bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide donor properties of hydroxyurea in patients with sickle cell disease
Authors: Gladwin Mark T. , Shelhamer James H. , Ognibene Frederick P. , Pease‐Fye Margaret E. , Nichols James S. , Link Beth , Patel Daksesh B. , Jankowski Marcin A. , Pannell Lewis K. , Schechter Alan N. , Rodgers Griffin P. 
Published: March 2003

Summary. Hydroxyurea therapy reduces the rates of vaso‐occlusive crisis in patients with sickle cell anaemia and recent data suggest that hydroxyurea treatment can generate nitric oxide (NO). Nitric oxide has been proposed as a novel therapy for sickle cell disease via a number of pathways. We therefore sought to determine whether hydroxyurea has NO donor properties in patients with sickle cell anaemia and explore potential mechanisms by which NO production could be therapeutic. Venous blood was collected from 19 fasting sickle cell anaemia patients, on chronic hydroxyurea therapy, at baseline and 2 and 4 h after a single morning dose of hydroxyurea, as well as 10 patients not taking hydroxyurea. The plasma and red cell NO reaction products nitrate, nitrite and nitrosylated‐	haemoglobin were measured using ozone‐based chemiluminescent assays (using vanadium, KI and I3– reductants respectively). Consistent with NO release from hydroxyurea, baseline levels of total nitrosylated haemoglobin increased from 300 nmol/l to 500 nmol/l (P = 0·01). Plasma nitrate and nitrite levels also significantly increased with peak levels observed at 2 h. Glutathionyl–haemoglobin levels were unchanged, while plasma secretory vascular cellular adhesion molecule‐1 levels were reduced in patients taking hydroxyurea (419 ± 40 ng/ml) compared with control patients with sickle cell anaemia (653 ± 55 ng/ml; P = 0·003), and were inversely correlated with fetal haemoglobin levels (r = −0·72; P = 0·002). These results demonstrate that hydroxyurea therapy is associated with the intravascular and intraerythrocytic generation of NO. The role of NO in the induction of fetal haemoglobin and possible synergy between NO donor therapy and classic cytostatic and differentiating medications should be explored.
Potential role of endothelin 1 in ischaemia-induced angiogenesis in critical leg ischaemia
Authors: Tsui J C S , Baker D M , Biecker E , Shaw S , Dashwood M R 
Published: March 2003

Abstract

Background
Ischaemia-induced angiogenesis occurs in critical leg ischaemia (CLI) and endothelin (ET) 1 may be involved in this process. The aim of this study was to quantify microvessels and study ET receptor expression and distribution in critically ischaemic leg muscle.

Methods
Leg muscle biopsies were taken from 12 patients with CLI and 12 patients with no leg ischaemia. Microvessels were identified immunohistochemically on muscle sections, and the number of immunopositive cells was quantified. ETAand ETB receptor messenger RNA (mRNA) expression was studied using real-time quantitative reverse transcriptase–polymerase chain reaction, and receptor binding was localized and assessed by in vitro autoradiography.

Results
The number of microvessels in CLI muscle biopsies was 2·6 times higher than that in controls (P &lt; 0·01). ETB receptor mRNA expression and binding were significantly increased in CLI tissue (P &lt; 0·05), while ETA receptor levels were not significantly raised. High-resolution autoradiography showed that ET receptor binding was associated with microvessels.

Conclusion
Angiogenesis occurs in CLI and raised ETB receptors within the muscle were associated with microvessels, suggesting that ET-1 may mediate angiogenesis via these receptors in critically ischaemic muscle.
Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours
Authors: Ohlsson B , Nilsson J , Stenram U , Åkerman M , Tranberg K-G 
Published: March 2003

Abstract

Background
The aim of the study was to investigate the value of percutaneous fine-needle aspiration cytology (FNAC) in the diagnosis and management of liver tumours.

Methods
FNAC followed by histopathological examination was carried out in 216 patients with suspected liver tumours. The final diagnosis was primary liver cancer in 106, colorectal metastases in 51, non-colorectal metastases in 46, benign tumour in nine and no tumour in four patients.

Results
Cytology resulted in correct classification of the lesion as benign or malignant in 87 per cent of patients, correct discrimination between primary and secondary malignancy in half of the patients, and a correct diagnosis of tumour type in one-third of patients. The tumour was erroneously classified as benign or malignant in 22 patients (11 per cent) and four patients (2 per cent) respectively. When FNAC showed malignancy, the predictive value was 98 per cent, whereas the predictive value was 27 per cent when it did not. FNAC guided investigations and treatment in one-quarter of patients. Implantation metastases were recorded in seven patients (3 per cent), including five (10 per cent) of 51 patients with colorectal liver metastases, and caused major local problems and death in four patients.

Conclusion
FNAC was valuable in about a quarter of patients with liver tumour. The risks of implantation metastases and a false-negative finding do not justify its use in candidates for curative therapy of liver tumours.
Late results concerning feasibility and compliance from a randomized trial of ultrasonographic screening for abdominal aortic aneurysm
Authors: Vardulaki K A , Walker N M , Couto E , Day N E , Thompson S G , Ashton H A , Scott R A P 
Published: March 2003

Abstract

Background
The study was an update at 10 years of a randomized trial of the efficacy of screening for abdominal aortic aneurysm (AAA). The extent of benefit, feasibility and compliance were examined, and reasons why this intervention may fail a proportion of those screened were identified.

Methods
A total of 6058 men aged 65 years and over were randomized to a group invited to attend ultrasonographic screening or to a control group. The mortality rate from AAA in the two arms of the trial was compared using a Poisson model. Analyses were by intention to treat.

Results
There was a 21 per cent reduction in mortality rate from AAA over the 10-year follow-up (relative risk 0·79 (95 per cent confidence interval 0·53 to 1·40)). The observed relative mortality reduction peaked at 4 years with a 52 per cent reduction in the study group. Eighteen of 24 AAA deaths in the study group were among those who did not attend the first screen, or failed to comply with the follow-up protocol.

Conclusion
A greater awareness of the benefits of full participation in a screening programme could provide a larger and sustained mortality reduction.
Liver fluke-associated cholangiocarcinoma
Authors: Watanapa P , Watanapa W B 
Published: March 2003

Abstract

Background
Infection with liver flukes has been reported to be associated with bile duct malignancy.

Methods
The review is based on a literature search (Medline) and, in some cases, direct contact with authors or principal investigators.

Results
A large body of evidence indicates that Opisthorchis viverrini is a definite cause of human cholangiocarcinoma, whereas Clonorchis sinensis is a probable cause. The evidence regarding Opisthorchis felineus is insufficient to assess its role in carcinogenesis. Possible mechanisms of carcinogenesis include chronic irritation, nitric oxide formation, intrinsic nitrosation and activation of drug-metabolizing enzymes. Early detection of bile duct malignancy is difficult and not clinically available at present, although cholangiocarcinoma-associated soluble antigen has been reported in an experimental study to be a useful early marker of cancer development. Long-term survival after surgical treatment of liver fluke-associated cancer is similar to that reported in patients without liver fluke infestation.

Conclusion
Liver fluke-associated cholangiocarcinoma is still a health problem in developing countries. Mechanisms of carcinogenesis should be explored further in order to reduce the impact of this disease.
Size of lesion is not a criterion for resection during management of giant liver haemangioma
Authors: Terkivatan T , Vrijland W W , den Hoed P T , de Man R A , Hussain S M , Tilanus H W , IJzermans J N M 
Published: March 2003

AbstractBackgroundThe unknown natural history and risk of complications of large haemangiomas may pose therapeutic dilemmas. The authors describe their experience with the management of giant haemangiomas.MethodsPatients with a giant haemangioma were identified by a survey of the hospital database. Forty-nine patients with a haemangioma of at least 4 cm in diameter presented between January 1990 and December 2000. Medical records were analysed retrospectively.ResultsEleven patients had surgical treatment and 38 were managed conservatively. The median diameter of the tumours was 8·0 cm in surgically treated patients and 6·0 cm in the group managed by observation. Surgery-related morbidity occurred in three patients, and abdominal complaints persisted in three of ten patients with a symptomatic lesion. During a median follow-up of 52 months, 12 non-operated patients had mild abdominal complaints, considered to be unrelated to the lesion. In these patients symptoms either diminished or became minimal during follow-up. Complications did not occur.ConclusionObservation of giant haemangiomas can be performed safely. The authors advocate resection of cavernous liver haemangiomas only in patients with persistent severe symptoms.
Proliferation in murine epidermis after minor mechanical stimulation Part 2. Alterations in keratinocyte cell cycle fluxes
Authors: Barthel D. , Matthé B. , Potten C.S. , Owen G. , Loeffler M. 
Published: March 2003

We have recently shown that a mild mechanical irritation (tape strip) of the epidermis on the back skin of adult mice induces a strong and long lasting increase in proliferative activity and cell production. This was revealed by following the fate of 3HTdR‐pulse labelled cells within the basal and suprabasal layers.To obtain further insight into the dynamics of cell kinetic changes we also performed double labelling experiments with 3HTdR and BrdUrd at various times after tape stripping. The technique for analysing the data had to account for a non stationary cell flux. A novel biometrical technique was developed which provides parameter estimates on the S‐phase duration, the cell cycle duration and a parameter characterizing the degree of nonstationarity.When applied to the mechanically irritated epidermis we observed that the cell flux through the S‐phase in the basal layer was accelerated by a factor of 10 between 18 and 36 h post tape strip. This activation declined slightly in the subsequent days and remained 4–6 fold higher than in the normal steady state for over 7 days post tape strip. The duration of the S‐phase was 3–5 h and showed little variation.We conclude that mild mechanical irritation only affecting the stratum corneum has major stimulatory effects on the cell kinetics of proliferative keratinocytes in the basal layer of the epidermis indicating the existence of a powerful regulatory mechanism.
SERCA activity is required for timely progression through G1/S
Authors: Simon V. R. , Moran M. F. 
Published: March 2003

Abstract.Changes in intracellular Ca2+ correlate with specific events in the cell cycle. Here we investigated the role of Ca2+ in the G1 phase. HEK 293 cells were arrested in mitosis and subjected to short‐term treatments that alter Ca2+ homeostasis prior to their release into G1. Treatment with thapsigargin (TG), an irreversible inhibitor of the sarco‐endoplasmic reticulum Ca2+ ATPase (SERCA) lengthened the G1 phase. Moreover, TG treatment also resulted in a dramatic alteration in cellular morphology and attachment and in the reduction of MAPK activity and lower levels of cyclin D1 and cyclin E proteins. Treatments with reagents that transiently increase or decrease cytosolic Ca2+ or that temporarily inactivate SERCA did not alter any of the above parameters. Cells expressing a TG‐resistant form of SERCA progressed normally through the G1/S transition after TG treatment. These results suggest that long‐term SERCA inactivation affects cell cycle‐dependent events and compromises progression through G1/S.
Sensitivity of human glioma U‐373MG cells to radiation and the protein kinase C inhibitor, calphostin C
Authors: Acevedo‐Duncan M. , Pearlman J. , Zachariah B. 
Published: March 2003

Abstract.We assessed the radiosensitivity of the grade III human glioma cell line U‐373MG by investigating the effects of radiation and the specific protein kinase C inhibitor, calphostin C on the cell cycle and cell proliferation. Irradiated glioma U‐373MG cells progressed through G1‐S and underwent an arrest in G2‐M phase. The radiosensitivity of U‐373MG cells to graded doses of either photons or electrons was determine by microculture tetrazolium assay. The data was fitted to the linear‐quadratic model. The proliferation curves demonstrated that U‐373MG cells appear to be highly radiation resistant since 8 Gy was required to achieve 50% cell mortality. Compared to radiation alone, exposure to calphostin C (250 n

m) 1 h prior to radiation decreased the proliferation of U‐373MG by 76% and calphostin C provoked a weakly synergistic effect in concert with radiation. Depending on the time of application following radiation, calphostin C produced an additive or less than additive effect on cell proliferation. We postulate that the enhanced radiosensitivity observed when cells are exposed to calphostin C prior to radiation may be due to direct or indirect inhibition of protein kinase C isozymes required for cell cycle progression.
Cell growth and cholesterol metabolism in human glucose‐ 6‐phosphate dehydrogenase deficient lymphomononuclear cells
Authors: B. Batetta , R. R. Bonatesta , F. Sanna , M. Putzolu , M. F. Mulas , M. Collu , S. Dessì 
Published: March 2003

Abstract. Atherosclerosis is an inflammatory‐fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth‐muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose‐6‐phosphate dehydrogenase (G6PD), the key enzyme of the hexose‐monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD‐normal (n = 5) and ‐deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]‐thymidine incorporation) cholesterol synthesis and esterification ([14C]‐acetate and [14C]‐oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT‐PCR) all increased following lectin stimulation in both normal and G6PD‐deficient cells. However, these parameters were significantly lower in G6PD‐deficient cells (P < 0.05). It is of interest that G6PD‐deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD‐deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases.
Cell kinetic studies in the murine ventral tongue epithelium: the effects of repeated exposure to keratinocyte growth factor
Authors: Potten C. S. , Booth D. , Cragg N. J. , O'Shea J. A. , Tudor G. L. , Booth C. 
Published: March 2003

Abstract. Keratinocyte growth factor (KGF) stimulates proliferation and differentiation in various epithelial systems. Three daily subcutaneous injections of 125 µg of this protein into mice induce dramatic changes in the histology and histometric measurements of the ventral tongue epithelium. The thickness of the epithelium is increased two‐fold and the number of cells beneath a 1‐mm length of the surface is increased 1.6‐fold. KGF also induces a four‐fold increase in the number of S phase cells labelled with tritiated thymidine in the basal layer on the third day after KGF administration. The increase in thickness and cellularity persist for at least 4 days after the end of the KGF injections. However, there is a dramatic fall in the number of S phase cells detected by 3HTdR pulse labelling 2 days after the end of the KGF treatment. There are indications that by 7 days after the 3‐day regimen of KGF treatment, both thickness and cellularity have fallen back to near control levels. Continued exposure to KGF over a period of 7 days does not result in any further increases in thickness, cellularity or proliferation. In fact, the proliferation decreases on the fifth, sixth and seventh days of KGF injection to control values on day 7. These changes in the epithelium following KGF treatment suggest that the thicker and more cellular epithelium may be more able to cope with an exposure to a cytotoxic agent and hence be protected in comparison with normal or vehicle‐treated epithelium.
A prospective study on quality of life and traumatic events in early life — a 30‐year follow‐up
Authors: Ventegodt S. 
Published: March 2003

Aim To investigate the connection between early life trauma and the quality of life some 30 years later in Denmark.Design Prospective, longitudinal study with questionnaire‐based follow‐up survey.Methods In ‘The Quality of Life Research Study of 10 000 Danes’, a newly designed questionnaire was mailed in February 1993 to 7222 persons from the Prospective Paediatric Cohort of persons born at the State University Hospital in Copenhagen (Rigshospitalet) between 1959 and 1961. Response rate was 64% (4626 people between the ages 31–33).Variables Mother’s attitude towards her pregnancy, child being placed in a children’s home, mother using antipsychotic drugs indicating acute, mental illness, child adopted in the first year of life and quality of life of the child 31–33 years later.Results Of the early life traumas studied, only relatively weak connections to the quality of life in later life were found.Conclusions These relatively weak findings suggest that the children that survive to adulthood are resilient to many adverse events in early life.
Enuresis and encopresis in a South Indian Population of Children
Authors: Hackett R , Hackett L , Bhakta P , Gowers S 
Published: March 2003

SummaryIntroductionThough bladder and bowel control are important developmental milestones in all cultures, the prevalence of enuresis and encopresis has rarely been studied in developing countries despite there being factors in these countries that could affect it. This study reports the prevalence and associations of enuresis and encopresis in children in Kerala, India.MethodThe parents of 1403 randomly selected 8–12‐year‐old children were interviewed. The prevalence of enuresis and encopresis was ascertained using Rutter’s A2 scale. Subsamples of children underwent psychiatric, physical and psychometric evaluations.ResultsOf the children, 18.6% had had an episode of enursis in the past year and 4.3% in the past week. Four per cent had had an episode of encopresis in the past year. Enuresis was associated with parents’ education, physical and psychiatric symptoms in the child, poor academic achievement and lax parental attitudes to toilet training. Encopresis was associated with male sex, physical and psychiatric symptoms, poor academic achievement, early separation and not having a toilet.DiscussionThe prevalence of enuresis compares with western countries, but encopresis is commoner. The associations of enuresis suggested a multifactorial model in which parental competence was prominent. This study de‐emphasized the importance of neurodevelopmental factors in enuresis and encopresis in this age group.
Attrition among adolescents and infants involved in a parenting intervention
Authors: Letourneau N 
Published: March 2003

SummaryAttrition was assessed in a randomized trial of a parenting intervention programme for adolescent mothers and their infants. Infants who were admitted to the neonatal intensive care unit, mothers who had partner difficulties, and mothers and infants who were visited for less than 60 min a week on average (typically in the control group) were more likely to miss one of the two follow‐up visits.
‘Not by bread alone’: impact of a structured 90‐minute play session on development of children in an orphanage
Authors: Taneja V. , Sriram S. , Beri R.S. , Sreenivas V. , Aggarwal R. , Kaur R. 
Published: March 2003

Abstract
Background and objectives
In developing countries, caring for the large number of babies in orphanages is very hard work. Whereas the physical needs of most of the children are met, play often gets neglected. Studies have repeatedly shown that babies in such institutionalized settings suffer from severe psychomotor retardation. The aim of this project was to develop an intervention programme of structured play. We hypothesized that such an intervention would result in acceleration of psychosocial development in otherwise healthy institutionalized children.
Design
Prospective longitudinal.
Setting
Mother Teresa’s Orphanage, run by Missionaries of Charity.
Subject

and methods
All 30 children in the orphanage aged 6 months–2.5 years, were assessed for their Motor, Mental and Social Quotients, using the Indian adaptation of Bailey’s Scale of Infant Development(DASII) and the Vineland’s Social Maturity Scale. A structured ‘Regime of Play’ was then built into the routine of the orphanage. A repeat developmental assessment was performed at the end of 3 months to assess the impact.
Results
Out of the original cohort of 30, 19 children were available for post‐intervention assessments. The remainder were adopted before their assessments. Their mean Motor Quotient rose from 63.7 to 81.7, mean Mental Quotient rose from 65.8 to 89.6 and the mean Social Quotient rose from 61.9 to 91.3, a gain of 18, 23 and 30 points respectively (p < 0.0001). There was also an overall change in the environment of the orphanage. Children became more active, playful, responsive and independent. Contrary to what caretakers assumed, their workload actually decreased. The responsiveness in the children awakened as a result of play, acted as a positive feedback for caretakers to continue the play sessions.
Conclusions
This study shows that short daily sessions of play can significantly improve the development of children in such institutions. It is vital to remember that children grow ‘Not by Bread Alone’.
What families with children with brittle bones want to tell
Authors: Claesson I. Bernehäll , Brodin J. 
Published: March 2003

AbstractOsteogenesis imperfecta or brittle bone disease (BBD) is a most unusual disease and a limited number of people in the world are suffering from it. Most studies focus on the medical aspects of the disease and very little has been done with regard to the pedagogical and psycho‐social aspects of the disease. This article is based on a questionnaire answered by 30 families, and interviews with 10 families with children and adolescents with BBD, and the purpose is to survey the consequences of the disease in daily life. Although medical treatment is of utmost importance, it is necessary to regard also other aspects, as it is significant to have a holistic view of the child in his/her environment.