bluuebunny/crossref_metadata_2025 huggingface dataset:
Predisposing Factors and Treatment Outcome in Fournier’s Gangrene
Authors: Gürdal Mesut , Yücebas Ergin , Tekin Ali , Beysel Melih , Aslan Rüknettin , Şengör Feridun
Published: May 2003

Objectives: To evaluate the etiologic factors and the effects of surgical debridement and adjunctive therapies on morbidity and mortality of Fournier’s gangrene. Methods: 27 males, 1 female, a total of 28 patients with a mean age of 58 years treated for Fournier’s gangrene were evaluated retrospectively. Results: Predisposing factors including diabetes, alcohol abuse, paraplegia and renal insufficiency were identifiable in 54% of the patients. Etiologic origin of the gangrene was urogenital, cutaneous and anorectal in 43, 25 and 11% of the patients, respectively. The pathology was limited to genitalia in 10, extending to perineum in 8, the umbilicus in 7 and even up to the axilla in 3 patients. Suprapubic cystostomy and colostomy were necessary in 18 and 2 cases, respectively. We used hyperbaric oxygen therapy in 2 and honey in 6 patients to accelerate wound healing. A repeat debridement was necessary in 39% of the cases. Plastic surgery and grafting were done in 14 patients. Our mortality rate was 7%. Conclusion: Early recognition of the pathology and aggressive surgical debridement are the mainstay of the management of Fournier’s gangrene. Additional strategies to improve wound healing and increase patient survival are also needed.
Prognostic Consequences of the Location of Positive Surgical Margins in Organ-Confined Prostate Cancer
Authors: Salomon Laurent , Anastasiadis Aristotelis G. , Antiphon Patrick , Levrel Olivier , Saint Fabien , De La Taille Alexandre , Cicco Antony , Vordos Dimitri , Hoznek Andras , Chopin Dominique , Abbou Clément-Claude
Published: May 2003

Introduction: The purpose of the present study was to evaluate and compare the risk of progression in organ-confined prostate cancers (stage pT2), according to the location of positive surgical margins. Materials and Methods: Between 1988 and 2001, 538 consecutive men underwent radical prostatectomy for localized prostate cancer. All patients had preoperative physical examinations, serum PSA assays (Hybritech assay, N.l. <4 ng/ml) and ultrasound-guided sextant biopsies to confirm diagnosis. Radical prostatectomy specimens were analyzed according to the Stanford protocol. Positive margins were classified as single or multiple and main locations (apex, bladder neck and posterolateral) were noted. Postoperative follow-up data were obtained through routine serum PSA assays. Biochemical recurrence was defined as a single postoperative PSA level >0.2 ng/ml. Biochemical progression was studied in patients with organ-confined tumors (stage pT2) according to the location of the single positive margin. Kaplan-Meier analysis was performed to determine the actuarial biochemical recurrence-free likelihood and the log-rank test was used for statistical analysis. Differences were considered significant when the p value was <0.05. Results: 371 patients had organ-confined tumors, and 60 patients (16.1%) had solitary positive margins (apex 26, bladder neck 14, posterolaterally 20). Eleven patients (18.3%) had biochemical progression. 5-year biochemical free progression was 54.5, 76.9 and 87.9% for apex, bladder and the posterolateral location, respectively (p < 0.05). Conclusions: In the present study, a positve surgical margin at the apex was associated with worse clinical prognosis compared to the bladder neck and posterolateral locations.
Prostate Lymphoscintigraphy and Radio-Guided Surgery for Sentinel Lymph Node Identification in Prostate Cancer
Authors: Wawroschek Friedhelm , Vogt Harry , Wengenmair Hermann , Weckermann Dorothea , Hamm Michael , Keil Mathias , Graf Gerhard , Heidenreich Peter , Harzmann Rolf
Published: May 2003

Introduction: Having in mind the promising results of lymphoscintigraphy and intraoperative gamma probe application for the detection of sentinel lymph nodes (SLN) in malignant melanoma, breast and penis cancer, we tried to identify the SLN in prostate cancer by applying a comparable technique. Materials and Method: 350 patients with prostate cancer were examined after providing informed consent. The day before pelvic lymphadenectomy technetium-99m nanocolloid was transrectally injected into the prostate under ultrasound guidance. A single central application was done per prostate lobe in most cases. Activity attained 90– 400 MBq, and the total injected volume was about 2–3 ml. Hereafter, lymphoscintigraphy was carried out. Those lymph nodes having been identified as SLN by means of gamma probe detection and lymphoscintigraphy were removed intraoperatively. Later, most of the cases had different types of pelvic lymphadenectomy. SLN received serial sections and immunohistochemistry, non-SLN step sections. Results: 335 patients showed at least 1 SLN in lymphoscintigraphy. 24.7% had lymph node metastases. In 2 patients, metastases in non-SLN were found without at least one SLN being affected (false-negative patient). Conclusion: Our experience suggests that the SLN identification is not only feasible in breast cancer and malignant melanoma, but also in prostate cancer with a comparable technique.
Pneumaturia in a Patient with Ectopic Vas deferens Opening in the Bladder and Agenesis of the Ipsilateral Seminal Vesicle
Authors: Magno C. , Galì A. , Inferrera A. , Macrì A. , Carmignani A. , Famulari C.
Published: May 2003

Ectopia of the vas deferens (EVD) combined with agenesis of the seminal vesicle, is a rare congenital abnormality. We describe a case of EVD with agenesis of the ipsilateral seminal vesicle, presenting with pneumaturia and frequent urinary tract infection.
Recurrent Eosinophilic Cystitis with Peripheral Eosinophilia and Hyperimmunoglobulinemia E
Authors: Matsuura Hiroshi , Sakurai Masaki , Arima Kiminobu
Published: May 2003

A case of recurrent eosinophilic cystitis with peripheral eosinophilia and hyperimmunoglobulinemia E, which responded successfully to initial and secondary steroid therapies is reported.
Angiomyolipoma with a Caval Thrombus
Authors: Schips L. , Ratschek M. , Gallé G. , Zigeuner R. , Trummer H. , Petritsch P.H. , Hubmer G.
Published: May 2003

We report the case of a female patient presenting with flank pain. Abdominal ultrasound revealed a tumor of 8 cm in diameter. After abdominal computerized tomography, the tumor was classified as angiomyolipoma with a tumor thrombus in the inferior vena cava. After nephrectomy, the diagnosis was confirmed histologically. To our knowledge, this is the 11th case of a renal angiomyolipoma extending into the vena cava.
Spontaneous Communication between a Simple Renal Cyst and the Pyelocaliceal System with a Gas-Producing Infection
Authors: Okubo Yuhei , Ogawa Masashi , Tochimoto Masato , Tsuchiya Akira
Published: May 2003

We present the extremely rare case of a 44-year-old woman who presented with right flank pain and high fever, which proved to be a case of spontaneous communication between a renal cyst and the pyelocaliceal system caused by increased pressure in the renal pelvic cavity exerted by a stone leading to infection.
Comparable Efficacy of Pantoprazole and Omeprazole in Patients with Moderate to Severe Reflux Esophagitis
Authors: Körner T. , Schütze K. , van Leendert R.J.M. , Fumagalli I. , Costa Neves B. , Bohuschke M. , Gatz G.
Published: May 2003

Aim: To compare the efficacy and tolerability of pantoprazole 40 mg and omeprazole MUPS 40 mg in patients with moderate to severe gastroesophageal reflux disease (GERD). Methods: In this randomized, double-blind, parallel-group, multicenter study conducted in Austria, Germany, Portugal, Switzerland and The Netherlands, patients with endoscopically confirmed moderate to severe GERD (Savary/Miller esophagitis grade II/III) were enrolled. They received a once-daily dose of either 40 mg pantoprazole or 40 mg omeprazole MUPS. Healing was determined by endoscopy after 4 weeks of treatment. If patients were not healed, treatment was extended for another 4 weeks. An additional endoscopy was performed in these cases after 8 weeks of treatment. Healing was determined by endoscopy after 4 and 8 weeks. In addition, treatment effect on symptoms was evaluated by the investigator using a questionnaire assessing heartburn, reflux regurgitation and pain on swallowing at each visit, as well as by a self-administered questionnaire comprising further 24 gastrointestinal symptoms. Analyses were performed for the intention-to-treat (ITT) and the per-protocol (PP) population. In addition, patients with high compliance (HC: 90% ≤110%) were considered in a separate group. Adverse events and the influence of the Helicobacter pylori status were investigated. Results: A total of 669 outpatients were enrolled in the study, with 337 patients receiving pantoprazole and 332 omeprazole MUPS. The PP population consisted of 552 patients, 282 treated with pantoprazole and 270 with omeprazole MUPS. The healing rates in both treatment groups were shown to be equivalent and were higher in patients who adhered closely to the administration protocol (HC). According to ITT (ITTHC) analyses, healing rates were 65.3% (77.4%) in the pantoprazole and 66.3% (74.7%) in the omeprazole group after 4 weeks. Furthermore, patients infected with H. pylori had slightly but not significantly higher healing rates than those with a negative test result. The safety profile of both treatments was comparable. Conclusion: Pantoprazole 40 mg and omeprazole MUPS 40 mg were equivalent with respect to healing after 4 and 8 weeks of treatment in patients with reflux esophagitis grade II/III. Overall, HC patients had higher healing rates than the regular compliant patients. Both drugs were well tolerated and safe.
Atheroprotective Effects of Long-Acting Dihydropyridine-Type Calcium Channel Blockers: Evidence from Clinical Trials and Basic Scientific Research
Authors: Preston Mason R.
Published: May 2003

Atherosclerosis is a systemic disease that can ultimately lead to ischaemia and infarction in the heart, brain and peripheral vasculature. According to the ‘response to injury’ hypothesis, endothelial dysfunction is the early event that allows penetration of lipids and inflammatory cells into the arterial wall, contributing to the development of the atherosclerotic lesion. Endothelial dysfunction is causally related to a variety of risk factors for atherosclerosis, including hyperlipidaemia and hypertension. Agents that restore endothelial function and NO bioavailability have beneficial anti-atherogenic activities and can improve cardiovascular outcomes; this has been observed with angiotensin-converting enzyme (ACE) inhibitors, statins and certain dihydropyridine-type calcium channel blockers (CCBs). In the Prospective Randomised Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), the CCB amlodipine provided significant clinical benefits compared with placebo, including a marked reduction in cardiovascular morbidity and a reduction in the progression of carotid atherosclerosis. As these beneficial effects of amlodipine have not been observed with other dihydropyridine-type CCBs, it has been proposed that this agent has distinct anti-atherosclerotic properties related to its strong lipophilicity and membrane location. Experimental support for this hypothesis has been obtained from various in vitro and in vivo models of atherosclerosis. These findings support a broader therapeutic role for third-generation dihydropyridine-type CCBs in the treatment of atherosclerosis.
Clinical Trials: Evidence and Unanswered Questions – Hyperlipidaemia
Authors: Deanfield John E.
Published: May 2003

It is now clear that the management of hypercholesterolaemia is important for the reduction of morbidity and mortality caused by cerebrovascular and coronary events. The landmark Scandinavian Simvastatin Survival Study was the first to show conclusively that lipid-lowering therapy with statins reduces the incidence of stroke. Subsequent trials, undertaken in a variety of different patient populations, have confirmed that statin therapy reduces the incidence of stroke by approximately one-third. This important benefit has been observed in men and women, the young and the elderly, and also in subjects with diabetes mellitus. In the recent Heart Protection Study, which recruited ‘high-risk’ vascular subjects, stroke risk reduction was demonstrated even among those subjects considered to have ‘low’ low-density lipoprotein (LDL) cholesterol levels. The benefits of statin therapy in stroke have been attributed to reductions in cholesterol and to other non-lipid-lowering effects of statins. Ongoing clinical trials such as TNT (Treating to New Targets) and IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid lowering) will test the ‘lower is better’ hypothesis. Using statins to lower LDL cholesterol to levels that are below current guidelines will provide additional benefits in stroke risk reduction. Most of the data on cholesterol reduction and cerebrovascular events have been derived from studies of patients with documented coronary heart disease (CHD). The ongoing SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial will examine the benefits of LDL cholesterol lowering in patients with previous stroke or transient ischaemic attack (TIA), but no history of coronary problems.
Blood Pressure and Lipid Lowering in the Prevention of Stroke: A Note to Neurologists
Authors: Amarenco Pierre
Published: May 2003

Stroke is the leading cause of adult disability and dependency in western society. Despite the determined efforts of basic science and clinical investigators, neuroprotective therapies for acute stroke have yet to be realised. Stroke prevention, therefore, remains the key route for reducing morbidity and mortality. Hypertension and hypercholesterolaemia are the most important modifiable risk factors for stroke. Several recent landmark studies have shown that lipid lowering with statins can reduce the risk of ischaemic stroke, as well as coronary heart disease. In addition, clinical trials evaluating the effects of blood pressure lowering have shown that antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs) and angiotensin II receptor antagonists can reduce stroke risk. Accumulating evidence suggests certain antihypertensive agents such as CCBs might also prevent the formation and progression of carotid atheroma, independently of their blood-pressure-lowering effects. It follows that rigorous identification and targeting of high- risk or stroke-prone individuals for blood pressure and lipid-lowering interventions should be of practical importance to all physicians involved in the management of stroke.
Lansoprazole Fast Disintegrating Tablet: A New Formulation for an Established Proton Pump Inhibitor
Authors: Baldi Fabio , Malfertheiner Peter
Published: May 2003

Lansoprazole is a proton pump inhibitor (PPI) which is an effective and well-tolerated treatment option in the management of acid-related disorders. Lansoprazole fast disintegrating tablet (LFDT) – a new, patient-friendly and more convenient formulation of lansoprazole which can be taken with or without water – is the first PPI to be made available as an orally disintegrating tablet. It represents an innovative drug delivery system, comprising enteric-coated microgranules of lansoprazole compressed with an inactive, rapidly dispersing matrix to form a tablet. When the tablet is placed on the tongue and sucked gently it disintegrates rapidly in the mouth, releasing the enteric-coated microgranules which are swallowed with the patient’s saliva without water. Alternatively, the tablet can be swallowed with a drink of water. Studies have shown that the bioavailability of LFDT is comparable to lansoprazole capsules, at both 15 and 30 mg doses; the indications and recommended dosages for LFDT are therefore identical to lansoprazole capsules. The new formulation may be of particular benefit to those with active life-styles who do not always have water available, patients who have difficulty in swallowing, and elderly patients.
Low-Density Lipoprotein Receptor and Apolipoprotein A-I and B Expression in Human Enterocytes
Authors: Sviridov Dmitri , Hoeg Jeffrey M. , Eggerman Thomas , Demosky Stephen J. , Safonova Irina G. , Brewer H. Bryan
Published: May 2003

Low-density lipoprotein receptor (LDL-R) was found to be expressed in human small intestine epithelial cells, enterocytes. The relative abundance of LDL-R mRNA and protein was compared with that of apolipoproteins A-I (apoA-I) and B (apoB) in enterocytes and two other cell types: CaCo-2 and HepG2. The LDL-R mRNA content was comparable in three cell types. Human enterocytes expressed 5.2- to 14-fold more apoA-I mRNA than the other cells. In contrast, HepG2 cells expressed 10-to 19-fold more apoB mRNA than CaCo-2 cells and human enterocytes. Immunoprecipitation of [35S]methionine pulse-labeled intracellular proteins from these cell types demonstrated that human enterocytes synthesize more apoA-I and apoB, while HepG2 cells synthesize a slightly higher amount of LDL-R.
Acenocoumarol Is Not a Safe Alternative for Anticoagulation in Phenprocoumon-Induced Hepatic Failure
Authors: Neef Markus , Kerekes Zsuzsanna , Fischer Hans-Peter , Sauerbruch Tilman , Spengler Ulrich
Published: May 2003

Acenocoumarol has been proposed repeatedly as a safe alternative drug regimen for oral anticoagulation in patients who have suffered phenprocoumon-induced fulminant hepatic failure. The current report describes 2 patients with phenprocoumon-induced hepatic failure, necessitating liver transplantation in 1 case, who showed recurrence of liver damage when oral anticoagulation with acenocoumarol was attempted. Thus, acenocoumarol may not be a safe therapeutic alternative for patients who survived severe phenprocoumon-induced hepatotoxicity.
Congenital Absence of the Portal Vein with Splenomegaly and Hypersplenism in a Young Woman
Authors: Appel Heiner , Loddenkemper Christoph , Schirmacher Peter , Dienes Hans Peter , Sieper Jochen , Rudwaleit Martin , Golder Werner , Zeitz Martin
Published: May 2003

Congenital absence of portal vein (CAPV) with a systemic shunt of enteric blood is a rare malformation. Twenty-seven cases have been reported to date; with the exception of 4 patients all cases had either liver anomalies or cardiac anomalies. CAPV is usually diagnosed before the age of 18 (25/27 cases). Here we present the case of a 33-year-old woman with CAPV without further anomalies. Beside suffering from circumscript scleroderma, splenomegaly and hypersplenism, the patient was otherwise healthy. Diagnosis was based on histological findings, angiography and CT scan. The liver biopsy showed portal tracts with inconspicuous arteries and bile ducts, but with severe loss of portal vein branches and minimal proliferation of bile ductules. In addition, the perivenular sinusoids were slightly dilated with focal parenchymal atrophy. Angiography showed a missing portal vein system and a missing splenic vein with drainage of the enteric blood through dilated perisplenic and perigastric collaterals to the azygos vein system. A CT scan revealed an empty liver hilus without portal vein. Here we discuss clinical aspects of this patient, show radiologic and histopathologic findings, and compare them to other cases in the literature.
Iodine Deficiency in Vegetarians and Vegans
Authors: Krajčovičová-Kudláčková M. , Bučková K. , Klimeš I. , Šeboková E.
Published: May 2003

Iodine content in food of plant origin is lower in comparison with that of animal origin due to a low iodine concentration in soil. Urinary iodine excretion was assessed in 15 vegans, 31 lacto- and lacto-ovovegetarians and 35 adults on a mixed diet. Iodine excretion was significantly lower in alternative nutrition groups – 172 µg/l in vegetarians and 78 µg/l in vegans compared to 216 µg/l in subjects on a mixed diet. One fourth of the vegetarians and 80% of the vegans suffer from iodine deficiency (iodine excretion value below 100 µg/l) compared to 9% in the persons on a mixed nutrition. The results show that under conditions of alternative nutrition, there is a higher prevalence of iodine deficiency, which might be a consequence of exclusive or prevailing consumption of food of plant origin, no intake of fish and other sea products, as well as reduced iodine intake in the form of sea salt.
Mechanism of Increased Plasma Glucose Levels after Oral Glucose Ingestion in Normal-Weight Middle-Aged Subjects
Authors: Rigalleau Vincent , Beylot Michel , Normand Sylvie , Pachiaudi Christiane , Laville Martine , Petitbois Cyril , Deleris Gérard , Baillet Laurence , Gin Henri
Published: May 2003

Background/Aims: To determine the decline in glucose tolerance in normal-weight middle-aged subjects, we performed a cross-sectional study using double-labelled oral glucose tolerance tests in 8 middle-aged (46.3 ± 0.9 years) and in 8 young (23.6 ± 0.5) subjects with similar normal body weight. Methods: Plasma glucose was labelled by an infusion of dideuterated glucose started 120 min before ingestion of 1 g/kg of naturally 13C-enriched corn starch glucose. Glucose levels, substrate oxidation (indirect calorimetry) and exogenous glucose oxidation (13C enrichment of expired CO2) were monitored for 330 min. Results: In the middle-aged subjects, the appearance of exogenous glucose was reduced (723 ± 52 mg/kg/330 min) compared to young subjects (864 ± 38; p < 0.05), and systemic glucose production was normal. Plasma glucose levels were increased due to a reduced glucose disappearance rate (middle aged: 1,046 ± 61 mg/kg/330 min vs. young 1,242 ± 67; p < 0.05), concerning both oxidative and non-oxidative disposal. This reduction was no longer apparent when the results were normalized for fat-free mass. Insulin levels were similar in young and middle-aged subjects. Conclusion: In normal-weight middle-aged individuals, glucose intolerance is mainly due to the reduction in the mass of fat-free glucose-utilizing tissues. The higher plasma glucose levels enable normal glucose supply to peripheral tissues, and increase splanchnic glucose uptake.
Effects of Short-Term Modified Fasting on Sleep Patterns and Daytime Vigilance in Non-Obese Subjects: Results of a Pilot Study
Authors: Michalsen A. , Schlegel F. , Rodenbeck A. , Lüdtke R. , Huether G. , Teschler H. , Dobos G.J.
Published: May 2003

Background: Periodically repeated short-term fasting is a frequently practised tradition worldwide. Empirical reports suggest that during fasting periods the quality of sleep and daytime performance are improved. The effects of a home-based 1-week modified fasting on sleep patterns and daytime vigilance and performance were analysed in 15 healthy non-obese volunteers. Methods: Sleep was measured by polysomnography before and after a 7-day fasting period; sleep inventories with assessment of daytime performance were collected throughout the observation period. Blood samples and urine were drawn at the beginning and at the end of fasting. Results: 13 subjects (12 females, 1 male; age 41.2 ± 13.4 years; BMI 23.9 ± 4.2 kg/m2) completed the fasting period; weight decreased from 66.5 ± 11.7 kg to 63 ± 11.9 kg. Compared to baseline, a significant decrease in arousals, a decrease in periodic leg movements (PLM) and a non-significant increase in REM sleep were observed at the end of fasting. Subjective sleep ratings showed a fasting-induced increase in global quality of sleep, daytime concentration, vigour and emotional balance. Clinical laboratory tests showed a decrease in serum magnesium; urinary melatonin excretion decreased moderately. Conclusion: This open pilot study demonstrates that along with a decrease in sleep arousals a 1-week fasting period promotes the quality of sleep and daytime performance in non-obese subjects. The observed decrease in PLM might point to a nutritional modification of brain dopaminergic functions. In terms of evolutionary development, an improved daytime performance during periods of food deprivation could have been beneficial for the success in search for food.
Effects of a Dietary Thermally Oxidized Fat on Thyroid Morphology and mRNA Concentrations of Thyroidal Iodide Transporter and Thyroid Peroxidase in Rats
Authors: Skufca P. , Brandsch C. , Hirche F. , Eder K.
Published: May 2003

Background/Aim: Recent studies demonstrated that feeding oxidized fats increases the concentrations of total and free thyroxine in blood of rats and pigs. This finding suggested that oxidized fats affect the function of the thyroid gland. This study investigates the effects of a thermally oxidized dietary fat on the morphology of the thyroid gland and on the expression of proteins (Na+/I– symporter, thyroid peroxidase) involved in the synthesis of thyroid hormones in rats at different dietary iodine concentrations. Methods: An experiment was conducted with 48 growing male Sprague-Dawley rats which were allotted to four groups of 12 animals each. According to a bifactorial experimental design, the rats received semisynthetic diets with 10% of either a fresh or an oxidized fat, with low (50 µg/kg) or adequate (400 µg/kg) iodine concentrations, over a period of 38 days. The oxidized fat was prepared by heating sunflower oil at a temperature of 55°C for a period of 5 weeks. The oxidized fat had much higher concentrations of lipid peroxidation products than the fresh fat as assessed by determining the peroxide concentrations (877 vs. 33 mEq O2/kg) and those of thiobarbituric acid reactive substances (25 vs. 0.7 µmol/kg). Results: Rats fed the diets containing oxidized fat had higher concentrations of total and free thyroxine in plasma, a greater height of thyroid epithelial cells, a smaller diameter of thyroid follicle lumen, a lower Na+/I– symporter mRNA concentration, and a higher thyroid peroxidase mRNA concentration than rats fed the fresh fat (p < 0.05 for all effects). The concentrations of triiodothyronine and thyrotropin were not different between rats fed the fresh fat and those fed the oxidized fat. The dietary iodine supply also had significant effects on some of the parameters analyzed. There were no interactions between type of fat and dietary iodine concentrations. Conclusion: The rat model used here shows that dietary oxidized fats affect the morphology and the function of the thyroid gland, irrespective of the dietary iodine supply.
Use of Olive Oil Based Emulsions as an Alternative to Soybean Oil Based Emulsions in Total Parenteral Nutrition and Their Effects on Liver Regeneration following Hepatic Resection in Rats
Authors: Ok Engin , Yilmaz Zeki , Karaküçük İnci , Akgün Hülya , Şahin Habibe
Published: May 2003

Background/Aim: The main objective of this study was to compare the effects of olive oil to those of soybean oil on liver tissue regeneration following hepatic resection in rats. Methods: Seventy albino Wistar rats were randomly assigned to seven groups which contained 10 rats each. Group 1 was the sham-treated group; groups 2 and 3 received total parenteral nutrition (TPN) containing soybean oil lipid emulsions (20% Lipofundin MCT/LCT) for 48 or 72 h; groups 4 and 5 received TPN containing olive oil (80%)/soybean oil (20%) lipid emulsions (ClinOleic 20%) for 48 or 72 h; group 6 was the control group for 48 h, and group 7 was the control group for 72 h. TPN was given via internal jugular vein, and 70% hepatic resection was performed in the study groups. In addition, hepatic resections with no TPN were performed in the control groups, except the sham group. Relative liver weight, mitotic index, proliferating cell nuclear antigen labeling index, and carnitine levels in liver tissue samples were used to assess hepatic regeneration. Thiobarbituric acid reactive substances were measured as an index of lipid peroxidation and oxidative tissue damage. Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were parameters for the liver function. Results: The relative liver weight increased significantly with minimal hepatosteatosis in the olive oil treated groups. Lipid peroxidation significantly decreased with near-normal serum levels of the liver function parameters in the olive oil/soybean oil treated groups, and mitotic index and proliferating cell nuclear antigen labeling index reached their maximum level in rats receiving TPN containing any kind of lipid emulsions for 48 h following resection. Conclusions: The use of olive oil/soybean oil lipid emulsions in TPN has important beneficial effects on the liver regeneration, and the antioxidant properties of olive oil originating from its natural components indirectly contribute to the liver regeneration in rats.
Reactive Oxygen Species Are Involved in Smoking-Induced Dysfunction of Nitric Oxide Biosynthesis and Upregulation of Endothelial Nitric Oxide Synthase
Authors: Barua Rajat S. , Ambrose John A. , Srivastava Sudhesh , DeVoe Mary C. , Eales-Reynolds Lesley-Jane
Published: May 2003

Background—

Our group has previously shown that human umbilical vein endothelial cells exposed to smokers’ serum decreased nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) activity in the presence of increased eNOS expression. In the present study, we examined whether these observations extended to human coronary artery endothelial cells (HCAECs). In addition, the role of reactive oxygen species in the observed alterations was examined.

Methods and Results—

HCAECs were incubated with serum from 10 nonsmokers and 15 smokers for 12 hours with or without the addition of either polyethylene glycol-superoxide dismutase (PEG-SOD, 300 U/mL), PEG-SOD+PEG-catalase (1000 U/mL), chelerythrine (3 μmol/L), or tetrahydrobiopterin (20 μmol/L). At the end of incubation, NO, eNOS protein, and eNOS activity were measured from the same culture. HCAECs incubated with smokers’ serum alone showed significantly lower NO production (
P
<0.05) and eNOS activity (
P
<0.005) but higher eNOS expression (
P
<0.005) compared with nonsmokers. In smokers, addition of PEG-SOD, PEG-SOD+PEG-catalase, or tetrahydrobiopterin significantly (
P
<0.05) improved NO levels and eNOS activity. Interestingly, in the same smokers, a significant decrease in eNOS expression was only seen with the addition of PEG-SOD+PEG-catalase (
P
<0.05) and treatment with PEG-SOD alone insignificantly increased eNOS expression.

Conclusions—

The present study indicates that in vitro, HCAECs show similar changes in NO biosynthesis as human umbilical vein endothelial cells when exposed to smokers’ serum and also confirms that oxidative stress plays a central role in smoking-mediated dysfunction of NO biosynthesis in endothelial cells. Furthermore, these data support other studies suggesting a role for hydrogen peroxide in the upregulation of eNOS.
Arginine Vasopressin in Advanced Vasodilatory Shock
Authors: Dünser Martin W. , Mayr Andreas J. , Ulmer Hanno , Knotzer Hans , Sumann Günther , Pajk Werner , Friesenecker Barbara , Hasibeder Walter R.
Published: May 2003

Background—

Vasodilatory shock is a potentially lethal complication of severe disease in critically ill patients. Currently, catecholamines are the most widely used vasopressor agents to support blood pressure, but loss of catecholamine pressor effects is a well-known clinical dilemma. Arginine vasopressin (AVP) has recently been shown to be a potent vasopressor agent to stabilize cardiocirculatory function even in patients with catecholamine-resistant vasodilatory shock.

Methods and Results—

Forty-eight patients with catecholamine-resistant vasodilatory shock were prospectively randomized to receive a combined infusion of AVP and norepinephrine (NE) or NE infusion alone. In AVP patients, AVP was infused at a constant rate of 4 U/h. Hemodynamic, acid/base, single-organ, and tonometrically derived gastric variables were reported before the study and 1, 12, 24, and 48 hours after study entry. For statistical analysis, a mixed-effects model was used. AVP patients had significantly lower heart rate, NE requirements, and incidence of new-onset tachyarrhythmias than NE patients. Mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index were significantly higher in AVP patients. NE patients developed significantly more new-onset tachyarrhythmias than AVP patients (54.3% versus 8.3%). Gastrointestinal perfusion as assessed by gastric tonometry was better preserved in AVP-treated patients. Total bilirubin concentrations were significantly higher in AVP patients.

Conclusions—

The combined infusion of AVP and NE proved to be superior to infusion of NE alone in the treatment of cardiocirculatory failure in catecholamine-resistant vasodilatory shock.
Treatment of Saphenous Vein Bypass Grafts With Ultrasound Thrombolysis
Authors: Singh Mandeep , Rosenschein Uri , Ho Kalon K.L. , Berger Peter B. , Kuntz Richard , Holmes, Jr David R.
Published: May 2003

Background—

Percutaneous coronary interventions (PCIs) in saphenous vein grafts (SVGs) with thrombus have a high frequency of distal embolization. Acolysis (therapeutic ultrasound) can break up thrombus in vitro in animal models and humans. Whether this is beneficial during percutaneous SVG interventions is unknown.

Methods and Results—

We performed a trial of coronary ultrasound thrombolysis in which patients with an acute coronary syndrome undergoing PCI in SVGs were randomly assigned to receive acolysis or abciximab. The primary end point was a successful procedure, defined as final luminal diameter stenosis 30% or less with Thrombolysis In Myocardial Infarction grade 3 flow and freedom from major adverse cardiac events (composite of death, Q-wave, and non–Q-wave myocardial infarction [MI], emergency bypass procedure, disabling stroke, and target lesion revascularization). Of 181 enrolled, 92 received acolysis and 89 abciximab. Angiographic procedural success was achieved in 63% of acolysis patients and 82% of abciximab patients (
P
=0.008). Incidence of major adverse cardiac events at 30 days was 25% with acolysis and 12% with abciximab (
P
=0.036), attributable mainly to a greater frequency of non–Q-wave MI with acolysis (19.6% versus 7.9%,
P
=0.03). The incidence of Q-wave MI was also higher with acolysis (5.4% versus 2.2%,
P
=nonsignificant). The primary end point was achieved in 53.8% of acolysis patients and 73.1% of abciximab patients (
P
=0.014).

Conclusions—

Use of therapeutic ultrasound in vein graft lesions in patients with acute coronary syndrome had poor angiographic outcome and increased the incidence of acute ischemic complications.
Anti-Platelet Factor 4/Heparin Antibodies
Authors: Williams R. Taylor , Damaraju Lakshmi V. , Mascelli Mary Ann , Barnathan Elliot S. , Califf Robert M. , Simoons Maarten L. , Deliargyris Efthymios N. , Sane David C.
Published: May 2003

Background—

We postulated that antibodies to platelet factor 4/heparin complex might contribute to recurrent ischemic events in patients with acute coronary syndrome.

Methods and Results—

We analyzed serum from patients enrolled in the placebo/unfractionated heparin arm of the GUSTO IV-ACS trial who had high likelihood of prior heparin exposure. We selected 109 patients without thrombocytopenia with the 30-day primary end point (death, myocardial infarction [MI], or revascularization) and 109 age-, gender-, and race-matched controls who did not achieve the primary end point. An ELISA for anti-platelet factor 4/heparin antibodies was performed using 48-hour serum samples. The analyses were done by blinded investigators, and the results were correlated with clinical outcomes. Twenty-three of 218 patients (10.6%) had anti-PF4/heparin antibodies. Patients with anti-PF4/heparin antibodies were more likely to have death or MI (30.4% versus 11.3%,
P
=0.011) or MI (21.7% versus 6.2%,
P
=0.008) than patients who were negative for the antibody. After multiple logistic regression analysis, anti-PF4/heparin antibodies remained a predictor of 30-day death or MI (odds ratio, 4.0; 95% CI, 1.4 to 11.3;
P
=0.0093) and MI (odds ratio, 4.6; 95% CI, 1.4 to 15.0;
P
=0.0108). The antibody was not associated with the composite end point (death, MI, or revascularization) or with death or revascularization alone.

Conclusions—

Antibodies to the platelet factor 4/heparin complex are a novel, independent predictor of myocardial infarction at 30 days in patients presenting with acute coronary ischemic syndromes. This finding may explain the previous association between thrombocytopenia and adverse events in patients with acute coronary syndrome and may have important implications for the choice of anticoagulant regimens.
Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure
Authors: Perin Emerson C. , Dohmann Hans F.R. , Borojevic Radovan , Silva Suzana A. , Sousa Andre L.S. , Mesquita Claudio T. , Rossi Maria I.D. , Carvalho Antonio C. , Dutra Helio S. , Dohmann Hans J.F. , Silva Guilherme V. , Belém Luciano , Vivacqua Ricardo , Rangel Fernando O.D. , Esporcatte Roberto , Geng Yong J. , Vaughn William K. , Assad Joao A.R. , Mesquita Evandro T. , Willerson James T.
Published: May 2003

Background—

This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility.

Methods and Results—

Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage ≥6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (
P
=0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (
P
=0.003) and a reduction in end-systolic volume (
P
=0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (
P
<0.0005) at 4 months after treatment.

Conclusions—

Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrow–derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function.
In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction
Authors: Kraitchman Dara L. , Heldman Alan W. , Atalar Ergin , Amado Luciano C. , Martin Bradley J. , Pittenger Mark F. , Hare Joshua M. , Bulte Jeff W.M.
Published: May 2003

Background—

We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model.

Methods and Results—

Adult farm pigs (n=5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16×10
7
cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals.

Conclusion—

MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.
Multicenter Study of Human Immunodeficiency Virus–Related Germ Cell Tumors
Authors: Powles T. , Bower M. , Daugaard G. , Shamash J. , De Ruiter A. , Johnson M. , Fisher M. , Anderson J. , Mandalia S. , Stebbing J. , Nelson M. , Gazzard B. , Oliver T.
Published: May 2003

Purpose: Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors.

Patients and Methods: Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases.

Results: Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy.

Conclusion: Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.
Chemotaxis of non‐compressed blood polymorphonuclear leukocytes from an adolescent with severe leukocyte adhesion deficiency
Authors: Malawista Stephen E. , de Boisfleury Chevance Anne , Brown Eric J. , Boxer Laurence A. , Law S.K.A.
Published: May 2003

We have defined the defect in a child with severe leukocyte adhesion deficiency‐1 (LAD) as resulting from a single amino acid shift in CD18 (from a C to T mutation at position 533) that prevents heterodimerization with the CD11 antigens to produce β2 integrins—the first reported patient homozygous for this defect. Although beset by frequent infections, the patient has survived to adolescence despite the lack of these important adhesion molecules. Consistent with his clinical course is the ability of his PMN to respond chemotactically in slide preparations, albeit with difficulty because of their poor purchase on substrate. The operant adhesins are unknown; his polymorphonuclear leukocytes (PMN) remain chemotactically responsive in the presence of antibodies to αvβ3 and β1 integrins and to integrin‐associated protein (IAP). These findings indicate that not all patients with severe LAD are candidates for early bone marrow transplantation. Am. J. Hematol. 73:115–120, 2003. © 2003 Wiley‐Liss, Inc.
Natural killer cell‐type body cavity lymphoma following chronic active Epstein‐Barr virus infection
Authors: Ogata Masao , Imamura Tomoyuki , Mizunoe Syunji , Ohtsuka Eiichi , Kikuchi Hiroshi , Nasu Masaru
Published: May 2003

We describe a 69‐year‐old female who developed natural killer cell‐type body cavity lymphoma following chronic active Epstein‐Barr virus (CAEBV) infection. Examination of the patient's pleural effusion revealed large abnormal lymphocytes, which were CD2+, CD7+, CD30+, CD56+, CD3−, and CD4−. No rearrangement of T cell receptor genes was detected. Clonal proliferation of Epstein‐Barr virus (EBV)‐infected cells in pleural effusion was demonstrated by Southern blot hybridization analysis. Human herpesvirus type‐8 (HHV‐8) DNA was not detected in these cells. The patient achieved a complete remission with combination chemotherapy. Prior to the clinical onset of lymphoma, high fever of unknown origin had persisted for 21 months. IgG antibodies to EBV‐viral capsid antigen and to EBV‐early antigens, types D and R were not high (1:160 and less than 1:10, respectively). Two months after the onset of fever, however, retrospective quantitative PCR assay revealed a high EBV DNA load in plasma, indicating that CAEBV infection had been the cause of the patient's recurrent fever. The remarkable features of this case are (i) the development of lymphoma following CAEBV infection that demonstrated a normal pattern of EBV‐specific antibodies, (ii) the development of HHV‐8‐negative body cavity lymphoma, and (iii) the effectiveness of combination chemotherapy. Am. J. Hematol. 73:126–130, 2003. © 2003 Wiley‐Liss, Inc.
Osseous fragility in Marshall–Smith syndrome
Authors: Diab Mohammad , Raff Michael , Gunther Daniel F.
Published: May 2003

Marshall–Smith syndrome is characterized by accelerated osseous maturation, craniofacial anomalies, failure to thrive, psychomotor delay, hypotonia, pulmonary dysfunction, and limited life expectancy. We describe a 7‐year‐old girl who, in addition to meeting these criteria for Marshall–Smith syndrome, had multiple fractures and skeletal anomalies. The purpose of this report is to draw attention to Marshall–Smith syndrome as one of the skeletal dysplasias characterized by osseous fragility. © 2003 Wiley‐Liss, Inc.
Melorheostosis in a family with autosomal dominant osteopoikilosis: Report of a third family
Authors: Debeer Philippe , Pykels E. , Lammens J. , Devriendt K. , Fryns J.‐P.
Published: May 2003

We describe a three‐generation family with clinical and radiological findings of osteopoikilosis in five and melorheostosis in one individual. The co‐occurrence of both rare bone disorders suggests that both conditions might be related as suggested previously by Butkus et al. [1997: Am J Med Genet 72:43–46] and Nevin et al. [1999: Am J Med Genet 82:409–414]. The findings in this family strengthen the hypothesis that osteopoikilosis is an autosomal dominant condition and that an early postzygotic second hit mutation in the second allele results in melorheostosis. © 2003 Wiley‐Liss, Inc.
Several genomic regions potentially containing QTLs for bone size variation were identified in a whole‐genome linkage scan
Authors: Deng Hong‐Wen , Shen Hui , Xu Fu‐Hua , Deng Hongyi , Conway Theresa , Liu Yong‐Jun , Liu Yao‐Zhong , Li Jin‐Long , Huang Qing‐Yang , Davies K.M. , Recker Robert R.
Published: May 2003

Bone size is an important determinant of osteoporotic fractures. For a sample of 53 pedigrees that contains more than 10,000 relative pairs informative for linkage analyses, we performed a whole‐genome linkage scan using 380 microsatellite markers to identify genomic regions that may contain QTLs of bone size (two dimensional measurement by dual energy X‐ray absorptiometry). We conducted two‐ and multi‐point linkage analyses. Several potentially important genomic regions were identified. For example, the genomic region 17q23 may contain a QTL for wrist (ultra distal) bone size variation; a LOD score of 3.98 is achieved at D17S787 in two‐point analyses and a maximum LOD score (MLS) of 3.01 is achieved in multi‐point analyses in 17q23. 19p13 may contain a QTL for hip bone size variation; a LOD score of 1.99 is achieved at D19S226 in two‐point analyses and a MLS of 2.83 is achieved in 19p13 in multi‐point analyses. The genomic region identified on chromosome 17 for wrist bone size seems to be consistent with that identified for femur head width variation in an earlier whole‐genome scan study. The genomic regions identified in this study and an earlier investigation on one‐dimensional bone size measurement by radiography are compared. The two studies may form a basis for further exploration with larger samples and/or denser markers for confirmation and fine mapping studies to eventually identify major functional genes and the associated etiology for osteoporosis. © 2003 Wiley‐Liss, Inc.