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The natural history of obesity in an obese population and associations with metabolic aberrations.

The natural history of obesity was examined in a nation-wide sample of 1,084 obese men and 1,367 obese women aged 37-59 years who were recruited into a registry of potential subjects for an intervention trial. The registry and intervention studies are jointly referred to as SOS ('Swedish Obese Subjects'). In the registry, the mean body mass index was 37.7 kg/m2 in men and 40.9 kg/m2 in women. Descriptive information on subjects' weight histories and the relative weights of their biological parents was collected by means of a self-administered questionnaire. At a physical examination shortly thereafter, weights, heights and selected cardiovascular risk factors were measured in the fasting state. Virtually all subjects reported weight loss attempts in the past, men and women reported having gained weight during adulthood at a considerably higher rate than that observed in population-based samples. Significant correlations were observed between relative weights of obese males and both of their biological parents, but not between obese women and either of their parents. Indices of medical risk were then examined in relation to individual weight histories. Familial predisposition did not relate to most aspects of current medical risk. However, later-onset obesity tended to be associated with greater cardiovascular risk, while prior weight loss was predictive of an improved risk factor profile. These latter associations were not dependent on a subject's current degree of obesity and were particularly consistent with respect to fasting insulin level.

Adult↗

Bidirectional superior cavopulmonary anastomosis: how young is too young?

OBJECTIVE: To define the lowest age at which the bidirectional superior cavopulmonary anastomosis can safely be used in infants with complex congenital heart defects. DESIGN: A retrospective analysis of clinical, echocardiographic, haemodynamic, and angiographic data in four consecutive patients undergoing bidirectional superior cavopulmonary anastomosis below the age of 2 months. PATIENTS: Between November 1990 and September 1993, four infants less than 8 weeks of age (3, 4, 6, and 7 weeks) underwent bidirectional superior cavopulmonary anastomosis as a primary palliation for complex heart disease. The indication for early surgical intervention was progression of cyanosis (n = 3) and high pulmonary blood flow causing heart failure (n = 1). In two infants with tricuspid atresia, surgery was performed through a right thoracotomy without the use of cardiopulmonary bypass. In one infant with double inlet left ventricle and discordant ventriculoarterial connection, cavopulmonary anastomosis was combined with an arterial switch procedure. The final infant had double inlet left ventricle with pulmonary atresia; the central pulmonary arteries were virtually discontinuous and each branch was supplied by a separate arterial duct. The central pulmonary arteries were reconstructed using the subaortic innominate vein. Temporary prostacyclin infusion was used in three patients in the immediate postoperative period. RESULTS: Early postoperative extubation (5, 7, and 48 h) was successful in three patients. The youngest child required ligation of the ductus arteriosus four days later because of severe upper body oedema. The postoperative course was complicated by prolonged effusions in two patients. All were alive and well 14-48 months postoperatively, with satisfactory systemic saturations (80-87%) and haemodynamic indices. CONCLUSIONS: This limited experience challenges the widely held belief that the bidirectional superior cavopulmonary anastomosis cannot be used as a primary palliation for complex heart disease in early infancy. A wider experience is required to determine the safety and indications for this approach.

Age Factors↗

Improvement of thrombocytopenia due to hypersplenism after transjugular intrahepatic portosystemic shunt placement in cirrhotic patients.

Thrombocytopenia secondary to hypersplenism is a well-known complication of portal hypertension. The effects of transjugular intrahepatic portosystemic shunt (TIPS) on hypersplenism have not been adequately studied. In this report, we describe 11 patients who had significant improvement in their thrombocytopenia due to hypersplenism after TIPS. There was a statistically significant improvement in the platelet counts after TIPS placement, in virtually every case during the follow-up period, although some patients had platelet counts less than 100,000/mm3 at the end of the follow-up period. Statistically significant hemodynamic improvement in the gradient pressure was observed immediately after TIPS. Furthermore, all patients tolerated the procedure well, and TIPS-related complications were encountered during the follow-up period. Our data suggest that TIPS is an effective, noninvasive alternative to surgical interventions in the management of hypersplenism in cirrhotic patients, who are generally high-risk surgical candidates.

Adult↗

Magnetic resonance imaging of acute reperfused myocardial infarction: intraindividual comparison of ECIII-60 and Gd-DTPA in a swine model.

PURPOSE: To compare a necrosis-avid contrast agent (NACA) bis-Gd-DTPA-pamoic acid derivative (ECIII-60) after intracoronary delivery with an extracellular agent Gd-DTPA after intravenous injection on magnetic resonance imaging (MRI) in a swine model of acute reperfused myocardial infarction (MI). METHODS: Eight pigs underwent 90 min of transcatheter coronary balloon occlusion and 60 min of reperfusion. After intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg, all pigs were scanned with T1-weighted MRI until the delayed enhancement of MI disappeared. Then they were intracoronarily infused with ECIII-60 at 0.0025 mmol/kg and imaged for 5 hr. Signal intensity, infarct-over-normal contrast ratio and relative infarct size were quantified, compared, and correlated with the results of postmortem MRI and triphenyltetrazolium chloride (TTC) histochemical staining. RESULTS: A contrast ratio over 3.0 was induced by both Gd-DTPA and ECIII-60. However, while the delayed enhancement with Gd-DTPA virtually vanished in 1 hr, ECIII-60 at an 80x smaller dose depicted the MI accurately over 5 hr as proven by ex vivo MRI and TTC staining. CONCLUSION: Both Gd-DTPA and ECIII-60 strongly enhanced acute MI. Comparing with fading contrast in a narrow time window with intravenous Gd-DTPA, intracoronary ECIII-60 persistently demarcated the acute MI, indicating a potential method for postprocedural assessment of myocardial viability after coronary interventions.

Animals↗

Chronic elevation of amyloid precursor protein expression in the neocortex and hippocampus of rats with selective cholinergic lesions.

Overexpression or aberrant processing of the beta-amyloid precursor protein (APP) and loss of cortical cholinergic function represent two hallmark pathological features of Alzheimer's disease, although it is still unclear whether these alterations take place independently or in an inter-related manner. In the present study, the possible relationships between altered APP expression and cholinergic hypofunction in the neocortex and hippocampus were addressed histologically following selective and complete (90-95%) removal of the basal forebrain cholinergic neurons by the 192 IgG-saporin immunotoxin, at a dose (5.0 microg, intraventricularly) producing profound and permanent cognitive deficits. Computer-aided densitometric analyses revealed, at 6 months post-lesion, a virtually complete loss of terminal cholinergic innervation in various neocortical and hippocampal regions (up to 80%), which correlated highly with the marked (up to 71%) increases in APP expression measured in the same territories. The present results indicate that the integrity of ascending basal forebrain cholinergic inputs to the neocortex and hippocampus may be required for the maintenance of physiological levels of APP expression in the same regions, thus providing a novel rationale for interventions aimed at restoring or enhancing cortical cholinergic neurotransmission.

Amyloid beta-Protein Precursor↗

Real-time electromagnetic navigation bronchoscopy to peripheral lung lesions using overlaid CT images: the first human study.

STUDY OBJECTIVES: To characterize the feasibility, accuracy, and safety of the superDimension/Bronchus system (SDBS) [superDimension, Ltd; Hertzliya, Israel] in navigating to previously unreachable peripheral lung lesions and obtaining biopsy specimens. DESIGN: Open-label, prospective, controlled clinical study. SETTING: Pulmonary institute of a university-affiliated municipal hospital. PATIENTS: Thirteen adult candidates for nonemergency bronchoscopy who gave informed consent to participate. INTERVENTIONS: The patients underwent flexible bronchoscopy using the SDBS, which is based on real-time CT-guided electromagnetic navigation and is capable of reaching peripheral lung masses beyond the reach of the bronchoscope. A position sensor was used to navigate to and sample the various target lesions for biopsy. MEASUREMENTS AND RESULTS: Three-dimensional chest CT was followed by SDBS methodology for marking anatomic landmarks and the target lesion on a virtual bronchoscopy screen and for sampling the lesion. The SDBS assisted in obtaining positive biopsy diagnoses in 9 of 13 cases (69%), with an average navigation accuracy of 5.7 mm. There were no SDBS-related adverse events. CONCLUSIONS: The SDBS is safe and effective in navigating to peripheral lung lesions located beyond the optic limits of a standard flexible bronchoscope.

Adult↗

Antiplatelet therapy from clinical trials to clinical practice.

A platelet-rich clot at the site of severe coronary stenosis, plaque erosion, or a recent plaque rupture is the common etiology of acute ischemic syndromes. Thus, antiplatelet therapy is the cornerstone in the management of these conditions. Aspirin in a dose ranging from 160 to 325 mg once daily should be administered to virtually all patients. In patients with severe disease, particularly those who have no acute angiography, clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Pharmaceuticals) in a dose of 75 mg once daily should add to the benefit of aspirin for up to a year after the event. Clopidogrel also is an alternative to aspirin where a true aspirin allergy exists. Intravenous platelet glycoprotein IIb/IIIa receptor inhibitors demonstrated a robust benefit when used in conjunction with coronary intervention and thus far have no role in medical therapy alone. Oral platelet glycoprotein IIb/IIIa receptor inhibitors are of no clinical value.

Clinical Trials as Topic↗

Rational approaches to the chemotherapy of medulloblastoma.

Medulloblastoma is the most common primary tumor of the CNS in childhood. Surgical intervention alone will not cure this tumor, and the addition of whole neuraxis irradiation has led to a 50 to 60 per cent, 5-year survival. The role of adjuvant chemotherapy is unclear, although certain subgroups of high-risk patients may benefit from this modality. Agents that have demonstrated activity against recurrent disease include vincristine, cyclophosphamide, cisplatin, methotrexate, dibromodulcitol, and the combination of procarbazine-vincristine-CCNU. However, responses are generally transient and virtually no cures are reported. New, rationally selected agents are clearly needed. In vitro and in vivo models of human medulloblastoma using the medulloblastoma-derived cell lines TE-671 and D283 Med may allow such an approach. Phase II trials using the drugs effective in these models may identify active agents that will ultimately increase survival when used in an adjuvant setting.

Animals↗

Active and inactive thyroid hormone levels in elective and acute surgery.

The changes in the plasma or serum concentration of thyrotrophin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5-triiodothyronine (reverse T3, rT3) and cortisol were examined in patients undergoing elective cholecystectomy (n = 10) or acute laparotomy due to peritonitis (n = 11). TSH and T4 showed no essential changes in either group. T3 was reduced already during initiation of anaesthesia and continued to fall during and after surgery in both groups. In the peritonitis group, T3 was reduced already before medical intervention. rT3 displayed changes opposite to those of T3. An increase in cortisol peceded the changes in T3 and rT3 in both groups. T3 and rT3 returned towards normal levels when the patients recovered and resumed oral nutrition. It seems likely that both elective and acute uncomplicated surgery is accompanied by a transient reduction in the extrathyroidal production of the most active hormone, T3, and by a reciprocal increase in the levels of the virtually inactive rT3. The underlying mechanism behind this metabolic adaptation is unclear but may be related to adrenocortical activation and/or to changes in the mode of nutrition.

Aged↗

The realization of a haptic (force feedback) interface device for the purpose of angioplasty surgery simulation.

Simulation is becoming an increasingly accepted method for training personnel for complex or high risk tasks. With the advent of modern Virtual Reality (VR) technology, such simulations are becoming more and more immersive. One significant limitation to the advance of this science is the challenges associated with simulating the touch or feel of various tasks in conjunction with VR simulations. This work has focused on creating and assessing the feasibility of haptic technology for high fidelity surgery simulation. It has culminated in a prototypical interface device to provide tactile feedback during the simulation of complex interventional radiology procedures such as Angioplasty. This device extends state of the art motion control, distributed computing processes, high resolution sensors for real-time feedback, and modular design techniques to accomplish these goals. The realization of the device, its capabilities, interfacing requirements, its limitations, and future extensions will be presented here.

Angioplasty, Balloon↗

Towards the implementation of the "basket of options" approach to helminth parasite control of livestock: emphasis on the tropics/subtropics.

The virtual reliance on anthelmintic drugs alone to control internal parasites of livestock is inappropriate and ultimately unsustainable. In the tropics and subtropics, widespread and high levels of anthelmintic resistance, particularly in nematode parasites of small ruminants, is rife. But more to the point, many farmers in these regions of the world are resource poor and cannot afford, or are reluctant to purchase drugs that may also be of dubious quality. As it is with any intervention, the benefits must outweigh the costs. This is not only in terms of conventional parameters such as reduced mortality and increasing productivity (meat, milk, fibre and traction power) of livestock, but also within the broad framework of helminths of veterinary/human importance, the aim should be a positive impact on reducing the threat of helminth zoonoses. However, understanding the issues involved and education of the end-users (farmers) is of fundamental importance, before any internal parasite control program should be promoted. Within the above context, we provide examples of how the "basket of options" approach could be adopted for the control of three quite disparate helminth problems in the tropics and subtropics, viz.: strongyle nematode infections of donkeys, the Taenia solium cysticercosis/taeniosis problem of pig and man and Haemonchus contortus infections in small ruminants. The "best practice" approaches can be defined as those "basket of options" that are practical, affordable, available and appropriate, whether to the commercial producer, or to the resource-poor farmer. Constraints that may restrict applying such options are accessibility to, and affordability of, suitable remedies and above all, the availability of information needed to make informed decisions in this regard.

Animal Husbandry↗

Epidemiology of Clostridium difficile-associated infections.

Clostridium difficile is responsible for 15-25% of cases of antibiotic-associated diarrhea (AAD) and for virtually all cases of antibiotic-associated pseudomembranous colitis (PMC). This anaerobic bacterium has been identified as the leading cause of nosocomial infectious diarrhea in adults and can be responsible for large outbreaks. Nosocomial C. difficile infection results in an increased length of stay in hospital ranging from 8 to 21 days. Risk factors for C. difficile-associated diarrhea include antimicrobial therapy, older age (>65 years), antineoplastic chemotherapy and length of hospital stay. Other interventions with high risk associations are enemas, nasogastric tubes, gastrointestinal surgery and antiperistaltic drugs. Prospective studies have shown that nosocomial transmission of C. difficile is frequent but often remains asymptomatic. Patients can be contaminated from environmental surfaces, shared instrumentation, hospital personnel hands and infected roommates. Once an outbreak starts, C. difficile may be spread rapidly throughout the hospital environment where spores may persist for months. Measures that are effective in reducing incidence of C. difficile infections and cross-infection include: (i) an accurate and rapid diagnosis, (ii) appropriate treatment, (iii) implementation of enteric precautions for symptomatic patients, (iv) reinforcement of hand-washing, (v) daily environmental disinfection, and (vi) a restrictive antibiotic policy. C. difficile is a common cause of infectious diarrhea and should be therefore systematically investigated in patients with nosocomial diarrhea.

Anti-Bacterial Agents↗

Staphylococcus aureus tricuspid valve endocarditis in young women after gynaecological events. A report of 3 cases.

Three cases of Staphylococcus aureus tricuspid valve endocarditis are reported; each was preceded by a gynaecological event. In 2 cases there was no overt pelvic sepsis and there had been no operative or instrumental intervention, but in the 3rd pelvic inflammatory disease was present, probably not as a result of interference. There are few reports in the recent literature of gynaecological events precipitating this condition; in contrast, intravenous narcotic abuse is well documented. In the literature there is insufficient stress laid on the fact that non-septic gynaecological events may cause the endocarditis. The difficulties in diagnosing tricuspid endocarditis, especially in a milieu where intravenous narcotic abuse is virtually unknown, are noted. When endocarditis is present in women known not to abuse narcotics, the absence of signs of pelvic inflammation may also cause difficulties in diagnosis.

Abortion, Spontaneous↗

[Comprehensive ultrasound study in surgical diseases of the adrenals].

Combined staged ultrasonic examination of 53 patients with surgical diseases of the adrenals (Icenko--Cushing's disease and hormonally active tumors) included preoperative transcutaneous ultrasonic examination, ultrasound-monitored spot fine needle aspiration biopsy, intraoperative and postoperative ultrasonic examinations. Transcutaneous ultrasonic examination was found to be little informative in Icenko--Cushing's disease, whereas in adrenal tumors it was virtually as sensitive as computer-aided tomography. Ultrasound-monitored spot fine needle aspiration biopsy proved to be a highly informative safe method, which helps morphologically diagnose the disease before surgery. Intraoperative ultrasonic examination helped reduce the surgical trauma in all the cases, and in patients with Icenko--Cushing's disease it gave an idea of the type of morphologic changes in the removed adrenal. Ultrasonic monitoring of tissue status at the site of intervention helped timely detect the postoperative complications.

Adolescent↗

Feeding gastrostomy: a critical review of its indications and mortality rate.

Gastrostomy can be a valuable adjunct to patient care, and percutaneous endoscopic gastrostomy is often considered the method of choice for gastrostomy placement. As with all surgical procedures, however, patient selection is important no matter how the gastrostomy is placed. In a retrospective review of 125 randomly selected patients having gastrostomy tube placement, there were certain groups of patients who received virtually no benefit from gastrostomy and may even have died sooner due to gastrostomy placement. The leading indication for gastrostomy placement was neurologic debilitation; the procedural mortality rate for these patients was 28%. However, patients with pulmonary cachexia or metastatic cachexia had much higher mortality rates: 90% and 37%, respectively. We believe patient selection has been imperfect and that certain patients should not have a gastrostomy tube. These patients suffer the moral indignation of persistent intervention and often die without receiving any real benefit.

Adolescent↗

Clinical and biochemical factors associated with prognosis after myocardial infarction at a young age.

OBJECTIVES: This study examined the effect of metabolic disturbances, hemostatic function, coronary artery disease severity and left ventricular function on the long-term prognosis after myocardial infarction in men < 45 years old. BACKGROUND: Heavy smoking; dyslipoproteinemias involving very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL); a family history of premature coronary artery disease; hyperinsulinemic responses to oral and intravenous glucose challenges; and defective fibrinolytic function characterize the young postinfarction patient, but the influence of these features on the long-term prognosis is virtually unknown. METHODS: Measurements of hemostatic function and metabolic and angiographic indicators of risk were included in a prospective cohort study of variables predictive of reinfarction, cardiac death and major coronary events within 6 to 9 years in 108 unselected nondiabetic men with a first myocardial infarction before age 45 years. RESULTS: During follow-up, 20 patients had sudden cardiac death, and 53 had a major coronary event (reinfarction, sudden cardiac death, bypass surgery or intervention by catheterization). In multivariate analysis, VLDL and global coronary atherosclerosis score predicted reinfarction; plasma plasminogen activator inhibitor-1 (PAI-1) activity and global coronary stenosis score predicted cardiac death; and VLDL triglyceride levels, global coronary atherosclerosis score and age predicted any major coronary event. CONCLUSIONS: This prospective cohort study shows that hypertriglyceridemia, impaired fibrinolytic capacity secondary to plasma PAI-1 activity elevation and extensive coronary artery disease increase the risk of recurrences in men with a first myocardial infarction before age 45 and contribute to the relatively poor long-term prognosis in this patient group.

Adult↗

Frequency- and orientation-dependent effects of mexiletine and quinidine on conduction in the intact dog heart.

Myocardial conduction depends on the magnitude of the fast inward sodium current as well as on cardiac fiber orientation, with more rapid propagation along myocardial fibers than across them. Although antiarrhythmic drugs depress the sodium current in a frequency-dependent fashion in vitro, their effects on conduction in the intact ventricle have been less well studied. We therefore evaluated the frequency- and orientation-dependent actions of mexiletine, quinidine, and their combination on epicardial conduction in 24 pentobarbital-anesthetized dogs. These interventions were chosen because the time constant of recovery from sodium-channel blockade by mexiletine in vitro is shorter than that from blockade by quinidine, and because we have previously shown that the combination of these drugs is often clinically effective when single-agent therapy fails. An electrode array that permitted measurement of conduction times in multiple orientations over short segments of epicardium without contamination by rapid Purkinje fiber propagation or by latency or virtual cathode effects at the stimulus site was developed for these studies. In all animals, the atrioventricular node was destroyed by injection of formalin to permit measurements over a wide range of cycle lengths (250 to 1500 msec). In the absence of drugs, conduction in any direction was frequency independent. In the presence of mexiletine, however, frequency-dependent increases in conduction times were found at cycle lengths of 600 msec or less; these changes were significantly greater in orientations for which baseline conduction was rapid. Quinidine, on the other hand, increased conduction times at all tested cycle lengths without significant orientation-dependent effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acoustic neuroma surgery: outcome analysis of patient-perceived disability.

OBJECTIVE: Numerous studies have investigated the outcome of acoustic neuroma (AN) treatment using classical medical measures. In an effort to describe the long-term lifestyle consequences of AN removal from the patient's perspective, patients filled out detailed questionnaires concerning their functional status. STUDY DESIGN: This was a retrospective survey. SETTING: This study was performed at a tertiary referral center. PATIENTS: A total of 130 late postoperative acoustic neuroma patients were surveyed a minimum of 6 months following surgery (average, 39 months). Survey response rate was 65% (130/200). MAIN OUTCOME MEASURES: The main outcome measures were the patient's perception of their hearing, balance, facial expression, and eye function in relation to its impact upon the activities of daily life. A comparison of pretreatment with long-term posttreatment functional levels. RESULTS: When asked to designate their "most significant" symptom, hearing loss was by far most prevalent (61.3%), followed by balance troubles (14.3%) and facial weakness (10.1%). The relatively low incidence of facial weakness as the patient's dominant complaint was somewhat surprising. When considering the incidence of each symptom, women were more likely to complain of facial weakness, dry eye, and headache, whereas men had a marginally higher incidence of hearing loss and imbalance. Patient age had no apparent influence upon either the distribution or severity of symptomatic complaints. Both hearing in the tumor ear and overall auditory function (e.g., the ability to understand in a restaurant) tended to worsen following surgery. One finding, which was both unanticipated and intriguing, was the improvement in sound localization ability reported by 57% of patients following surgery. Although the proportion of patients complaining of frequent tinnitus increased postoperatively, the number of patients who found the tinnitus troublesome decreased markedly. In terms of balance function, only 31% preoperatively and 15% postoperatively described themselves as free of balance difficulties. An aid to ambulation (e.g., cane, walker) was needed in five patients (4%) preoperatively, two of whom regained the ability to walk independently following tumor removal. CONCLUSIONS: These functional outcome data provide much useful information to both patient and clinician to consider when contemplating the optimal course of AN management. Although virtually all acoustic neuroma patients have some degree of persistent symptoms over the long-term, the data indicates that most of these are attributable to the tumor itself as opposed to the after effects of its surgical removal. The relatively slight differences between preoperative and late postoperative symptom profiles was a rather unanticipated finding. As the degree of disability tends to increase with larger tumor sizes, these data tend to support a policy of early intervention.

Adolescent↗