bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Second-Trimester Free β-hCG as an Isolated Finding and Pregnancy Outcomes
Authors: Brajenović-Milić Bojana , Tišlarić Dubravka , Žuvić-Butorac Marta , Bačić Josip , Petrović Oleg , Ristić Smiljana , Mimica Marko , Kapović Miljenko
Published: November 2004

Objective: To investigate the relationship between unexplained elevated second-trimester free β-human chorionic gonadotropin (β-hCG) levels and pregnancy complications as well as adverse pregnancy outcomes. Methods: The study cohort comprised 2,110 non-smoking women with chromosomal and structurally normal fetuses at low-risk for both Down’s syndrome (risk <1:250) and neural tube defects (maternal serum α-fetoprotein <2.0 MoM). A free β-hCG value of ≧2.0 MoM was used to define the populations with elevated levels of free β-hCG. Descriptive statistics, χ2 test, Fisher’s exact test, and logistic regression analysis were used for statistical analysis, and p < 0.05 was considered statistically significant. Results: The mean maternal age of the study group was significantly lower than in controls (27.9 ± 4.3 and 30.6 ± 5.1 years, respectively, p < 0.05), while the proportion of primigravidas was significantly higher compared to that of controls (p < 0.05). After adjustment of the 2 groups according to maternal age and parity, we observed an increased incidence of preeclampsia among women with elevated free β-hCG levels in relation to controls (p < 0.05). However, a logistic regression analysis demonstrated that the free β-hCG level was not a predictor of the occurrence of preeclampsia. No significant relationship was found with the incidence of gestational diabetes, oligohydramnios, polyhydramnios, pregnancy-related hypertension, intrauterine growth retardation, preterm delivery, spontaneous abortion and stillbirths (p > 0.05).
Prenatal Diagnosis of Trisomy 2 Mosaicism: A Case Report
Authors: Sifakis Stavros , Velissariou Voula , Papadopoulou Eleftheria , Petersen Michael B. , Koumantakis Eugenios
Published: November 2004

We report a case of trisomy 2 mosaicism detected upon amniocentesis in a woman with advanced maternal age. A mos 47,XY,+2(4)/46,XY(21) karyotype was revealed using standard GTG banding. There were no pathological sonographic findings and the fetal size was normal for gestational age at 16th week. The use of serial high-resolution ultrasound examination of the fetus to detect major abnormalities was offered as an option to the parents who, however, decided for termination of the pregnancy. Fetal autopsy did not reveal any malformations. Trisomy 2 mosaicism is associated with variable phenotypic abnormalities without a specific pattern, intrauterine growth restriction, fetal demise or stillbirth. The rarity of trisomy-2 mosaicism in prenatal diagnosis, as well as the increased risk of an abnormal outcome makes the diagnostic approach and genetic counseling difficult.
Prenatal Diagnosis of Common Aneuploidies Using Multiplex Quantitative Fluorescent Polymerase Chain Reaction
Authors: El Mouatassim S. , Becker M. , Kuzio S. , Ronsin C. , Gil S. , Nouchy M. , Druard L. , Forestier F.
Published: November 2004

Objective: Prenatal diagnosis of foetal trisomies is usually performed by cytogenetic analysis. This requires lengthy laboratory procedures and it is expensive. Here, we report a retrospective study of quantitative fluorescent polymerase chain reaction (QF-PCR) for prenatal detection of trisomies 13, 18 and 21. Methods: QF-PCR was performed on a total of 447 amniotic fluids blindly analysed without any knowledge of the cytogenetic results and 43 samples with known karyotype. All samples were tested with at least 4 small tandem repeat markers specific for each chromosome 13, 18 or 21. Results: QF-PCR results on amniotic fluid were consistent with conventional cytogenetic data. QF-PCR detected 5 cases of trisomy 21, 2 cases of trisomy 18, 1 case of trisomy 13 and 1 case with Klinefelter’s syndrome. Conclusions: QF-PCR has proved to be very useful in clinical settings, since it allows the detection of major numerical disorders in a few hours after sampling and thus reduces parental anxiety.
Sonographic Findings of Fetuses with an Empty Renal Fossa and Normal Amniotic Fluid Volume
Authors: Yuksel Atıl , Batukan Cem
Published: November 2004

Objective: To review the antenatal sonographic findings and postnatal follow-up of fetuses with empty renal fossa (ERF) and normal amniotic fluid volume. Methods: Sonographic examinations of 13,705 fetuses were retrospectively analyzed and all fetuses with at least one ERF and normal antenatal amniotic fluid volume were included in this study. Results: Forty cases with antenatal ERF were diagnosed. Prenatal diagnosis consisted of pelvic kidney (n = 24), unilateral renal agenesis (n = 13), horseshoe kidney (n = 2) and crossed fused renal ectopia (n = 1). The prevalence of ERF in the low-risk population approximated 3.2‰. There was no serious renal complication during a mean follow-up period of 30 months except one case of crossed fused renal ectopia requiring hemodialysis. Conclusion: The underlying cause of ERF in the majority of cases with normal amniotic fluid volume is renal ectopia. Prenatal ultrasonography seems to be highly reliable in diagnosing these anomalies. Prognosis is favorable in the absence of additional extraurinary malformations.
Inhibition of Rat Intestinal Cl– Secretion by 4,5-Dimethylresorcinol
Authors: Ogata Norio , Shibata Takashi
Published: November 2004

Wood creosote, a mixture of phenolic compounds, inhibits enterotoxin-induced intestinal fluid secretion, suggesting that one of its constituents suppresses transepithelial Cl– secretion from the intestinal mucosa. To identify an active constituent in wood creosote that inhibits intestinal Cl– secretion through Cl– channels, we first examined its effect on Cl– secretion using a cultured cell line transfected with complementary DNA encoding a Cl–channel and a Cl–-sensitive fluorescent dye. We next assayed chromatographic fractions of wood creosote for the inhibitory activity on Cl– secretion using a Ussing chamber. We found that 4,5-dimethylresorcinol, identified by gas chromatography-mass spectrometry, inhibited intestinal Cl– secretion dose-dependently when added to a serosal, but not mucosal, surface of rat jejunum, a half-inhibitory concentration being 3.8 µg/ml (28 µmol/l). It was strongly suggested that this effect was due to inhibition of Cl– channels.
Clinical Correlation between the Consumption of Nicotine and Cotinine Concentrations in Urine and Serum by Competitive Enzyme-Linked Immunosorbent Assay
Authors: Ziegler Ulrich E. , Kauczok Jens , Dietz Ulrich Andreas , Reith H.Bernd , Schmidt Karsten
Published: November 2004

Different negative effects of smoking are known (e.g. postoperative complications), which lead, especially in plastic surgery, to unsatisfactory results. The aim of this study was to examine the appropriateness of a cotinine enzyme-linked immunosorbent assay (ELISA) for routine usage in operative disciplines. By correlation of smoking habits and concentration of cotinine in serum and urine, we tried to ascertain reference values for smokers, passive smokers and non-smokers. The reliability and sensitivity of the cotinine ELISA concerning nicotine exposure need to be proven. 165 (108 men, 57 women) test persons were examined by detecting cotinine in serum and urine by ELISA. The study shows a very good sensitivity, precision and reproducibility of the cotinine ELISA according to the laboratory criteria. The test shows significance of a good differentiation between smokers, passive smokers and non-smokers in urine. In serum, cotinines are excellent to differentiate between smokers and non-smokers/passive smokers. Urine and serum tests demonstrate valid and comparable results.
Effects of Two Fluoridation Measures on Erosion Progression in Human Enamel and Dentine in situ
Authors: Ganss C. , Klimek J. , Brune V. , Schürmann A.
Published: November 2004

The aim of the present study was to evaluate the effects of fluoride on erosive mineral loss in human enamel and dentine using a cyclic de- and remineralisation model in situ. The study was a three-treatment (5 days each) crossover design involving 4 (enamel) or 6 (dentine) healthy volunteers. Samples were recessed in palatal mouth appliances and worn day and night except during meals and were demineralised extraorally with 0.05 M citric acid (pH 2.3) for 6 × 5 min daily. Fluoridation was performed with toothpaste (SnF2/Olaflur; 0.14% F–) for 3 × 5 min daily (toothpaste fluoridation) or with toothpaste in combination with a mouthrinse (SnF2/Olaflur; 0.025% F–) for 3 × 5 min daily and with a gel (NaF/Olaflur, 1.25% F–) on days 1 and 3 instead of the toothpaste (intensive fluoridation). In the control group no fluoridation was performed. Mineral loss (µm) was determined with the use of longitudinal microradiography. In enamel, mineral loss was 40.7 ± 15.1 µm in the control group, 18.3 ± 12.4 µm after toothpaste fluoridation and 5.0 ± 12.2 µm after intensive fluoridation. The respective values for dentine were 49.0 ± 15.4, 35.0 ± 15.5 and 19.8 ± 12.0 µm. All differences were statistically significant (p ≤ 0.001). The results indicate that intensive fluoridation is effective in preventing enamel and dentine from mineral loss even under severely erosive conditions.
Urinary Excretion of Vascular Endothelial Growth Factor Is Increased in Children with Reflux Nephropathy
Authors: Konda Ryuichiro , Sato Hiroshi , Sakai Kiyohide , Abe Yuko , Fujioka Tomoaki
Published: November 2004

Background: We determined the urinary levels of vascular endothelial growth factor (VEGF) in patients with reflux nephropathy to elucidate its clinical significance as a predictor of the development of renal damage. Patients and Methods: Seventy-two patients (47 boys and 25 girls) aged 10–18 years with reflux nephropathy were studied. Vesicoureteral reflux was resolved surgically in all cases at least 2 years before enrollment. Urinary VEGF, α1-microglobulin and albumin levels were determined using morning spot urine samples. Plasma VEGF, serum creatinine and β2-microglobulin levels were measured simultaneously. The severity of renal scarring and right and left kidney function were assessed by 99mTc dimercaptosuccinic acid renal scan. Results: No significant correlation was found between the plasma and urinary VEGF levels. Urinary VEGF increased significantly with the increase in severity of renal scarring (p < 0.0001). Urinary VEGF levels correlated significantly with serum β2-microglobulin (p < 0.002) and urinary α1-microglobulin (p < 0.03). No significant correlation of urinary VEGF levels with serum creatinine and urinary albumin levels was found. Nearly 60% of the patients with elevated urinary VEGF had normal levels of serum β2-microglobulin and/or urinary α1-miocroglobulin. Conclusions: Urinary VEGF level appears to reflect its production in the kidney. Since urinary VEGF shows a propensity to elevate before the increase in serum β2-microglobulin and/or urinary α1-microglobulin, urinary VEGF may serve as an early indicator of the development of reflux nephropathy.
Could Plasma Cystatin C Be Useful as a Marker of Hemodialysis Low Molecular Weight Proteins Removal?
Authors: Campo Andrea , Lanfranco Giacomo , Gramaglia Luciana , Goia Franco , Cottino Roberto , Giusto Viglino
Published: November 2004

Background: Plasma cystatin (pCyst) is a well-assessed tool for measuring renal function, and it could also play a part in hemodialysis adequacy. Methods: pCyst and other uremic toxins (urea, creatinine, parathyroid hormone, prolactin) were assessed before and after a dialysis session in 18 hemodialysis patients: 7 on bicarbonate hemodialysis (BHD) and 11 on mixed convective dialysis (MCD; 6 standard hemodiafiltration and 5 acetate-free biofiltration). Plasma levels and reduction ratios (RR) were then compared between the BHD and MCD groups. Results: The mean pre-dialysis pCyst level is nearly the same in both groups (5.3 ± 0.8 vs. 5.7 ± 1 mg/l, p = ns), although a substantial decrease occurs after MCD only (mean 2.4 ± 1 vs. 6.2 ± 2.2 mg/l after BHD, p = 0.002). The mean pCyst RR (PCRR) of 55.5% after MCD is poorly related to prolactin and urea RR, fairly comparable to parathyroid hormone RR and very close to creatinine RR (58.4%). Conclusions: Only MCD removes pCyst, but the amount of removal is different for other low molecular weight proteins (prolactin and parathyroid hormone) and similar for creatinine, a classic ‘little molecule’. In view of the discrepancy of these findings, the use of pCyst in hemodialysis still seems premature and needs further studies.
Age-Dependent Telomere Attrition as a Potential Indicator of Racial Differences in Renal Growth Patterns
Authors: Tchakmakjian L. , Gardner J.P. , Wilson P.D. , Kimura M. , Skurnick J. , Zielke H.R. , Aviv A.
Published: November 2004

Background: Racial differences in the predilection to salt sensitivity may arise from different renal growth patterns. To test this idea, we monitored age-dependent telomere attrition rate, reflecting largely the replicative history of somatic cells, in the outer renal cortex and the inner renal medulla of African Americans and Caucasians. Methods: Telomere length, determined by the mean length of the terminal restriction fragments (TRF), was measured in specimens from 58 African-American and 63 Caucasian males, ages 1 day to 71 years. Results: In the outer renal cortex, TRF length attrition rate was significantly slower in African Americans (–0.021 ± 0.0064 kb/year) than in Caucasians (–0.060 ± 0.0094 kb/year) (p = 0.0007). In both ethnic groups the TRF length attrition rate was slower in the inner medulla than in the outer renal cortex, but without significant racial differences. Conclusions: The proximal tubule is the most abundant nephron structure in the outer renal cortex. Less proliferative growth of proximal tubular cells in kidneys from African Americans may be one factor explaining the slower age-dependent telomere attrition rate in the outer renal cortex of African Americans than in Caucasians.
Inhibitory Effects of Ligustrazine, a Modulator of Thromboxane-Prostacycline-Nitric Oxide Balance, on Renal Injury in Rats with Passive Heyman Nephritis
Authors: Wang Yingwei , Tong Jianxia , Tang Renxian , Dong Hongyan , Xu Jinghua
Published: November 2004

Aims: To explore the effects of ligustrazine on proteinuria, urinary TxB2 (metabolism of thromboxane A2, TxA2) and 6-keto-PGF1α (metabolism of prostacyclines I2, PG I2), glomerular inducible nitric oxide(NO) synthase (iNOS) mRNA, urinary NO–3/NO–2 (decomposing products of NO) and pathological changes in rats with passive Heymann nephritis (PHN). Methods: A rat PHN model was induced by intravenous injection of rabbit anti-rat renal tubular antigen (Tub-Ag) antiserum, and ligustrazine was given intraperitoneally into PHN rats every 2 days for 1–5 weeks. Then, proteinuria, urinary TxB2 and 6-keto-PGF1α, glomerular iNOS mRNA, and urinary NO–3/NO–2 were measured by sulfosalicylic acid, radioimmunoassay (RIA), Northern blot and nitric acid reductase methods, respectively. Moreover, the damage to the renal tissue of the rats was observed under light and electron microscopy and immunofluorescence (IF). Results: The urinary TxB2 in PHN rats was significantly higher than that in control rats, but the PHN rats treated with ligustrazine had significantly less proteinuria, urinary TxB2 and tissue lesions, and more urinary 6-keto-PGF1α, glomerular iNOS mRNA and urinary NO–2/NO–3 than the PHN rats without the administration of ligustrazine. Conclusion: These data indicate that ligustrazine has inhibitory roles on the glomerular injury of PHN rats, which may associate with modulating the balance of TxA2-PGI2 and elevating synthesis of NO to a certain extent.
Efficacy of Treatment with Calcipotriol/Betamethasone Dipropionate Followed by Calcipotriol Alone Compared with Tacalcitol for the Treatment of Psoriasis vulgaris: A Randomised, Double-Blind Trial
Authors: Ortonne J.-P. , Kaufmann R. , Lecha M. , Goodfield M.
Published: November 2004

Background: A two-compound product containing calcipotriol 50 µg/g and betamethasone dipropionate 0.5 mg/g (Daivobet®, Dovobet®) has been demonstrated to be an effective, once daily, treatment for psoriasis vulgaris. Objective: To compare the efficacy and safety of treatment with the two-compound product for 4 weeks followed by calcipotriol for 4 weeks, with that of tacalcitol for 8 weeks in patients with stable psoriasis vulgaris. Methods: 501 patients were randomised to double-blind treatment with the two-compound product followed by calcipotriol 50 µg/g once daily, or to tacalcitol 4 µg/g once daily. Results: Treatment with the two-compound product/calcipotriol was significantly more effective than tacalcitol in terms of mean percentage PASI reduction (65.0 vs. 33.3% at week 4 and 59.0 vs. 38.4% at week 8; p < 0.001 for both). Conclusion: A treatment regimen comprising calcipotriol/betamethasone ointment (Daivobet) for 4 weeks followed by calcipotriol for 4 weeks is superior to tacalcitol ointment for 8 weeks in patients with psoriasis vulgaris.
Successful Treatment of Recalcitrant Chronic Actinic Dermatitis with Tacrolimus
Authors: Schuster Christian , Zepter Karoline , Kempf Werner , Dummer Reinhard
Published: November 2004

Therapeutically, chronic actinic dermatitis is a problematic condition. Frequently applied sunscreen usually fails to mitigate the clinical symptoms, and steroids – while efficient – exert many undesired side-effects with prolonged usage. We present a case of chronic actinic dermatitis responding well to topically applied tacrolimus (Protopic®) in combination with chemical and physical UV protection.
Clinicopathological and Biological Characteristics of Esophageal Squamous Cell Carcinoma Associated with Head and Neck Cancer
Authors: Matsumoto Masataka , Natsugoe Shoji , Okumura Hiroshi , Ishigami Sumiya , Takatori Hiroyuki , Nakashima Hiroshi , Takao Sonshin , Aikou Takashi
Published: November 2004

Objective: Esophageal cancer has been reported to be frequently associated with cancer of the head and neck. The iodine dye method is reportedly useful to detect early esophageal cancer. The aim of this study was to clarify clinicopathological and biological characteristics of esophageal squamous cell carcinoma associated with head and neck cancer (HN group). Methods: Thirty-seven patients of the HN group who underwent esophagectomy were examined clinicopathologically compared to 42 patients with esophageal cancer alone (SE group). All resected specimens were histologically studied after iodine dye staining, and p53 and cyclin D1 (CD1) expression were immunohistochemically examined in esophageal cancer. Results: The HN group had more multiple iodine-unstained lesions and multiple primary cancers within the esophagus compared with the SE group (p = 0.0027, p = 0.067, respectively). There was no significant difference in smoking, drinking, family history and the other clinicopathological factors between the HN and SE groups. Coexpression of p53 and CD1 was found to be significant in the HN group (p = 0.03). Conclusions: The coexistence of multiple iodine-unstained lesions, multiple cancers in the esophagus and overexpression of p53 and CD1 is suggested as a risk factor for the HN group.
Capecitabine with Weekly Paclitaxel for Advanced Breast Cancer: A Phase I Dose-Finding Trial
Authors: Uhlmann Catrina , Ballabeni Pierluigi , Rijken Natalie , Brauchli Peter , Mingrone Walter , Rauch Daniel , Pestalozzi Bernhard C. , Rochlitz Christoph , Aebi Stefan
Published: November 2004

Objective: To determine the maximum tolerated dose (MTD), toxicity and activity of combined weekly paclitaxel and capecitabine in patients with metastatic breast cancer. Methods: Sixteen patients with metastatic breast cancer, of whom 15 were evaluable for toxicity and response, were enrolled in 7 Swiss centers. Paclitaxel 80 mg/m2 was given intravenously on days 1, 8 and 15. Capecitabine was administered orally on days 1 through 14 using five different dose levels. Both drugs were given in a 21-day schedule. Results: Capecitabine could be administered at doses commonly used for the drug as a single agent, i.e. 1,250 mg/m2 twice daily in combination with weekly paclitaxel. Hematological and other toxicities did not appear to be dose-limiting; however, significant skin and nail toxicities were observed. A response or stable disease was observed in 87% of patients [13/15; exact 95% confidence interval (CI) 60–98%], with 2 complete responses, 4 partial responses (overall response rate 40%, exact 95% CI 16–68%) and 7 patients with stable disease for at least 9 weeks. Conclusion: The phase I evaluation of capecitabine in combination with fixed-dose weekly paclitaxel did not allow the definition of an MTD of capecitabine based on the predefined criteria. Instead, the dose for the phase II evaluation was determined based on the occurrence of toxicity in later courses and on experience with other regimens containing capecitabine. Capecitabine (1,000 mg/m2 twice daily, days 1–14, every 3 weeks) with paclitaxel (80 mg/m2 weekly) is a promising combination for advanced breast cancer now being investigated in a phase II trial.
Thymidylate Synthase Expression in Normal Colonic Mucosa: A Predictive Marker of Toxicity in Colorectal Cancer Patients Receiving 5-Fluorouracil-Based Adjuvant Chemotherapy
Authors: Santini Daniele , Vincenzi Bruno , Perrone Giuseppe , Rabitti Carla , Borzomati Domenico , Caricato Marco , La Cesa Annalisa , Grilli Claudia , Verzì Alfio , Coppola Roberto , Tonini Giuseppe
Published: November 2004

Objectives: We retrospectively evaluated the relevance of thymidylate synthase (TS) expression in normal colonic mucosa as a predictive factor of toxicity in colorectal cancer patients receiving adjuvant fluorouracil (5-FU)-based chemotherapy. Methods: TS expression was immunohistochemically assessed on normal colonic mucosa from 50 patients with colorectal cancer Dukes’ stages B (15 patients) and C (35 patients) treated with 5-FU-based adjuvant chemotherapy. Results: The incidence of grade 2–3 diarrhea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (p < 0.0001). Moreover, patients with low TS expression in normal colonic mucosa developed weight loss and worsening of the performance status (according to ECOG score) more commonly than patients with high TS expression (p = 0.005 and p = 0.02, respectively). Furthermore, low TS expression in normal colonic mucosa significantly correlated with a higher rate of a delay of chemotherapy courses, dose reduction and treatment discontinuation. Conclusions: Immunohistochemical TS expression in normal colonic mucosa may represent an important predictive parameter for identifying a subset of patients with a high risk of developing severe 5-FU-related toxicities.
Prognostic Significance of Serine 392 Phosphorylation in Overexpressed p53 Protein in Human Esophageal Squamous Cell Carcinoma
Authors: Matsumoto Manabu , Furihata Mutsuo , Kurabayashi Atsushi , Sasaguri Siro , Araki Keijiro , Hayashi Hideki , Ohtsuki Yuji
Published: November 2004

Objective: Posttranscriptional modification involving phosphorylation of wild-type p53 has been considered to play a role in the stabilization of p53. Little is known, however, about the role of phosphorylation of mutant p53 overexpressed in tumors. The aim of this study is to determine the phosphorylation state of p53 in tumors and its contribution to tumor development. Methods: Using immunohistochemical techniques, we examined the phosphorylation of Ser392 and 15 sites in p53 overexpressed in 137 esophageal squamous cell carcinomas (ESCCs). The relationships between the phosphorylation and the expression of cell cycle regulators, Ki-67 labeling index (LI), apoptotic index, clinicopathological factors, and patient prognosis were tested statistically. Results: Of the 137 samples examined, staining for Ser392 phosphospecific p53 antibody was detected in 53 (38.7%) cases, corresponding to 58.9% of 90 p53-positive cases, whereas only 3 (2.2%) were positive for Ser15 phosphospecific p53 antibody. A significant correlation was identified between Ser392 phosphorylation and high levels of Ki-67 LI (p = 0.0271), lymphatic invasion (p = 0.0246), and poorer prognosis for patients with stage II and III advanced tumors (p = 0.0136). Using multivariate analysis, Ser392 phosphorylation was recognized as an independent prognostic factor (p = 0.0136). Conclusions: These findings suggest that p53 protein overexpressed in ESCCs is frequently phosphorylated at Ser392, and that the Ser392 phosphorylation might contribute to tumor progression of ESCCs.
How Do Dermatological Vehicles Influence the Horny Layer?
Authors: Gloor M.
Published: November 2004

Emulsifying agents in aqueous solution lead to dehydration of the horny layer of the epidermis and damage to the barrier. This is only partly true if emulsifying agents are constituents of emulsions. Water-in-oil (W/O) emulsions cause an improvement in the hydration of the horny layer and barrier function. In the case of an additional effect of wash solutions, a partial or complete abolition of the drying out and barrier-damaging effect of the wash solution results. Oil-in-water (O/W) emulsions without glycerol have no effect on the moisture of the horny layer or indeed increase it, but they lead to considerable damage to the barrier and irritation. In wash tests, they do not induce any protective effect. With micro-emulsions this is still more the case and, moreover, they can also lead to exsiccation. As a result of the addition of glycerol, the barrier-damaging effect can be abolished. Also in stress tests with wash solutions, the damage to the horny layer is reduced by glycerol-containing O/W emulsions. Whereas the penetration-promoting effect of O/W emulsions without glycerol is best, only W/O emulsions or glycerol-containing O/W emulsions are suitable for atopic dermatitis. A hydrating effect on the stratum corneum was also found in a propylene glycol ointment.
Transdermal Iontophoresis of Insulin
Authors: Pillai O. , Panchagnula R.
Published: November 2004

The delivery of large peptides through the skin poses a significant challenge, and various strategies are under active investigation for enhancing the transdermal permeation. For large peptides, it is difficult to achieve significant permeation using iontophoresis alone. Hence a combination of fatty acids with iontophoresis was hypothesized to result in higher enhancement than achieved with either of them alone. Saturated fatty acids and cis unsaturated fatty acids were studied in combination with iontophoresis using excised rat skin. The skin was pretreated for 2 h with an ethanolic (EtOH) solution of 5% w/v or v/v fatty acids, namely lauric acid (LA), oleic acid (OA), linoleic acid (LOA) and linolenic acid (LLA), followed by either passive or iontophoretic permeation (0.5 mA/cm2 for 6 h). Fourier transform infrared spectroscopy (FT-IR) was used to investigate the biophysical changes on treatment with fatty acid/EtOH or neat fatty acid, mainly focusing on the infrared region at 2,920, 1,710 and 1,720 cm–1. Unsaturated fatty acids showed higher enhancement than LA, and the enhancement increased with the number of double bonds. On the other hand, in the presence of iontophoresis, LA/EtOH showed the highest enhancement. Neat LOA did not show any significant difference (p > 0.05) compared to the LOA/EtOH combination. FT-IR studies revealed that fatty acids act by interacting with the skin lipids. All the fatty acids showed synergistic enhancement when combined with iontophoresis. The flux enhancement was highest with LA, which in the presence of iontophoresis showed 20 times enhancement of insulin flux in comparison to passive flux and 9 times enhancement as compared to iontophoresis alone. Flux enhancement of unsaturated fatty acids was in the following decreasing order LOA > OA > LLA.
Increase in Serum Ionized Calcium during Diffusive Dialysis Does Not Affect Left Ventricular Diastolic Function
Authors: Ie Eric H.Y. , Vletter Wim B. , ten Cate Folkert J. , Weimar Willem , Zietse Robert
Published: November 2004

An increase in serum Ca2+ during hemodialysis (HD) may lead to impaired left ventricular (LV) relaxation. Since LV diastolic function assessment in dialysis patients is hampered by preload dependence of Doppler measurements, we tested the effect of HD without ultrafiltration (UF) on these measurements. Transmitral E and A velocities, and mitral annulus e and a velocities were measured in 10 patients before and after 1 h of HD without UF. Dialysate Ca2+ was 1.75 mmol/l. Serum Ca2+ after 1 h (1.31 mmol/l; 1.28–1.46 mmol/l) was higher (p = 0.002) than before HD (1.24 mmol/l; 1.09–1.32 mmol/l). E/A (0.8; 0.4–2.8) and e/a (0.7; 0.4–1.3) after 1 h were not different than E/A (0.8; 0.6–5.1) and e/a (0.7; 0.4–1.8) before HD. The increase in serum Ca2+ does not lead to a change in Doppler parameters of LV diastolic function. Changes in these parameters after combined HD-UF are related to preload, not to serum Ca2+.
Pathogen Burden, Inflammation, Proliferation and Apoptosis in Human In-Stent Restenosis
Authors: Skowasch Dirk , Jabs Alexander , Andrié René , Dinkelbach Sabine , Schiele Thomas M. , Wernert Nicolas , Lüderitz Berndt , Bauriedel Gerhard
Published: November 2004

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions (977 ± 315 vs. 431 ± 148 cells/mm2; p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation.
Mannheim Intima-Media Thickness Consensus
Authors: Touboul P.-J. , Hennerici M.G. , Meairs S. , Adams H. , Amarenco P. , Desvarieux M. , Ebrahim S. , Fatar M. , Hernandez Hernandez R. , Kownator S. , Prati P. , Rundek T. , Taylor A. , Bornstein N. , Csiba L. , Vicaut E. , Woo K.S. , Zannad F.
Published: November 2004

Intima-media thickness (IMT) is increasingly used in clinical trials as a surrogate end point for determining the success of interventions that lower risk factors for atherosclerosis. The necessity for unified criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is addressed in this consensus statement. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness of ≧1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is recommended in all epidemiological and interventional trials dealing with vascular diseases to improve characterization of the population investigated. The consensus concludes that there is no need to ‘treat IMT values’ nor to monitor IMT values in individual patients apart from few exceptions. Although IMT has been suggested to represent an important risk marker, it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of studies incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.
Effects of Leptin on Intracellular Calcium Concentrations in Isolated Porcine Somatotropes
Authors: Glavaski-Joksimovic Aleksandra , Rowe Eric W. , Jeftinija Ksenija , Scanes Colin G. , Anderson Lloyd L. , Jeftinija Srdija
Published: November 2004

Leptin, the product of the obese gene, is a protein that is secreted primarily from adipocytes. Leptin can influence the function of the pituitary gland through its action on the hypothalamus, but it can also directly act at the level of the pituitary gland. The ability of leptin to induce an increase in intracellular Ca2+ concentration ([Ca2+]i) in somatotropes was examined in dispersed porcine pituitary cells using a calcium imaging system. Somatotropes were functionally identified by the application of human growth hormone releasing hormone. Leptin increased [Ca2+]i in porcine somatotropes in a dose-dependent manner. The application of 100 nM leptin for 3 min did not have a significant effect on [Ca2+]i, while a 3-min application of 1 µM leptin increased [Ca2+]i in about 50% of the somatotropes (p < 0.01). The application of a second leptin challenge (1 µM) evoked a response in only 18% of the observed somatotropes. The stimulatory effect of leptin was abolished in low calcium saline and blocked by nifedipine, an L-calcium channel blocker, suggesting an involvement of calcium channels. Pretreatment of the cultures with AG 490, a specific Janus kinase inhibitor, and with SB 203580, a mitogen-activated protein kinase (MAP kinase) inhibitor, abolished the increase in [Ca2+]i evoked by leptin. In the presence of Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, the magnitude of the increase in [Ca2+]i evoked by 1 µM leptin was not significantly changed. However, in the presence of L-NAME only 24% of the somatotropes responded to leptin, while in parallel control cultures 70% of the somatotropes responded to leptin. These results imply an involvement of Janus kinase/signal transducer and activator or transcription, MAP kinase and NOS-signaling pathways in the stimulatory effect of leptin on porcine somatotropes.
Vasopressin Stimulates Ventromedial Hypothalamic Neurons via Oxytocin Receptors in Oxytocin Gene Knockout Male and Female Mice
Authors: Ragnauth André K. , Goodwillie Andrew , Brewer Cornelia , Muglia Louis J. , Pfaff Donald W. , Kow Lee-Ming
Published: November 2004

A wealth of neuropharmacological data demonstrates that oxytocin (OT) actions in the mammalian forebrain support a wide variety of affiliative behaviors and repress aggressive behaviors. Based on that literature, it was expected that reproductive and affiliative behaviors would be vastly decreased and aggression markedly increased in OT gene knockout (OTKO) mice. The initial publications reporting the behaviors of these mice did not include such phenotypes. Here, we compared single-unit activities recorded from the ventromedial hypothalamus in tissue slices of male and female OTKO mice and their wild-type littermate to test two hypotheses about OT functional genomics. First, we proposed that in OTKO mice, a very similar 9-amino-acid neuropeptide, arginine vasopressin (a likely gene duplication product), can ‘cross over’ and compensate for the lack of OT. This hypothesis was confirmed in both males and females. Further, we proposed that because of the lifelong absence of OT in OTKO, OT receptors would be more sensitive to OT in the knockout animals. We tested this idea in males and found that it was correct. Thus, an answer to the ‘OTKO paradox’ is put forth, with implications for OT-sensitive behaviors in a variety of species.
Tissue pH Determination for the Detection of Metabolically Active, Inflamed Vulnerable Plaques Using Near-Infrared Spectroscopy: An in-vitro Feasibility Study
Authors: Khan Tania , Soller Babs , Naghavi Morteza , Casscells Ward
Published: November 2004

Detection of vulnerable plaques as the underlying cause of myocardial infarction is at the center of attention in cardiology. We have previously shown that infiltration of inflammatory cells in atherosclerotic plaques renders these plaques relatively hot and acidic, with substantial plaque temperature and pH variation. The objective of this investigation was to determine whether near-infrared diffuse reflectance spectroscopy (NIRS) could be used to non-destructively measure the tissue pH in atherosclerotic plaques. NIRS and tissue pH electrode measurements were taken on freshly excised carotid plaques maintained under physiological conditions. The coefficient of determination between NIRS and the pH microelectrode measurement was 0.75 using 17 different areas. The estimated accuracy of the NIRS measurement was 0.09 pH units. These results demonstrate the feasibility of using NIRS tissue pH in freshly excised atherosclerotic plaques in light of marked pH heterogeneity and warrants future in-vivo investigations on pH measurement of atherosclerotic plaques.
Resumption and Maintenance of Employment after a First Acute Myocardial Infarction: Sociodemographic, Vocational and Medical Predictors
Authors: Drory Yaacov , Kravetz Shlomo , Koren-Morag Nira , Goldbourt Uri
Published: November 2004

In a community cohort of 833 women and men aged <60 years, employed at the time of a first acute myocardial infarction (AMI), the relation of sociodemographic, vocational, and medical variables to the following three aspects of employment was investigated longitudinally: resumption of employment anytime within 5 years after AMI, resumption of employment within 3 months of the AMI, and maintenance of employment 5 years after AMI. Different sets of characteristics of persons with a first AMI were related to the different criteria of employment. Only sociodemographic and vocational variables were related to early resumption of employment, whereas maintenance of employment 5 years after AMI was influenced by both medical and nonmedical variables. These results support the importance of examining different aspects of resumption and maintenance of employment after AMI. They also suggest that early resumption of employment after AMI and employment anytime 5 years after AMI are more a function of the sociodemographic and vocational characteristics of the person with the AMI than of that person’s medical condition, whereas long-term maintenance of employment after an AMI is also related to the person’s medical condition.
Nonhabitual Seizures in Patients with Implanted Subdural Electrodes
Authors: Fountas Kostas N. , King Donald W. , Jenkins Patrick D. , Smith Joseph R.
Published: November 2004

The implantation of subdural electrodes has been widely employed in the invasive monitoring of patients with medically refractory epilepsy. The use of subdural electrodes, though, has been associated with rare but occasionally troublesome complications. We report the occurrence of nonhabitual seizures after implanting subdural grid electrodes. Among 57 patients diagnosed with medically refractory epilepsy who were evaluated in our department over a 12-month period, 21 patients underwent craniotomy for subdural grid/strip electrode implantation. Subdural grids and strips (AdTech, Racine, Wisc., USA) were used for continuous video EEG monitoring. In 3 patients, during subdural monitoring, consistent nonhabitual seizure activity was recorded. This was both clinically and electrographically different than the patients’ habitual seizures. The patients’ nonhabitual seizures disappeared postoperatively after removing the implanted electrodes. The occurrence of nonhabitual seizures, though quite rare, could lead to mislocalization of an epileptogenic focus. This complication might be the result of direct mechanical cortical irritation or chemical irritation caused by blood breakdown products. The occurrence of nonhabitual seizures comes to add itself to the existing list of complications associated with employment of subdural electrodes for invasive monitoring.
Potential Confounding by Intermediate Phenotypes in Studies of the Genetics of Ischaemic Stroke
Authors: Flossmann Enrico , Schulz Ursula G.R. , Rothwell Peter M.
Published: November 2004

Background: Family history (FHx) of stroke is perceived to be an important risk factor for ischaemic stroke. However, there are several intermediate phenotypes that are often involved in the aetiology of ischaemic stroke and that have a substantial genetic component themselves. We studied FHx of ischaemic heart disease (IHD), hypertension (HTN) and diabetes mellitus (DM) as risk factors for ischaemic stroke. Methods: We performed a systematic review of case-control and cohort studies reporting on FHxIHD, FHxHTN or FHxDM as risk factors for stroke using bibliographic databases, and by hand searching reference lists and journals. Odds ratios of FHx as a risk factor for stroke were calculated within individual studies. We included unpublished data from two Oxfordshire population-based studies to assess effects on subtypes of ischaemic stroke. Results: We identified 54 studies that investigated the odds of stroke conferred by a positive FHx, 24 of which reported data on FHx of one or more intermediate phenotypes in addition to FHx of stroke. Most studies reported an increased frequency of FHxIHD and FHxHTN in stroke patients versus controls. The association was significant in 6 out of 14 studies for FHxIHD and 4 out of 11 studies for FHxHTN. In contrast, FHxDM was not associated with stroke. FHxIHD was particularly associated with large vessel strokes (OR 1.72, CI 1.3–2.2, p = 0.00004). Conclusions: FHxIHD and FHxHTN are both risk factors for stroke. It is likely that the apparent heritability of stroke is partly accounted for by heritability of HTN and large vessel atherosclerosis. Analyses of heritability of stroke and candidate gene studies should be adjusted accordingly.
Burden of Informal Caregiving for Stroke Patients
Authors: van Exel N.J.A. , Koopmanschap M.A. , van den Berg B. , Brouwer W.B.F. , van den Bos G.A.M.
Published: November 2004

Background: We assessed the objective and subjective burden of caregiving for stroke patients and investigated which characteristics of the patient, the informal caregiver and the objective burden contribute most to subjective burden and to the condition of feeling substantially burdened. Methods: We studied a sample of 151 stroke survivors and their primary informal caregivers. We collected data through patient and caregiver interviews 6 months after stroke. Results: Both the level of subjective burden and the condition of feeling substantially burdened were associated with both caregiver’s and patient’s health-related quality of life, patient’s age, and the number of caregiving tasks performed. Conclusions: These conditions can be used in clinical practice to identify potentially vulnerable caregivers in need of support and at risk of adverse health effects. Monitoring stroke survivors as well as their family caregivers at discharge may help to prevent or alleviate caregiver burden.
Prothrombin 20210A and Oral Contraceptive Use as Risk Factors for Cerebral Venous Thrombosis
Authors: Gadelha Telma , André Charles , Jucá Andreza A.V. , Nucci Márcio
Published: November 2004

Background: This study investigates the association between cerebral vein thrombosis (CVT) and the mutations FV 1691A (factor V Leiden), PT 20210A and MTHFR 677TT and acquired factors including oral contraceptive (OC) use. Methods: 26 patients (21 females) and 217 healthy controls (134 females) were studied. Multiple regression analysis was performed. Results: The frequency of the three mutations in cases and controls were: PT 20210A, 23 versus 1%, odds ratio (OR) 21.40 (95% CI 4.29–118.75), p < 0.001; FV 1691A, 8 versus 1%, OR 5.94 (95% CI 0.66–46.9); MTHFR 677TT, 4 versus 7%, OR 0.54 (95% CI 0.03–4.08). OC use was more frequent in female patients over 14 years old than in controls (84 vs. 40%, OR 8.15, 95% CI 2.09–37.13, p < 0.001). The model that best explained the thrombotic risk included PT 20210A and OC use. Conclusions: PT 20210A and OC use are the main thrombophilic risk factors predisposing to CVT and should be routinely investigated in patients with this disease.
Lumbar Puncture and Dural Sinus Thrombosis – A Causal or Casual Association?
Authors: Canhão Patrícia , Batista Paulo , Falcão Filipa
Published: November 2004

Background: A few cases of cerebral venous thrombosis (CVT) were reported after a lumbar puncture (LP), suggesting a causal association. The purpose of our study was to document that LP might predispose to CVT by decreasing blood flow velocities (BFV) in veins or dural sinus. Methods: We performed a transcranial Doppler ultrasound study to register the mean BFV of the straight sinus (SS) before, during and after LP. Results: Thirteen patients were studied. LP induced a decrease of 47% of mean BFV in the SS. The mean decrease of BFV was significant immediately at the end (p = 0.003), 30 min after (p = 0.015) and more than 6 h after LP (p = 0.008). Conclusions: LP induced a sustained decrease of mean BFV in the SS. The decrease of venous blood flow is a possible mechanism contributing to the occurrence of CVT.
Butyrate Increases Apoptosis Induced by Different Antineoplastic Drugs in Monocytic Leukemia Cells
Authors: Ramos M.G. , Rabelo F.L.A. , Brumatti G. , Bueno-da-Silva A.E. , Amarante-Mendes G.P. , Alvarez-Leite J.I.
Published: November 2004

Background: Apoptosis is an essential form of cell death, the failure of which can lead to cancer development. Cancer including leukemia is usually treated with chemotherapeutic drugs that can be effective, but frequently problems are encountered that impair the success of the treatment. Butyrate is a short-chain fatty acid that can have many effects on different cells, including apoptosis. Methods: The effect of a combination treatment with butyrate and antineoplastic agents Ara-C, etoposide and vincristine is evaluate on the leukemic cell line THP-1. Results: We show that butyrate increased apoptosis induced by the three agents as seen by measurement of DNA content, annexin exposure and morphological characteristics. We also demonstrate that the process of apoptosis induced by butyrate and chemotherapeutic drugs involves the participation of caspases and induced activation of caspase-3, -8 and -9. Conclusions: We believe that butyrate could be a promising therapeutic agent for the treatment of leukemia in combination with other antineoplastic drugs.
Efficacy of Quinupristin-Dalfopristin against Methicillin-Resistant Staphylococcus aureus and Vancomycin-Insensitive S. aureus in a Model of Hematogenous Pulmonary Infection
Authors: Yanagihara Katsunori , Okada Makiko , Fukuda Yuichi , Imamura Yoshifumi , Kaneko Yukihiro , Ohno Hideaki , Higashiyama Yasuhito , Miyazaki Yoshitsugu , Tsukamoto Kazuhiro , Hirakata Yoichi , Tomono Kazunori , Kadota Jun-Ichi , Tashiro Takayoshi , Murata Ikuo , Kohno Shigeru
Published: November 2004

Background: Quinupristin-dalfopristin (Q-D) is a mixture of quinupristin and dalfopristin, which are semisynthetic antibiotics of streptogramin groups B and A, respectively. Methods: We compared the effect of Q-D to that of vancomycin (VCM) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA). Results: Treatment with Q-D resulted in a significant decrease in the number of viable bacteria in the lungs of mice in an MRSA infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean ± SEM): 2.99 ± 0.44, 6.38 ± 0.32, 5.75 ± 0.43 and 8.40 ± 0.14 log10 CFU/lung, respectively]. Compared with VCM, high-dose Q-D significantly reduced the number of bacteria detected in the VISA hematogenous infection model [Q-D 100 mg/kg, Q-D 10 mg/kg, VCM and control (mean ± SEM): 5.17 ± 0.52, 7.03 ± 0.11, 7.10 ± 0.49 and 7.18 ± 0.36 log10 CFU/lung, respectively]. Histopathological examination confirmed the effect of Q-D. Conclusion: Our results suggest that Q-D is potent and effective in the treatment of MRSA and VISA hematogenous pulmonary infections.