bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to HIV antiretroviral therapy in HIV+ Ugandan patients purchasing therapy
Authors: Byakika-Tusiime J , Oyugi J H , Tumwikirize W A , Katabira E T , Mugyenyi P N , Bangsberg D R
Published: January 2005

Our objective was to determine the level of adherence and reasons for non-adherence to antiretroviral therapy (ART) among HIV-positive (HIV+) people on ART in a resource-limited setting. Patients receiving ART were recruited into the cross-sectional study from three treatment centres in Kampala, Uganda. The number of missed doses over the last three days was assessed by structured patient interviews and dichotomized at ±95% adherence. Reasons for non-adherence were assessed with both structured patient interviews and unstructured qualitative interviews. Independent predictors of non-adherence were assessed with multivariate logistic regression. In all, 304 HIV-infected persons on ART were enrolled into the study. Factors associated with non-adherence were marital status (odds ratio (OR) = 2.93, 95% confidence interval (CI) 1.32–6.50) and low monthly income <50 US$ [OR = 2.77, 95% CI 1.64–4.67]. We concluded that levels of self-reported adherence in patients receiving ART in Kampala are comparable to levels in resource-rich settings with inability to purchase and secure a stable supply as a major barrier to adherence.
The outcome of oropharyngeal gonorrhoea treatment with different regimens
Authors: Manavi K , Young H , McMillan A
Published: January 2005

Little is known of the efficacy of different antibiotics for the treatment of oropharyngeal gonorrhoea in routine clinical practice. The aim of the study was to investigate the treatment outcome of oropharyngeal gonorrhoea with different antibiotics.

Case-notes of culturally proven oropharyngeal gonorrhoea diagnosed between January 1998 and January 2003 were reviewed for the antibiotic of choice and the result of test-of–cure (TOC) seven and 14 days after treatment. Of 117 episodes of pharyngeal gonorrhoea, 77 episodes (66%) were followed up with one TOC and 25 (21%) had two TOC. Treatment failure was recorded in 10% (8/77) of episodes: the failure rate was 28% (4/14) in patients treated with amoxicillin 3 g/probenecid 1 g stat and 11% (4/35) in those treated with ciprofloxacin 500 mg stat.

The failure rate in treating pharyngeal gonorrhoea supports the need for a pharyngeal TOC culture as part of routine follow-up for patients infected at this site. As only 66% of patients had a TOC culture, efforts should be made to increase the number of patients having a TOC.
A shrinking service: can it mislead people into thinking there is less disease?
Authors: Kozakis L , Maiti H
Published: January 2005

This study looks at the impact of reduced clinical services on infection rates in a small suburban genitourinary medicine clinic, and compares the rates with the national trends. Data were gathered from the KC60 reports and compared with national data on the Health Protection Association Website. Between 1996 and 2001, waiting time for appointments increased along with the number of patients not attending appointments. There was an apparent drop in the number of cases of chlamydial infection in contrast to a national increase; however, when the figures were adjusted for the fall in clinic size, a small rise was seen. The incidence of gonorrhoea, in contrast, rose in excess of national trends, and new HIV/AIDS diagnoses tripled. A disproportionate number of wart virus infections were seen. It seems that long waits for appointments and high DNA rates are skewing diagnosis rates for the clinic, and the shrinking service appears not to be meeting the community's needs.
Gender-specific predictors of genital herpes vaccine acceptance in a college population
Authors: Auslander B A , Rosenthal S L , Succop P A , Mills L M , Stanberry L R , Bernstein D I
Published: January 2005

Vaccines represent one promising method for reducing the sexually transmitted disease (STD) epidemic. This study evaluated whether influences on the decision to accept a genital herpes vaccine differed by gender. In all, 518 college students completed a questionnaire on sexual history, health beliefs, and acceptance of a potential genital herpes vaccine. Each predictor variable plus a gender interaction term were analysed in separate logistic regression models. Follow-up analyses were performed by gender for outcomes that displayed significant interactions. Results indicated that a prior history of an STD and increased perception of risk for acquiring genital herpes were significant predictors of vaccine acceptance for men, while younger age and concerns about vaccine safety were significant predictors for women. Endorsement of a vaccine strategy targeting sexually experienced people was an influential factor for both genders, but was a much stronger one for women. Results suggest that gender-specific strategies may be crucial to genital herpes vaccine acceptance.
Strategies for diagnosis of bacterial vaginosis in a resource-poor setting
Authors: Posner S F , Kerimova J , Aliyeva F , Duerr A
Published: January 2005

This study evaluated Amsel's criteria, the FemExam® card and pH plus amine methods for the diagnosis of bacterial vaginosis (BV) in a resource-poor setting. Two hundred Azerbaijani women participated in a study about reproductive health that included a gynaecological examination and an interviewer-administered survey. Using the WHO syndromic diagnosis algorithm, nearly all women (99%) had abnormal vaginal discharge. The prevalence of BV by Gram stain was 35%; using pH plus amine, the FemExam® card and Amsel's criteria, prevalence ranged from 29% to 49%. No behavioural or demographic characteristics were associated with BV as diagnosed by Gram stain. The sensitivity ranged from 0.59 to 0.74 and specificity from 0.65 to 0.92 using the three methods. The pH plus amine test is better than syndromic management protocols, and although it is not the most sensitive or specific of the three methods it will be easiest to implement in resource-poor settings.
Does where we live matter? Community characteristics and HIV and sexually transmitted disease prevalence in southwestern China
Authors: Yang Xiushi
Published: January 2005

Studies of HIV/sexually transmitted diseases (STDs) in China have paid little attention to community characteristics that may be conducive to HIV/STD risky behaviours and to the spread of the epidemics. Using data from a community survey and employing both correlation and multiple regression analysis, this paper examines the county-level determinants of the prevalence of HIV/STD risky behaviours and infections. The results suggest that community social and behavioural norms predict significantly the prevalence of illicit drugs and commercial sex and that the prevalence of the two HIV/STD risky behaviours reinforces each other. The analysis also shows that migration significantly increases prevalence of HIV and STDs, as does prevalence of injecting drug use and commercial sex. Overall, HIV and STDs are found not to be diseases of poverty but more likely byproducts of social and behaviour changes associated with development and urbanization.
Impact of chronic hepatitis C infection on outcomes of patients with an advanced stage of HIV-1 infection in an area of low prevalence of co-infection
Authors: Hung C-C , Chen M Y , Hsieh S M , Hsiao C F , Sheng W H , Chang S C
Published: January 2005

To ascertain whether hepatitis C (HCV) co-infection affects the progression of HIV infection, we initiated an eight-year prospective observational study at a university hospital in Taiwan where seroprevalences of HCV antibody and HIV antibody were low. Fifty-three (12.0%) consecutive non-haemophiliac HIV1-infected patients with HCV co-infection and 387 (88.0%) patients without HCV and hepatitis B co-infection were enrolled between June 1994 and June 2002 and observed until December 2002. Outcomes evaluated included the risk for acute hepatitis, hepatic decompensation, HIV disease progression and mortality, and changes of CD4+ count and plasma viral load (PVL) after initiation of highly active antiretroviral therapy (HAART) at the end of the study. The baseline CD4+ count, PVL and proportion of patients with AIDS-defining opportunistic illnesses (OI) at study entry were similar between patients with HCV co-infection and those without co-infection, but HCV-co-infected patients were older (39 versus 35 years, P = 0.01) and had a higher proportion of intravenous drug use (17.0% versus 0.8%, P < 0.001). After a total observation duration of 1137 patient-years (PY) (median, 791 days; range, 3–3053 days), the incidence of acute hepatitis in HCV-co-infected patients was 13.89 per 100 PY (95% confidence interval [CI], 13.31–14.49) and that in patients without co-infection was 6.39 per 100 PY (95% CI, 6.24–6.55 per 100 PY), with an adjusted odds ratio (OR) of 2.769 (95% CI, 1.652–4.640). At the end of the study, CD4+ count increased by 137 × 106 and 157 × 106/L in patients with and without HCV co-infection, respectively, ( P = 0.47). The proportions of achieving undetectable PVL (<400 copies/mL) after HAART was similar (76.7% versus 74.9%, P = 0.79). The adjusted OR for development of new AIDS-defining OI was 1.826 (95% CI, 0.738–4.522) in HCV-co-infected patients as compared with HCV- uninfected patients. The adjusted hazards ratio for death of HCV-co-infected patients when compared with those without co-infection was 0.781 (95% CI, 0.426–1.432). Our findings suggested that HCV co-infection was associated with a significantly higher risk for acute hepatitis in HIV-infected patients receiving antiretroviral therapy, but it had no adverse impact on virological, immunological and clinical responses to HAART and survival when compared with patients without HCV and HBV co-infection.
Fatal Kaposi's sarcoma-associated immune reconstitution following HAART initiation
Authors: Crane Heidi M , Deubner Heike , Huang Jane C , Swanson Paul E , Harrington Robert D
Published: January 2005

This unique report describes a fatal case of immune reconstitution syndrome associated with Kaposi's sarcoma (KS). This case also illustrates the possibility of cryptic visceral KS with minimal cutaneous disease, as well as the potential for differential responses of cutaneous and visceral KS to treatment.
The emerging HIV/AIDS epidemic in Georgia
Authors: Tkeshelashvili-Kessler Alexander , del Rio Carlos , Nelson Kenrad , Tsertsvadze Tergiz
Published: January 2005

The first case of HIV in Georgia was diagnosed in 1989. Through December 2002, a total of 375 cases of HIV infection were reported. However, the World Health Organization estimates that the true number of infections may be closer to 1700. In all, 70% of reported cases are among injection drug users. Based on the UNAIDS classification, Georgia is a 'low-level HIV country' with an HIV prevalence of less than 1% in all groups, including drug users. However, there is a high prevalence of hepatitis B and C, suggesting a significant risk for the spread of HIV. Georgia, a newly independent republic, is experiencing an increase in injection drug use, a rise in sexually transmitted infections and commercial sex trade that create a fertile soil for the potential rapid spread of HIV. However, it is also a country with a unique window of opportunity for limiting the spread of HIV.
New technology and partner notification - why aren't we using them?
Authors: Tomnay J E , Pitts M K , Fairley C K
Published: January 2005

Partner notification is crucial to the effective control of sexually transmissible infections (STIs) and has not changed substantially over recent years. New technology for communication has been rapidly adopted in our communities but little work has been carried out about its role in contact tracing. Text messaging, emails and the Internet could be useful tools for both provider and patient referral but considerable ethical considerations are involved. Technology is available to help protect the basic tenets of confidentiality and privacy but more thorough exploration of these methods is required to establish efficacy and appropriateness in contact tracing. This research is important if we are to procure an evidence base for future contact tracing strategies rather than allowing these methods to become commonplace at the initiation of our clients.
Audit of the management of victims of sexual assault in a city centre genitourinary medicine clinic
Authors: Thompson C
Published: January 2005

A total of 113 individuals (101 women, 12 men) who had experienced sexual assault (SA) attended the genitourinary medicine clinic. Of the 60 patients who were seen at a dedicated clinic for victims of SA, the median age was lower, a greater number had reported to the police and the interval between assault and attendance was shorter, compared with the 53 who attended the routine walk-in service. However, the majority of the men attended routine clinics.

Drug-facilitated rape was reported in 20%, excess alcohol in 10% and the use of violence in 20% cases.

Overall, the prevalence of sexually transmitted infections was the same as the total clinic population.
Multicentre audit of the treatment of uncomplicated urinary tract infection in South Thames
Authors: Newell A , Bunting P , Anson K , Fox E ,   South Thames GU Medicine Audit Group
Published: January 2005

A regional audit report on the management of uncomplicated urinary tract infections (UTIs) in genitourinary (GU) medicine clinics in the UK in South Thames (South London, Kent, Surrey and Sussex). The majority of centres use trimethoprim as first-line treatment for uncomplicated UTIs. The incidence of trimethoprim resistance was 22.6%. The group has therefore recommended that cephalexin should be the first choice antibiotic for suspected UTIs within GU medicine.
Unilateral gonococcal ophthalmia without genital infection: an unusual presentation in an adult
Authors: Harry Tubonye C , Black Peter D
Published: January 2005

We present the case of unilateral gonococcal ophthalmia without concomitant genital infection seen in an adult, with the potential for visual impairment if not adequately recognized and promptly treated.
Improving access to genitourinary medicine by satellite clinics: an evaluation of the use of pump-priming funding
Authors: Challenor Rachel , Pinsent Susan , Baker Debbie
Published: January 2005

Pump-priming funding was used to implement a three-month pilot project of two satellite clinics. We conducted a review to determine the impact of the satellite clinics on the local genitourinary (GU) medicine service and the level of success with reference to priorities in the National Strategy for Sexual Health and HIV. A total of 140 patients attended a university clinic and 52 attended a market town clinic. In all, 14% of university clinic and 15% of market town patients were chlamydia positive. Targets for offering/uptake of HIV testing (as outlined in the National Strategy) for 2004 were all met, and those for 2007 were all met except for one. Both satellites were judged successful. After effective implementation of a satellite service, staffing could be transferred to general practitioners with special interest in GU medicine/nurse specialists. This could allow additional satellites to be developed without compromising the main service, helping to improve access to local GU medicine services and promoting local clinical networks.
Mutational analysis of the DEAD-box RNA helicase eIF4AII characterizes its interaction with transformation suppressor Pdcd4 and eIF4GI
Authors: ZAKOWICZ HALINA , YANG HSIN-SHENG , STARK CRISTI , WLODAWER ALEXANDER , LARONDE-LEBLANC NICOLE , COLBURN NANCY H.
Published: January 2005

Eukaryotic initiation factor (eIF) 4A unwinds secondary and tertiary structures in the 5′-untranslated region of mRNA, permitting translation initiation. Programmed cell death 4 (Pdcd4) is a novel transformation suppressor and eIF4A-binding partner that inhibits eIF4A helicase activity and translation. To elucidate the regions of eIF4A that are functionally significant in binding to Pdcd4, we generated point mutations of eIF4A. Two-hybrid analysis revealed that five eIF4A mutants completely lost binding to Pdcd4 while four eIF4A mutants retained wild-type levels of binding. The residues that, when mutated, inactivated Pdcd4 binding specified ATP binding, ATP hydrolysis, or RNA binding. With the exception of the Q-motif mutant eIF4AP56L, the eIF4A mutants inactivated for Pdcd4 binding were inactivated for binding to eIF4G (GM, GC, or both) and for enhancing translation. Several eIF4A mutants showing wild-type level binding to Pdcd4 were also inactivated for binding to eIF4G and for enhancing translation. Thus, significant dissociation of eIF4A’s Pdcd4- and eIF4G-binding regions appears to occur. Because three of the four eIF4A mutants that retained Pdcd4 binding also suppressed translation activity in a dominant-negative manner, the structure that defines the Pdcd4-binding domain of eIF4A may be necessary but is insufficient for translation. A structural homology model of eIF4A shows regions important for binding to Pdcd4 and/or eIF4G lying on the perimeters of the hinge area of eIF4A. A competition experiment revealed that Pdcd4 competes with C-terminal eIF4G for binding to eIF4A. In summary, the Pdcd4-binding domains on eIF4A impact both binding to eIF4G and translation initiation in cells.
Interaction of RRF and EF-G from E. coli and T. thermophilus with ribosomes from both origins—insight into the mechanism of the ribosome recycling step
Authors: RAJ V. SAMUEL , KAJI HIDEKO , KAJI AKIRA
Published: January 2005

Ribosome recycling factor (RRF), elongation factor-G (EF-G), and ribosomes from Thermus thermophilus (tt-) and Escherichia coli (ec-) were used to study the disassembly mechanism of post-termination ribosomal complexes by these factors. With tt-RRF, ec-EF-G can release bound-tRNA from ec-model post-termination complexes. However, tt-RRF is not released by ec-EF-G from ec-ribosomes. This complex with tt-RRF and ec-ribosomes after the tRNA release by ec-EF-G is regarded as an intermediate of the disassembly reaction. Not only tt-RRF, but also mRNA, cannot be released from ec-ribosomes by tt-RRF and ec-EF-G. These data suggest that the release of RRF from ribosomes is coupled or closely related to the release of mRNA during disassembly of post-termination complexes. With tt-ribosomes, ec-EF-G cannot release ribosome-bound ec-RRF even though they are from the same species, showing that proper interaction of ec-RRF and ec-EF-G does not occur on tt-ribosomes. On the other hand, in contrast to a published report, tt-EF-G functions with ec-RRF to disassemble ec-post-termination complexes. In support of this finding, tt-EF-G translocates peptidyl tRNA on ec-ribosomes and catalyzes ec-ribosome-dependent GTPase, showing that tt-EF-G has in vitro translocation activity with ec-ribosomes. Since tt-EF-G with ec-RRF can release tRNA from ec-post-termination complexes, the data are consistent with the hypothesis that the release of tRNA by RRF and EF-G from post-termination complexes is a result of a translocation-like activity of EF-G on RRF.
Identification and characterization of critical cis-acting sequences within the yeast Ty1 retrotransposon
Authors: BOLTON ERIC C. , COOMBES CANDICE , EBY YOLANDA , CARDELL MATTIAS , BOEKE JEF D.
Published: January 2005

The yeast long terminal repeat (LTR) retrotransposon Ty1, like retroviruses, encodes a terminally redundant RNA, which is packaged into virus-like particles (VLPs) and is converted to a DNA copy by the process of reverse transcription. Mutations predicted to interfere with the priming events during reverse transcription and hence inhibit replication are known to dramatically decrease transposition of Ty1. However, additional cis-acting sequences responsible for Ty1 replication and RNA dimerization and packaging have remained elusive. Here we describe a modular mini-Ty1 element encoding the minimal sequence that can be retrotransposed by the Ty1 proteins, supplied in trans by a helper construct. Using a mutagenic screening strategy, we recovered transposition-deficient modular mini-Ty1-HIS3 elements with mutations in sequences required in cis for Ty1 replication and integration. Two distinct clusters of mutations mapped near the 5′-end of the Ty1 RNA. The clusters define a GAGGAGA sequence at the extreme 5′-end of the Ty1 transcript and a complementary downstream UCUCCUC sequence, 264 nt into the RNA. Disruption of the reverse complementarity of these two sequences decreased transposition and restoration of complementarity rescued transposition to wild-type levels. Ty1 cDNA was reduced in cells expressing RNAs with mutations in either of these short sequences, despite nearly normal levels of Ty1 RNA and VLPs. Our results suggest that the intramolecular interaction between the 5′-GAGGAGA and UCUCCUC sequences stabilizes an RNA structure required for efficient initiation of reverse transcription.
Poor Agreement among Prothrombin Time International Normalized Ratio Methods: Comparison of Seven Commercial Reagents
Authors: Horsti Juha , Uppa Helena , Vilpo Juhani A
Published: January 2005

Background: Prothrombin time (PT) has long been the most popular test for monitoring oral anticoagulation therapy. The International Normalized Ratio (INR) was introduced to overcome the problem of marked variation in PT results among laboratories and the various recommendations for patient care. According to this principle, all reagents should be calibrated to give identical results and the same patient care globally. This is necessary for monitoring of single patients and for application of the results of anticoagulation trials and guidelines to clinical practice.

Methods: We took blood samples from 150 patients for whom oral anticoagulation had been prescribed. Plasmas were separated and PTs determined by use of seven commercial reagents and four calibrator sets. The differences in results were assessed by plotting, for each possible pair of methods, the differences in INR values for each sample against the mean INR value (Bland-Altman difference plots).

Results: Mean results differed significantly (P <0.001) for 17 of 21 possible paired comparisons of methods. Only two pairs of methods produced very similar results when assessed for problems of substantial differences in INR values; a significant, systematic increase in the difference with INR; and a significant systematic increase in the variation in difference with increasing INR values.

Conclusions: The agreement among several (and perhaps most) commercial INR methods is poor. The failure of current calibration strategies may severely compromise both the monitoring of individual patients and the application of oral anticoagulation guidelines and trial results to clinical practice.
Exocytosis in excitable cells: a conserved molecular machinery from yeast to neuron
Authors: Lledo PM
Published: January 2005

One of the basic cellular functions of nearly every cell type is the exocytotic release of synthesized molecules, stored and packaged into intracellular vesicles or granules. A variety of approaches has been used to identify and characterize the molecules that mediate vesicular trafficking along the secretory pathway. The findings obtained with these approaches suggest that common mechanisms may underlie a wide variety of vesicle-mediated transport steps. This review presents some of the recent findings regarding the study of the cellular mechanisms which control neurotransmitter and hormone release from neurons and endocrine cells respectively, and focuses on regulation of these mechanisms. The similarities between these two cell types can be seen as evidence to support the hypothesis according to which the regulated exocytosis apparatus could have evolved from a constitutive fusion machinery to which some key modulators have been added. Insight into secretory vesicles will be relevant not only to the understanding of vesicular trafficking or cell polarity but also to the understanding of higher nervous functions resulting from synaptic plasticity.
Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: clinical, laboratory and genetic findings
Authors: Korenke GC , Roth C , Krasemann E , Hufner M , Hunneman DH , Hanefeld F
Published: January 2005

X-linked adrenoleucodystrophy (ALD) has been shown to be one of the most frequent causes of Addison's disease in men. It is characterized by an impaired peroxisomal beta-oxidation of very long chain fatty acids and is associated with mutations of the ALD gene resulting in a defective peroxisomal membrane transport protein. There is a striking variability of endocrinological and neurological symptoms in patients with ALD, with no clearly evident correlation between mutations of the ALD gene and the different neurological phenotypes. No data on endocrinological symptoms and the ALD genotype have been published so far. We report endocrinological, clinical, laboratory and molecular genetic data from 55 patients with ALD from 34 families. Endocrinological symptoms of adrenal insufficiency were observed in 33 patients, 20 of whom showed additional neurological symptoms of cerebral ALD or adrenomyeloneuropathy. Isolated neurological symptoms were seen in 12 patients; in nine patients there were neither endocrinological nor neurological symptoms. Mutations of the ALD gene (n = 28) were detected in 50 patients (including nine sets of brothers) from 32 families. No correlation was found between the ALD gene mutation and endocrinological dysfunction. However, we found that all sets of brothers were concordant for the endocrinological phenotype (cortisol synthesis was reduced in two sets and normal in seven sets), whereas four sets showed a discordant neurological phenotype. As yet unknown hereditary factors other than mutations within the ALD gene may interfere with the endocrinological phenotype more strongly than with the neurological phenotype of ALD.
Melatonin concentration before and during testosterone replacement in primary hypogonadic men
Authors: Rajmil O , Puig-Domingo M , Tortosa F , Viader M , Garcia Patterson A , Schwarzstein D , de Leiva A
Published: January 2005

OBJECTIVE: To study circadian levels of melatonin in primary hypogonadic adult men before and after testosterone treatment. DESIGN AND METHODS: Circadian serum melatonin profiles were studied in six men with primary hypogonadism before and during testosterone substitution and compared with an age-matched control group (n = 6). RESULTS: Hypogonadal patients had higher plasma melatonin concentrations than the control group during day time (34.2 +/- 8.8 compared with 5.4 +/- 0.5 ng/l, means +/- SD; P < 0.005) and night-time (74.8 +/- 34.5 compared with 30.8 +/- 3.2 ng/l). A 3 months course of testosterone replacement treatment in the hypogonadal group was followed by a diminution of the amplified melatonin circadian rhythm, with lower mean values both during the day (34.2.8 +/- 8 compared with 12.7 +/- 2.45 ng/l, P < 0.001) and at night (74.8 +/- 34.5 compared with 41.5 +/- 13.5 ng/l, P < 0.01), and a decrease in the total area under the curve (958 +/- 318 compared with 475.5 +/- 222.9, P = 0.046). There was a significant negative correlation between melatonin (r = -0.69) and testosterone concentrations. CONCLUSIONS: These data indicate that diminished testosterone in male primary hypogonadism is associated with enhanced plasma levels of melatonin, and that testosterone substitution treatment induces a deamplification of the circadian rhythm of melatonin values in humans.
Leptin levels are strongly correlated with those of GH-binding protein in prepubertal children
Authors: Bjarnason R , Boguszewski M , Dahlgren J , Gelander L , Kristrom B , Rosberg S , Carlsson B , Albertsson-Wikland K , Carlsson LM
Published: January 2005

OBJECTIVE: Nutritional status is an important determinant of growth, and previous studies have indicated that this is due, at least in part, to an increased target-tissue sensitivity to GH. An attractive candidate for mediating this effect is leptin, a hormone secreted by the adipose tissue. The aim of this study was to investigate if there was a connection between GH-binding protein (GHBP) and leptin. DESIGN AND METHODS: We investigated the relationship between serum levels of leptin and those of GHBP in 229 prepubertal children. These included 107 healthy children with normal GH secretion, 55 GH-deficient (GHD) children and 55 children born small for gestational age (SGA) sampled on one occasion for GHBP and leptin, and 12 healthy children followed longitudinally at monthly interval for 1 year. RESULTS: In the healthy children and in those born SGA, the serum concentration of GHBP was positively correlated with that of leptin (r = 0.65, P < 0.001; r = 0.74, P < 0.001 respectively). There was no correlation between GHBP and leptin in the group of children with GHD (r = 0.27, not significant). This means that leptin alone explained 42% of the variation of GHBP in the healthy group and 55% in the SGA group. The correlation remained after adjustment for body mass index and age in the healthy children (r = 0.57, P < 0.0001, r2 = 0.33) and for children born SGA (r = 0.74, P < 0.0001, r2 = 0.55). There was a positive correlation between the intra-individual monthly changes in GHBP and changes in leptin respectively, in the 12 healthy children followed longitudinally, the mean of the correlation coefficients was 0.38 (median = 0.29; range 0.03 to 0.86; P < 0.05). CONCLUSIONS: There was a highly significant correlation between serum levels of leptin and those of GHBP, except in children with GHD. The possibility that leptin could mediate the effects of body fat mass on GH sensitivity, therefore, merits further investigation.
Occult eutopic Cushing's syndrome--failure of simultaneous bilateral petrosal sinus sampling to diagnose pituitary-dependent Cushing's syndrome
Authors: Heppner C , Becker K , Saeger W , Gunther RW , Allolio B , Krone W , Winkelmann W
Published: January 2005

Simultaneous bilateral inferior petrosal sinus (IPS) sampling has been repeatedly proposed to be a highly specific approach for the diagnosis of Cushing's disease and 100% sensitivity in detecting autonomous pituitary ACTH secretion by an adenoma has been reported in a large series. We now report on a patient suffering from ACTH-dependent Cushing's syndrome in whom repeated bilateral IPS sampling failed to detect a central/peripheral gradient diagnostic for autonomous pituitary ACTH secretion during initial evaluation. Applying lysine vasopressin as the corticotroph secretatogue, the maximum central/peripheral gradient was 1.0 before and 1.1 following stimulation. Moreover, results of high dose dexamethasone and corticotrophin releasing hormone administration suggested ectopic ACTH secretion. Since thorough diagnostic procedures failed to localise a suspected carcinoid tumour, occult ectopic Cushing's syndrome was diagnosed. Eight years later, a pituitary macroadenoma was detected by magnetic resonance imaging (MRI), IPS catheterisation then revealed a maximal central/ peripheral gradient of 9.3 before and 20.4 after the intravenous administration of lysine vasopressin. Resected tumour tissue was classified as a typical densely granulated ACTH cell adenoma. We conclude that repeated MRI scans should be included in the follow-up of patients with a diagnosis of occult ectopic Cushing's syndrome to avoid the risk of overlooking 'occult eutopic Cushing's syndrome'.
Use of In-111 pentetreotide scintigraphy in the diagnosis of a midgut carcinoid causing Cushing's syndrome
Authors: Segu VB , Mahvi DM , Wilson MA , Hale SJ , Warner TF , Meredith M , Shenker Y
Published: January 2005

A 57-year-old man presented with clinical features of hypercortisolism and was diagnosed with ACTH-dependent Cushing's syndrome. Biochemical testing showed partial suppression of urinary free cortisol with high dose dexamethasone. Initial computed tomography (CT) of the chest and abdomen, and magnetic resonance imaging of the pituitary were negative. In-111 pentetreotide scintigraphy with single photon emission computerized tomography revealed two 'hot' lesions in the abdomen which were then confirmed by subsequent directed thin-slice abdominal CT and small bowel barium study. At surgery, two segments of ileum, adjoining mesentery and lymph nodes were resected. Histopathology was consistent with a malignant carcinoid tumor of the ileum which stained intensely for ACTH. Plasma ACTH, and serum and urinary cortisol normalized postoperatively. To our knowledge, this is the first reported case of ileal carcinoid tumor causing Cushing's syndrome with premortem diagnosis. Another unique feature of this case is that In-111 pentetreotide scan provided the decisive clue to localization of the tumor.
Amiodarone induces a different pattern of ultrastructural change in the thyroid to iodine excess alone in both the BB/W rat and the Wistar rat
Authors: Pitsiavas V , Smerdely P , Li M , Boyages SC
Published: January 2005

Amiodarone (AMD)-induced toxicity can be a life-threatening complication which limits the use of amiodarone as an anti-arrhythmic agent. The aim of the present study was to determine the nature of AMD toxicity by comparing ultrastructural changes induced by AMD and equivalent amounts of iodide in two animal models, the Wistar and the autoimmune BB/W rat. Rats were divided into control (water), AMD- (30 mg AMD/kg) or iodide-treated (10 mg/kg) groups. Thyroids were removed at 15 weeks and processed for electron microscopy. We found that AMD induced specific ultrastructural changes of thyroid cytotoxicity in both rat models, which were distinct compared with changes induced by excess iodide alone. Specific changes included marked distortion of thyroid architecture, evidence of necrosis and apoptosis, inclusion bodies, lipofuscinogenesis and markedly dilated endoplasmic reticulum (ER). Our data indicate that AMD is directly cytotoxic to the thyroid an effect mediated by disruption of subcellular organelle function. ER dilatation is suggestive that AMD cytotoxicity may be mediated through disruption of the protein sorting pathways leading to a drug-induced form of ER storage disease. The predilection of the thyroid to AMD may be explained by the additive effects of excess iodine and AMD drug toxicity on protein sorting pathways.
Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the control of prolactin secretion in prepubertal male rats
Authors: Aguilar E , Tena-Sempere M , Aguilar R , Gonzalez D , Pinilla L
Published: January 2005

The role of N-methyl-D-aspartate (NMDA) in the control of prolactin (PRL) secretion was analysed in prepubertal male rats. In experiment 1, males of different ages were decapitated after administration of NMDA or vehicle. In experiment 2, 30-day-old males were killed at different times after administration of vehicle, NMDA, MK-801 (a non-competitive NMDA antagonist) or NMDA plus MK-801. In experiment 3, 23-day-old males were sham-orchidectomized or orchidectomized. Orchidectomized males were or were not implanted with Silastic capsules containing different amounts of testosterone. On day 30, the animals were decapitated after administration of vehicle, NMDA or MK-801. In experiment 4, 30-day-old male rats were decapitated after being injected with vehicle, NMDA, Nw-nitro-L-arginine methyl ester (NAME) (an inhibitor of nitric oxide (NO) synthase), or NMDA plus NAME. Serum PRL concentrations, and dopamine pituitary and hypothalamic content were measured. In experiment 5, males pretreated with vehicle or NAME were killed after administration of the precursor of serotonin synthesis 5-hydroxytryptophan (5-HTP), the 5-HT1 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or the 5-HT2 agonist (+/-) 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). Finally, the effects of NMDA, NAME and sodium nitroprusside (SNP) were tested in dispersed adenohypophyseal cells. We found that: (1) antagonism of NMDA receptors with MK-801 decreased PRL secretion in intact, orchidectomized and orchidectomized-testosterone treated male rats; (ii) NMDA inhibited PRL release in vivo through an increase in dopamine release and this effect was potentiated by NAME and prevented by testosterone; (iii) NMDA inhibited PRL, secretion in vitro and this effect was observed in presence of both SNP and NAME; (iv) NAME blocked the stimulatory effects of 5-HTP and DOI on PRL secretion. We conclude that endogenous glutamate stimulates PRL release and that NO might have a pivotal role in the mechanisms involved in the control of PRL release, inhibiting the release of dopamine and modulating the effects of NMDA and 5-HT.
Paracrine regulation of cellular interactions in the testis: factors in search of a function
Authors: Schlatt S , Meinhardt A , Nieschlag E
Published: January 2005

Throughout evolution, gamete generation and sex hormone production are the two processes combined in the testis. The local proximity of sex steroid-producing cells and spermatogenic cells allows multiple cellular interactions to occur and thereby facilitates the modulation and/or synchronisation of both testicular functions. This mini review provides an introduction to the vast variety of different testicular cell types, the unique bi-compartmental organization of the testis, the many factors being released in the testis and the different forms of cellular interactions occurring between testicular cells. Selected members of two groups of signal molecules (sex steroids, growth factors) are described in detail and specific examples for the intratesticular actions of signalling factors are presented.
Reduced gastric inhibitory polypeptide but normal glucagon-like peptide 1 response to oral glucose in postmenopausal women with impaired glucose tolerance
Authors: Ahren B , Larsson H , Holst JJ
Published: January 2005

OBJECTIVE: The gastrointestinal hormones, gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are both released from the gut after oral glucose ingestion and stimulate insulin secretion. This study examined the release of these hormones in subjects with impaired glucose tolerance (IGT), which precedes the development of non-insulin-dependent diabetes. DESIGN AND METHODS: Six postmenopausal women with IGT, aged 59 years, underwent a 75 g oral glucose tolerance test and plasma levels of GIP and GLP-1 were determined regularly during the following 2 h. The results were compared with those in seven age- and weight-matched women with normal glucose tolerance (NGT). RESULTS: Basal plasma levels of GIP and GLP-1 were not different between the groups. In response to the oral glucose ingestion, plasma levels of both GIP and GLP-1 increased in both groups. The plasma GIP increase after glucose ingestion was, however, reduced in women with IGT. Thus, the GIP response as determined as the area under the curve for the 60 min after oral glucose was 34.8 +/- 3.2 pmol/l per min in women with IGT versus 56.4 +/- 7.8 pmol/l per min in those with NGT (P = 0.021). In contrast, the GLP-1 response to oral glucose was not different between the groups. By definition, the glucose response to oral glucose was markedly increased in women with IGT, and the insulin response during the second hour after glucose ingestion was exaggerated. CONCLUSIONS: The GIP response to oral glucose is impaired in postmenopausal women with IGT, whereas the plasma GLP-1 response is not affected.
Clinical trials of GH treatment in patients with Turner's syndrome in Japan--a consideration of final height. The Committee for the Treatment of Turner's Syndrome
Authors: Takano K , Ogawa M , Tanaka T , Tachibana K , Fujita K , Hizuka N
Published: January 2005

Clinical trials of human GH (hGH) therapy in Turner's syndrome were started in 1986. Between 1986 and 1990. 362 patients were enrolled; 115 were treated for more than 6 years. The age at the start of treatment ranged from 5 to 18 years (mean 10 years). Fifty-one patients received hGH at a weekly dosage of 0.5 IU/kg and 64 received 1.0 IU/kg by daily s.c. injection. Both treatment groups showed a statistically significant growth increase during the initial 4 years of treatment. The rate of increase in height was significantly greater for the initial 2 years with the high dose than with the low dose. The increases in height over 6 years of treatment (expressed by S.D. score for chronological age) were 1.48 +/- 0.8 with 0.5 IU/kg per week and 1.80 +/- 1.0 with 1.0 IU/kg per week. To date, 260 patients have stopped GH therapy. In 32% of them, the height attained was above the -2 S.D. value for normal girls. In 27%, the growth rate was not sufficient when they stopped treatment. The mean final height (growth rate < or = 1.0 cm/year) of patients treated for more than 6 years was 142.2 +/- 6.5 cm (n = 15) with 0.5 IU/kg per week, and 144.3 +/- 3.9 cm (n = 15) with 1.0 IU/kg per week. The adult height was improved by GH treatment, although final height did not differ statistically between the two dose regimens. No remarkable adverse events occurred during the treatment. These results indicate that hGH treatment improves the final height in patients with Turner's syndrome.
The effects of two doses of replacement growth hormone on the biochemical, body composition and psychological profiles of growth hormone-deficient adults
Authors: Carroll PV , Littlewood R , Weissberger AJ , Bogalho P , McGauley G , Sonksen PH , Russell-Jones DL
Published: January 2005

This study examined the effects of growth hormone (GH) replacement on the insulin-like growth factor-I (IGF-I), body composition and psychological profiles of GH-deficient adults. We assessed whether two doses of GH produced different effects on these variables and whether patients who, at the end of the study chose to remain on long-term GH replacement responded differently to those who chose to abandon therapy. Forty-two adults (aged 42.9 +/- 1.9 years (mean +/- S.E.M.)) with documented GH deficiency entered two studies (24 in study 1, 18 in study 2). Biochemical, body composition and psychological profiles were assessed at baseline, and after 6 months and 1 year. Psychological assessments were performed using well-established, independent, validated 'Quality of Life' questionnaires (Nottingham Health Profile (NHP) and the Psychological General Well-Being Schedule (PGWB)). The study protocols differed only in the doses of growth hormone (0.024 mg/kg per day and 0.012 mg/kg per day respectively). Comparison between studies and between patients eventually continuing and abandoning GH therapy was performed. GH replacement was associated with significant changes in IGF-I levels (P < 0.001), body composition (P < 0.01) and self-perceived well-being (NHP, P < 0.01; PGWB, P < 0.01). The higher dose of GH produced a greater IGF-I response than the lower dosage (44.6 +/- 7.3 vs 26.2 +/- 3.6 nmol/l, P < 0.05), but no better psychological response (NHP, P = 0.22; PGWB, P = 0.23). Those deciding to continue replacement therapy did not respond differently to those choosing to abandon therapy with respect to IGF-I (P = 0.72), body composition (P = 0.38) and psychological assessment (NHP, P = 0.29; PGWB, P = 0.24). GH replacement in GH-deficient adults was associated with significant improvements in self-perceived well-being as well as changes in body composition and other variables. This improvement was similar at two different doses of replacement GH. Those patients electing to continue on long-term replacement did not achieve a demonstrably different psychological, body composition or biochemical benefit to those patients deciding to discontinue replacement.
Impaired vasopressin suppression and enhanced atrial natriuretic hormone release following an acute water load in primary aldosteronism
Authors: Kimura T , Yamamoto T , Ohta M , Ota K , Shoji M , Funyu T , Mori T , Sahata T , Omata K , Abe K
Published: January 2005

The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) and their involvement in renal water and electrolyte metabolism in primary aldosteronism in humans were studied. An oral acute water load (20 ml/kg body weight) was given to each of 12 patients before and after surgical removal of their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured simultaneously, and renal water and electrolyte metabolism and tubular functions were determined. The same water load was given to seven normal subjects and the same parameters were determined. In the presence of mineralocorticoid excess before the operation, plasma AVP was relatively low compared with plasma osmolality (Posm), but was not suppressed in response to decreases in Posm after the water load. Baseline plasma ANH was high and increased further after the water load; urinary dilution and diuresis both remained normal. After the operation, baseline plasma AVP was normal and decreased in response to the decrease in Posm after the water load, with normal urinary dilution and diuresis. Baseline plasma ANH was normal, and did not increase after the water load. The ratio of urinary K and Na clearances and distal tubular reabsorption of Na increased before the operation. These results suggest that there are perturbations of AVP and ANH release in primary aldosteronism, despite the normal urinary dilution after a water load.
Resistance to vasopressin action on the kidney in patients with Cushing's disease
Authors: Knoepfelmacher M , Pradal MJ , Dio RD , Salgado LR , Semer M , Wajchenberg BL , Liberman B
Published: January 2005

OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.