bluuebunny/crossref_metadata_2025 huggingface dataset:
Inducible Nitric Oxide Synthase Mediates Hypoxia-Induced Hypoxia-Inducible Factor-1α Activation and Vascular Endothelial Growth Factor Expression in Oxygen-Induced Retinopathy
Authors: He Tao , Ai Ming , Zhao Xiao-Hui , Xing Yi-Qiao
Published: December 2007

Objective: Previous studies provided evidence that many factors contribute to retinal angiogenesis, including inducible nitric oxide synthase (iNOS), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). But the role of nitric oxide generated by iNOS in the regulation of expression of hypoxia-inducible genes in retinopathy of prematurity remains unclear. So we sought to better define the molecular basis of this iNOS-dependent regulation. Methods: In this study, using immunohistochemistry, real-time PCR and Western blotting technologies, we investigated the changes of iNOS, HIF-1α, VEGF and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) expressions. Results: Hypoxia- induced overexpression of iNOS, HIF-1α, VEGF, PI3K/Akt and phosphorylated PI3K/Akt was observed in the untreated retinopathy of the prematurity group. Administration of the selective iNOS inhibitor aminoguanidine hemisulfate markedly decreased the expression of these genes. Conclusions: These results indicate that iNOS mediates HIF-1α activation and VEGF expression in retinal angiogenesis and that the PI3K/Akt signaling pathway may play a role in this process.
DNA Hypermethylation Status of Multiple Genes in Papillary Thyroid Carcinomas
Authors: Ishida Eiwa , Nakamura Mitsutoshi , Shimada Keiji , Higuchi Tomonori , Takatsu Keisuke , Yane Katsunari , Konishi Noboru
Published: December 2007

Objective: The aim of this study was hypermethylation of multiple genes for papillary thyroid carcinomas (PTCs). Methods: We examined 39 lesions using methylation-specific PCR to assess hypermethylation in genes, including p16INK4a, p14ARF, RB1, p27Kip1and 06-MGMT. Homozygous deletions of p16INK4a and p14ARF were investigated by differential PCR, all with reference to clinicopathological factors. Results: We foundmethylation of p16INK4a in 35.9% (14/39); p14ARF in 2.6% (1/39); RB1 in 23.1% (9/39); p27Kip1 in 15.4% (6/39),and 06-MGMT in 15.4% (6/39). Hypermethylation of at least one of these genes was apparent in 66.7% (26/39). Homozygous deletions of p14ARF and p16INK4a were detected in 7.7 (3/39) and 2.6% (1/39), respectively. In cases with p16INK4a alterations, tumors were significantly increased. A history of chronic thyroid disease and lymphocytic infiltration was significantly associated with p14ARF alterations, without regional lymph node metastases. Conclusions: Our data suggest that alterations in p16INK4a, mainly hypermethylation, may be linked to tumor growth but not tumor development, while alterations in p14ARF may contribute to the induction of chronic inflammation-related PTCs.
Anti-Tumor Effects of Liposome-Encapsulated Titanium Dioxide in Nude Mice
Authors: Chihara Yoshitomo , Fujimoto Kiyohide , Kondo Hideaki , Moriwaka Yukiko , Sasahira Tomonori , Hirao Yoshihiko , Kuniyasu Hiroki
Published: December 2007

Anatase particles of titanium dioxide (TiO2) absorb ultraviolet (UV) light which is shorter than 415 nm. Photoexcited TiO2, a strong oxidizer, is expected to inhibit malignant cell growth. Liposomes accelerate endophagocytosis to the cytoplasm of encapsulated materials. In this study, we examined anti-tumor effects of TiO2 and liposome-encapsulated TiO2 (LT) with UVA irradiation by an air pouch cancer model using NBT-II bladder cancer cells, which simulates bladder cancer. Injection of TiO2 or LT into the air pouch was followed by UVA irradiation via the opened pouch. Tumors of TiO2 + UVA and LT + UVA groups showed more pronounced necrotic areas, apoptotic indices, nitrotyrosine formation, tumor growth inhibition and increased survival compared with control groups. Especially the LT + UVA group showed more remarkable anti-tumoral effects than the TiO2 + UVA group, which was associated with higher TiO2 incorporation. These findings suggest that LT might be more effective than noncoated TiO2 in the treatment of bladder cancer.
Gaps and Limitations of Psychological Interventions for Bipolar Disorders
Authors: Scott Jan , Colom Francesc
Published: December 2007

Objective: To highlight gaps or limitations in applying evidence-based psychological therapies as an adjunct to medication in the management of bipolar disorders. Method: General and specific gaps in knowledge or perceived limitations were determined by the authors and published examples were identified illustrating these potential barriers to the use or application of adjunctive therapies. Results: Research on the benefits of psychological therapies in bipolar disorders has progressed dramatically in the last decade. There are some uncertainties that need to be further investigated. These can be broadly classified as: for whom should therapy be provided, what therapy and when should therapy be commenced. The latter can be seen from the perspective of both current mental state as well as length of history and number of recurrences. Other issues frequently highlighted by researchers in the field relate to mediators and moderators of therapy effects. Conclusion: Gaps in our knowledge about therapy for bipolar disorder mirror those that exist whenever new treatments, including medications, are introduced into routine clinical practice. Many of these key questions relate to differences between efficacy and effectiveness of adjunctive therapies, the long-term durability of any benefits and mechanisms by which therapies achieve their effects. These can be explored using currently existing scientific paradigms.
Duloxetine Does Not Relieve Painful Physical Symptoms in Depression: A Meta-Analysis
Authors: Spielmans Glen I.
Published: December 2007

Background:Duloxetine inhibits both serotonin and norepinephrine reuptake and is marketed as a treatment for both the core emotional symptoms and painful physical complaints that often accompany depression. Some studies have found that duloxetine is efficacious in treating painful symptoms associated with depression but these findings have been inconsistent. Several narrative review articles have reached positive conclusions about the efficacy of duloxetine as an analgesic in depression but there has been no quantitative systematic review regarding the impact of duloxetine on pain among this population. A meta-analysis of data pertaining to duloxetine’s purported analgesic effects on depressed patients was thus undertaken. Methods:Studies were selected through searching Medline and Cochrane Trial databases as well as examining Lilly’s public clinical trial database. A random effects model was used. Results: Across five trials, the results indicate a very small (d = 0.115) and statistically nonsignificant (p = 0.057) analgesic effect for duloxetine. Additionally, some of the relevant data on duloxetine’s effects have not been reported fully, making it likely that the obtained results reflect an overestimate of its true impact on painful physical symptoms in depression. Discussion:The current analysis is based on a small number of studies; further trials may yield significant results favoring duloxetine. Based upon the currently available evidence, the marketing of duloxetine as an antidepressant with analgesic properties for people with depression does not appear to be adequately supported.
Cognitive versus Behavior Therapy: Processes of Change in the Treatment of Obsessive-Compulsive Disorder
Authors: Anholt Gideon E. , Kempe Pieter , de Haan Else , van Oppen Patricia , Cath Danielle C. , Smit Johannes H. , van Balkom Anton J.L.M.
Published: December 2007

Background: Behavior therapy [exposure and response prevention (ERP)] and cognitive therapy (CT) have proven effective in the treatment of obsessive-compulsive disorder. Direct comparisons between these treatment modalities have exposed no differences in efficacy. However, very little research has been conducted into the differences between the change processes in ERP and CT. This investigation is a first attempt to study change by measuring scores on a weekly basis rather than at specific stages in the treatment and follow-up. Methods: We used the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at weekly intervals to rate and compare the severity of the obsessions and compulsions of 61 completers of either CT or ERP. The aim was to ascertain whether the process of change in CT is different from the process of change in ERP. We expected that ERP would primarily affect behavior, thus reducing compulsions first, while CT would primarily affect thought, thus reducing obsessions first. Results: Firstly, no differences were found between ERP and CT with respect to the change process for obsessions and compulsions. Secondly, it emerged that changes in compulsions predicted all treatment effects better than changes in obsessions. Conclusions: These results suggest that reduction of compulsions is the process through which both ERP and CT affect change.
Systemic Family Therapy in Schizophrenia: A Randomized Clinical Trial of Effectiveness
Authors: Bressi Cinzia , Manenti Stefano , Frongia Patrizia , Porcellana Matteo , Invernizzi Giordano
Published: December 2007

Background: Although evidence suggests the effectiveness of cognitive and behaviorally oriented family therapies for schizophrenia, no specific randomized study has been carried out on Systemic Family Therapy (SFT). The purpose of this longitudinal prospective study was to evaluate the clinical effectiveness of SFT in the treatment of patients suffering from schizophrenia, as compared with a control case sample composed of patients undergoing routine psychiatric treatment. The study included a 2-year follow-up period and was conducted following the Milan School model. Methods: The case sample in the study was made up of 20 patients treated with SFT associated with routine psychiatric treatment, and 20 patients undergoing routine psychiatric treatment alone. Both groups of patients were re-evaluated at the end of treatment (T1) and 12 months after the end of treatment (T2) to assess the clinical course of the illness. Results: At the end of the follow-up period, we noticed an improved clinical course and a better pharmacological compliance in the group of patients treated with SFT. In the experimental case sample, 3 subjects (15%) had relapsed, compared to 13 patients (65%) in the control group (p = 0.03). No significant difference was found in the 2nd year of follow-up. Conclusions: Our study provides an innovative contribution with regard to the evaluation of the clinical effectiveness of SFT in the treatment of schizophrenic patients. The clinical results were significant, and we thus feel justified in continuing to use this type of therapy in integrated interventions involving schizophrenic patients.
Posttraumatic Embitterment Disorder in Comparison to Other Mental Disorders
Authors: Linden Michael , Baumann Kai , Rotter Max , Schippan Barbara
Published: December 2007

Background: The term ‘posttraumatic embitterment disorder’ (PTED) was recently introduced to describe a subtype of adjustment disorders, characterized by prolonged embitterment, severe additional psychopathological symptoms and great impairment in most areas of life in reaction to a severe negative but not life threatening life event. The aim of this study is an empirical description and validation of the clinical concept of PTED, by comparing clinically defined PTED patients with patients suffering from other mental disorders on measures of posttraumatic stress and psychopathological distress. Methods: Fifty inpatients, suffering from PTED according to previously defined clinical diagnostic criteria, were compared with another 50 patients, matched by age and gender, who did not meet clinical criteria for PTED but for other mental disorders. Psychiatric diagnoses were assessed by the Mini International Neuropsychiatric Interview. Self-report measures included the Bern Embitterment Scale, the Impact of Event Scale, the PTED Self-Rating Scale and the SCL-90. Results: According to the Mini International Neuropsychiatric Interview both groups fulfilled the criteria for many disorders with a significantly higher occurrence of major depression and chronic adjustment disorder but less generalized anxiety disorder lifetime in PTED patients. Patients with PTED scored significantly higher on the global scores and on most subdimensions of the SCL-90, the Impact of Event Scale, the Bern Embitterment Scale and the PTED Self-Rating Scale. Conclusions: Clear differences were found between PTED patients and patients with other mental disorders in regard to the quality and intensity of psychopathological as well as posttraumatic stress symptoms. PTED can help further subclassify and specify adjustment and reactive disorders.
Repetitive Transcranial Magnetic Stimulation in Bulimia Nervosa: Preliminary Results of a Single-Centre, Randomised, Double-Blind, Sham-Controlled Trial in Female Outpatients
Authors: Walpoth M. , Hoertnagl C. , Mangweth-Matzek B. , Kemmler G. , Hinterhölzl J. , Conca A. , Hausmann A.
Published: December 2007

Background: Bulimia nervosa (BN) is often associated with depressive symptoms and treatment with antidepressants has shown positive effects. A shared deficient serotonergic transmission was postulated for both syndromes. The left dorsolateral prefrontal cortex was argued to regulate eating behaviour and to be dysfunctional in eating disorders. Methods: Fourteen women meeting DSM-IV criteria for BN were included in a randomised placebo-controlled double-blind trial. In order to exclude patients highly responsive to placebo, all patients were first submitted to a one-week sham treatment. Randomisation was followed by 3 weeks of active treatment or sham stimulation. As the main outcome criterion we defined the change in binges and purges. Secondary outcome variables were the decrease of the Hamilton Depression Rating Scale (HDRS), the Beck Depression Inventory (BDI) and the Yale-Brown Obsessive Compulsive Scale (YBOCS) over time. Results: The average number of binges per day declined significantly between baseline and the end of treatment in the two groups. There was no significant difference between sham and active stimulation in terms of purge behaviour, BDI, HDRS and YBOCS over time. Conclusion: These preliminary results indicate that repetitive transcranial magnetic stimulation (rTMS) in the treatment of BN does not exert additional benefit over placebo. A larger number of patients might clarify a further role of rTMS in the treatment of BN.
Treatment of Osteogenesis Imperfecta: Who, Why, What?
Authors: Glorieux Francis H.
Published: December 2007

Introduction: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone fragility and reduced bone mass. It may present with a wide range of severity. About 85% of the cases are linked to mutations in one of the two genes encoding type I collagen. In other cases of OI, there are mutations in the expression of a cartilage-related protein or of 3-prolyl-hydroxylase.Increased bone turnover rate, due to the repair activity triggered to replace weak tissue, is the rule. Often, disuse bone loss further compounds the decrease in bone mass. These findings justify the use of bisphosphonates to reduce osteoclast-mediated bone resorption, and so tilt the remodeling balance towards an increase in bone mass. Conclusions: Cyclical intravenous pamidronate administration reduces bone pain, and increases bone mass and density. No negative effects on growth or fracture repair have been observed. There is an increase in size of vertebral bodies and thickening of cortical bone, which translates into decreased fracture incidence and improved ambulation. However, the long-term consequences of low bone turnover in children with OI are unknown at the present time. Innovative surgery and specific occupational and physiotherapy programs are integral parts of the treatment protocol. This approach will prevail until gene-based therapies become clinically applicable.
Endocrine Consequences of Adult Traumatic Brain Injury
Authors: Behan Lucy Ann , Agha Amar
Published: December 2007

Background: Traumatic brain injury (TBI) is the most common cause of death and disability in young adults living in industrialised countries. Over the last few years, there has been an increasing awareness that hypopituitarism can complicate TBI in a significant proportion of survivors: at least 25% of TBI survivors develop one or more pituitary hormone deficiencies. This remarkably high frequency has changed the traditional concept that hypopituitarism was a rare complication of TBI and suggests that most cases of posttraumatic hypopituitarism remain undiagnosed and untreated in clinical practice. It is therefore reasonable to infer that posttraumatic hypopituitarism may make an important contribution to the high rates of physical and neuropsychiatric morbidity in patients with head injury. Conclusions: There is clearly a need for identification as well as appropriate and timely management of hormone deficiencies in TBI patients to reduce morbidity, aid recovery and rehabilitation and avoid the long-term complications of pituitary failure.
Neonatal Diabetes
Authors: Shield J.P.H.
Published: December 2007

Background: Nine distinct genetic conditions have been identified in the last 12 years causing neonatal diabetes mellitus through failure of normal pancreatic development, islet cell dysfunction or β-cell destruction. This review will focus on the three conditions about which our understanding of the pathology – and in some cases the treatment options – has greatly increased: transient neonatal diabetes mellitus, permanent neonatal diabetes due to ‘channelopathies’ and immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome. Conclusions: Effective treatment of neonatal diabetes requires thorough understanding of the disease processes underlying this highly variable condition. As our knowledge of pancreatic development and physiology expands, so, too, do the treatment options for some patients.
Experience from the German Pegvisomant Observational Study
Authors: Strasburger Christian J. , Buchfelder Michael , Droste Michael , Mann Klaus , Stalla Günter K. , Saller Bernhard
Published: December 2007

Background:The German Pegvisomant Observational Study (GPOS) was created immediately after marketing authorisation was received in Germany for Somavert®(pegvisomant) for the treatment of patients with acromegaly. In August 2006, the database underwent its fifth interim analysis of 263 patients, the vast majority of whom previously had insufficient disease control with other treatment modalities. The GPOS documents both safety and efficacy aspects of the treatment of patients with acromegaly by the first growth hormone-receptor antagonist, pegvisomant. This treatment led to normalization of disease activity in most patients, had favourable effects on glucose metabolism and improved signs and symptoms of the disorder. The safety profile indicates that pegvisomant treatment is well tolerated, and tumour growth is noted to occur at the same rate as for somatostatin analogue treatment. Transaminase elevations occurred in 16 of the 263 patients but spontaneously resolved in eight of them and promptly normalised in five patients who discontinued treatment. GPOS is presently the largest database of pegvisomant-treated patients, and it comprises more than 87% of all patients treated with pegvisomant in Germany. Conclusions: The GPOS database provides important information about treatment modalities, safety and efficacy of pegvisomant in patients with acromegaly.
Genetics of Puberty
Authors: Herbison Allan E.
Published: December 2007

Background: Puberty is controlled by genetic and environmental factors. This review examines the genetic basis for puberty by evaluating known gene mutations associated with disordered puberty in humans. At present, at least 17 different single-gene mutations are recognized as being associated with delayed or absent puberty in humans. Several of these genes are involved in the development of the olfactory nervous system, with mutations typically resulting in anosmia/hyposmia and hypogonadotropic hypogonadism, otherwise known as Kallmann syndrome. The biological basis for the association between smell and fertility is strong as development of the gonadotropin-releasing hormone (GnRH) neurons, responsible for regulating fertility, is intricately associated with development of the olfactory system. Other gene mutations, including the recently discovered kisspeptin-GPR54 signalling system, affect puberty by directly or indirectly modulating the functioning of the GnRH neurons and pituitary gonadotrophs. Together, these single-gene mutations are presently estimated to account for approximately 30% of individuals with disorders of puberty. Conclusions: A large number of different genes are involved in the complex process of bringing about reproductive competency. In addition to the genetic mutations associated with precocious and delayed puberty, the oligogenic aetiology of these conditions is being increasingly appreciated.
Introduction and Management of Puberty in Girls
Authors: de Muinck Keizer-Schrama Sabine M.P.F.
Published: December 2007

Background: Management of puberty in the hypogonadal girl remains controversial. Estrogens have profound effects on growth and development. Oral estrogens, the most widely used form, undergo first-pass metabolism in the liver and alter many aspects of hepatic function. Transdermal estrogens are not subject to first-pass metabolism and are effective at mimicking spontaneous pubertal estrogen levels resulting in normal pubertal development. Age-appropriate induction of puberty should be initiated at 12 to 13 years of age; delaying puberty any longer may compromise quality of life during adolescence. Estrogens should be started at a low dose, approximately one-tenth to one-eighth of the adult replacement dose, and then increased gradually over a period of 2 to 4 years. Generally, progestins are added after 2 years of estrogen therapy. With these treatment regimens, breast development typically proceeds at a normal pace; however, the effects on uterine dimensions are less clear. Concomitant treatment with oral dehydroepiandrosterone (or dehydroepiandrosterone sulfate) advances pubic hair development in the adolescent girl with panhypopituitarism. Conclusions: In the hypogonadal girl, puberty should be induced with very low doses of transdermal estradiol at 12 to 13 years of age with gradual dose escalations over 2 to 4 years. Combination estrogen/androgen therapy in girls with hypogonadism should be explored in future research.
Prenatal and Neonatal Diagnosis and Treatment of Congenital Adrenal Hyperplasia
Authors: Speiser Phyllis W.
Published: December 2007

Background: Clinical management of patients with congenital adrenal hyperplasia (CAH) involves treating hormonal deficiencies, addressing issues related to genital ambiguity, avoiding morbidities and communicating with the family about risk of CAH in other members. This article briefly reviews the prenatal and neonatal diagnosis of CAH caused by steroid 21-hydroxylase deficiency, as well as treatment options and neonatal screening approaches. Conclusions: Screening for CAH can reduce adrenal crises, avoid incorrect sex assignments, lower mortality (especially in males) and avoid inappropriate somatic growth and precocious puberty.
Growth in Patients with Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
Authors: Dörr Helmuth G.
Published: December 2007

Background: One important goal in the management of children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is to achieve normal growth. Reviewing available data published over the last few years on growth and height outcomes in CAH patients, it becomes evident that an acceptable height can be achieved by many CAH patients. However, linear growth and final adult height may be stunted in some patients due to factors related to the timing of diagnosis, the age at therapy onset, the start of therapy, the adequacy of metabolic control, the quality of therapy, patient compliance and the experience of the treating physician. In children with CAH who have a poor height prognosis, additional treatment options should be considered. Conclusions: Treatment of children with CAH requires individualized approaches to prevent long-term growth failure.
A Review of the Management of Two Common Clinical Problems Found in Patients with Cystic Fibrosis: Cystic Fibrosis-Related Diabetes and Poor Growth
Authors: Hardin Dana S.
Published: December 2007

Background: Cystic fibrosis-related diabetes (CFRD) and glucose intolerance often occur in teens and adults with CF. The initial deficiency is an impaired first-phase insulin response; as patients age, peak insulin response is delayed and less robust than normal. Decreased insulin sensitivity (insulin resistance) is also present in patients with CF. Insulin is the only currently recommended therapy for all types of CFRD, and many clinicians find that basal/bolus regimens are optimal. Another common finding in children with CF is poor linear growth and inadequate weight gain. Recombinant human growth hormone (rhGH) is being explored in this patient population; studies overall show improvements in height and weight, without development of glucose intolerance. Conclusions: rhGH may be a useful growth-promoting therapy in children with CF.
Lymphocytic Hypophysitis
Authors: Molitch Mark E. , Gillam Mary P.
Published: December 2007

Background:Lymphocytic hypophysitis is a disorder of the pituitary gland that presents as a sellar mass lesion and/or hypopituitarism. It causes pituicyte destruction and hypopituitarism and is speculated to have an autoimmune basis. Diagnosis: Lymphocytic hypophysitis should be considered in the differential diagnosis of pituitary masses and/or hypopituitarism in females who are pregnant or in the early postpartum period, especially in cases associated with other autoimmune diseases or unusual patterns of hormone deficiencies. A definitive diagnosis requires tissue biopsy. A presumptive clinical diagnosis can be made based on a history of gestational or postpartum hypopituitarism, a contrast-enhancing sellar mass with imaging features characteristic of lymphocytic hypophysitis, a pattern of pituitary hormone deficiency with early loss of adrenocorticotrophic hormone and thyroid-stimulating hormone unlike that typically found with macroadenomas, relatively rapid development of hypopituitarism and a degree of pituitary failure disproportionate to the size of the mass.Symptoms resulting from partial or panhypopituitarism occur in approximately 80% of cases and multiple deficiencies are found in approximately 75% of cases. Management:Appropriate management remains controversial. Corticosteroid therapy has been advocated as a means of attenuating inflammation, but given the uncertainty of its efficacy and the known adverse effects, such therapy does not seem justified for most patients. The optimal surgical strategy involves partial resection of the mass to decompress the surrounding structures. All patients with lymphocytic hypophysitis require appropriate replacement therapy for deficient hormones. Long-term follow-up is mandatory to monitor for the development of other hormonal deficits.
Hypopituitarism Oddities: Craniopharyngiomas
Authors: Karavitaki Niki
Published: December 2007

Craniopharyngiomas are tumours associated with significant long-term pituitary dysfunction. The rates of anterior pituitary hormone deficits are not influenced by treatment modality and do not differ between childhood- and adult-onset disease. The apparent paradox of growth in the absence of growth hormone (GH) has been reported in children with this tumour and is not, as yet, completely understood. GH replacement therapy offers significant benefits for both children and adults (although adult patients are less likely to lose weight or body fat). Based on results of retrospective studies, GH therapy does not seem to increase the risk of tumour recurrence.
Adult Consequences of Congenital Adrenal Hyperplasia
Authors: Arlt Wiebke , Krone Nils
Published: December 2007

Background: Congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency accounts for 95% of all CAH cases and is one the most common inborn metabolic disorders. While consensus and guidelines on therapeutic management in infancy and childhood are available, data regarding the treatment of adults with CAH are scarce. This review highlights the issues that need to be addressed when caring for the adult CAH patient. Issues include glucocorticoid and mineralocorticoid replacement, adrenal crisis, female and male fertility, genetic counselling, prenatal dexamethasone treatment, pregnancy and the odds of long-term morbidity and mortality in these patients. Conclusions: Large-scale audit studies are urgently required to help optimise management and long-term outcome of these patients, as are optimisation of glucocorticoid replacement and biochemical monitoring tools. It is very important that the adult CAH patient receive regular monitoring by a multidisciplinary team at the secondary- or tertiary-care level.
Excess Mortality in Acromegaly
Authors: Holdaway I.M.
Published: December 2007

Background: Increased production of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in patients with acromegaly is associated with a twofold increase in mortality compared with the general population. The range of standardised mortality rates in various studies ranges from 1.2 to 3.6. Predictors of Mortality: Multivariate analysis has indicated that post-treatment serum GH levels and, in a number of studies, serum IGF-I levels are the most powerful predictors of outcome. Normal IGF-I concentrations and random GH levels <2.5 µg/l measured by polyclonal radioimmunoassay result in optimal outcome. Other factors adversely influencing mortality include hypertension and a long interval between onset of the disorder and diagnosis. Conclusions: Analysis of recent reports suggests that adoption of treatment guidelines with appropriate post-treatment target ranges for GH and IGF-I, together with the availability of newer methods to control GH oversecretion, has significantly improved patient outcomes.
Mortality and Reduced Growth Hormone Secretion
Authors: Stochholm Kirstine , Christiansen Jens , Laursen Torben , Gravholt Claus Højbjerg
Published: December 2007

Background: Data regarding the mortality rates of patients with growth hormone deficiency (GHD), whether or not treated with growth hormone (GH), are limited, but an increased mortality rate among hypopituitary patients compared with the general population has been documented. Cardiovascular disease has been suggested as a primary cause of death, whereas cancer statistics might be influenced by the number of malignancies causing the pituitary disease. Furthermore, differences in mortality rates in females and males have been reported. Methods: Epidemiological studies of mortality in hypopituitary and GHD patients were identified and reviewed. Results: Most studies showed an increased mortality rate in hypopituitary and GHD patients and an increased mortality among female compared with male patients. There is a possibility that differences between patients with adult-onset and childhood-onset GHD might also exist. Two studies showed a normal mortality rate in GHD patients treated with GH compared with the general population. Conclusions: Although an increased mortality rate in hypopituitary patients is well documented, further research is needed to provide more reliable estimates of the actual causes. Caution should be taken in the interpretation of results regarding mortality and GH treatment due to the limited amount of data and the limitations of the study designs.
Long-Acting Forms of Growth Hormone-Releasing Hormone and Growth Hormone: Effects in Normal Volunteers and Adults with Growth Hormone Deficiency
Authors: Clemmons David R.
Published: December 2007

Background: Growth hormone (GH) replacement therapy in adults and children has found broad acceptance by endocrinologists and patients, but the need for daily injections remains a significant barrier to more widespread use. Long-acting Formulations: Several approaches have been taken to develop long-acting forms of GH and to extend the half-life of GH-releasing factor. Each of these preparations has been tested in experimental animal models and found to extend the half-life of GH and GH-releasing hormone (GHRH) and to increase mean daily GH levels. Frequent sampling following administration of long-acting GHRH showed that the greatest increases occurred in trough GH levels, which increased 7.8-fold. The extended GH half-life and increased trough levels resulted in increases in insulin-like growth factor I (IGF-I) levels, which increased 1.4- to 4.1-fold and extended the duration of the IGF-I increase from 7 to 14 days. These increases in GH and IGF-I levels allow these compounds to be administered much less frequently, and several studies have shown that IGF-I levels can be maintained in a therapeutically effective range with much less frequent GH administration. Safety: Complications other than those generally associated with GH therapy include nodule formation and lipoatrophy at the injection sites. One long-term study of a long-acting formulation demonstrated that growth could be effectively stimulated in GH-deficient children, but that the peak growth velocity was only about 80% of that seen following daily subcutaneous GH injections. Subcutaneous nodule formation in some patients may have contributed to noncompliance and thus to the difference in growth velocity. Conclusions: Different types of GH and GHRH formulations have been developed with extended half-lives. In general, these preparations are pharmacokinetically and pharmacodynamically effective, extend GH half-lives with longer sustained elevation of IGF-I and permit much less frequent GH administration. Thus, it may be possible to develop a therapeutically effective form of GH for use in long-term treatment. The precise efficacy and safety assessments to use in monitoring long-term GH administration have not been definitively established.
Long-Acting Hydrocortisone for Glucocorticoid Replacement Therapy
Authors: Johannsson Gudmundur , Filipsson Helena , Bergthorsdottir Ragnhildur , Lennernäs Hans , Skrtic Stanko
Published: December 2007

Background: Glucocorticoid (GC) deficiency is a consequence of various disorders that are by themselves rare. Because of this low prevalence, the low cost of GC replacement therapy and the belief that existing outcomes are good, there has been little interest in development of new and improved pharmaceutical products for treatment of GC deficiency. However, GC replacement therapy is complex: diurnal variation of endogenous cortisol must be replicated, GC needs may change during times of physical and psychological stress and there is no biomarker of its action that can be used to monitor individual dose response. Current Limitations: Recent data suggest that the outcome of established long-term GC replacement therapy may not be as good as previously believed. Short-acting GCs such as hydrocortisone (HC) and cortisone acetate for replacement therapy require 2 to 3 administrations per day. Developing Alternatives: Drug delivery system technologies are now available that could permit design and manufacture of a formulation that could accommodate once-daily administration of HC. Such a formulation would enable more physiological serum cortisol-time profiles than are possible with currently available formulations. This short review provides some background on GC replacement therapy, along with recent data on the outcome of patient groups with GC insufficiency, and briefly discusses some general principles for a controlled-release (‘long-acting’) HC formulation.
The Epidemiology and Management of Pituitary Incidentalomas
Authors: Daly Adrian F. , Burlacu Maria Cristina , Livadariu Elena , Beckers Albert
Published: December 2007

Prevalence:The prevalence of pituitary tumors has been a topic of controversy for many years. Autopsy and radiological series show that pituitary incidentalomas may be present in one of six people. Recent epidemiological data suggest that clinically apparent pituitary adenomas have a prevalence of approximately one in 1,000 people in the general population. The disconnect between these two prevalence rates underlines the common clinical quandary of how to manage pituitary incidentalomas, particularly those lacking clinical signs/symptoms or hormonal abnormalities. Management:The natural history of incidentalomas suggests that periodic hormonal, clinical and radiological follow-up is the optimal approach. In the absence of tumor growth or relevant symptoms, screening can be continued intermittently or curtailed based on the clinical judgment of the physician. In the presence of hormonal hypersecretion, the management of pituitary incidentalomas, whether they are micro- or macroadenomas, should follow accepted clinical guidelines. For incidental pituitary macroadenomas without hormonal hypersecretion, clinical management should also include assessments for visual field impairment or hypopituitarism. In such cases, regular radiological and hormonal follow-up is required to identify tumor growth or the appearance of new symptoms. In the presence of tumor growth or new hormonal abnormalities, surgical options should be considered and discussed with the patient.
Congenital Brain Tumors in a Series of Seven Patients
Authors: Nejat Farideh , Kazmi Syed Shuja , Ardakani Shahin Behjati
Published: December 2007

Background: Congenital brain tumors are very rare. We review these tumors in patients younger than 2 months diagnosed in our Department. Methods: Seven congenital brain tumors were diagnosed during 5 years. Clinical and radiological findings and prognosis were analyzed. Results: The study included 5 female and two male infants. Two cases were diagnosed antenatally by means of ultrasonography. All patients presented with intracranial hypertension. All neuroimaging studies revealed nonhomogenous tumors with cystic and solid components, except for the case with choroid plexus papilloma (CPP). Hydrocephalus was evident in all of them. Most were infratentorial lesions. There were three teratomas, one primitive neuroectodermal tumor, one ependymoblastoma and one CPP. Six patients were operated on, with one intraoperative death. Two passed away postoperatively with aspiration pneumonia. One patient died due to complications of chemotherapy and another one due to tumor recurrence 1 year after surgery. Only the patient with CPP is alive after 2 years. Conclusions: Today, the availability of noninvasive imaging procedures such as computerized tomography scan and magnetic resonance imaging has improved the diagnosis of congenital brain tumors. In spite of development in prenatal diagnosis, appropriate pre- and postoperative management, the mortality associated with these tumors still remains high. The final prognosis in these patients is still discouraging despite early surgery and operative and anesthetic improvements. CPP is accompanied by the best prognosis, whereas teratoma and primitive neuroectodermal tumors have the worst prognosis.
Pediatric Vertebral and Spinal Epidural Tumors: A Retrospective Review of Twelve Cases
Authors: Karagoz Guzey Feyza , Emel Erhan , Aycan Abdurrahman , Bas N. Serdar , Seyithanoglu M. Hakan , Ozkan Nezih , Karabulut Cem
Published: December 2007

Objective: Pediatric vertebral tumors are rare, and most of the reported series have limited numbers of cases. Diagnosis of these tumors is difficult because of the patients’ age and the rarity of the lesions. We aimed to report the clinical, radiological and pathological characteristics in a small series of pediatric vertebral and spinal epidural tumors and to discuss diagnostic and treatment difficulties. Materials and Methods: Twelve consecutive pediatric cases with vertebral or spinal epidural tumors were reviewed retrospectively. Results: The mean age was 12.6 years, and male and female patients were equal in number. The most common symptom was pain. There were some neurological or local findings in all patients, and there were some positive results on plain radiographs in all cases except 2. The tumors were removed totally in 9 cases. There were histologically malignant lesions in 3 and benign lesions in 9 cases. Three patients with malignant tumors were treated by radiotherapy and 2 by chemotherapy. One patient with thoracic hemangioma was also treated by embolization after surgery. One case with cervical Dabska’s tumor died due to air embolization. The other patients were followed for 48.3 months. The preoperative neurological deficits were resolved completely in all patients except the one with only biopsy performed at the last follow-up. There were no new spinal deformities on follow-up. Conclusion: Children with vertebral tumors and spinal epidural tumors usually present with pain and neurological deficits or local findings, and there are some indications on plain radiographs. Therefore, a careful physical examination and detailed evaluation of radiographs may minimize the rate of misdiagnosis and underestimation. Most of these tumors are benign, therefore, their outcome is good, and cure may be possible for many of the cases.
Protective Effect of Sildenafil (Viagra) in Transient Spinal Cord Ischemia
Authors: Kıymaz Nejmi , Yılmaz Nebi , Mumcu Çiğdem , Anlar Ömer , Özen Süleyman , Kayaoğlu Çetin Refik
Published: December 2007

Prospective study of the neuroprotective activity of sildenafil in a rat spinal ischemia model. The present study involved 21 male Sprague-Dawley rats. The animals were divided into 3 groups. Physiological serum was administered intraperitoneally to the 8 rats in the control group at the beginning of reperfusion for a period of 20 min after abdominal aortal occlusion. Sildenafil (Viagra®) was administered as a single 10-mg/kg/day intraperitoneal dose to the 8 rats in the sildenafil group at the beginning of reperfusion after 20 min of abdominal aortal occlusion. No occlusion was performed and no agent was administered to the 5 rats in the sham group, but the abdominal aorta was reached by means of surgical intervention. Before the animals were sacrificed, several physiological and biochemical parameters were investigated, preoperative and postoperative motor functions were also assessed, and somatosensory evoked potential (SEP) monitoring and histopathological examinations were carried out. No differences were found between the physiological and biochemical parameters in each of the 3 groups. Neurological scoring performed after reperfusion demonstrated a significant improvement in the neurological results relative to those of the control group over 48 h in subjects that received sildenafil. These animals also showed better 24-hour SEP results, measured in terms of extended latency and decreased amplitude, than the control animals. A histopathological study showed reduced ischemic symptoms in rats that received sildenafil compared with those in the control group. However, no anomalies were observed in the sham group with respect to the histopathological and neurological findings. These results indicate that neurological damage due to spinal-cord ischemia-reperfusion injury can be reduced by sildenafil.
Delayed Intrauterine Repair of an Experimental Spina Bifida with a Collagen Biomatrix
Authors: Eggink A.J. , Roelofs L.A.J. , Feitz W.F.J. , Wijnen R.M.H. , Lammens M.M.Y. , Mullaart R.A. , van Moerkerk H.T.B. , van Kuppevelt T.H. , Crevels A.J. , Verrijp K. , Lotgering F.K. , van den Berg P.P.
Published: December 2007

Background/Purpose: The aim of the study was to evaluate whether a collagen biomatrix is useful for delayed intrauterine coverage of a surgically created spina bifida in a fetal lamb. Methods: In 20 fetal lambs, surgery was performed at 72 or 79 days’ gestation. In 15 lambs a spina bifida was created surgically. In 8 lambs it was covered with a collagen biomatrix 2 weeks later and in 7 lambs it was left uncovered. Five lambs served as sham operated controls. Neurological examination was performed at 1 week of age and afterwards the lambs were sacrificed for further histological evaluation. Results: None of the 5 surviving lambs with the defect covered showed loss of spinal function and the architecture of the spinal cord was preserved in 4 of the 5 lambs. In the uncovered group, 1 of the 4 surviving lambs had loss of spinal function, 5 lambs were available for histological evaluation and 4 of them showed disturbance of the architecture of the spinal cord. Conclusions: Collagen biomatrices can be used for intrauterine coverage of an experimental spina bifida and can preserve the architecture of the spinal cord. Neurological outcome is not different between fetuses with their spinal cord covered and fetuses with uncovered cords.
Treatment of Cerebrospinal Fluid Shunting Complications in a Nigerian Neurosurgery Programme
Authors: Komolafe Edward O. , Adeolu Augustine A. , Komolafe Morenikeji A.
Published: December 2007

Background/Aims: For a century since the first cerebrospinal fluid (CSF) shunt surgery, ventriculoperitoneal (VP) shunt insertion for the treatment of hydrocephalus has routinely been performed. A lot of common and rare complications following this procedure have been reported in 24–47% of the cases. The aim of this paper was to present our experience with the treatment of hydrocephalus in our centre and highlight our management of two unusual complications with the available resources. Methods: Retrospective clinical review. Results: A total of 86 patients with hydrocephalus were seen in our unit. There were 52 males and 34 females (male:female ratio 3:2). The age of the patients ranged from 1 day to 68 years. The majority of the patients (92%) were below 5 years of age. Sixty-five patients had shunting procedures [VP shunt: 62 (95.4%); endoscopic third ventriculostomy: 3 (4.6%)]. Of the 62 patients with VP shunts, 16 (25.8%) had complications while 2 of the 3 patients with endoscopic third ventriculostomies had complications. The complications following the VP shunts were CSF shunt sepsis (n = 12; 19.4%), abdominal complications (n = 3; 4.8%), subdural haematoma (n = 2; 3.2%) and scalp necrosis in 1 patient. Conclusion: VP shunt procedures have come to stay and will remain with us despite recent advances such as endoscopic third ventriculostomy. Care should be taken to prevent all complications whether common or rare by paying particular attention to patient selection, shunt selection and surgical details. The adaptation of local technology and justified use of limited facilities and resources can go a long way in the management of both common and rare complications in developing nations.
Hydrocephalus following Bilateral Jugular Venous Thrombosis in a Child: Case Report and Review of the Literature
Authors: Ibrahim Ibrahim , Rahme Ralph , Hourani Roula , Ali Youssef , Melki Imad , Rizk Tony
Published: December 2007

Hydrocephalus resulting from bilateral thrombosis of the jugular veins has been rarely described in the literature. We report the case of an 18-month-old girl who was diagnosed with this condition following total parenteral nutrition. We also review the literature relevant to this subject and discuss the pathophysiology of hydrocephalus in the setting of bilateral jugular venous thrombosis.
Prolonged Cricopharyngeal Muscle Spasm after Resection of the Cervical Vagus Nerve in a 15-Year-Old
Authors: Bhayani Mihir K. , MacCracken Ellen , Frim David , Baroody Fuad M.
Published: December 2007

Cervical vagal schwannomas are rare pediatric head and neck neoplasms that present a surgical challenge if the nerve is intimately involved with the mass. In some instances, resection of the vagus nerve with the mass is required. This will usually result in vocal cord paralysis and uncommonly dysphagia due to unilateral cricopharyngeal spasm. We present a case in which these two complications resulted in significant dysphagia and aspiration, which improved with expectant management.