bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of quinacrine in the treatment of prion disease
Authors: Yung Lotus , Huang Yong , Lessard Pierre , Legname Giuseppe , Lin Emil T , Baldwin Michael , Prusiner Stanley B , Ryou Chongsuk , Guglielmo B Joseph
Published: January 2005

Background

Prion diseases are caused by the accumulation of an aberrantly folded isoform of the prion protein, designated PrPSc. In a cell-based assay, quinacrine inhibits the conversion of normal host prion protein (PrPC) to PrPSc at a half-maximal concentration of 300 nM. While these data suggest that quinacrine may be beneficial in the treatment of prion disease, its penetration into brain tissue has not been extensively studied. If quinacrine penetrates brain tissue in concentrations exceeding that demonstrated for in vitro inhibition of PrPSc, it may be useful in the treatment of prion disease.

Methods

Oral quinacrine at doses of 37.5 mg/kg/D and 75 mg/kg/D was administered to mice for 4 consecutive weeks. Plasma and tissue (brain, liver, spleen) samples were taken over 8 weeks: 4 weeks with treatment, and 4 weeks after treatment ended.

Results

Quinacrine was demonstrated to penetrate rapidly into brain tissue, achieving concentrations up to 1500 ng/g, which is several-fold greater than that demonstrated to inhibit formation of PrPSc in cell culture. Particularly extensive distribution was observed in spleen (maximum of 100 μg/g) and liver (maximum of 400 μg/g) tissue.

Conclusions

The documented extensive brain tissue penetration is encouraging suggesting quinacrine might be useful in the treatment of prion disease. However, further clarification of the distribution of both intracellular and extracellular unbound quinacrine is needed. The relative importance of free quinacrine in these compartments upon the conversion of normal host prion protein (PrPC) to PrPSc will be critical toward its potential benefit.
Regional risks and seasonality in travel-associated campylobacteriosis
Authors: Ekdahl Karl , Andersson Yvonne
Published: January 2005

Backgound

The epidemiology of travel-associated campylobacteriosis is still largely unclear, and various known risk factors could only explain limited proportions of the recorded cases.

Methods

Using data from 28,704 notifications of travel-associated campylobacteriosis in Sweden 1997 to 2003 and travel patterns of 16,255 Swedish residents with overnight travel abroad in the same years, we analysed risks for travel-associated campylobacteriosis in 19 regions of the world, and looked into the seasonality of the disease in each of these regions.

Results

The highest risk was seen in returning travellers from the Indian subcontinent (1,253/100,000 travellers), and the lowest in travellers from the other Nordic countries (3/100,000 travellers). In Africa, large differences in risk between regions were noted, with 502 /100,000 in travellers from East Africa, compared to 76/100,00 from West Africa and 50/100,000 from Central Africa. A distinct seasonal pattern was seen in all temperate regions with peaks in the summer, while no or less distinct seasonality was seen in tropical regions. In travellers to the tropics, the highest risk was seen in children below the age of six.

Conclusions

Data on infections in returning travellers together with good denominator data could provide comparable data on travel risks in various regions of the world.
Comparison of nested PCR and real time PCR of Herpesvirus infections of central nervous system in HIV patients
Authors: Drago Lorenzo , Lombardi Alessandra , De Vecchi Elena , Giuliani Giuseppe , Bartolone Rosaria , Gismondo Maria Rita
Published: January 2005

Background

Molecular detection of herpesviruses DNA is considered as the reference standard assay for diagnosis of central nervous system infections. In this study nested PCR and real time PCR techniques for detection of Herpes simplex virus type 1 (HSV-1), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in cerebrospinal fluid of HIV patients were compared.

Methods

Forty-six, 85 and 145 samples previously resulted positive for HSV-1, CMV and EBV by nested PCR and 150 randomly chosen negative samples among 1181 collected in the period 1996–2003 were retrospectively reassessed in duplicate by real time PCR and nested PCR.

Results

Samples giving positive results for CMV, HSV-1 and EBV with nested PCR were positive also with real time PCR. One of the negative samples resulted positive for HSV and one for EBV. Real time PCR showed comparable sensitivity and specificity vs nested PCR.

Conclusion

Real time PCR proved to be a suitable method for diagnosis of herpesvirus infections in CNS, showing comparable sensitivity and being less time consuming than nested PCR.
Age-specific prevalence, transmission and phylogeny of TT virus in the Czech Republic
Authors: Saláková Martina , Němeček Vratislav , König Jaroslav , Tachezy Ruth
Published: January 2005

Background

TT virus is prevalent worldwide, but its prevalence and genotype distribution in Central and East-Europe has not been determined. The high prevalence of TTV in multiply-transfused patients points to the importance of a parenteral mode of transmission, but since more than half of the general population is infected other possible routes of transmission must be considered.

Methods

In our study, we investigated the epidemiology, transmission and phylogeny of TTV in the Czech Republic. The following groups were selected: a control group of 196 blood donors, 20 patients with hemophilia, 49 intravenous drug users, 100 sex workers, 50 penitentiary prisoners, 208 healthy children aged 1 to 14 years, 54 cord blood samples, 52 patients with non-A-E hepatitis, 74 patients with hepatitis C, and 51 blood donors with increased ALT levels. Primers specific for the non-coding region were used. The genotype distribution was studied in 70 TTV-positive samples.

Results

The prevalence rate of TTV among the Czech population was 52.6%. We have shown that TTV is not transmitted prenatally. Children were infected after birth with two peaks: one at the age of two years and the other after the beginning of primary school. Adults have shown a further increase in the TTV prevalence with age. The highest TTV prevalence was found in the group of patients who had received multiple blood transfusions. The TTV prevalence rate in subjects at an increased risk of sexual transmission was not significantly higher than in the general population. Genotypes G2 and G1 were most prevalent among the Czech population, followed by G8 and G3. The subjects positive for markers of HBV and/or HCV infection tested significantly more often TTV DNA positive, which is suggestive of a common route of transmission of these three infections.

Conclusions

This study on TTV prevalence, mode of transmission and age-specific prevalence is the most extensive study performed in Central and Eastern Europe. It showed insights into the epidemiology of TTV infection, but failed to associate TTV infection with clinical manifestations.
Can somatostatin control acute bleeding from oesophageal varices in Schistosoma mansoni patients?[ISRCTN63456799]
Authors: Chatterjee Shyama , Van Marck Eric
Published: January 2005

Background

Management of patients with bleeding oesophageal varices comprises of mainly diagnostic endoscopy, sclerotherapy and band ligation. One of the major problems to do any of the above is the active bleeding which makes any intervention difficult. The neuropeptide hormone somatostatin administered exogenously has caused a reduction in portal hypertension and variceal bleeding in patients suffering from liver cirrhosis. We believe that the symptomatic use of somatostatin for variceal bleeding in Schistosoma mansoni infected subjects can reduce bleeding, thereby alleviating the pathology caused by schistosomiasis.

Methods/design

We herein present a study protocol for establishing this neuropeptide as a potential therapeutic agent in schistosomiasis. Adolescent subjects, age range varying from 12–17 years will be selected, based on several inclusion criteria, most important being infection with Schistosoma mansoni with bleeding from oesophageal varices in the last 24 hours. One group of schistosomiasis patients will be treated with somatostatin and praziquantel, the other with propanolol and praziquantel. Survival graphs will be set up to correlate somatostatin administration with survival time. A two part questionnaire will be set up to control treatment outcomes. The pre-treatment part of the clinical questionnaire will identify inclusion criteria questions, the post-treatment part of the questionnaire will identify treatment outcomes.

Discussion

We expect that the administration of somatostatin as a bolus followed by a 24 hour long infusion, will stop bleeding immediately, delay rebleeding as compared to the control study group and delay mortality in the somatostatin treated subjects.
Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi
Authors: van Lettow Monique , Harries Anthony D , Kumwenda Johnny J , Zijlstra Ed E , Clark Tamara D , Taha Taha E , Semba Richard D
Published: January 2005

Background

Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis.

Methods

In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, α-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting.

Results

Body mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 μmol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Wasting, defined as BMI<18.5 was present in 59% of study participants and was independently associated with a higher risk of low carotenoids, and vitamin A and selenium deficiency. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids.

Conclusions

These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.
Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study
Authors: Cole John W , Roberts Stacy C , Gallagher Margaret , Giles Wayne H , Mitchell Braxton D , Steinberg Karen K , Wozniak Marcella A , Macko Richard F , Reinhart Laurie J , Kittner Steven J
Published: January 2005

Background

The genes encoding proteins in the thrombomodulin-protein C pathway are promising candidate genes for stroke susceptibility because of their importance in thrombosis regulation and inflammatory response. Several published studies have shown that the Ala455Val thrombomodulin polymorphism is associated with ischemic heart disease, but none has examined the association with stroke. Using data from the Stroke Prevention in Young Women Study, we sought to determine the association between the Ala455Val thrombomodulin polymorphism and the occurrence of ischemic stroke in young women.

Methods

All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. We compared 141 cases of first ischemic stroke (44% black) among women 15 to 44 years of age with 210 control subjects (35% black) who were identified by random digit dialing and frequency matched to the cases by age and geographical region of residence. Data on historical risk factors were collected by standardized interview. Genotyping of the thrombomodulin Ala455Val polymorphism was performed by pyrosequencing.

Results

The A allele (frequency = 0.85) was associated with stroke under the recessive model. After adjustment for age, race, cigarette smoking, hypertension, and diabetes, the AA genotype, compared with the AV and VV genotypes combined, was significantly associated with stroke (odds ratio 1.9, 95% CI 1.1–3.3). The AA genotype was more common among black than white control subjects (81% versus 68%) but there was no significant interaction between the risk genotype and race (adjusted odds ratio 2.7 for blacks and 1.6 for whites). A secondary analysis removing all probable (n = 16) and possible (n = 15) cardioembolic strokes demonstrated an increased association (odds ratio 2.2, 95% CI 1.2–4.2).

Conclusions

Among women aged 15 to 44 years, the AA genotype is more prevalent among blacks than whites and is associated with increased risk of early onset ischemic stroke. Removing strokes potentially related to cardioembolic phenomena increased this association. Further studies are needed to determine whether this polymorphism is functionally related to thrombomodulin expression or whether the association is due to population stratification or linkage to a nearby functional polymorphism.
Morphological brain differences between adult stutterers and non-stutterers
Authors: Jäncke Lutz , Hänggi Jürgen , Steinmetz Helmuth
Published: January 2005

Background

The neurophysiological and neuroanatomical foundations of persistent developmental stuttering (PDS) are still a matter of dispute. A main argument is that stutterers show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect speech fluency. The major aim of this study was to determine whether adults with PDS have anomalous anatomy in cortical speech-language areas.

Methods

Adults with PDS (n = 10) and controls (n = 10) matched for age, sex, hand preference, and education were studied using high-resolution MRI scans. Using a new variant of the voxel-based morphometry technique (augmented VBM) the brains of stutterers and non-stutterers were compared with respect to white matter (WM) and grey matter (GM) differences.

Results

We found increased WM volumes in a right-hemispheric network comprising the superior temporal gyrus (including the planum temporale), the inferior frontal gyrus (including the pars triangularis), the precentral gyrus in the vicinity of the face and mouth representation, and the anterior middle frontal gyrus. In addition, we detected a leftward WM asymmetry in the auditory cortex in non-stutterers, while stutterers showed symmetric WM volumes.

Conclusions

These results provide strong evidence that adults with PDS have anomalous anatomy not only in perisylvian speech and language areas but also in prefrontal and sensorimotor areas. Whether this atypical asymmetry of WM is the cause or the consequence of stuttering is still an unanswered question.
Successful obstetrical management of 110-day intertwin delivery interval without cerclage: counseling and conservative management approach to extreme asynchronous twin birth
Authors: Ghulmiyyah Labib M , Wehbe Salim A , Schwartz Seth A , Sills Eric Scott
Published: January 2005

Background

This report describes a patient counseling approach and non-surgical management of a dichorionic-diamniotic twin pregnancy where delivery of the second twin followed the delivery of the first by 110 days.

Case presentation

An early transvaginal sonogram at 19 1/2 weeks suggested cervical dilation with protruding amniotic membranes. Tocolytic and antibiotic therapy was initiated; no cerclage was placed. Spontaneous rupture of membranes and cord prolapse occurred 48 h later, resulting in delivery of a stillborn female infant. Conservative management was offered after counseling for possible risks associated with maternal sepsis, need for extended hospitalization, potential for hysterectomy and death. The cervix appeared closed after delivery and the umbilical cord was ligated, with subsequent spontaneous cord retraction in utero. Reassuring fetal status was observed for twin B without evidence of contractions or chorioamnionitis. A viable male infant (2894 g) was delivered vaginally at 35 1/2 weeks.

Conclusions

This report outlines a counseling approach useful for patients with premature delivery of one twin, and presents application of conservative obstetrical management principles for the aftercoming twin even when delivery interval is extreme.
Protocol for a randomised controlled trial of a decision aid for the management of pain in labour and childbirth [ISRCTN52287533]
Authors: Roberts Christine L , Raynes-Greenow Camille H , Nassar Natasha , Trevena Lyndal , McCaffery Kirsten
Published: January 2005

Background

Women report fear of pain in childbirth and often lack complete information on analgesic options prior to labour. Preferences for pain relief should be discussed before labour begins. A woman's antepartum decision to use pain relief is likely influenced by her cultural background, friends, family, the media, literature and her antenatal caregivers. Pregnant women report that information about analgesia was most commonly derived from hearsay and least commonly from health professionals. Decision aids are emerging as a promising tool to assist practitioners and their patients in evidence-based decision making.

Decision aids are designed to assist patients and their doctors in making informed decisions using information that is unbiased and based on high quality research evidence. Decision aids are non-directive in the sense that they do not aim to steer the user towards any one option, but rather to support decision making which is informed and consistent with personal values.

Methods/design

We aim to evaluate the effectiveness of a Pain Relief for Labour decision aid, with and without an audio-component, compared to a pamphlet in a three-arm randomised controlled trial. Approximately 600 women expecting their first baby and planning a vaginal birth will be recruited for the trial.

The primary outcomes of the study are decisional conflict (uncertainty about a course of action), knowledge, anxiety and satisfaction with decision-making and will be assessed using self-administered questionnaires. The decision aid is not intended to influence the type of analgesia used during labour, however we will monitor health service utilisation rates and maternal and perinatal outcomes. This study is funded by a competitive peer-reviewed grant from the Australian National Health and Medical Research Council (No. 253635).

Discussion

The Pain Relief for Labour decision aid was developed using the Ottawa Decision Support Framework and systematic reviews of the evidence about the benefits and risks of the non-pharmacological and pharmacological methods of pain relief for labour. It comprises a workbook and worksheet and has been developed in two forms – with and without an audio-component (compact disc). The format allows women to take the decision aid home and discuss it with their partner.
The DiAMOND trial protocol: a randomised controlled trial of two decision aids for mode of delivery among women with a previous caesarean section [ISRCTN84367722]
Authors: Montgomery Alan A ,   the DiAMOND Study Group
Published: January 2005

Background

Caesarean section (CS) has become an increasingly common method of delivery worldwide, rising in the UK from 9% of deliveries in 1980 to over 21% 2001. This increase, and the question of whether CS should be available to women on request, has been the subject of considerable debate, and national reports and guidelines have specifically highlighted the importance of patient choice in the decision making process. For women who have already experienced CS, the UK National Institute of Clinical Excellence recommends that the decision should consider maternal preferences and priorities in addition to general discussion of the overall risks and benefits of CS. Decision aids for many different medical treatment and screening decisions have been developed and evaluated, but there is relatively little evidence for the use of decision aids for choice of mode of delivery among women with a previous CS. The aim of the study is to evaluate two interventions to assist decision making about mode of delivery among pregnant women with one previous CS.

Methods/design

Women with one previous CS are recruited to the trial during their booking visit at approximately 12–20 weeks' gestation in participating maternity units in Bristol, Weston and Dundee. Using central randomisation, women are allocated to one of three arms: information programme and website; decision analysis; usual care. Both interventions are computer-based, and are designed to provide women with detailed information about the potential outcomes for both mother and baby of planned vaginal delivery, planned CS and emergency CS. The decision analysis intervention additionally provides a recommended 'preferred option' based on maximised expected utility. There are two primary outcomes (decisional conflict and actual mode of delivery), and five secondary outcomes (anxiety, knowledge, perceptions of shared decision making; satisfaction with decision making process, proportion of women attempting vaginal delivery). Primary follow up for the questionnaire measures is at 36–37 weeks' gestation, and a total of 660 women will be recruited to the study. The primary intention-to-treat analyses will comprise three pair-wise comparisons between decision analysis, information and usual care groups, for each of the two primary outcomes. A qualitative study will investigate women's experiences of the decision making in more depth, and an economic evaluation from the perspective of the NHS will be conducted.

Discussion

Provision of information to women facing this decision appears variable. The DiAMOND study aims to inform best practice in this area by evaluating the effectiveness of two interventions designed to aid decision making.
The in vitroeffect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours
Authors: Knight Louise A , Di Nicolantonio Federica , Whitehouse Pauline , Mercer Stuart , Sharma Sanjay , Glaysher Sharon , Johnson Penny , Cree Ian A
Published: January 2005

Background

Activation of the epidermal growth factor receptor (EGFR) triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa') is an orally active tyrosine kinase inhibitor (TKI) targeted to the ATP-binding domain of EGFR (HER1; erbB1).

Methods

In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA) to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan) against a variety of solid tumours (n = 86), including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC) and sarcoma. The IC50 and IC90 were calculated for each single agent or combination. To allow comparison between samples the IndexSUM was calculated based on the percentage tumour growth inhibition (TGI) at each test drug concentration (TDC). Gefitinib was tested at concentrations ranging from 0.0625–2 microM (TDC = 0.446 microg/ml). This study represents the first use of a TKI in the assay.

Results

There was heterogeneity in the degree of TGI observed when tumours were tested against single agent gefitinib. 7% (6/86) of tumours exhibited considerable inhibition, but most showed a more modest response resulting in a low TGI. The median IC50 value for single agent gefitinib in all tumours tested was 3.98 microM. Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics. In 59% (45/76) of tumours tested, the addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or combination (of these, 11% (5/45) had a >50% decrease in their IndexSUM). In 38% of tumours (29/76), the TGI was decreased when the combination of gefitinib + cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3% (2/76) there was no change observed.

Conclusion

The in vitro model suggests that gefitinib may have differential effects in response to concomitant cytotoxic chemotherapy with the agents tested during this study. The mechanism involved may relate to the effect of TKIs on growth rate versus their effect on the ability of the cell to survive the stimulus to apoptosis produced by chemotherapy.
SMAC is expressed de novoin a subset of cervical cancer tumors
Authors: Espinosa Magali , Cantu David , Lopez Carlos M , De la Garza Jaime G , Maldonado Vilma A , Melendez-Zajgla Jorge
Published: January 2005

Background

Smac/Diablo is a recently identified protein that is released from mitochondria after apoptotic stimuli. It binds IAPs, allowing caspase activation and cell death. In view of its activity it might participate in carcinogenesis. In the present study, we analyzed Smac expression in a panel of cervical cancer patients.

Methods

We performed semi quantitative RT-PCR on 41 cervical tumor and 6 normal tissue samples. The study included 8 stage I cases; 16 stage II; 17 stage III; and a control group of 6 samples of normal cervical squamous epithelial tissue.

Results

Smac mRNA expression was below the detection limit in the normal cervical tissue samples. In contrast, 13 (31.7%) of the 41 cervical cancer biopsies showed detectable levels of this transcript. The samples expressing Smac were distributed equally among the stages (5 in stage I, 4 in stage II and 4 in stage III) with similar expression levels. We found no correlation between the presence of Smac mRNA and histology, menopause, WHO stage or disease status.

Conclusions

Smac is expressed de novo in a subset of cervical cancer patients, reflecting a possible heterogeneity in the pathways leading to cervical cancer. There was no correlation with any clinical variable.
BAG-1 haplo-insufficiency impairs lung tumorigenesis
Authors: Götz Rudolf , Kramer Boris W , Camarero Guadalupe , Rapp Ulf R
Published: January 2005

Background

BAG-1 is a multifunctional co-chaperone of heat shock proteins (Hsc70/Hsp70) that is expressed in most cells. It interacts with Bcl-2 and Raf indicating that it might connect protein folding with other signaling pathways. Evidence that BAG-1 expression is frequently altered in human cancers, in particular in breast cancer, relative to normal cells has been put forward but the notion that overexpression of BAG-1 contributes to poor prognosis in tumorigenesis remains controversial.

Methods

We have evaluated the effect of BAG-1 heterozygosity in mice in a model of non-small-cell lung tumorigenesis with histological and molecular methods. We have generated mice heterozygous for BAG-1, carrying a BAG-1 null allele, that in addition express oncogenic, constitutively active C-Raf kinase (SP-C C-Raf BxB) in type II pneumocytes. SP-C C-Raf BxB mice develop multifocal adenomas early in adulthood.

Results

We show that BAG-1 heterozygosity in mice impairs C-Raf oncogene-induced lung adenoma growth. Lung tumor initiation was reduced by half in BAG-1 heterozygous SP-C C-Raf BxB mice compared to their littermates. Tumor area was reduced by 75% in 4 month lungs of BAG-1 haploinsufficient mice compared to mice with two BAG-1 copies. Whereas BAG-1 heterozygosity did not affect the rate of cell proliferation or signaling through the mitogenic cascade in adenoma cells, it increased the rate of apoptosis.

Conclusion

Reduced BAG-1 expression specifically targets tumor cells to apoptosis and impairs tumorigenesis. Our data implicate BAG-1 as a key player in oncogenic transformation by Raf and identify it as a potential molecular target for cancer treatment.
Atypical presentation of hepatocellular carcinoma: a mass on the left thoracic wall
Authors: Çoban Şahin , Yüksel Osman , Köklü Seyfettin , Ceyhan Koray , Baykara Meltem , Dökmeci Abdulkadir
Published: January 2005

Background

Hepatocellular carcinoma is a common malignancy for which chronic hepatitis B infection has been defined as the most common etiologic factor. The most frequent metastatic sites are the lung, bone, lymphatics, and brain, respectively. Metastases to the chest wall have been reported only rarely.

Case presentation

We report a patient with hepatocellular carcinoma who presented with an isolated metastatic mass on the left anterolateral chest wall in the axillary region.

Conclusions

Metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor can not be radiologically identified.
Penile metastasis from primary transitional cell carcinoma of the renal pelvis: first manifestation of systemic spread
Authors: Pomara Giorgio , Pastina Ilaria , Simone Maurizio , Casale Paolo , Marchetti Gabriella , Francesca Francesco
Published: January 2005

Background

Almost one-third of all penile metastases are detected at the same time as a primary tumor, whereas the remaining two-thirds are detected a mean of 18 months after the discovery of the primary tumor. Cutaneous metastasis of transitional cell carcinoma (TCC) is extremely rare and generally accepted as the late manifestation of a systemic spread.

Case presentation

We report the first case of simultaneous penile and lung metastases from a primary TCC of the renal pelvis in a 76-year-old man, that occurred 8 years after a left nephroureterectomy.

Conclusions

This case report underscores the importance of physical examinations of the skin of patients who undergo surgical procedures for TCC from bladder as well as from the upper urinary tract, including those seemingly without metastatic disease, because of the possibility of skin and penile metastatic spread.
Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines
Authors: Plummer Howard K , Yu Qiang , Cakir Yavuz , Schuller Hildegard M
Published: January 2005

Background

Previous research has indicated that at various organ sites there is a subset of adenocarcinomas that is regulated by beta-adrenergic and arachidonic acid-mediated signal transduction pathways. We wished to determine if this regulation exists in breast adenocarcinomas. Expression of mRNA that encodes a G-protein coupled inwardly rectifying potassium channel (GIRK1) has been shown in tissue samples from approximately 40% of primary human breast cancers. Previously, GIRK channels have been associated with beta-adrenergic signaling.

Methods

Breast cancer cell lines were screened for GIRK channels by RT-PCR. Cell cultures of breast cancer cells were treated with beta-adrenergic agonists and antagonists, and changes in gene expression were determined by both relative competitive and real time PCR. Potassium flux was determined by flow cytometry and cell signaling was determined by western blotting.

Results

Breast cancer cell lines MCF-7, MDA-MB-361 MDA-MB 453, and ZR-75-1 expressed mRNA for the GIRK1 channel, while MDA-MB-468 and MDA-MB-435S did not. GIRK4 was expressed in all six breast cancer cell lines, and GIRK2 was expressed in all but ZR-75-1 and MDA-MB-435. Exposure of MDA-MB-453 cells for 6 days to the beta-blocker propranolol (1 μM) increased the GIRK1 mRNA levels and decreased beta2-adrenergic mRNA levels, while treatment for 30 minutes daily for 7 days had no effect. Exposure to a beta-adrenergic agonist and antagonist for 24 hours had no effect on gene expression. The beta adrenergic agonist, formoterol hemifumarate, led to increases in K+ flux into MDA-MB-453 cells, and this increase was inhibited by the GIRK channel inhibitor clozapine. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a high affinity agonist for beta-adrenergic receptors stimulated activation of Erk 1/2 in MDA-MB-453 cells.

Conclusions

Our data suggests β-adrenergic receptors and GIRK channels may play a role in breast cancer.
An unusual pathological finding of chronic lymphocitic leukemia and adenocarcinoma of the prostate after transurethral resection for complete urinary retention: case report
Authors: Ballario Riccardo , Beltrami Paolo , Cavalleri Stefano , Ruggera Lorenzo , Zorzi Maria Grazia , Artibani Walter
Published: January 2005

Background

We describe a patient who underwent transurethral resection of the prostate for urinary obstructive symptoms and had histological findings of adenocarcinoma of the prostate with prostatic localization of chronic lymphocitic leukemia (CLL).The contemporary presence of CLL, adenocarcinoma of the prostate and residual prostatic gland after transurethral resection has never been reported before and the authors illustrate how they managed this unusual patient.

Case presentation

A 79-years-old white man, presented with acute urinary retention, had a peripheral blood count with an elevated lymphocytosis (21.250/mL) with a differential of 65.3% lymphocytes and the prostate-specific antigen (PSA) value was 3.38 ng/mL with a percent free PSA of 8.28%. The transrectal ultrasound (TRUS) indicated an isoechonic and homogenic enlarged prostate of 42 cm3 and the abdomen ultrasound found a modest splenomegaly and no peripheral lymphadenophaty. The patient underwent transurethral resection of the prostate and had a pathological finding of adenocarcinoma in the prostate with a Gleason Score 4 (2+2) of less than 5% of the material (clinical stage T1a), associated with a diffused infiltration of chronic lymphocitic leukemia elements.

Conclusions

The incidental finding of a prostatic localization of a low-grade non-Hodgkin's lymphoma does not modify eventually further treatments for neither prostate cancer nor lymphoma. The presence of a low-grade and low-stage lymphoma, confirmed by a hematological evaluation, and the simultaneous evidence of an adenocarcinoma after transurethral resection of the prostate for acute urinary retention do not require any immediate treatment due to its long-term survival rate and the follow-up remains based on periodical PSA evaluation and complete blood count.
Gait unsteadiness and fall risk in two affective disorders: a preliminary study
Authors: Hausdorff Jeffrey M , Peng Chung-Kang , Goldberger Ary L , Stoll Andrew L
Published: January 2005

Background

In older adults, depression has been associated with increased fall risk, but the reasons for this link are not fully clear. Given parallels between major depression and Parkinson's disease, we hypothesized that major depression and related affective disorders would be associated with impairment in the ability to regulate the stride-to-stride fluctuations in gait cycle timing.

Methods

We measured stride-to-stride fluctuations of patients with two forms of mood disorders, unipolar major depressive disorder (MDD) and bipolar disorder, and compared their gait to that of a healthy control group. The primary outcomes were two measures of gait unsteadiness that have been associated with fall risk: stride time variability and swing time variability.

Results

Compared to the control group, the two patient groups tended to walk more slowly and with decreased swing time and increased stride time. However, none of these differences was statistically significant. Compared to the control group, swing time variability was significantly larger in the subjects with bipolar disorder (p < 0.0001) and in the subjects with MDD (p < 0.0004).

Conclusions

Patients with MDD and patients with bipolar disorder display gait unsteadiness. This perturbation in gait may provide a mechanistic link connecting depression and falls. The present findings also suggest the possibility that measurement of variability of gait may provide a readily quantifiable objective approach to monitoring depression and related affective disorders.
Negative and positive childhood experiences across developmental periods in psychiatric patients with different diagnoses – an explorative study
Authors: Saleptsi Evangelia , Bichescu Dana , Rockstroh Brigitte , Neuner Frank , Schauer Margarete , Studer Karl , Hoffmann Klaus , Elbert Thomas
Published: January 2005

Background

A high frequency of childhood abuse has often been reported in adult psychiatric patients. The present survey explores the relationship between psychiatric diagnoses and positive and negative life events during childhood and adulthood in psychiatric samples.

Methods

A total of 192 patients with diagnoses of alcohol-related disorders (n = 45), schizophrenic disorders (n = 52), affective disorders (n = 54), and personality disorders (n = 41) completed a 42-item self-rating scale (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses personal positive experiences (competence and safety) and negative experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas, and alcohol and drugs abuse) during four developmental periods, beginning from early childhood to adulthood. Patients were recruited from four Psychiatric hospitals in Germany, Switzerland, and Romania; 63 subjects without any history of mental illness served as controls.

Results

The amount of positive experiences did not differ significantly among groups, except for safety scores that were lower in patients with personality disorders as compared to the other groups. On the other side, negative experiences appeared more frequently in patients than in controls. Emotional neglect and abuse were reported in patients more frequently than physical and sexual abuse, with negative experiences encountered more often in late childhood and adolescence than in early childhood. The patients with alcohol-related and personality disorders reported more negative events than the ones with schizophrenic and affective disorders.

Conclusions

The present findings add evidence to the relationship between retrospectively reported childhood experiences and psychiatric diagnoses, and emphasize the fact that a) emotional neglect and abuse are the most prominent negative experiences, b) adolescence is a more 'sensitive' period for negative experiences as compared to early childhood, and c) a high amount of reported emotional and physical abuse occurs in patients with alcohol-related and personality disorders respectively.
The lack of public health research output from India
Authors: Dandona Lalit , Sivan Yegnanarayana S , Jyothi Mukkamala N , Bhaskar VS Udaya , Dandona Rakhi
Published: January 2005

Background

Systematic assessment of recent health research output from India, and its relation with the estimated disease burden, is not available. This information would help understand the areas in health research that need improvement in India to enhance the health of India's population.

Methods

The health research output from India during 2002, which was accessible in the public domain, was assessed by searching PubMed and other internet health literature databases, and was related to the disease burden suggested by the Global Burden of Disease Study. The main outcome measures were number of health papers with abstracts in basic, clinical and public health sciences; quality-adjusted research output based on the impact factors of journals in which the papers were published; classification of papers in disease/condition categories and comparison of research output with the estimated disease burden in each category. Comparison of the health papers from India during 2002 included in PubMed was done with those from Australia during one quarter of 2002.

Results

Of the 4876 health papers from India in 2002 in PubMed, 48.4%, 47.1% and 4.4% were in basic, clinical and public health sciences, respectively. Of the 4495 papers based on original research, only 3.3% were in public health. Quality-adjusted original research output was highest for non-communicable diseases (62% of total). Of the total quality-adjusted original research output, the proportions in injuries (0.7%), cardiovascular diseases (3.6%), respiratory infections (0.2%), diarrhoeal diseases (1.9%), perinatal conditions (0.4%), childhood cluster diseases (0.5%), unipolar major depression (0%), and HIV/AIDS (1.5%) were substantially lower than their proportional contribution to the disease burden in India. Human resources, health policy, health economics, and impact assessment of interventions were particularly poorly represented in public health research. The Australia-India ratio for quality-adjusted health research output per unit gross domestic product was 20 and for public health research output was 31.

Conclusions

Good-quality public health research output from India is grossly inadequate, and strategic planning to improve it is necessary if substantial enhancement of population health were to be made possible. There is inordinately low relative research output in several diseases/conditions that cause major disease burden in India.
Mineral water intake reduces blood pressure among subjects with low urinary magnesium and calcium levels
Authors: Rylander Ragnar , Arnaud Maurice J
Published: January 2005

Background

Several previous epidemiological studies have shown a relation between drinking water quality and death in cardiovascular disease whereas others have not found such a relationship. An intervention study was undertaken to evaluate the effect of water with added magnesium and natural mineral water on blood pressure.

Methods

A group of 70 subjects with borderline hypertension was recruited and consumed 1) a water low in minerals, 2) magnesium enriched water or 3) natural mineral water, in a random, double blind fashion during four weeks.

Results

Among persons with an initial low excretion of magnesium or calcium in the urine, the urinary excretion of magnesium was increased in the groups consuming the two waters containing magnesium after 4 weeks. A significant decrease in blood pressure was found in the group consuming mineral water at 2 and 4 weeks.

Conclusion

The results suggest that minerals taken in water are significant for the body burden and that an intake of mineral water among persons with a low urinary excretion of magnesium or calcium may decrease the blood pressure. Further studies should investigate the extent of mineral deficiency in different populations and the efficiency of different vehicles for supplying minerals, particularly magnesium and calcium.
Interaction among general practitioners age and patient load in the prediction of job strain, decision latitude and perception of job demands. A Cross-sectional study
Authors: Vanagas Giedrius , Bihari-Axelsson Susanna
Published: January 2005

Background

It is widely recognized and accepted that job strain adversely impacts the workforce. Individual responses to stressful situations can vary greatly and it has been shown that certain people are more likely to experience high levels of stress in their job than others. Studies highlighted that there can be age differences in job strain perception.

Methods

Cross-sectional postal survey of 300 Lithuanian general practitioners. Psychosocial stress was investigated with a questionnaire based on the Reeder scale. Job demands were investigated with the Karasek scale. The analysis included descriptive statistics; logistic regression beta coefficients to find out predictors and interactions between characteristics and predictors.

Results

Response rate was 66% (N = 197). Logistic regression as significant predictors for job strain assigned – duration of work in primary care; for job demands- age and duration of working in primary care; for decision latitude- age and patient load.

The interactions with regard to job strain showed that GP's age and job strain are negatively associated to a low patient load. Lower decision latitude for older GP age is strongly related to higher patient load. Job demands and GP age are slightly positively related at low patient load.

Conclusions

Lithuanian GP's have high patient load and are at risk of stress, they have high job demands and low decision latitude. Older GP's perceive less strain, lower job demands and higher decision latitude in case of low patient load. Young GP's decision latitude has week association to patient load. Regarding to the changes in patient load younger GP's perceive it more sensitively as changes in job demands.
Validity of self reported male balding patterns in epidemiological studies
Authors: Taylor Rosalind , Matassa Julia , Leavy Justine E , Fritschi Lin
Published: January 2005

Background

Several studies have investigated the association between male pattern baldness and disease such as prostate cancer and cardiovascular disease. Limitations in the lack of standardized instruments to measure male pattern baldness have resulted in researchers measuring balding patterns in a variety of ways. This paper examines the accuracy and reliability of assessment of balding patterns by both trained observers and men themselves, using the Hamilton-Norwood classification system.

Methods

An observational study was carried out in Western Australia with 105 male volunteers aged between 30 and 70 years. Participants completed a short questionnaire and selected a picture that best represented their balding pattern. Two trained data collectors also independently assessed the participant's balding pattern using the same system and the men's self assessment was compared with the trained observer's assessment. In a substudy, observers assessed the balding pattern in a photo of the man aged 35 years while the man independently rated his balding at that age.

Results

Observers were very reliable in their assessment of balding pattern (85% exact agreement, κ = 0.83). Compared to trained observers, men were moderately accurate in their self-assessment of their balding status (48–55% exact agreement, κ = 0.39–0.46). For the substudy the exact agreement between the men and the observers was 67% and the agreement within balding groups was 87%.

Conclusions

We recommend that male balding patterns be assessed by trained personnel using the Hamilton-Norwood classification system. Where the use of trained personnel is not feasible, men's self assessment both currently and retrospectively has been shown to be adequate.
Randomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary disease [ISRCTN21676344]
Authors: Black Peter N , Morgan-Day Althea , McMillan Tracey E , Poole Phillippa J , Young Robert P
Published: January 2005

Background

Prophylactic treatment with N-acetylcysteine (NAC) for 3 months or more is associated with a reduction in the frequency of exacerbations of chronic obstructive pulmonary disease (COPD). This raises the question of whether treatment with NAC during an acute exacerbation will hasten recovery from the exacerbation.

Methods

We have examined this in a randomised, double-blind, placebo controlled trial. Subjects, admitted to hospital with an acute exacerbation of COPD, were randomised within 24 h of admission to treatment with NAC 600 mg b.d. (n = 25) or matching placebo (n = 25). Treatment continued for 7 days or until discharge (whichever occurred first). To be eligible subjects had to be ≥ 50 years, have an FEV1 ≤ 60% predicted, FEV1/VC ≤ 70% and ≥ 10 pack year smoking history. Subjects with asthma, heart failure, pneumonia and other respiratory diseases were excluded. All subjects received concurrent treatment with prednisone 40 mg/day, nebulised salbutamol 5 mg q.i.d and where appropriate antibiotics. FEV1, VC, SaO2 and breathlessness were measured 2 hours after a dose of nebulised salbutamol, at the same time each day. Breathlessness was measured on a seven point Likert scale.

Results

At baseline FEV1 (% predicted) was 22% in the NAC group and 24% in the control group. There was no difference between the groups in the rate of change of FEV1, VC, SaO2 or breathlessness. Nor did the groups differ in the median length of stay in hospital (6 days for both groups).

Conclusions

Addition of NAC to treatment with corticosteroids and bronchodilators does not modify the outcome in acute exacerbations of COPD.