its use are neurological deficits of the cervical spinal cord with active mobility of the shoulder and elbow flexion in tetraplegics, ideally in C5/6 tetraplegics. A further precondition for the implantation of this system is an intact reflex arc of the muscles that are to be stimulated, i.e. of the forearm and hand. Central defects such as hemiparesis, cerebral palsies or athetoid disorders or peripheral nerve palsies (e.g. brachial plexus lesions) are no good indications for the implantation of the Freehand system. We report on patient selection criteria, preoperative percutaneous electrical stimulation, the surgical procedure itself with optional active tendon transpositions, the intensive postoperative rehabilitation program until the patient is able to use the system independently and the life-long after-care.

Research design and statistical procedures used in the Journal of Family Practice.

To determine whether articles published in The Journal of Family Practice contain statistical content that is easily understood by the general reader, all original articles published during a two-year period were reviewed to determine the frequency of use of different research designs and statistical procedures. Eighty-eight percent of the articles used the cross-sectional design. No statistical methods were reported in 46 percent of the articles; 13 percent reported descriptive statistics only. The chi-square statistic and t test were the most commonly used statistical procedures. Readers of The Journal of Family Practice, therefore, needed only an elementary knowledge of statistics to understand the statistical content of three quarters of the original articles.