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V Vella

Publications and source records attributed to V Vella.

18 recordsLinked to original sources
PubMed2001

Tyrosine kinase inhibitor STI571 enhances thyroid cancer cell motile response to Hepatocyte Growth Factor.

The Hepatocyte Growth Factor (HGF) and its receptor Met are physiological regulators of cell migration. HGF and Met have also been implicated in tumor progression and metastasis. We show here that the tyrosine kinase inhibitor STI571 has a stimulatory effect on HGF-induced migration and branching morphogenesis in thyroid cancer but not in primary or immortalized thyroid epithelial cells. These stimulatory effects of STI571 are observed at a concentration that is clinically relevant. The STI571-enhanced motile response can be correlated with an increase in the Met receptor tyrosine phosphorylation as well as ERK and Akt activation by HGF. Interestingly, one of the targets of STI571, namely the c-Abl tyrosine kinase, is activated by HGF and is recruited at the migrating edge of thyroid cancer cells. These data suggests that c-Abl and/or STI571-inhibited tyrosine kinases can negatively regulate the Met receptor to restrain the motile response in thyroid cancer cells.

Antineoplastic Agents↗
PubMed2001

Immunostaining for Met/HGF receptor may be useful to identify malignancies in thyroid lesions classified suspicious at fine-needle aspiration biopsy.

The receptor for hepatocyte growth factor (Met) is not expressed in the normal thyroid but it is overexpressed in most thyroid carcinomas. We evaluated whether Met immunostaining of cytological smears from fine-needle aspiration biopsy (FNAB) may be useful for the preoperative diagnosis of thyroid cancer. Notably, routine cytological examination often fails to distinguish well-differentiated follicular carcinomas and a proportion of papillary carcinomas (low-grade papillary carcinomas and papillary carcinomas follicular variant [FVPTC]) from benign lesions: all these lesions are usually classified as suspicious. We examined 80 thyroid lesions diagnosed as suspicious at cytology that had subsequently undergone surgery. The histologic diagnosis had been: papillary carcinomas (n = 14), FVPTC (n = 11), follicular carcinomas (n = 25), atypical follicular adenomas (n = 5), follicular adenomas (n = 20), and nodular goiters (n = 5). We also studied typical papillary carcinomas (n = 30) and nodular goiters (n = 10), all correctly diagnosed at cytology. In lesions classified suspicious at routine cytology, Met immunostaining was positive in 12 of 14 (85.7%) papillary carcinomas, 8 of 11 (72.7%) FVPTC, 7 of 25 (28%) follicular carcinomas, and 5 of 5 atypical adenomas. In contrast, none of the 25 lesions cytologically suspicious but benign at histology were positive. These data suggest that Met immunostaining of suspicious cytological smears are useful for identifying malignant lesions, especially those with a papillary histotype.

Adenocarcinoma, Follicular↗
PubMed2001

The IGF system in thyroid cancer: new concepts.

In recent years, the activation of the insulin-like growth factor (IGF) system in cancer has emerged as a key factor for tumour progression and resistance to apoptosis. Therefore, a variety of strategies have been developed to block the type I IGF receptor (IGF-I-R), which is thought to mediate the biological effects of both IGF-I and IGF-II. However, recent data suggest that the IGF signalling system is complex and that other receptors are involved. To unravel the complexity of the IGF system in thyroid cancer, IGF-I and IGF-II production, and the expression and function of their cognate receptors were studied. Both IGFs were found to be locally produced in thyroid cancer: IGF-I by stromal cells and IGF-II by malignant thyrocytes. Values were significantly higher in malignant tissue than in normal tissue. IGF-I-Rs were overexpressed in differentiated papillary carcinomas but not in poorly differentiated or undifferentiated tumours, whereas insulin receptors (IRs) were greatly overexpressed in all tumour hystotypes, with a trend for higher values in dedifferentiated tumours. As a consequence of IR overexpression, high amounts of IR/IGF-I-R hybrids (which bind IGF-I with high affinity) were present in all thyroid cancer histotypes. Because of recent evidence that isoform A of IR (IR-A) is a physiological receptor for IGF-II in fetal life, the relative abundance of IR-A in thyroid cancer was measured. Preliminary data indicate that overexpressed IRs mainly occur as IR-A in thyroid cancer. These data indicate that both IR/IGF-I-R hybrids and IR-A play an important role in the overactivation of the IGF system in thyroid cancer and in IGF-I mitogenic signalling in these tumours. J Clin PATHOL: Mol Pathol

Carcinoma, Papillary↗
PubMed1999

Insulin/IGF-I hybrid receptors play a major role in IGF-I signaling in thyroid cancer.

The insulin-like growth factor-I (IGF-I) plays an important role in determining the biological behavior of a variety of malignancies. We measured IGF-I, its receptor and related receptors in thyroid cancer. IGF-I was present both in normal thyroid tissue and in thyroid cancer tissue and it was produced by stromal cells but not by thyrocytes. Values were significantly higher in malignant than in normal tissue. IGF-I receptors (IGF-I-Rs) and the homologous insulin receptors (IRs) were found overexpressed in both thyroid cancer cell lines (n = 4) and specimens (n = 17) as compared to normal values. In addition, high levels of hybrid IGF-I/insulin receptors (IR/IGF-I-Rs) were present in both thyroid cancer specimens and cell lines. IR/IGF-I-R hybrids were the most represented type of receptor in 14/17 specimens and exceeded the IGF-I-R content in all cases. Hybrid content correlated with the IR and IGF-I-R content, suggesting that in thyroid tissue hybrid formation occurs by random assembly of IR and IGF-I-R half receptors. Hybrid receptor autophosphorylation was stimulated by IGF-I with high affinity. In cells with a high IR/IGF-I-Rs content, blocking antibodies specific to these receptors substantially inhibited IGF-I induced cell growth. These data indicate that the IGF-I system is overactivated in thyroid cancer and that IR/IGF-I-R hybrid receptors play an important role in IGF-I mitogenic signaling in these tumors.

Cell Line↗
PubMed1999

Endoscopic palliation of esophageal and cardial cancer: neodymium-yttrium aluminum garnet laser therapy.

The aim of this study was to evaluate the impact of laser palliation on symptoms such as dysphagia and bleeding in patients with esophageal and cardial carcinomas. From November 1992 to October 1997, 174 patients with unresectable esophageal and cardial carcinomas were treated with neodymium-yttrium aluminum garnet laser therapy. The indications for palliative treatment were advanced tumor in 96 patients and high surgical risk in 78. The tumor involved the esophagus and cardia in 107 and 67 patients respectively. The mean length of the tumors was 6 cm. Two laser sessions (range 1-4) were necessary for recanalization. During the follow-up, the average interval between the laser sessions was 2 months. Overall, no early and late complications or hospital mortality occurred. The quality of palliation was excellent or good in 82%, of the patients. The mean survival time was 6 months, and mortality was not related to the procedure. Endoscopic laser therapy in patients with vegetant or hemorrhagic carcinomas may represent the best therapy, with acceptable morbidity and mortality rates and satisfactory functional results.

Adult↗
PubMed1999

[Palliative treatment of esophageal and cardial carcinoma].

Recent series reported increasing incidence of esophageal and cardial cancers with prognosis still severe in spite of surgical progress. The late diagnosis reduces the chance of radical surgery; on the other hand about 80-90% of patients develop local or distant recurrence. Therefore the treatment of esophageal and cardial cancer is often palliative: surgical resection is reserved only to selected cases. Endoscopic palliation was the treatment of choice in a total of 265 patients 174 of which received laser therapy and 91 prosthesis intubation. The results it good in about 80% of cases.

Adenocarcinoma↗
PubMed1995

Determinants of nutritional status in south-west Uganda.

In a cross-sectional survey carried out of 4320 children 0-59 months old in South-west Uganda various socio-economic and environmental factors were related to poor nutritional status. Diarrhoea was strongly associated with all the anthropometric parameters examined, suggesting a bidirectional influence of diarrhoea on malnutrition and of malnutrition on diarrhoea. The other most important variables independently associated with one or more anthropometric parameters were: distance from a health unit, living in a household not able to hire labour, and whose members worked on other people's land, religion, parental education, crowding conditions, sanitation, acreage, ownership of cow, father's occupation, birth order, ethnicity, and prolonged breastfeeding. This data indicates that a range of specific interventions are likely to be necessary for the improvement of nutrition in this community.

Anthropometry↗
PubMed1994

Determinants of stunting and recovery from stunting in northwest Uganda.

BACKGROUND: Socioeconomic deprivation is associated with unhealthy living conditions and insufficient nutrient intake which affect linear growth. This study investigates the major risk factors which influence stunting in Northwest Uganda, the age range at which growth failure is more likely to occur, and the age at which chances of recovery are higher. METHODS: In February-March 1987, 1072 children < 5 years, were selected from 30 villages in Arua district (Northwest Uganda) and included in a longitudinal study. The children were measured for length and height; household socioeconomic and environmental variables were collected in order to assess risk factors for the future development of stunting. Two years after baseline, the height of the children was measured again. RESULTS: Children who were < 29 months old at baseline were at higher risk for linear growth faltering in the following 2 years; income, mother's education and presence of stunting at baseline were significant predictors of stunting. However, being stunted at age < 6 months or between 54 and 59 months old carried the same risk of remaining stunted after 2 years, and the probability of recovering from stunting was the same in every age group. CONCLUSIONS: These results suggest that, in this population, linear growth is influenced by environmental factors. It is a dynamic process continuing beyond the first 2-3 years of life, and the probability of catching up is very similar across all age groups < 5 years old. Recovery from stunting is more associated with mother's education than with income.

Age Factors↗
PubMed1994

A computer simulation of household sampling schemes for health surveys in developing countries.

BACKGROUND: Cluster sample surveys of health and nutrition in rural areas of developing countries frequently utilize the EPI (Expanded Programme on Immunization) method of selecting households where complete enumeration and systematic or simple random sampling (SRS) is considered impractical. The first household is selected by choosing a random direction from the centre of the community, counting the houses along that route, and picking one at random. Subsequent households are chosen by visiting that house which is nearest to the preceding one. METHODS: Using a computer, and data from a survey of all children in 30 villages in Uganda, we simulated the selection of samples of size 7, 15 and 30 children from each village using SRS, the EPI method, and four different modifications of the EPI method. RESULTS: The choice of sampling scheme for households had very little effect on the precision or bias of estimates of prevalence of malnutrition, or of recent morbidity, with EPI performing as well as SRS. However, the EPI scheme was inefficient and showed bias for variables relating to child care and for socioeconomic variables. Two of the modified EPI schemes (taking every fifth house and taking separate EPI samples in each quarter of the community) performed in general much better than EPI and almost as well as SRS. CONCLUSIONS: These results suggest that the unmodified EPI household sampling scheme may be adequate for rapid appraisal of morbidity prevalence or nutritional status of communities, but that it may not be appropriate for surveys which cover a wider range of topics such as health care, or seek to examine the association of health or nutrition with explanatory factors such as education and socioeconomic status. Other factors such as cost and the ability to monitor interviewers' performance should also be taken into account.

Bias↗
PubMed1994

Anthropometry as a predictor for mortality among Ugandan children, allowing for socio-economic variables.

Length, height, weight and mid-upper arm circumference (MUAC) were measured in 4320 children aged between 0 and 59 months, and their socio-economic status was assessed, in 31 villages in Southwest Uganda during March-April 1988. A follow-up survey assessed the mortality of the children during the 12 months following anthropometry. Mortality rates were higher in those with low anthropometric indices at the first survey. MUAC was the most sensitive predictor of mortality followed by weight-for-age, height-for-age and weight-for-height. MUAC increased the predictive power of other parameters whereas the other parameters did not increase the predictive power of MUAC. MUAC below 12.5, 11.5 and 10.5 cm predicted 10.9%, 18.7% and 36.5% of the deaths respectively. Nutritional status was worse in the low socio-economic group but the predictive power of anthropometry for mortality was not influenced by socio-economic status. This suggests that nutrition per se has an influence on mortality which is independent of socio-economic status.

Age Factors↗
PubMed1993

Construction of a socio-economic index to facilitate analysis of health data in developing countries.

In order to plan, implement and monitor health interventions for the most deprived sector of the population, it is necessary to identify socioeconomic groups at risk. Multiple Correspondence Analysis was used to construct a socio-economic index based on data collected from a sample of 2698 households in South-West district of the Ugandan Republic in 1988. This study is a part of the baseline survey done by the Government of Uganda in collaboration with UNICEF. Its aim was to reduce the incidence of death of children below 5 years from diarrhea. Two factorial axes, representing respectively the socio-cultural and the anthropological conditions, explained more than 80% of the total variability. Among the 11 variables employed the most useful in characterizing the socio-economic classification were: father's occupation, parent's literacy, father's professional position and ownership of a radio. A classification in 7 levels was obtained. The first two levels are characterized as professionals and civil servants. The bottom two levels include households where both parents are illiterate and where father's primary activity is agricultural at a subsistence level. The three middle levels represent a transitional situation. In order to classify the family into the different levels, the other related variables, such as father's professional position or ownership of radio or father's religion or presence of latrine proved to be very useful. A flow chart which identifies which level a household belongs to was constructed. A general and valid observation is that families classified into the last two levels (6 and 7) constituted the population at risk for health conditions.

Adult↗
PubMed1993

Anthropometry and childhood mortality in northwest and southwest Uganda.

Two longitudinal studies were carried out in northwest and southwest Uganda to examine the relationship between anthropometry and childhood mortality. Although the prevalence of malnutrition was significantly different between the two geographic areas, the relative risk for mortality associated with low levels of anthropometry was similar. When the anthropometric parameters were compared among each other, mid-upper arm circumference was found to be the most powerful predictor of mortality. The findings of this study confirm that mid-upper arm circumference is the indicator of choice to identify children at higher risk of death.

Anthropometry↗
PubMed1992

Determinants of child mortality in south-west Uganda.

Anthropometric and sociodemographic variables were taken from 4320 children in a baseline survey carried out in March-April 1988 in the district of Mbarara, south-west Uganda. After 12 months a follow-up survey assessed the mortality of the children during the preceding year. Lack of ownership of cattle, recent arrival in the village, using candles for lighting, being of birth order higher than 5 and having a father with less than 8 years of schooling were significantly associated with child mortality. The addition of mid-upper arm circumference significantly improved the logistic model of socioeconomic variables and mortality and did not diminish the predictive power of socioeconomic variables in relation to increased mortality. This suggests that nutritional status and specific socioeconomic factors are both, independently, important predictors of child mortality.

Anthropometry↗
PubMed1992

Determinants of child nutrition and mortality in north-west Uganda.

An anthropometric survey of children aged 0-59 months in north-west Uganda in February-March 1987 indicated a high prevalence of stunting but little wasting. Use of unprotected water supplies in the dry season, prolonged breast-feeding, and age negatively affected nutrition; in contrast, parental education level improved nutrition. Mortality during the 12 months following the survey was higher among those who had low weight-for-age and weight-for-height, but children who had low height-for-age did not have higher mortality. Weight-for-age was the most sensitive predictor of mortality at specificities > 88%, while at lower specificity levels weight-for-height was the most sensitive. Children whose fathers' work was associated with the distillation of alcohol had a higher risk of mortality than other children. The lowest mortality was among children whose fathers were businessmen or who grew tobacco.

Age Factors↗
PubMed1990

Aortic aneurysms--who should do them?

All patients undergoing abdominal aortic aneurysm repairs in a district general hospital between 1 January 1983 and 31 December 1987 were reviewed. Of the 76 cases, 53 were planned and 23 were ruptured aneurysms. The male:female ratio was 4.4:1, and the age range was 47-84 years (mean 67.6 +/- 6.97 years). Half underwent an ultrasound scan, showing a maximum diameter range of 3-12 cm. Fifty-seven (75%) had tube grafts, and 19 (25%) bifurcation grafts. The 30-day mortality was 3.7% for planned cases, and 26% for ruptured cases. The principal operator in 55 (72.5%) cases was a consultant; consultant anaesthetists were involved in 61.3% cases. We conclude that aneurysm surgery can safely be performed in a district general hospital by a general surgeon with an interest in vascular surgery.

Aged↗
PubMed1984

A review of the etiology of multiple sclerosis.

The geographic distribution of multiple sclerosis and the influence of migration on the risk of contracting it point to an environmental factor as cause of the disease. This environmental factor might be a virus which might produce the demyelination process through an autoimmune reaction against components of the central nervous system. The other possible cause of multiple sclerosis is a genetic susceptibility, inferred from the higher risk for the disease found among relatives of patients with multiple sclerosis and on the association between the disease and some histocompatibility antigens of the HLA system. Both theories seem to be correct, with the environmental factors(s) causing multiple sclerosis only in the presence of a genetic susceptibility.

Age Factors↗
PubMedDate not supplied

Weight, height and arm circumference of children under 5 in the district of Mbarara, south-west Uganda.

This paper describes the growth of weight, height and arm circumference (MUAC) in children aged under 5 years and living in the south-west area of Uganda. The survey was carried out in 1988 and was based on a random sample of 31 villages of the Mbarara district. A total of 4320 children were measured by a team of 20 trained assessors. From these children a reference group was made up of the 3654 known to be still alive after 1 year. Growth charts were drawn by smoothing the non-parametric percentiles of the distribution of height, weight and MUAC for age and of weight for height. The anthropometric characteristics of children living in south-west Uganda differ considerably from those of children on which the FELS/NCHS/WHO references are based. Between 1 and 5 years of age, the median difference between Mbarara and American children increases from 1.5 to 3 kg for weight, from 4 to 7 cm for height, and from 1.5 to 2.5 cm for MUAC. These results imply that the use of the international reference may lead to low specificity and predictive values in screening malnourished children living in an underdeveloped country such as Uganda. The charts here proposed may apply to populations with a lifestyle similar to that of inhabitants of south-west Uganda, both from a nutritional and socioeconomic viewpoint.

Arm↗