bluuebunny/crossref_metadata_2025 huggingface dataset:
Uptake and Protection against Oxidative Stress by Estrogen Esters in THP-1 Human Macrophage Cell Lines
Authors: Abplanalp W. , Ravi Subbiah M.T.
Published: April 2003

Estrogen replacement therapy offers protection from coronary artery disease in postmenopausal women. However, there is serious concern that long-term unopposed estrogen use increases the risk of breast and endometrial cancer through estrogen-receptor-driven mechanisms. In this communication, we have explored an alternate route of estrogen delivery to macrophages using hydrophobic derivatives that associate with lipoproteins. Unlike free estradiol (E2), long-chain fatty acid esters of E2 associate extensively with low-density lipoprotein (LDL). In THP-1 cells, E2 esters accumulated to a significantly higher level when compared to E2 in the presence of LDL. In the presence of oxidized LDL even greater amounts of E2 esters accumulated in cells. In THP-1 cells, E2 esters were capable of preventing the azo-bis-induced increase in oxidative stress (hydrogen peroxide formation). These studies suggest that (a) hydrophobic esters of estrogens that associate with LDL can be delivered to macrophages and (b) these esters can effectively function as antioxidants protecting against oxidative stress.
Insulin Response Patterns Contribute to Different Perinatal Risks in Gestational Diabetes
Authors: Yamada Hideto , Hirayama Kato Emi , Tsuruga Ritsuko , Ebina Yasuhiko , Kobashi Gen , Sagawa Tadashi , Makita Zenji , Koike Takao , Fujimoto Seiichiro
Published: April 2003

The aim of this study was to evaluate the insulin dynamics of patients with gestational diabetes mellitus (GDM) and to compare perinatal outcomes according to the insulin response patterns. Twenty-two out of 925 consecutive women examined were diagnosed as having GDM. One hundred and ten women who experienced a normal pregnancy were used as controls. Plasma glucose levels and insulin responses were evaluated by a 2-hour 75-gram oral glucose tolerance test (OGTT). Immunoreactive insulin (IRI), the area under the curve (AUC) of glucose (AUCg) and insulin (AUCi), and the insulinogenic index (II = ΔIRI 30 min/ΔBS 30 min) were measured. The GDM patients were divided into three subgroups, consisting of hyper-, normo- and hypoinsulinemic groups, according to the mean ± 2 SD of the AUCi obtained from the controls. Clinical and laboratory findings were compared among the GDM subgroups and controls. The GDM patients showed impaired insulin secretion to glucose stimuli, with low plasma insulin levels (at 30 min) and reduced insulin/glucose ratios (at 30 and 60 min) early in the 75-gram OGTT. The II and AUCi/AUCg values of GDM patients were reduced as compared with those of controls. These reduced insulin responses were remarkable in hypo- and normoinsulinemic GDM patients, but were not detected in hyperinsulinemic GDM patients. The number of babies large for their gestational age in normo- and hypoinsulinemic GDM patients was significantly higher than that in hyperinsulinemic GDM patients or controls. Hyperinsulinemic GDM patients had a high frequency of pregnancy-induced hypertension (40%). The body mass index prior to pregnancy of hyperinsulinemic GDM patients was significantly higher than that of normoinsulinemic GDM patients or controls. It was demonstrated that not only insulin secretion, but also perinatal clinical characteristics, differed among the GDM subgroups. The heterogeneity of the disease was thus confirmed.
Transient Bilateral Osteoporosis of the Hip in Pregnancy
Authors: Axt-Fliedner R. , Schneider G. , Seil R. , Friedrich M. , Mink D. , Schmidt W.
Published: April 2003

Osteoporosis of the hip is a rare complication of pregnancy, the diagnosis of which can only be determined by radiologic means. Differentiation between osteonecrosis and osteoporosis remains problematic in some cases. Magnetic resonance imaging was reported as useful for the diagnosis of osteoporosis. Treatment of osteoporosis of the hip in pregnancy should be conservative including physical therapy, restricted weight bearing and analgetic therapy. We report an unusual case of bilateral transient osteoporosis of the hip in pregnancy.
Magnetic Resonance Imaging in the Preoperative Determination of Tumor Resectability in Previously Irradiated Groin Tumor
Authors: Abulafia Ovadia , Matthews Roland , Holcomb Kevin , Buhl Ann , Lee Yi-Chun
Published: April 2003

We present an unusual case in which magnetic resonance (MR) imaging was utilized in the preoperative determination of resectability of a large inguinal tumor. The patient had previously presented with a large fungating, surgically nonresectable mass, which impinged upon the anterior ramus of the pubic bone. Following chemotherapy and radiation, the mass appeared more mobile and surgically resectable. Due to fibrosis and induration, the relationship of the tumor and underlying femoral vascular bundle were unclear. MR imaging clearly depicted that the tumor was sufficiently distant from the vessels, to allow safe resection with an adequate surgical margin. Resection was performed with clear lateral and deep margins. Histopathology demonstrated squamous cell carcinoma of the inguinal skin replacing subcutaneous tissue.
Carney Complex – An Unexpected Finding during Puerperium
Authors: Schulz Solveig , Redlich Anke , Köppe Ingrid , Reschke Kirsten , Weise Wolfgang
Published: April 2003

Carney complex is an extremely rare, autosomal dominant, multi-system disorder characterized by multiple neoplasias and lentiginosis. The genetic defect responsible for this complex has been localized to the short arm of chromosome 2 (2p16). The most prevalent clinical manifestations in patients with Carney complex are spotty skin pigmentation, skin and cardiac myxomas, Cushing’s syndrome and acromegaly. Here we report the case of a 31-year-old woman with a spontaneous pregnancy. At 32 weeks of gestation, she was admitted to our Department of Obstetrics with hypertension and severe back pain. In addition, she had unusual pigmentation and typical cushingoid features. One day after admission, the pregnancy was terminated by emergency cesarian section because of preeclampsia and pathological CTG. During the postoperative period the severe back pain persisted, and radiographic evaluation revealed a collapse of L2/L3 with severe osteopenia. A CT scan showed a mass in the right suprarenal area. Histopathological examination revealed a primary pigmented nodular adrenocortical disease. After biochemical confirmation of the diagnosis of Cushing’s syndrome, it was recognized that the patient met the diagnostic criteria for Carney complex.
Local Immune Response in Squamous Cell Carcinoma of the Uterine Cervix
Authors: Hachisuga Toru , Fukuda Koichi , Kawarabayashi Tatsuhiko
Published: April 2003

The role of Langerhans cells as antigen-presenting cells was examined in cervical carcinomas. Frozen samples were obtained from 34 women with stage Ib and II cervical carcinomas. Langerhans cells (CD1), T lymphocytes (CD4 and CD8), B lymphocytes (CD22), and natural killer (CD57, NK) cells were all quantitatively assessed in cervical carcinomas using immunohistochemical methods. These results were related to the MHC class I and II expression on the tumor cells. The majority of Langerhans cells were distributed among cancer cells and they were positively correlated with CD4+, NK and B cells in cervical carcinomas. This is suggestive of the presence of local immune response. The numbers of Langerhans, CD4+, CD8+ and NK cells did not significantly correlate with age at operation, lymph node metastases or depth of cervical wall invasion. The downregulation of MHC class I expression found in 8 (24%) carcinomas was not associated with the decrease in the number of immunologic cells. The upregulation of MHC class II expression found in 26 (76%) carcinomas was significantly associated with the increase in the number of Langerhans cells (p < 0.007). However, the association between the upregulation of MHC-II expression and CD4+ cells did not reach statistical significance (p < 0.07). This is probably due to a small case in this study. MHC-II-restricted immunity may partly contribute to the local immune response in stages Ib and II squamous cell carcinoma of the uterine cervix.
Effect of Cellular DNA Content on the Prognosis of Epithelial Ovarian Cancers
Authors: Ozalp S. , Yalcin O.T. , Gulbas Z. , Tanir H.M. , Minsin T.
Published: April 2003

Objective: To assess the cellular DNA status of epithelial ovarian cancers with regard to clinicopathological findings and its effect on prognosis. Materials and Methods: Twenty-six consecutive patients with a diagnosis of epithelial ovarian cancer who had been treated by primary surgery and six courses of platinum-based chemotherapy were enrolled in this study. Second-look laparotomy (SLL) was performed in all cases following confirmation of the clinical remission state. Surgical stage, tumor grade, initial tumor volume, residual tumor volume, histopathologic differentiation, and SLL findings were analyzed in correlation with DNA ploidy and DNA index. DNA analysis was performed via DNA flow cytometry through paraffin-embedded tissue specimens. Results: Of 26 patients, flow cytometric studies revealed 16 aneuploidy cases (61.5%). DNA index values ranged from 1.1 to 1.82 (average 1.29 ± 0.28). The flow cytometry coefficient of variation mean value was set to 6.7. Taking the cutoff value of 1.2 for DNA indices, a fairly good correlation was detected between DNA ploidy and DNA indices (p < 0.001). The aneuploidy incidence was found to be high in advanced and poorly differentiated tumors (p < 0.05). There was statistically more residual tumor volume in aneuploid tumors during primary cytoreductive surgery and also higher recurrence rates following six courses of chemotherapy compared with diploid tumors (p < 0.05). No significant correlation was detected between the histopathologic subtypes and tumor volume (p > 0.05). Residual tumor volumes were larger in cases with DNA indices of 1.2 yielding higher residual tumor volume following surgery and being in good correlation with SLL results (p < 0.05). The mean survival rates of cases with aneuploid tumor and a DNA index of >1.2 were low compared to those with diploid tumors and DNA indices of <1.2 tumors (p < 0.05). Conclusion: DNA ploidy and DNA indices are important prognosticators for malignant epithelial ovarian tumors. They should be evaluated together with the patient’s clinical status and other prognostic factors.
Modulatory Effect of Acetylcholine on Gonadotropin-Stimulated Human Granulosa Cell Steroid Secretion
Authors: Kornya L. , Bódis J. , Koppán M. , Tinneberg H.R. , Török A.
Published: April 2003

The aim of this study was to explore the direct action of acetylcholine on gonadotropin-stimulated progesterone (P) and estradiol (E2) secretion of human granulosa cells (GCs) cultured in serum-free medium. Human GCs were isolated from preovulatory follicular fluid aspirated from 22 women undergoing in vitro fertilization at the University Women’s Hospital of Tübingen. The production of progesterone and E2 was measured in the presence and absence of acetylcholine, carbachol, atropine, luteinizing hormone (LH) or follicle-stimulating hormone (FSH) using radioimmunoassay. Statistical analysis of the data was performed by ANOVA and Newman-Keuls test. Administration of acetylcholine or carbachol (10–5M) resulted in a significant increase in P and E2 secretion. This response was specifically blocked by the muscarinic receptor antagonist atropine. Similarly, carbachol resulted in a significant increase in P and E2 output, though the response to it was somewhat reduced when compared to that evoked by acetylcholine. Acetylcholine did not show any additive effect on LH-stimulated P secretion, while it augmented the stimulatory effect of FSH on P release. In contrast, carbachol markedly diminished the stimulatory effect of LH on P secretion, while it caused no change in FSH-induced P output. When administered together, acetylcholine did not modify the stimulatory effect of FSH on E2 secretion, however, it markedly elevated LH-induced E2 output. Similar to this, carbachol significantly increased LH-induced E2 release, however it decreased FSH-stimulated E2 secretion. We suggest that acetylcholine has a direct modulatory effect on gonadotropin-stimulated steroid production of GCs, an effect that is mediated via muscarinic receptors. This effect may have a physiological role in the regulation of GC function during the menstrual cycle.
Influence of Melatonin on Basal and Gonadotropin-Stimulated Progesterone and Estradiol Secretion of Cultured Human Granulosa Cells and in the Superfused Granulosa Cell System
Authors: Bódis J. , Koppán M. , Kornya L. , Tinneberg H.R. , Török A.
Published: April 2003

The aim of this study was to explore the direct action of melatonin (Me) on basal and gonadotropin-stimulated progesterone (PG) and estradiol (E2) secretion of human granulosa cells (GCs) cultured in serum-free medium and in a superfused GC system. Human GCs were isolated from preovulatory follicular fluid aspirated from 34 women undergoing in vitro fertilization at the University Women’s Hospital of Tübingen. PG and E2 production was measured in the presence and absence of Me, propranolol, LH or FSH using radioimmunoassay. Statistical analysis of the data was performed by ANOVA and Newman-Keuls test. Me stimulated E2 secretion in a dose-dependent manner. Propranolol did not cause any change in E2 secretion, and when given with Me, it only partially blocked but could not entirely prevent E2 output. There was no statistically significant effect of Me on PG production when Me was administered at concentrations between 10–4 and 10–8 M. However, at 10–3 M Me significantly suppressed PG output of granulosa cells. LH and FSH significantly stimulated the secretion of both steroid hormones. Me significantly reduced LH- and FSH-induced E2 secretion, as well as LH-stimulated PG output, while it caused only a slight, yet significant decrease in PG secretion. In the superfused GC system, FSH and LH resulted in a significant stimulatory effect on PG release. Me did not modify the stimulatory effect of FSH on PG, while it caused some delay in LH-stimulated PG release. Propranolol and Me had no stimulatory effect on PG release. On the basis of our results we suggest that Me has a direct modulatory effect on basal E2 and gonadotropin-stimulated E2 and PG secretion of human GCs. The observed effect may play a physiological role in the regulation of GC function during the menstrual cycle.
Frequency of Factor V, Prothrombin and Methylenetetrahydrofolate Reductase Gene Variants in Preeclampsia
Authors: D’Elia Angela V. , Driul Lorenza , Giacomello Roberta , Colaone Roberta , Fabbro Dora , Di Leonardo Cristina , Florio Pasquale , Petraglia Felice , Marchesoni Diego , Damante Giuseppe
Published: April 2003

Background: The association between thrombophilic variants (Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene) with preeclampsia was investigated in a north-eastern Italian population. Methods: Fifty-eight preeclamptic (PE) women and 74 normal pregnancies were evaluated. Genotypes were determined by polymerase chain reaction. Results: The frequency of heterozygous carriers of the factor V Leiden was similar between PE women (5.2%) compared to the control subjects (4.1%; p 0.76). Also the frequencies of G20210A and C677T mutations were similar between PE and control subjects. Conclusions: In this population, we found no difference in the prevalence of genetic risk factors for thrombosis in women with preeclampsia compared with control subjects.
Ist der Anstieg der Sectiofrequenz ein Qualitätsmangel oder ein Indikationswandel?
Authors: Winter R. , Hepp H. , Haller U.
Published: April 2003

Die Sectiofrequenz ist kontinuierlich im Ansteigen. Die Berücksichtigung des Patientinnenwunsches bei der Indikationsstellung zum Geburtsmodus hat sich an der Grazer Klinik zu einem schwer einschätzbaren Faktor entwickelt. Lag die Sectiofrequenz im Jahr 1999 noch bei 13,8%, so wird sie im Jahre 2000 17,2% betragen. Die Akzeptanz der Wunschsectio ist bei den Frauen hoch. Der Anstieg der Sectiofrequenz wird wesentlich von paramedizinischen Faktoren beeinflusst. Die Geburtshilfe scheint sich immer mehr in Richtung Geburtschirurgie zu entwickeln. Ob dieser Wandel einen Qualitätsverlust darstellt, wird erst in Zukunft beantwortet werden können.
Psychologische Aspekte der Ultraschalluntersuchung während der Schwangerschaft
Authors: Schönholzer S.M. , Götzmann L. , Zimmermann R. , Buddeberg C.
Published: April 2003

Umfragen zufolge besteht heute eine breite Befürwortung des routinemässigen Einsatzes der Ultraschalldiagnostik während der Schwangerschaft. Für die oft postulierten positiven Auswirkungen von Ultraschalluntersuchungen auf das psychische Befinden werdender Mütter liegt bislang keine eindeutige empirische Evidenz vor. Zwar fühlen sich die meisten schwangeren Frauen durch die Visualisierung des Kindes emotional berührt; längerfristig wirkt sich die Ultraschalluntersuchung aber weder auf die Bindung zum Kind noch auf gesundheitsrelevantes mütterliches Verhalten aus. Vieles spricht dafür, dass die in mehreren Studien gefundene kurzfristige angst- und stressreduzierende Wirkung der Ultraschalluntersuchung lediglich darin besteht, dass Ängste, die vor der Untersuchung entstehen, gemildert werden. Bisher ist noch nicht geklärt, ob durch die frühzeitige sonografische Feststellung einer fetalen Fehlbildung eher ein psychischer Verarbeitungsprozess in adaptiver und adäquater Weise gefördert oder ob die Schwangerschaft und die sich entwickelnde Beziehung zwischen Mutter und Kind belastet wird. Die vorliegende Arbeit gibt einen Überblick über den aktuellen Forschungsstand bezüglich der Akzeptanz und der psychologischen Wirkung der routinemässigen Ultraschalldiagnostik während der Schwangerschaft.
Wirksamkeit und Verträglichkeit zweier Zephalosporine in der perioperativen Antibiotikaprophylaxe bei abdominalen und vaginalen Hysterektomien und gynäkologischen Laparotomien
Authors: Regidor P.-A. , Bier U.W. , Preuss M.J.H.A. , Eickhoff C. , Hillger H. , Kienle E. , Schindler A.E.
Published: April 2003

Ziel der vorliegenden Untersuchung war es, die Wirksamkeit und Verträglichkeit zweier Zephalosporine in der perioperativen Antibiotikaprophylaxe bei Patientinnen, die einer abdominalen oder vaginalen Hysterektomie oder einer gynäkologischen Laparotomie unterzogen wurden, zu testen, um die Rate postoperativer Störungen der Wundheilung zu verringern. Insgesamt wurden 199 Patientinnen prospektiv in zwei Gruppen randomisiert. Die erste Gruppe (n = 100) erhielt perioperativ 1 g Cefotiam (Spizef®) und 0,5 g Metronidazol (Clont®) intravenös 30 min vor der Operation, während die zweite Gruppe (n = 99) 2 g Cefoxitin (Mefoxitin®) intravenös erhielt, ebenfalls 30 min vor der Operation. Die Wirksamkeit der Prophylaxe wurde sowohl klinisch als auch aufgrund von laborchemischen Parametern objektiviert. Bei 97 Patientinnen (97%) der Cefotiam-Gruppe und bei 94 Patientinnen (94%) der Cefoxitin-Gruppe traten keine Wundheilungsstörungen auf. Keine postoperativen systemischen Infektionen wurden bei 81% der Cefotiam-Gruppe und 85% der Cefoxitin-Gruppe beobachtet. 98% der Patientinnen der Cefotiam-Gruppe und 97% der Patientinnen der Cefoxitin-Gruppe wiesen eine sehr gute bzw. gute Verträglichkeit der Medikation auf. In beiden Gruppen traten, durch die Antibiotikaprophylaxe bedingt, jeweils nur bei 3 Patientinnen Übelkeit bzw. Erbrechen auf. Die Untersuchung ergab im gesamten Kollektiv sehr niedrige Infektionsraten. Cefotiam in niedriger Dosierung und Metronidazol waren genauso wirksam wie Cefoxitin. Zephalosporine der zweiten Generation in Kombination mit Metronidazol können daher als sehr wirksame und nebenwirkungsarme Antibiotika bei der Prophylaxe lokaler Infektionen angesehen werden.
Ausstossung eines Deziduapolypen aus dem nichtgraviden Uterushorn bei einer Schwangerschaft mit Uterus bicornis
Authors: Schießl B. , Hantschmann P. , Brucker C.
Published: April 2003

Anhand eines Fallberichtes wird die seltene Komplikation der Bildung und der Ausstossung eines Deziduapolypen aus dem nichtgraviden Uterushorn während einer Schwangerschaft mit Uterus bicornis beschrieben. Der klinische Verlauf wird dargestellt und die Bedeutung der pränatalen Ultraschalldiagnostik diskutiert.
Psychosoziale und psychosomatische Basiskompetenz des Frauenarztes – von der inneren Überzeugung zum lernbaren Curriculum
Authors: Bitzer J. , Tschudin S. , Schwendke A. , Alder J.
Published: April 2003

Neben den kommunikativen Fertigkeiten und der ärztlichen Ge- sprächsführung (Teil 1 in Gynäkol Geburtshilfliche Rundsch 2001; 41:158–165) ist das biopsychosoziale Modell von Gesundheit und Krankheit der zweite wesentliche Bestandteil einer psychosozialen und psychosomatischen Basiskompetenz. In diesem Modell werden gleichzeitig und gleichberechtigt biologisch-somatische und psychosoziale Faktoren in der Diagnostik und Therapie berücksichtigt. Zur Erfassung möglicher krankmachender psychosozialer Faktoren eignen sich in der Praxis folgende, dem Erleben der Patientinnen naheliegende Kategorien: Verhalten, Stress, Konflikte und Entwicklungsstörungen. Diese Kategorien sind im Wesentlichen nicht objektiv messbar, sondern erschliessen sich dem Arzt/der Ärztin durch die Konsultation mit Hilfe der folgenden drei Funktionen: Erfassung und Beschreibung der Probleme (körperlich, psychisch, sozial) der Patientin durch patientenzentrierte Kommunikation; Schaffung, Aufrechterhaltung und Beendigung einer therapeutischen, hilfreichen Beziehung durch Wahrnehmung und Umgang mit Emotionen; Entwicklung eines Lösungsplanes und Hilfe bei der Umsetzung durch Informationsvermittlung und Verhaltensbeeinflussung.
Ovarialtuberkulose
Authors: Steller J.
Published: April 2003

Die Tuberkuloserate in Deutschland und in den westlichen Industrienationen ist stabil; weltweit gehört die Tuberkulose zu den wichtigsten Infektionskrankheiten. Aussiedler und Asylbewerber stellen bei neuen Tuberkuloseerkrankungen einen hohen Patientenanteil. Der Anteil an Multiresistenzen bei Patienten aus der ehemaligen Sowjetunion ist mit 15% überdurchschnittlich hoch. Anhand der Präsentation einer Patientin mit isolierter Ovarialtuberkulose sollen neben der Einordnung in Risikogruppen auch die differentialdiagnostischen Möglichkeiten und Grenzen aufgezeigt werden.
Intravascular Ultrasound: Technique, Measurements and Angioplasty Guidance
Authors: Gaster Anne Louise , Thayssen Per
Published: April 2003

Coronary angiography has been the gold standard for decades for the evaluation of coronary artery disease. Although it offers the best overview of coronary artery anatomy, it has been known to underestimate the amount and severity of coronary artery lesions. This is probably due to the method being based on luminography, with the evaluation of the seat of coronary artery disease, the vessel wall, based on deduction. Intravascular ultrasound (IVUS) provides the investigator with the possibility of direct inspection of the vessel lumen as well as the vessel wall independently of vessel tortuosity, vessel overlap and ostial position. Thus, equivocal angiographically imaged vessels can be investigated by supplementing coronary angiography with IVUS. By guiding percutaneous coronary intervention with IVUS and angiography, a lower target vessel revascularisation rate can be expected, presumably due to the more physiologically correct device sizing possible. It seems that although IVUS guidance represents an incremental cost, long-term costs are reduced due to the lower revascularisation rates. Which lesions to guide by IVUS and angiography and which can be guided by angiography alone has still not been clarified in randomised trials.
Nesiritide: A Promising New Drug for the Treatment of Decompensated Heart Failure
Authors: Burger Mary R. , Burger Andrew J.
Published: April 2003

Heart failure is characterized by sodium and fluid retention, sympathetic overactivity, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. Current treatment for acute heart failure consists of vasodilators, diuretics and inotropes. Nesiritide (human B-type natriuretic peptide) is a promising new class of drugs that has been given to almost 1,000 patients in numerous clinical investigations. The clinical development of nesiritide included dosing studies (utilizing repetitive boluses, continuous infusions, or a combination of bolus plus infusion), pivotal efficacy trials, and comparative safety studies, which have repeatedly demonstrated that intravenous nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while increasing cardiac index and stroke volume. Improvement in both clinical assessment and signs and symptoms of heart failure has been reported by patient and physician alike. Plasma levels of neurohormones and endothelin-1 are significantly reduced with nesiritide treatment. Compared with dobutamine, nesiritide is not proarrhythmic and does not affect heart rate. In comparison with intravenous nitroglycerin in the treatment of decompensated heart failure, nesiritide improves hemodynamics and symptomatology (dyspnea) faster and more effectively than nitroglycerin. Fewer patients receiving nesiritide reported any adverse event. Incidence of hypotension was comparable, but more intravenous nitroglycerin patients developed headache and abdominal pain. Current research supports an important role for the use of nesiritide in the treatment of decompensated heart failure.
The Role of the Insulin-Like Growth Factor System in the Developing Brain
Authors: Werther George A. , Russo Vincenzo , Baker Naomi , Butler Gary
Published: April 2003

Insulin-like growth factors (IGFs) play a central role in brain growth and development, with IGF-1, its receptors and binding proteins (IGFBPs) being highly expressed, particularly in the olfactory bulb (OB), representing a local paracrine system. A potential role of IGFBPs in transporting and targeting IGFs to their receptors is supported by the finding that abundant IGFBP-2 is associated with cell surface proteoglycans. An OB organ culture system expressing IGF-1 and IGFBPs represents an in vitro injury model. Although IGF-1 is potently antiapoptotic for neurons and oligodendrocytes, marked gliosis and IGFBP-3 expression are seen, similar to in vivo injury responses, where intraventricular injection of IGF-1 postinjury enhances neuronal survival by blocking apoptosis. In contrast, des (1–3) IGF-1, which has low affinity for IGFBPs, is ineffective, supporting a transport or receptor targeting role for local IGFBPs. We conclude that the IGF system plays a crucial cell survival and growth role in the developing and injured brain and that IGFs have significant therapeutic potential.
Children Born Small-for-Gestational Age: Postnatal Growth and Hormonal Status
Authors: Albertsson-Wikland Kerstin , Boguszewski Margaret , Karlberg Johan
Published: April 2003

It is generally recognized that children born small-for-gestational age (SGA) have a 5–7 times higher risk of short stature than children born at normal size. It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and is affected by intrauterine growth retardation. This study was undertaken to characterize the postnatal growth pattern and the final height of children born SGA, as part of a population- based study (n = 3,650), from birth to final height, and to evaluate the hormonal status in another group of prepubertal children born SGA (n = 134) without postnatal catch-up growth. The majority (88%) of ‘healthy’ full-term singleton SGA infants achieved catch-up growth during the first 2 years of life, and most of the increase in height occurred by 2 months of age. The SGA children who remained short at 2 years of age had a higher risk of short stature later in life. The risk of having a short final height (<–2 SDS) was five times higher for children with a low birth weight and seven times higher for those with a low birth length in comparison with children with a normal birth size. Moreover, about 20% of all children of short stature were born SGA. As a group, children born SGA will have a final height, expressed in SDS, as they had during the prepubertal years. This is in contrast to children, who became short postnatally. During puberty, these short children will have a mean height gain of 0.6 SDS for girls and 0.7 SDS for boys. The mean estimated secretion rate for growth hormone (GH) was lower in the short children born SGA compared with the reference groups born at an appropriate size for gestational age, of either short (p < 0.05) or normal stature (p < 0.001). Moreover, in the youngest children born SGA (2–6 years of age) a different pattern of GH secretion was found, with a high basal GH level, low peak amplitude, and high peak frequency. The majority of the children born SGA had levels of GH-binding protein within the range previously reported for normal children. However, the levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3) and leptin were significantly reduced compared with the reference values (p < 0.001, p < 0.01 and p < 0.001, respectively). In conclusion, the low spontaneous GH secretion rate and a disturbed GH secretion pattern, together with low serum levels of IGF-I, IGFBP-3 and leptin, might contribute to the reduced postnatal growth in some of the subgroup of children born SGA who remained short during childhood.
Methods of Assessing the Quality of Diabetes Care
Authors: Fuller John H.
Published: April 2003

To monitor the progress of the improvement of diabetes care several methods are available such as clinical databases, epidemiological studies, and mortality and morbidity statistics. Developments in information technology have made clinical databases such as the DiabCare System a method of high potential because of high generalisability and the potential participation of many clinicians. Epidemiological studies utilize standardized methods to assess disease outcomes and to quantify risk factors. For example, the EURODIAB IDDM Complications Study indicated that life-style factors may have a direct influence on the risk of complications: 21% of 272 patients aged 15–19 years were smokers, rising to above 30% in those aged 20 and above (n = 1,193). This was associated with poor glycemic control in all age groups. Mortality and mortality statistics have the problem of under-ascertainment but they still provide evidence for substantial excess rates in young IDDM subjects with wide regional variations. Thus, for analysing the outcomes of improvements in the quality of care all available information sources have to be utilized, taking care to assess their accuracy and generalisibility.
Eating Disorders in Young Women with Type 1 Diabetes
Authors: Daneman Denis , Olmsted Marion , Rydall Anne , Maharaj Sherry , Rodin Gary
Published: April 2003

Disordered eating attitudes and behavior are common and persistent in adolescent and young adult females with type 1 diabetes, and are associated with impaired metabolic control and a higher risk of diabetes-related complications. Specific aspects of diabetes and its management, e.g. weight gain associated with initiation of insulin treatment or improved metabolic control, and dietary restraint, may trigger the body dissatisfaction and drive for thinness that accompany eating disturbances. Health care providers should be aware of the possible association between eating disturbances and diabetes, and also of the types of behavior, particularly insulin omission for weight loss, that are common in these young women. Therapy will depend on the severity of the eating disturbance. Group psychoeducation, incorporating a nondeprivational approach to eating, may prove effective, especially in those with milder degrees of eating and weight psychopathology.
Clinical and Experimental Effects of Growth Hormone Secretagogues on Various Organ Systems
Authors: Svensson Johan , Bengtsson Bengt-Åke
Published: April 2003

A new class of growth hormone (GH) secretagogues (GHS) has been developed. In rats, the GHS hexarelin exerts cardioprotective effects. In humans, GHS increase growth velocity in children with short stature/GH deficiency. In adults, a combined infusion of GH releasing peptide-2 and thyrotropin releasing hormone increases circulating concentrations of GH as well as that of insulin-like growth factor-I. In healthy volunteers, oral GHS administration reverses diet-induced catabolism, and in healthy obese men, oral GHS treatment increases fat-free mass. However, little is known about the possible direct effects of GHS and there are few long-term studies. Therefore, it is not yet possible to fully evaluate the use of GHS.
Mechanism of Puberty
Authors: Brook C.G.D.
Published: April 2003

The hypothalamo-pituitary-gonadal axis in children is fully functional in fetal life and immediately after birth. The reason why it declines with advancing years of childhood is not clear but gonadotropin pulsatility is at a nadir at 6 years of age. From that time pulsatile gonadotropin starts to reappear but, again, the reason why this happens is completely unknown. All of the events of puberty can be ascribed to pulsatile gonadotropin-releasing hormone stimulation causing pulsatile gonadotropin stimulation of sex steroids. The sex steroids explain the development of the pubertal characteristics; the fact that girls have an earlier growth spurt than boys is explained by the differential effect of oestradiol and testosterone on hypothalamic control of pituitary growth hormone secretion.
Treatment of Late Puberty
Authors: Brook C.G.D.
Published: April 2003

The induction of puberty is physically and emotionally disturbing. For that reason, low doses of medication need to be introduced and increased slowly, regardless of the age at which treatment is started. In boys with growth delay, the growth spurt may be induced earlier in the sequence of pubertal developmental by using oxandrolone, but puberty itself is induced by slowly increasing doses of testosterone. For girls with ovarian failure, oestradiol should be introduced from the age of 8 or 9 years, but doses should be very cautiously increased in order to allow time for cosmetic development of breasts and growth of the uterus.
Growth Hormone Hypersecretion in a Girl with Neurofibromatosis Type 1 and an Optic Nerve Glioma: Resolution following Chemotherapy
Authors: Drake A.J. , Lowis S.P. , Bouffet E. , Crowne E.C.
Published: April 2003

Growth hormone hypersecretion is extremely rare in childhood. We report a girl with neurofibromatosis type 1, an extensive optic nerve glioma and growth hormone hypersecretion. She was treated with chemotherapy to prevent further extension of her sight-threatening tumour. Three years after chemotherapy her growth hormone hypersecretion has resolved although she has gone on to develop precocious puberty.
Glucocorticoid Effects on the Diurnal Rhythm of Circulating Leptin Levels
Authors: Nishiyama Mitsuru , Makino Shinya , Suemaru Shuso , Nanamiya Wakako , Asaba Koichi , Kaneda Tadafumi , Mimoto Tomoko , Nishioka Tatsuya , Takao Toshihiro , Hashimoto Kozo
Published: April 2003

It is known that circulating leptin shows diurnal variation with a nocturnal rise; however, the mechanisms generating this rhythm have not been fully elucidated. Glucocorticoids are a potent stimulator of leptin secretion, and there is a reciprocal relationship between circulating leptin and glucocorticoid levels. We hypothesized that glucocorticoids could modulate the diurnal rhythm of circulating leptin. We therefore explored the diurnal variation of leptin under situations in which subjects showed no or some shift of glucocorticoid diurnal rhythm, such as prednisolone-administered humans, and adrenalectomized and corticosterone-replaced (ADX+B) rats. The peak level of plasma cortisol immunoreactivity was shifted from early morning to noon by prednisolone administration. The nocturnal increment of plasma leptin in prednisolone-administered patients (71.2 ± 14.2% from 08:00 h value) was significantly greater than that in normal volunteers (12.2 ± 7.5% from 08:00 h value), but the timing of nadir and the peak of plasma leptin was not shifted. In normal rats, the plasma concentration of leptin showed the diurnal rhythm with the bottom at 16:00 h and the top between midnight and early morning. The amplitude of leptin diurnal rhythm was significantly reduced in ADX+B rats (08:00 h: 3.0 ± 0.2, 16:00 h: 2.7 ± 0.2, 00:00 h; 3.7 ± 0.2 ng/ml) compared with sham operated rats (08:00 h: 3.0 ± 0.2, 16:00 h 2.2 ± 0.2, 00:00 h: 4.7 ± 0.4 ng/ml); but ADX+B rats still retained similar timing of nadir and the peak of plasma leptin as observed in sham rats. These results indicate that glucocorticoids enhance the amplitude of leptin diurnal rhythm, and are consistent with previous findings showing that glucocorticoids increase leptin secretion. Glucocorticoids appear to play modulatory, but not essential roles in generating leptin diurnal rhythm.
Evaluation of Cutaneous Modifications in Seventy-Seven Growth Hormone-Deficient Children
Authors: Conte Françoise , Diridollou Stéphane , Jouret Béatrice , Turlier Virginie , Charveron Marie , Gall Yvon , Rochiccioli Pierre , Bieth Eric , Tauber Maïthé
Published: April 2003

Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin surface lipid and hydration were evaluated using noninvasive methods in 77 growth hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD children. We showed that in GHD children, dermis was thinner (0.70 ± 0.10 vs. 0.80 ± 0.10 mm, p < 0.0001 for prepubertal children and 0.81 ± 0.10 vs. 0.94 ± 0.11 mm, p < 0.0001 for pubertal children), stiffer (178.5 ± 57.3 vs. 113.09 ± 37 kPa, p < 0.0001 for prepubertal children and 172.5 ± 61.7 vs. 117.3 ± 42.5 kPa for pubertal children, p < 0.001) and less elastic (0.44 ± 0.09 vs. 0.39 ± 0.06 (nonelasticity index), p < 0.01 for prepubertal children and 0.39 ± 0.05 vs. 0.33 ± 0.04, p < 0.001 for pubertal children) compared to controls. Fourteen GHD children were re-evaluated after 1 year of GH treatment: dermal thickness and skin stiffness were significantly improved (p < 0.001 and p < 0.05 respectively) while elasticity was not modified. During the same period, 11 controls did not show any significant cutaneous modification. IGF-1 values, but not IGFBP-3 values, correlated positively with dermal thickness in GHD children, before and after 1 year of GH treatment. To conclude, GHD children exhibited specific cutaneous modifications. In a subset of GHD children, we showed that these modifications were influenced by GH treatment. More extensive studies are needed to see if these changes correlated with other GH effects.
Increased Bone Mineral Density and Serum Leptin in Non-Obese Girls with Precocious Pubarche: Relation to Low Birthweight and Hyperinsulinism
Authors: Ibáñez Lourdes , Potau Neus , Ong Ken , Dunger David B. , De Zegher Francis
Published: April 2003

Background: Hyperinsulinism and hyperandrogenism have the capacity to increase bone mineral density (BMD) and serum leptin, independently of body fat mass. We therefore assessed lumbar BMD and serum leptin in girls with the sequence of a low birthweight and precocious pubarche (PP) in childhood, in whom hyperinsulinism and hyperandrogenism have been described. Methods: Fifty-two non-obese PP girls were studied (age range 6.9–14.9 years). Serum leptin was also measured in 42 control girls, matched for age, body mass index and pubertal stage. Results: BMD SDS, measured by dual-energy X-ray absorptiometry, was elevated in PP girls compared to the population reference (0.39 ± 0.18 SDS; p = 0.03) and bone age, assessed from hand radiographs, was significantly advanced compared to chronological age (1.2 ± 0.1 years; p < 0.0005). Conclusion: Compared to control girls, PP girls had higher leptin levels for degree of body mass index (PP girls: 9.4 ± 0.6 ng/ml; controls: 7.8 ± 0.6 ng/ml; p = 0.01). In PP girls, serum leptin was inversely related to birthweight (r = –0.32, p = 0.01) and positively related to free androgen index (FAI) (r = 0.71, p < 0.0005). BMD SDS was also inversely related to birthweight (r = –0.26, p < 0.05) and positively related to serum leptin (r = 0.42, p < 0.05), FAI (r = 0.45, p < 0.05) and mean serum insulin during oral glucose tolerance testing (MSI) (r = 0.59, p < 0.0005). In multiple regression, MSI was the strongest determinant of BMD SDS (β = 0.50, p = 0.002). In conclusion, elevated BMD and serum leptin in non-obese PP girls were related to degrees of low birthweight, hyperinsulinism and hyperandrogenism. The characteristic hyperinsulinism of PP girls is proposed to be the key variable in this constellation.
Neuroimmunoregulation of Androgens in the Adrenal Gland and the Skin
Authors: Alesci Salvatore , Bornstein Stefan R.
Published: April 2003

Human adrenals produce large quantities of androgens, especially DHEA which is the most abundant circulating hormone in the human body. Adrenal androgens are regulated by several factors, including pituitary ACTH and an intricate intraadrenal network involving immune cells, cytokines and neuroendocrine factors. The skin is a major target of androgens and androgen receptors are expressed in the epidermis, dermis, sebaceous glands and hair. In addition, the skin has the capacity to metabolize androgens into more powerful compounds. Similar to the adrenal gland, there is an intradermal neuro-immune network involving the local expression of cytokines and neuropeptides. Dysregulation of androgens in the adrenals and/or the skin is associated with acne, hirsutism and androgenic alopecia. Therefore, understanding the mechanisms of these intricate networks is of both basic and clinical relevance and may help to develop new strategies for the treatment of androgen-dependent skin disorders.
The Role of Melanocortins in Skin Homeostasis
Authors: Böhm Markus , Luger Thomas A.
Published: April 2003

Melanocortins are structurally related bioactive peptides which are produced by many extra-neural tissues including the skin. All of the melanocortins (α, β, and γ-melanocyte-stimulating hormone and adrenocorticotropin) have melanotropic activity but can elicit many other effects on skin cells. On the basis of in vitro and in vivo findings melanocortins have been shown to regulate immune and inflammatory responses, hair growth, exocrine gland activity and extracellular matrix composition. These effects are mediated by melanocortin receptors among which the melanocortin-1 receptor is most ubiquitously expressed by human skin cells. Simultaneous expression of melanocortins and their receptors suggest a complex autocrine and/or paracrine regulatory network whose disruption invariably affects skin homeostasis. Expression of melanocortin receptors on various skin cell types further indicates novel pharmacological targets for the treatment of skin diseases.
Development of Efficient Transient Transfection Systems for Introducing Antisense Oligonucleotides into Human Epithelial Skin Cells
Authors: Fimmel Sabine , Saborowski Antje , Orfanos Constantin E. , Zouboulis Christos C.
Published: April 2003

Systemic treatment with antisense oligonucleotides is confounded by the dual problems of potential cytotoxicity of antisense oligonucleotides and carrier molecules such as cationic lipids. Treatment of pathologic conditions affecting the skin may avoid these problems to a large degree due to local application. The success of antisense strategies has been limited by the poor uptake of the transfection reagent and inadequate intracellular compartmentalization. Human skin epithelial cells, therefore, are attractive experimental tools for testing both in vitro and in vivo antisense therapies. In the present study, we determined commercially available liposomes which reproducibly induced a nontoxic increase of oligonucleotide uptake in cultured SZ95 sebocytes and keratinocytes. The final protocol for SZ95 sebocytes was a 4-hour incubation with DOTAP in a 2:1 (w/w) lipid/oligonucleotide ratio in serum-free medium. The fluorescein-labeled (ATCG)5 random oligonucleotide molecules were detected within the nucleus. The optimum transfection system for primary keratinocytes was poly-L-ornithine (12 µg/ml) in a medium without bovine pituitary extract over 4 hours. The uptake of the oligonucleotide increased in the presence of the polycation and oligonucleotide molecules were localized in the cytoplasm of keratinocytes. Oligonucleotide transfection with the help of cationic lipids did not affect the expression of androgen receptor and of the house-keeping gene β-actin. Thus, cationic lipids are useful for delivery of antisense oligonucleotides into skin cells in vitro and may be used for topical application on animal and human skin.
Cross-Cultural Differences in the Management of Children and Adolescents with Diabetes
Authors: Greene A.C. , Tripaldi M. , Chiarelli F. , McKiernan P. , Morris A. , Newton R. , Greene S.
Published: April 2003

Glycaemic control deteriorates frequently in adolescents with diabetes. There is a considerable body of work on the effect of psychological aspects of management in this age group, but few randomized controlled trials of the effect of specific behavioural therapy and lifestyle modification on the improvement of glycaemic control. Of recent interest have been the observations from the Hvidøre Study Group on cross-cultural differences in glycaemic control. The average glycosylated haemoglobin in 22 centres, across 18 countries, varied in young people, with HbA1c levels ranging from 7.6 to 10.2%. No obvious differences in management were identified in this survey that could account for the disparities in glycaemic control. Data from the Scottish Study Group demonstrated similar variation in average glycaemic control in centres across a single culture. Using the qualitative methodology of anthropological research, some specific factors were identified that appear to influence young people’s response to diabetes management and strategies employed by health professionals in their advice and care of the diabetes, particularly in relation to intensive insulin regimens. The main cultural factors influencing glycaemic control appear to be communication, reciprocal support between young people and professional heart carers and family structure within an individualistic, as against an egalitarian, society. Shared beliefs about teenage risk behaviour together with the medicalization of adolescence within medical culture also appears to be highly influential. The aim of this educational discussion group was to explore how a variety of health care professionals from distinctive cultures approach diabetes care delivery in this age group. The specific success and difficulties in different cultures in managing the young person with diabetes were investigated. Also discussed was how qualitative research methodology may generate further research in this area.
Continuous Monitoring of Blood Glucose
Authors: Robert Jean-Jacques
Published: April 2003

Continuous blood glucose monitoring aims to: better evaluate glycaemic variations; better detect hypoglycaemia; and, ultimately, automatize insulin delivery (artificial β cell). The sensors can be fully implantable, with the challenge of constructing durable systems to avoid repeated implantations. In-dwelling needle-like electrodes and microdialysis fibres with a pump that brings the dialysate to the glucose sensor are inserted in the subcutaneous tissue through the skin. The GlucoWatch is an almost non-invasive technique that extracts the extracellular fluid by iontophoresis. In these systems, the glucose oxidase generates the electrical signal, proportional to the glucose concentration. Non-invasive techniques aim at measuring the glucose concentration without breaching the skin, using absorption of light in the infrared spectrum. These techniques have not reached the necessary reliability for use as glycaemic alarms, and even less as artificial β cells. Currently, glucose sensors are mainly used as glycaemic holters to help in the management of insulin therapy.