bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrocystic Disease of Vulvar Ectopic Breast Tissue
Authors: Baykal C. , Tulunay G. , Usubutun A. , Küçükali T. , Ozer S. , Demir O.F.
Published: July 2004

Introduction: Mammary glands located in the vulvar region have been named as ectopic breast tissue or anogenital mammary glands by different authors. Literature on pathologies of ectopic breast tissue located in the vulvar region is rare. Most of the reports are about the malignancies arising from this ectopic tissue. Case Report: We report a case of fibrocystic disease of the mammary glands in the vulva in a 25-year-old pregnant woman. Her disease was exaggerated during pregnancy. Conclusion: Ectopic breast tissue in the vulva is a rare entity and fibrocystic disease of this tissue has rarely been reported in the English literature.
Screening for Retinopathy of Prematurity: Is It Painful?
Authors: Belda Sylvia , Pallás Carmen R. , de la Cruz Javier , Tejada Pilar
Published: July 2004

Background: Screening programmes for retinopathy of prematurity have shown to reduce unfavourable visual outcome and to be cost-effective. Following present recommendations, almost 1% of all newborn babies should therefore be screened and undergo at least one ophthalmologic examination. This is a skilled procedure that requires drug instillation and manipulation of the ocular globe with scleral indentation. The objective of this study is to describe the side effects of this ophthalmic exam with special focus on the occurrence of pain. Methods: This was an observational study with a before-after analysis where all neonates undergoing an ophthalmologic exam during a 4-month period in a third level hospital were included. CRIES pain score was determined before the exam, 5 min after and 24 h after the screening manoeuvre. Blood pressure and pulse rate were determined in addition to the mentioned measurements 30 min after the ophthalmologic examination.Minimum oxygen saturation, apnoeas, gastrointestinal side effects (like vomiting and gastric aspirates), the need for respiratory assistance or for intensive care unit admission were recorded within 24 h before and after the procedure. Results: 27 preterm neonates underwent an ophthalmologic examination and were included in the study. CRIES pain score was significantly higher 5 min after and 24 h after the screening procedure than before. This difference was also observed after stratification for birth weight and gestational age. No other study variable modified this time effect. No significant changes in blood pressure and pulse rate were shown after the ophthalmic exam. Vomiting was present in 4% of the newborns, gastric aspirates in 22% and apnoeas in 41% after the examination. Ten percent of the explored preterm babies needed increased respiratory assistance and 4% had to be transferred from the intermediate care unit to the intensive care because of severe apnoeas. Comments: An increase in pain score was shown after retinopathy of prematurity screening examination. Physiologic variable changes do not last long enough to evaluate the impact of certain procedures. Multivariate pain scores (like CRIES) should be used in everyday practice. It seems that the ophthalmologic examination in preterm babies might be painful and further studies should identify the best strategy to prevent pain during the retinopathy of prematurity screening manoeuvre.
Nuclear Dynamics of Parthenogenesis of Human Oocytes: Effect of Oocyte Aging in vitro
Authors: Sengoku Kazuo , Takuma Naoyuki , Miyamato Toshinobu , Yamauchi Tomofumi , Ishikawa Mutsuo
Published: July 2004

We investigated in detail the nuclear kinetics of oocyte activation of aged human oocytes following combined activation treatment with calcium ionophore and puromycin. Two types of oocytes were used: (a) 1-day-old oocytes after 20–24 h retrieval, and (b) 2-day-old oocytes after 44–50 h retrieval. A total of 185 unfertilized aged oocytes, 91 1-day-old and 94 2-day-old oocytes, were fixed at 1, 2, 4, 6 and 8 h after activation treatment and then metaphase II (MII), anaphase or telophase II (A/T II) or pronuclear stage were recorded. We demonstrated that a combined calcium ionophore and puromycin treatment induced a high activation rate in both 1-day-old (95.6%) and 2-day-old oocytes (95.2%). Our results also demonstrated that the nuclear progression was faster in 2-day-old oocytes than in 1-day-old oocytes, although nuclear progression in parthenogenetically activated human oocytes requires the longer time periods compared with ICSI fertilization. It is concluded that combined treatment of the calcium ionophore and puromycin allows a high rate of parthenogenetic activation and the nuclear kinetics of parthenogenetically activated human oocytes appears to be more rapid in in vitro aging oocytes.
Aberrant Serum Adiponectin Levels in Women with Uterine Leiomyomas
Authors: Chen Hung-Sheng , Chan Te-Fu , Chung Yueh-Fang , Su Jinu-Huang , Yuan Shyng-Shiou F.
Published: July 2004

Background:Adiponectin is an adipocyte-secreted hormone. Serum adiponectin levels are inversely correlated with insulin resistance, and low plasma adiponectin levels have been demonstrated in type 2 diabetic patients. However, information on serum adiponectin levels in gynecological disorders is mostly lacking. In this study, we analyzed the possible correlation between serum adiponectin levels and uterine leiomyomas. Methods: Serum adiponectin levels, determined by radioimmunoassay, were compared in women with uterine leiomyomas (n = 47) and normal controls (n = 46). Results: Serum adiponectin levels in women with uterine leiomyomas (16.4 ± 0.9 µg/ml) were significantly lower (p < 0.05) than those in the normal controls (19.5 ± 1.0 µg/ml). Furthermore, there was an inverse correlation between serum adiponectin levels and body mass index, in both women with leiomyomas and normal controls. Conclusions: Serum adiponectin levels are significantly decreased in myomatous patients.
Gamma-Tocopherol – An Underestimated Vitamin?
Authors: Wagner Karl-Heinz , Kamal-Eldin Afaf , Elmadfa Ibrahim
Published: July 2004

The main research activities of the last decades on tocopherols were mainly focused on α-tocopherol, in particular when considering the biological activities. However, recent studies have increased the knowledge on γ-tocopherol, which is the major form of vitamin E in the diet in the USA, but not in Europe. γ-Tocopherol provides different antioxidant activities in food and in-vitro studies and showed higher activity in trapping lipophilic electrophiles and reactive nitrogen and oxygen species. The lower plasma levels of γ- compared to α-tocopherol might be discussed in the light of different bioavailability, but also in a potential transformation from γ- into α-tocopherol. From the metabolism end product, only that of γ-tocopherol (2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman), but not that of α-tocopherol, was identified to provide natriuretic activity. Studies also indicate that only the γ-tocopherol plasma level served as biomarker for cancer and cardiovascular risk. Therefore, this paper provides a comprehensive review on γ-tocopherol with emphasis on its chemistry, biosynthesis, occurrence in food, different intake linking to different plasma levels in USA and Europe, absorption and metabolism, biological activities, and possible role in human health.
Fasting Respiratory Quotient as a Predictor of Long-Term Weight Changes in Non-Obese Women
Authors: Marra Maurizio , Scalfi Luca , Contaldo Franco , Pasanisi Fabrizio
Published: July 2004

Background/Aims: The identification of metabolic and environmental predictors of excess body fat is still far from being achieved. The aim of this study was to evaluate whether respiratory quotient in non-obese women is a predictor of body weight changes after a 6-year follow-up period. Methods: Forty-three non-obese healthy women participated in the study. Their baseline general characteristics were: age 40.5 ± 12.8 years; height 159 ± 7 cm; weight 61.8 ± 10.1 kg, and body mass index (BMI) 24.4 ± 3.8 kg/m². At baseline basal metabolic rate and respiratory quotient were determined by indirect calorimetry, while weight and BMI were recorded at the first observation and after the 3- and 6-year follow-ups. Results: At the first observation basal metabolic rate was 5,360 ± 713 kJ/day and respiratory quotient 0.850 ± 0.052. After 6 years, with weight changes equal to 1.4 ± 4.5 kg, baseline respiratory quotient was a significant predictor (p < 0.05) of changes in body weight or BMI together with baseline BMI. Conclusions: This follow-up study confirms that a high respiratory quotient (measured on free diet) predisposes to weight gain, especially in women with the highest baseline respiratory quotient (above the 90th percentile of the distribution for this variable).
Inhibition of Growth Hormone Secretion in Mild Primary Hyperparathyroidism
Authors: Coiro Vittorio , Volpi Ricardo , Capretti Luigi , Finardi Lorenzo , Magotti Maria-Grazia , Manfredi Guido , Chiodera Paolo , Saccani Jotti Gloria
Published: July 2004

Introduction: Impairment in growth hormone (GH) secretion has been reported to occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml) plasma PTH and free Ca levels. Patients with these characteristics are relatively few, whereas the great majority of patients with biochemically diagnosed PHP are asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels. We wondered whether also patients in these latter conditions show a defective GH secretory pattern. Methods: In order to answer this question, 8 female subjects (mean age ± SE: 44 ± 1.3 years) were selected at the time of a checkup examination from a larger population of persons in fairly good clinical condition. Inclusion criteria were plasma PTH values slightly above the normal range (up to 50% higher than the maximum limit) with free Ca levels in the upper normal range or slightly higher (experimental group). Normal values in our laboratory are ionized calcium: 1.22–1.42 mmol/ml and plasma PTH: 12–72 pg/ml. A group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle normal range and significantly lower than values found in the experimental group was also selected and used as control. Experimental and control groups were tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30 min and arginine plus GH-releasing hormone (GHRH; 1 µg/kg BW in an intravenous bolus injection). The GH responses to these challenging stimulations were compared between groups. Results: Basal serum GH values were similar in all subjects. Both arginine and arginine plus GHRH induced a significant GH rise in both groups; however, the GH responses were significantly lower in the experimental than in the control group. Mean GH peak was 27.7 and 14.6 times higher than baseline after arginine and 57.5 and 26.6 times higher than baseline after arginine plus GHRH in the control and experimental group, respectively. No significant correlation was observed between PTH or Ca levels and the GH responses to challenging stimuli in any group. Conclusion: These data show that impairment in GH secretion is associated with slightly elevated levels of PTH in the presence of serum Ca values in the upper normal range. GH responses to stimulations were reduced by about 50% in our hyperparathyroid subjects. A long-time duration of this relatively small decline of GH secretory activity may be supposed to contribute to age-related catabolic processes in a large number of patients with mild primary hyperparathyroidism.
Decreased Intercellular Communication and Connexin Expression in Mouse Aortic Endothelium during Lipopolysaccharide-Induced Inflammation
Authors: Simon Alexander M. , McWhorter Andrea R. , Chen HwuDauRw , Jackson Charity L. , Ouellette Yves
Published: July 2004

The role of gap junctional intercellular communication during inflammatory processes is not well understood. In particular, changes in the expression and function of vascular endothelial connexins (gap junction proteins) in response to inflammatory agents has not been fully investigated. In this study, we used intercellular dye transfer methods to assess interendothelial communication in aortic segments isolated from mice treated with or without intraperitoneal lipopolysaccharide (LPS), a potent inflammatory mediator. LPS treatment resulted in a 49% decrease in endothelial dye coupling 18 h after injection. Western blots indicated that LPS treatment also caused a reduction in endothelial connexin40 (Cx40) levels to 33% of control levels. Connexin37 (Cx37) levels decreased only slightly after LPS treatment to 79% of control levels. We also examined endothelial communication in aortic segments isolated from Cx37–/– and Cx40–/– mice. LPS treatment caused a significantly greater decrease in dye transfer in endothelium isolated from Cx37–/– animals compared with endothelium from Cx40–/– animals (71 vs. 26% decrease). LPS injection caused a reduction in Cx40 levels in Cx37–/– endothelium, whereas LPS actually increased Cx37 levels in Cx40–/– endothelium. These results suggest that LPS mediates changes in endothelial gap junction-mediated communication, at least in part, through modulation of Cx40 and Cx37 levels.
Effects of Inhaled Corticosteroids on Systemic Blood Pressure in Preterm Infants
Authors: Ng P.C. , Fok T.F. , Liu F. , Lee C.H. , Ma K.C. , Wong E.
Published: July 2004

Objective: To assess the effect of inhaled fluticasone propionate on (i) systemic blood pressure, and (ii) the need for volume expanders (crystalloids and colloids) and inotropes for blood pressure support in preterm, very low birth weight (VLBW) infants. Methods: Ventilated VLBW infants, less than 32 weeks of gestation, with respiratory distress syndrome were randomised to receive a 14-day course of either fluticasone propionate (500 µg/puff, 2 puffs every 12 h; n = 27) or placebo (n = 26) with a metered dose inhaler-spacer device. The response of treatment was assessed by comparing the use of volume expanders, inotropes, and the average and the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups. Results: There were no significant differences in the average or the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups. However, the total volume of crystalloids and colloids requirement was significantly greater in control than in treated infants (p = 0.03). There was also a trend towards greater consumption of the total cumulative dose of dopamine in the control infants (p = 0.10). Conclusions: Fluticasone-treated infants required significantly less volume of crystalloids and colloids for blood pressure support compared with control infants. Further larger scale studies are required to determine whether inhaled corticosteroids could minimise the use of volume replacement therapy and inotropes in the treatment of hypotension in preterm infants in the early postnatal period.
Effects of Co-Administration of Ibuprofen-Lysine on the Pharmacokinetics of Amikacin in Preterm Infants during the First Days of Life
Authors: Allegaert K. , Cossey V. , Langhendries J.P. , Naulaers G. , Vanhole C. , Devlieger H. , van Overmeire B.
Published: July 2004

The aim of this study was to assess the effects of intravenous co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin during the first days of life in preterm infants. The pharmacokinetics of amikacin were retrospectively calculated in a cohort of 73 neonates (gestational age <31 weeks) who received either ibuprofen-lysine or placebo following inclusion in the multicentre ibuprofen prophylaxis study. Assuming a one-compartment model with instantaneous input and first-order output, there was no significant difference in the median distribution volume (0.63 vs. 0.59 liters/kg), but the median serum half-life (16.4 vs. 12.4 h) of amikacin was significantly longer (p < 0.02), and the clearance (0.36 vs. 0.6 ml/kg/min; p < 0.005) of amikacin was significantly lower in infants who received ibuprofen-lysine. We conclude that the time interval between consecutive amikacin administrations should be prolonged, if ibuprofen-lysine is co-administered.
Diagnosis of Acute Renal Failure in Very Preterm Infants
Authors: Choker G. , Gouyon J.B.
Published: July 2004

This study was designed to improve the definition of acute renal failure (ARF) in very preterm infants. Twenty-eight newborn infants with gestational age ≤32 weeks were prospectively studied in the first 5 days of life and made up a control group as they did not present risk factors for vasomotor renal insufficiency. Renal insufficiency was defined as an increase in daily serum creatinine concentration above the 99th interval limit obtained in this control group, i.e., 43 µmol/l on day 1 and/or 21 µmol/l on day 2 and/or 14 µmol/l/day on day 3 and/or 22 µmol/l/day on day 4. According to this definition, 20 very preterm infants with ARF were identified. As compared with the control group, the ARF group showed more prolonged oliguric episodes, lower diuresis, insufficient weight loss (in spite of a reduction in water intake) and also more episodes with natremia <130 mEq/l (35 vs. 0%; p < 0.05) and/or kalemia >6 mEq/l (40 vs. 11%; p < 0.05). Therefore, assessment of daily changes in serum creatinine concentration in very preterm infants allows the diagnosis of clinically significant reduction in glomerular filtration rate.
Botulinum Toxin for the Treatment of Genital Pain Syndromes
Authors: Romito Silvia , Bottanelli Mara , Pellegrini Maria , Vicentini Silvana , Rizzuto Niccolò , Bertolasi Laura
Published: July 2004

Our purpose was to test the effect of botulinum toxin injections on hypertonic pelvic floor muscles of patients suffering from genital pain syndromes. We report two cases of women complaining of a genital pain syndrome resistant to pharmacological therapies and rehabilitation exercises associated with a documented involuntary tonic contraction of the levator ani muscle as a defense reaction triggered by vulvar pain. We performed botulinum toxin injections into the levator ani with the intent to relieve pelvic muscular spasms. Within a few days after the injections both the patients reported a complete resolution of the painful symptomatology, lasting for several months. Our experience suggests that botulinum injections are indicated in patients with genital pain syndrome with documented pelvic muscle hyperactivity, whose symptoms arise not only from genital inflammation and lesions, but also, and sometimes chiefly, from levator ani myalgia.
Analysis of the Contribution of Galanin Receptors 1 and 2 to the Central Actions of Galanin-Like Peptide
Authors: Krasnow Stephanie M. , Hohmann John G. , Gragerov Alexander , Clifton Donald K. , Steiner Robert A.
Published: July 2004

Galanin-like peptide (GALP) shares partial sequence identity with galanin and exhibits agonistic activity at two of the galanin receptor subtypes (GALR1 and GALR2) in vitro. The goal of these experiments was to determine whether galanin receptors mediate the effects of central GALP administration on food intake, body weight, and luteinizing hormone (LH) secretion in the mouse. We first evaluated the effects of intracerebroventricular injections of GALP or its vehicle alone in GALR1 knockout mice, GALR2 knockout mice, and their respective wild-type controls. GALP reduced food intake and body weight after 24 h to a similar degree in wild-type, GALR1 knockout, and GALR2 knockout mice. The wild-type, GALR1 knockout, and GALR2 knockout mice also exhibited significant increases in serum levels of LH following the GALP injections. To help delineate the biologically active moiety of the GALP molecule, we injected wild-type mice with shorter fragments of the full-length GALP peptide. Neither GALP(1–21) (the fragment containing the galanin-homologous sequence) nor GALP(22–60) (the C-terminal portion of the GALP molecule lacking sequence identity with galanin) had any discernable effect on food intake, body weight or circulating LH. These observations demonstrate that neither GALR1 nor GALR2 are essential for mediating the effects of GALP on feeding, body weight or LH secretion. Furthermore, the galanin-homologous region of the GALP molecule is not sufficient to mimic the effects of full-length GALP. Together, these findings argue against the hypothesis that GALP signals solely through galanin receptors in vivoand suggest the existence of a yet-to-be-identified GALP-specific receptor.
Surgery for Peptic Ulcer Today
Authors: Paimela H. , Oksala N.K.J. , Kivilaakso E.
Published: July 2004

Background: During the past 20 years medical therapy of peptic ulcer disease (PUD) has dramatically improved. Simultaneously there has been a significant improvement in living and dietary habits. Quite presumably, all these significant events are reflected in the incidence and results of surgery for peptic ulcerations. Aim: To study the incidence, methods and mortality of surgery for PUD. Methods: The nationwide data between 1987 and 1999 were obtained from the National Research and Development Centre for Welfare and Health. In the analysis the codes of the ICD 9–10 were used. Results: The annual incidence of elective surgery for PUD decreased from 15.7 to 1.7 operations (per 105 inhabitants, mean of 2 consecutive years) between 1987 and 1999 (p < 0.05). Simultaneously, the annual incidence of emergency surgery increased from 5.2 to 7.0 operations (per 105 inhabitants, p < 0.05). In 1987, local procedures (duodeno-/gastrorrhaphy or duodeno-/gastrostomy and suture) were applied in 25% of operations for PUD, whereas in 1999 they were 90% of the methods in PUD surgery. The overall annual mortality from PUD surgery remained 8% between 1987 and 1999. Conclusions: Elective ulcer surgery has virtually disappeared and parietal cell vagotomy has become history, whereas the incidence of emergency surgery increased significantly between 1987 and 2000, with the exception of the most recent years. Local procedures are overwhelmingly applied in emergency surgery and more extensive surgery is unnecessary. Nevertheless, the overall surgical mortality remained 8% between 1987 and 1999.
Drug Toxicity in the Neonate
Authors: McIntyre John , Choonara Imti
Published: July 2004

The incidence of adverse drug reactions in neonates is thought to be at least 10%. The physiology of the newborn infant is different to that of both paediatric patients and adults. This therefore predisposes to certain types of drug toxicity, which are described below. Medication errors are also a significant problem in the neonatal period due to the lack of appropriate formulations designed for neonates.
Is There Significant Improvement in Neonatal Outcome after Treating pPROM Mothers with Amnio-Infusion?
Authors: De Carolis Maria Pia , Romagnoli Costantino , De Santis Marco , Piersigilli Fiammetta , Vento Giovanni , Caruso Alessandro
Published: July 2004

The aim of this study was to determine the effects of amnio-infusion treatment on fetal and neonatal mortality and neonatal pulmonary development in women with singleton pregnancies and premature rupture of the membranes occurring at a gestational age of <26 weeks and who had severe oligohydramnios. The treated group of 45 consenting women received serial amnio-infusion and was compared with the control group of 44 women who underwent waiting treatment. Our study confirmed a higher number of live births in the treated group, especially in cases with a gestational age at rupture (GAR) of <20 weeks. Furthermore, even if GAR is an important factor for predicting pulmonary hypoplasia, amnio-infusion treatment reduces the probability of pulmonary hypoplasia. In fact, over 20 weeks, amnio-infusion treatment significantly reduces the risk of pulmonary hypoplasia even if normal lung development cannot be guaranteed.
Intravenous Leiomyomatosis with Cardiac Extension
Authors: Saitoh Maki , Hayasaka Tadashi , Nakahara Kenji , Ohmichi Masahide , Shimazaki Yasuhisa , Kurachi Hirohisa
Published: July 2004

Intravenous leiomyomatosis with cardiac extension is an extremely rare uterine tumor. We report here a case of a patient with a uterine leiomyoma which extended into the right atrium through the left ovarian vein, progressing into the left renal vein along the inferior vena cava. Complete one-stage removal of the tumor was performed using cardiopulmonary bypass, and the patient has shown a favorable outcome. Successful therapy for intravenous leiomyomatosis is dependent on total surgical excision of the tumor, cessation of ovarian function and avoidance of postoperative estrogen replacement therapy.
Hyperinnervation and Mast Cell Activation May Be Used as Histopathologic Diagnostic Criteria for Vulvar Vestibulitis
Authors: Bornstein Jacob , Goldschmid Nimrod , Sabo Edmund
Published: July 2004

Objective: Vestibulitis is currently diagnosed based only on clinical criteria. To achieve histopathological diagnostic criteria, we carried out a computerized image analysis method. Methods: Vestibular tissues removed from 40 women with severe vestibulitis were immunostained for mast cell count and degranulation by C-kit and mast cell tryptase, respectively. Vestibular nerve cells total area was evaluated after S-100 stain. Controls were 7 women aged 18–48. The images were converted to a digital signal, and analyzed using Image Proplus V4 software. Results: We found a significant increase in inflammatory infiltrate, number of mast cells and degranulated mast cells in vestibulitis compared to normal controls. The inflammatory cells were localized around the superficial minor vestibular glands. The total nerve fiber area was ten times higher in vestibulitis patients than in controls. A significant positive correlation was found between the total nerve fiber area and the number of mast cells in the vestibulitis group of patients. Conclusion: We documented two diagnostic histopathological criteria for vestibulitis: (1) the presence of eight or more mast cells per 10 × 10 microscopic field, and (2) the total calculated area of the nerve fibers is ten times higher than expected. These findings re-establish the inflammatory nature of the vestibulitis. It is speculated that the trigger for the local outburst of nerve fibers could be related to the activation of the mast cells by a topical agent.
Dopamine Transporter as a Marker of Neuroprotection in Methamphetamine-Lesioned Mice Treated Acutely with Estradiol
Authors: D’Astous Myreille , Gajjar Tapasdip M. , Dluzen Dean E. , Di Paolo Thérèse
Published: July 2004

Our laboratories have shown the positive effect of estradiol on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and methamphetamine (MA)-induced striatal dopamine (DA) depletion. Most studies on E neuroprotection use chronic administration of the steroid to evaluate its beneficial effect. In the present report, we investigated the neuroprotective potential of 17β-estradiol-3-benzoate (E) under acute conditions when administered 24, 12 or 0.5 h before MA. The effects of E on striatal DA and dihydroxyphenylacetic acid (DOPAC) contents, and DA transporter (DAT) protein and mRNA were measured using high-performance liquid chromatography, autoradiography and in situ hybridization, respectively. We observed neuroprotection with an acute dose of E, and also that protection presents a different time course for each dopaminergic marker. DAT mRNA responded more quickly to E than its protein (at 0.5 h vs. 24 h). Also, E treatment 12 h prior to MA resulted in ‘normal’ (equal to control) DA content, while DAT protein was still decreased as compared to control values. These different responses for each marker may represent different mechanisms of action of E (genomic versus nongenomic). Since most experimental studies use DA content as the sole indicator of nigrostriatal toxicity and examine a single time point following chronic E administration, the present results demonstrate the importance of evaluating differences in temporally dependent responses of DA, DAT protein and mRNA, to achieve a more comprehensive indication of the nigrostriatal state and the means by which E can function as a neuroprotectant in this system.
Integrilin Dose Optimization Using Cone Plate Analyzer – What Have We Learned Thus Far
Authors: Kaluski Edo , Kaluski Edo , Malleihov Ilia , Malleihov Ilia , Savion Naftali , Savion Naftali , Varon David , Varon David , Winkler Robert , Winkler Robert , Vered Zvi , Vered Zvi , Cotter Gad , Cotter Gad
Published: July 2004

Objectives: To assess platelet inhibition by cone and plate analyzer (CPA) in patients with acute coronary syndromes (ACS) receiving eptifibatide (Integrilin). Background: With the current use of glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors during ACS and percutaneous coronary interventions (PCI), the need to measure platelet activity and optimize dosing became apparent. CPA is a novel technique to assess platelet activity in high shear stress conditions, mimicking arterial flow. Method: 40 consecutive patients with ACS received eptifibatide [2 intravenous boluses (180 µg/kg each) spaced 10 min apart, and subsequently a maintenance drip (2 µg/kg/min)]. All patients received aspirin, clopidogrel and unfractionated heparin or enoxaparin in conventional doses. Blood was obtained at baseline, 30 min and 3 h, after eptifibatide initiation, and was sent out for CPA core lab, blinded to patient therapy, characteristics, and sampling time. Results: At 30 min and 3 h only 45 and 60% of patients, respectively, reached GP-IIb/IIIa blockade of ≧95%. 25 and 15%, respectively, had <85% GP-IIb/IIIa blockade. No demographic, clinical, or laboratory predictors for eptifibatide resistance could be identified. Conclusion: <85% GP-IIb/IIIa blockade occurs in a high proportion of patients with ACS treated with eptifibatide. The clinical significance of this phenomenon, and the optimal way to assess and treat it warrant additional research. It is essential, however, to measure platelet activity or GP-IIb/IIIa occupancy in response to therapy, since no demographic, clinical, and laboratory predictors of eptifibatide refractoriness can be identified at this time at the bedside.
Role of JAK/STAT Pathway in IL-6-Induced Activation of Vascular Smooth Muscle Cells
Authors: Watanabe Susumu , Mu Wei , Kahn Andrew , Jing Naijie , Li Jin H. , Lan Hui Y. , Nakagawa Takahiko , Ohashi Ryuji , Johnson Richard J.
Published: July 2004

Background/Aims: IL-6, an inducer of the acute-phase response, is linked with the development of vascular disease and atherosclerosis. One mechanism likely involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6 can induce VSMC proliferation and the release of monocyte chemoattractant protein-1 (MCP-1). We hypothesized that this stimulation occurs via the JAK (janus-activated kinase)/STAT (signal and transducers and activators of transcription) signaling pathway. Methods: Rat VSMC were stimulated with IL-6 in the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 (by Western), MCP-1 (by ELISA) and DNA synthesis (by 3H-thymidine incorporation) was determined. Results: IL-6 rapidly induced phosphorylation of STAT 3 in a dose- and time-dependent manner with a peak expression at 30 min. IL-6 also stimulated MCP-1 protein production and DNA synthesis dose dependently. 50 µM of AG490, a specific JAK 2 inhibitor, partially inhibited STAT 3 activation and MCP-1 production, with near complete inhibition of DNA synthesis. Conclusion: The JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA synthesis in rat VSMC. These studies implicate a role of the JAK/STAT pathway in the development of vascular disease and atherosclerosis.
Evaluation of GERD Symptoms during Therapy. Part I
Authors: Bardhan K.D. , Stanghellini V. , Armstrong D. , Berghöfer P. , Gatz G. , Mönnikes H.
Published: July 2004

Background/Aims: The changes in gastroesophageal reflux disease (GERD)-related symptoms on treatment are variously described, but currently available questionnaires have shortcomings. We therefore developed a self-assessment reflux questionnaire (ReQuestTM). This article describes the process of development and testing. Materials and Methods: For the first version of ReQuestTM the symptom spectrum of GERD and the various symptom descriptions were investigated. The 67 identified symptom descriptions were condensed empirically into 6 dimensions, to which a 7th dimension on general well-being was added. The symptom burden of the dimensions was measured by frequency and/or intensity. ReQuestTM was translated into different languages and then tested in focus groups. The initial validation was based on data from a clinical trial of patients with erosive GERD, treated with pantoprazole 20 or 40 mg daily for 28 days. Factor analyses determined the contribution of each symptom to the different dimensions. Additionally, correlation analyses between the identified factors and the dimensions were performed. Results: On the basis of factor analyses, ReQuestTM was reduced to a 60-item scale. The factors generated correlated strongly with the dimensions and confirmed the empirical process mathematically. Conclusion: ReQuestTM provides a valuable, self-assessment tool for evaluating the daily treatment response in patients with erosive GERD.
Evaluation of GERD Symptoms during Therapy. Part II
Authors: Mönnikes H. , Bardhan K.D. , Stanghellini V. , Berghöfer P. , Bethke T.D. , Armstrong D.
Published: July 2004

Background/Aims: Evaluation of the response of gastroesophageal reflux disease (GERD) symptoms to treatment would be facilitated by a brief, valid, reliable and responsive, self-assessed GERD-sensitive scale. We therefore developed the Reflux Questionnaire (ReQuest™). This publication describes the psychometric evaluation and validation of ReQuest™. Methods: This second phase of development was based on data from a clinical trial of patients with erosive GERD who received pantoprazole 20 or 40 mg daily for 28 days and completed weekly the long, and daily the short version of ReQuest™. The psychometric analyses of ReQuest™ included internal consistency, test-retest reliability and responsiveness. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale (GSRS) and the Psychological General Well-Being (PGWB) scale. Results: Validation of ReQuest™ indicated very high internal consistency (Cronbach’s α = 0.90) and test-retest reliability (intraclass correlation coefficient 0.94 (long-long) and 0.86 (short-short)). This was also the case for the two subscales ReQuest™-GI and ReQuest™-WSO with Cronbach’s α coefficients of 0.84 and 0.81. Responsiveness was high with a responsiveness index of >0.8 at day 28. Construct validity was good. Conclusion: ReQuest™ is a highly reliable, valid and responsive self-assessment tool for evaluating treatment response in patients with erosive GERD, and can be applied daily.
Adult Height Distribution in Subjects Born Small for Gestational Age
Authors: Jaquet D. , Collin D. , Lévy-Marchal C. , Czernichow P.
Published: July 2004

The aim of the study was to investigate the post-natal growth of subjects born small for gestational age (SGA) by describing adult height distribution and by testing the effects of parental, neonatal and pregnancy-related parameters on the risk for adult short stature. The study population was made of adults selected on birth data from a maternity registry and born either small (SGA, n = 734, birth weight <10th percentile) or appropriate for gestational age (AGA, n = 886, 25th < birth weight <75th percentile) in whom anthropometric parameters were measured at 22 years of age. The SGA group demonstrated significantly reduced body size in comparison to the AGA group with a mean loss of 0.7 standard deviation (SD) in adult height. The frequency of adult short stature (<–2 SD) was 10.3% in the SGA group vs. 2.4% in the AGA group (p = 0.0001), adult height <–2.5 SD was observed in only 3.7% of the SGA group. Maternal (OR = 0.31 (0.16–0.62), p = 0.0001) and paternal (OR = 0.45 (0.31–0.67), p = 0.0001) heights and subjects birth length (OR = 0.78 (0.62–0.99), p = 0.04) significantly influenced the risk of adult short stature. In summary, post-natal growth defect remains moderate in the majority of subjects born SGA and <4% only will end up with severe short stature requiring GH therapy according to most current recommendations. The role of parental height and birth length suggests that adult short stature in SGA subjects results at least in some cases from a familial and likely genetic growth disorder with antenatal onset.
Dose-Response Effects of Estrogen and Tamoxifen upon Methamphetamine-Induced Behavioral Responses and Neurotoxicity of the Nigrostriatal Dopaminergic System in Female Mice
Authors: Mickley Katherine R. , Dluzen Dean E.
Published: July 2004

In the present experiment we evaluated the dose-response effects of estrogen (estradiol benzoate; EB) and tamoxifen (TMX) in modulating the acute behavioral and chronic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA) system in ovariectomized (OVX) mice. EB over a range of doses from 1–40 µg resulted in a neuroprotective effect upon the NSDA system as defined by both a preservation of striatal dopamine (DA) concentrations and a decrease in DOPAC/DA ratios. Interestingly, the neuroprotective effect of the 1-µg EB dose occurred in the absence of any statistically significant effect upon the bioassay parameter of uterine weight. With the exception of an increase in stereotypy time as a response to the 40-µg dose, EB at any of the doses tested failed to alter any acute behavioral responses evoked by MA. In response to TMX, a statistically significant NSDA neuroprotectant response was obtained for DOPAC/DA ratios, but not DA concentrations, to doses ranging from 12.5 to 500 µg. No statistically significant effects upon uterine weights were obtained for any of the doses of TMX tested. Behaviorally, TMX at 500 µg had the effect of increasing the amount of time spent in the center of the cage. Taken together these results demonstrate: (1) EB and TMX at relatively low doses can exert a neuroprotective effect against MA; (2) these neuroprotective effects of EB and TMX can occur in the absence of an effect upon the bioassay parameter – uterine weights; (3) the parameter of DOPAC/DA ratio may indicate a more sensitive index of NSDA neuroprotection, and (4) modulatory effects of EB and TMX upon acute behavioral responses of the NSDA system to MA can be distinguished from their neuroprotective actions.
Short Stature with Normal Growth Hormone Stimulation Testing: Lack of Evidence for Partial Growth Hormone Deficiency or Insensitivity
Authors: Nwosu Benjamin U. , Coco Marilena , Jones Joy , Barnes Kevin M. , Yanovski Jack A. , Baron Jeffrey
Published: July 2004

Objectives: To test the hypothesis that children with short stature and peak stimulated GH (pGH) of 7–10 µg/l have partial GH deficiency and to test the hypothesis that short children with normal pGH but low IGF-I levels have partial GH deficiency or partial GH insensitivity. Design and Patients: Retrospective analysis of the clinical and biochemical profiles of 76 children who underwent an evaluation for short stature (height <5th percentile) that included two, sex steroid-primed GH stimulation tests. Results: Patients with pGH <7 µg/l (n = 14) differed significantly from those with pGH >7 µg/l (n = 62), having greater midparental height (MPH) SDS, a greater disparity between height SDS and MPH SDS, and lower IGF-I SDS. Patients with pGH of 7–10 µg/l (n = 12) did not have characteristics intermediate between those with pGH <7 µg/l and those with pGH ≧10 µg/l, but instead resembled those with pGH ≧10 µg/l. Patients with pGH ≧7 µg/l, but low IGF-I (<–2 SDS) (n = 5), did not show characteristics intermediate between those with pGH <7 µg/l and those with pGH ≧7 µg/l and normal IGF-I. Conclusions: These data do not support either the hypothesis that children with pGH of 7–10 µg/l have partial GH deficiency or the hypothesis that children with normal pGH but subnormal IGF-I levels have partial GH deficiency or insensitivity.
Induction Sirolimus and Delayed Graft Function after Deceased Donor Kidney Transplantation in the United States
Authors: Simon James F. , Swanson S. John , Agodoa Lawrence Y.C. , Cruess David F. , Bohen Erin M. , Abbott Kevin C.
Published: July 2004

Background/Aims: Previous studies have reported a link between the use of induction sirolimus (INDSRL) and delayed graft function (DGF) after kidney transplantation. However, none have had sufficient power to adjust for all factors known to be associated with DGF. Methods: We conducted a retrospective cohort study of US deceased donor kidney transplantation recipients in the United States Renal Data System (USRDS) from January 1, 2000 to May 31, 2001. Logistic regression analysis was used to model adjusted odds ratios (AOR) for the development of DGF, adjusted for other factors previously reported to be associated with DGF. Results: Among 8,319 patients meeting inclusion criteria, 361 patients received INDSRL, of whom 98 (27.1%) had DGF, compared to 22.5% among patients who did not receive INDSRL. In multivariate analysis, INDSRL was associated with an increased risk of DGF, with an adjusted odds ratio of 1.42 (95% CI: 1.07–1.90). Other factors associated with DGF were similar to those previously reported. INDSRL was not significantly associated with graft loss at 1 year in Cox regression. Conclusions: INDSRL was independently associated with DGF in US deceased donor kidney transplantation recipients, adjusted for all other factors previously shown to be associated with DGF.
Stroke in Young Patients: Etiopathogenesis and Risk Factors in Different Age Classes
Authors: Cerrato P. , Grasso M. , Imperiale D. , Priano L. , Baima C. , Giraudo M. , Rizzuto A. , Azzaro C. , Lentini A. , Bergamasco B.
Published: July 2004

The aim of our study was to evaluate the etiopathogenesis and the vascular risk factors in a consecutive series of patients with juvenile ischemic stroke. We enrolled 273 patients (158 males and 115 females), aged between 16 and 49 years, with ischemic cerebrovascular events (ICVE), including transient ischemic attack (TIA) or stroke, referred to our neurology ward between January 1994 and December 2001. Our protocol included medical history, cardiac and neurological examinations, assessment of risk factors and laboratory tests. The instrumental assessment included transthoracic echocardiography (70%), transesophageal echocardiography (60%), conventional angiography (30%), MR angiography (30%), cranial computed tomography (100%) and brain MRI (48%). The ICVE was a stroke in 60% of the cases, a reversible ischemic neurologic deficit in 14% and a TIA in 26%. Thirty-three patients were aged less than 29, 59 were aged between 30 and 39 and 181 between 40 and 49. The percentage of females was higher in patients aged less than 29 while males were prevalent in the 4th and 5th decade. The patients were subtyped according to etiopathogenesis. A large-vessel disease (LVD) was diagnosed in 43 patients (16% of the cases), mostly in patients aged more than 40 years (36 cases). A small-vessel disease (SVD) was found in 48 patients (17% of cases), mostly in patients aged more than 40 years (41 cases). A cardioembolic stroke (CE) was diagnosed in 66 patients (24% of the cases). In the majority of the cases, the cardiopathies were at low-uncertain embolic risk: patent foramen ovale (PFO, 39 cases, in 8 patients associated with an atrial septal aneurism), atrial septal aneurism (12 cases) and myxomatous mitral valve prolapse (3 cases). Stroke due to other causes was found in 51 patients (19% of the cases). Arterial dissection, more frequently involving the carotid region, was diagnosed in 35 patients. Coagulopathies and vasculitis were found in 5 and 6 patients, respectively. Stroke of unknown etiology was found in 65 patients (24% of the cases) with a homogeneous distribution among decades. Our study highlights the role of minor cardiac sources of embolism and arterial dissection in the etiology of juvenile ischemic stroke, whereas coagulopathies and vasculitis are less relevant. LVD and SVD were relevant only in the 5th decade.
Vascular Endothelial Growth Factor and Matrix Metalloproteinase 9 Expression in Human Carotid Atherosclerotic Plaques: Relationship with Plaque Destabilization via Neovascularization
Authors: Papalambros Efstathios , Sigala Fragiska , Georgopoulos Sotiris , Panou Nikol , Kavatzas Nikolaos , Agapitos Manolis , Bastounis Elias
Published: July 2004

Background: The aim of this study was to evaluate the potential impact of vascular endothelial growth factor (VEGF) on carotid plaque destabilization in association with matrix metalloproteinase 9 (MMP-9) production. Methods: Expression of VEGF and MMP-9 were determined immunohistochemically in 53 human endarterectomized atherosclerotic carotid plaques. The relationship to carotid plaque characteristics, clinical data and histological morphology was investigated. Results: VEGF and MMP-9 had parallel overexpression in the inflammatory cells, especially in the neovascularized plaque lesions and around the cholesterol crystals. Strong expression of VEGF was evident in symptomatic patients (p < 0.057), in high-degree stenosis (p = 0.005), and in patients with ischemic infarct in brain scan (p = 0.021). No relation was proved between molecule expression and plaque ultrasonic characteristics. Conclusions: An intense expression of VEGF and MMP-9 in carotid plaques is related to plaque instability, high degree of stenosis and presence of symptomatic carotid occlusive disease.
Link between Linear Hyperintensity Objects in Cerebral White Matter and Hypertensive Intracerebral Hemorrhage
Authors: Hiroki Masahiko , Miyashita Kotaro , Oe Hiroshi , Takaya Shigetoshi , Hirai Shunsaku , Fukuyama Hidenao
Published: July 2004

Background: We retrospectively studied the relationship between linear hyperintensity objects (LHOs) on T2-weighted magnetic resonance images (MRI) in the cerebral white matter and the occurrence of hypertensive intracerebral hemorrhage (HIH). Methods: Forty-nine hypertensive patients with a fixed imaging condition MRI were classified into three groups: HIH (n = 17), ischemic stroke due to hypertensive vasculopathy (n = 19), and hypertension only (n = 13). After assessing clinical and radiological background information among these groups and the reliability of LHO measurements, polynomial logistic regression analysis was used to identify the factors relating to HIH. Results: HIH had a significantly higher LHO number (p = 0.002) and larger diameter (p = 0.007). The LHO number showed an excellent interrater (ĸ = 0.91, 95% CI = 0.87–0.94, SEM = 6.2%) and intrarater reliability (ĸ = 0.95, 95% CI= 0.92–0.97, SEM = 4.8%), and was the most significant independent indicator of HIH (OR = 1.29, 95% CI = 1.05–1.60, p = 0.017). The number of microbleeds was an additional indicator (OR = 3.73, 95% CI = 1.10–12.65, p = 0.034). Conclusions: LHOs are closely linked to HIH. A prospective, longitudinal study is needed to clarify whether LHOs can predict HIH.