Late-delayed cerebral involvement in systemic non-Hodgkin lymphoma: a second primary tumor or a tardy recurrence?

BACKGROUND: Central nervous system involvement is a well recognized complication of systemic non-Hodgkin lymphoma. Most central nervous system recurrences occur within the first 2 years after the initial diagnosis and are considered to represent clonally related recurrence of systemic disease. The authors attempted to investigate the clonal relation between the late-delayed central nervous system involvement and the original systemic tumor. METHODS: The authors studied archival, formalin fixed, paraffin embedded tissue samples from 8 patients with isolated cerebral involvement diagnosed > 3 years after their initial presentation with aggressive, systemic, B-cell non-Hodgkin lymphoma. The rearranged immunoglobulin heavy-chain variable region genes (VH) from both sites were amplified by polymerase chain reaction and were sequenced when necessary. RESULTS: In three of five patients who had interpretable results, a distinct, monoclonal, VH family-specific band profile was obtained from the cerebral and systemic lymphoma. In the other two patients, a similar VH band pattern was observed and also was compared using direct sequencing, which demonstrated sequence differences between tumors from the two sites. CONCLUSIONS: Clonal variance between the cerebral and systemic lymphoma in these patients suggested the possibility that some instances of late-delayed recurrence in the central nervous system represent a second, new B-cell lymphoma rather than a true recurrence of the original systemic tumor, a finding that may have significant clinical and biologic implications.     

Thyroid scintigraphy and perchlorate discharge test in the diagnosis of congenital hypothyroidism

Quantitative thyroid scanning using low doses of technetium-99m sodium pertechnetate was performed on 147 infants (55 males and 92 females) with congenital hypothyroidism detected through the national neonatal screening programme. Thirty-two (21.8%) were athyrotic, while 62 (42.2%) had an ectopic thyroid and 53 (36%) had a eutopic gland with increased^99mTc uptake (mean 17%; range, 5%-38%). The perchlorate discharge test (PDT) was performed in nine of the infants with ectopic glands and 15 with eutopic glands; the findings were consistent with an organification defect in 22 cases (seven ectopic and 15 eutopic). Thyroid scintigraphy and PDT can add useful aetiological, genetic and prognostic information in the clinical evaluation of infants with congenital hypothyroidism detected by neonatal screening.     

Smoking in Saudi Arabia and its relation to coronary artery disease

Objectives

The health hazards related to smoking are well known. Smoking is a recognized risk factor for coronary artery disease (CAD). Despite rejection of smoking by the Saudi community, we are still seeing smokers in our population. This study is designed to determine the prevalence of smoking in the Kingdom of Saudi Arabia (KSA), and to find out its relation to CAD. This study is part of the Coronary Artery Disease In Saudis (CADIS) study.

Methods

This health survey was conducted by collecting data regarding smoking status among adult Saudis aged between 30 and 70 years of both sexes in KSA over a five year period from 1995 up to 2000. The study sample was of normal distribution and representative of all regions of KSA. The data were analyzed to provide the prevalence of smoking and its relation with CAD.

Results

The total number of subjects was 17,350, and current smokers were 2217; accordingly the overall prevalence of smoking among Saudis was 12.8%. Males (1555) were significantly smoking more than females (662) with a prevalence of 18.7% and 7.3%, respectively (P < 0.0001). Smoking is more prevalent among Saudis living in urban, northern, western, and eastern regions compared to other regions of KSA. Smokers are more likely to develop CAD compared to non-smokers (P < 0.0001).

Conclusions

Smoking is a prevalent health problem among Saudis that requires intervention for eradication. We found clear association between cigarettes smoking and CAD particularly among males. Persistent education of the health hazards related to smoking is recommended particularly at early age in-order to prevent initiation of smoking.     

Hyperlipidemia in Saudi Arabia

OBJECTIVE: To determine the prevalence of hyperlipidemia among Saudis of both genders in rural and urban communities. METHODS: Selected Saudis in the age group of 30-70 years were studied over a 5-year period between 1995 and 2000 in Saudi Arabia. Data were obtained from history, physical examination, and analysis of fasting plasma lipids. The data were analyzed to classify individuals with hypercholesterolemia (HC) (total cholesterol > or =5.2 mmol/l), and hypertriglyceridemia (HT) (total triglycerides > or =1.69 mmol/l). Logistic regression analysis was performed to provide a risk assessment model and correlation with other coronary artery disease (CAD) risk factors. RESULTS: The number of study samples included in the final analysis was 16,819. The prevalence of HC was 54% with mean cholesterol level of 5.4+/-1.52 mmol/l. Prevalence of HC among males was 54.9% and 53.2% for females, while 53.4% among urban Saudis and 55.3% for rural Saudis. Hypertriglycemia prevalence was 40.3% with mean triglycerides level of 1.8+/-1.29 mmol/l. Males had statistically significant higher HT prevalence of 47.6% compared to 33.7% in females (p<0.0001). CONCLUSION: Hyperlipedimia is reaching higher prevalence rates in KSA. This finding may suggest that CAD will soon be a major health problem. Reduction in obesity by adopting healthier eating habits, and increasing physical activity are of considerable importance to our community.     

Role of promoter methylation in regulation of the mammalian heparanase gene

Mammalian heparanase (endo-beta-glucuronidase) degrades heparan sulfate proteoglycans and is an important modulator of the extracellular matrix and associated factors. The enzyme is preferentially expressed in neoplastic tissues and contributes to tumour metastasis and angiogenesis. To investigate the epigenetic regulation of the heparanase locus, methylation-specific and bisulfite PCR were performed on a panel of 22 human cancer cell lines. Cytosine methylation of the heparanase promoter was associated with inactivation of the affected allele. Despite lack of sequence homology, extensively methylated CpG islands were found both in human choriocarcinoma (JAR) and rat glioma (C-6) cells which lack heparanase activity. Treatment of these cells with demethylating agents (5-azacytidine, 5-aza-2'-deoxycytidine) resulted in stable dose- and time-dependant promoter hypomethylation accompanied by reappearance of heparanase mRNA, protein and enzymatic activity. An inhibitor of histone deacetylase, Trichostatin A, failed to induce either of these effects. Upregulation of heparanase expression and activity by demethylating drugs was associated with a marked increase in lung colonization by pretreated C-6 rat glioma cells. The increased metastatic potential in vivo was inhibited in mice treated with laminaran sulfate, a potent inhibitor of heparanase activity. We propose a model wherein expression of mammalian heparanase gene is modulated by the interplay between trans-activating genetic and cis-inhibitory epigenetic elements in its promoter.