Apolipoprotein AI-CIII, B, and CII gene polymorphisms in patients with non-insulin dependent diabetes mellitus. Association with hyperlipemia

BACKGROUND: Dislipidaemia is an usual feature in patients affected by non insulin dependent diabetes mellitus. Several studies show that this disease could be genetically determined. The aim of this study was to ascertain whether any of the genetic polymorphism remaining in three apolipoprotein loci (apolipoprotein AI-CIII, B100 and CII) is related with the presence of dislipidaemia in non insulin dependent diabetes mellitus patients. PATIENTS AND METHODS: 53 non insulin dependent diabetes mellitus patients with less than 5 years evolution and treated only with diet, were included. 86 healthy persons were included as the control group. The lipidic parameters analyzed were: cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein AI, B and lipoprotein (a). The following polymorphic variants were analyzed: RFLP-Sacl of the apolipoprotein AI-CIII-AIV cluster, RFLP-Xbal of the apolipoprotein B100 region and the RFLP-Taql of the apolipoprotein E-CI-CII cluster. RESULTS: There were no genetic nor allelic differences in the distribution of the genes, between controls and diabetic patients. Regarding the apolipoprotein CII gen, the diabetic patients with the T2T2 genotype had higher triglyceride levels (p < 0.01) compared with the remaining genotypes and compared with the control group having the same genotype (p < 0.01) matched for sex, age and body mass index. There was no difference in the metabolic parameters' distribution related to the genotypic distribution of the apolipoproteins AI-CIII and B100 genes. CONCLUSIONS: The apolipoprotein CII can be related with the presence of hypertriglyceridaemia in non insulin dependent diabetes mellitus patients.     

Apolipoprotein(a) size polymorphism in young adults with ischemic stroke

Gastrin and cholecystokinin (CCK) are two major regulatory peptides synthesized by human gut and brain tissues as well as by selected tumors, in particular gastrin-producing neuroendocrine tumors. In the present study we have evaluated gastrin and CCK gene expression in a group of primary human tumors, including neuronal, renal, and myogenic stem cell tumors, using in situ hybridization techniques. In addition, CCK-A and CCK-B receptors were evaluated in the same group of tumors with receptor autoradiography. Most tumors had gastrin messenger ribonucleic acid (mRNA): 10 of 11 medulloblastomas, 5 of 5 central primitive neuroectodermal tumors, 11 of 11 Ewing sarcomas, 8 of 10 neuroblastomas, 4 of 4 Wilms' tumors, 5 of 5 rhabdomyosarcomas, and 10 of 10 leiomyosarcomas. CCK mRNA was restricted predominantly to Ewing sarcomas (9 of 11) and leiomyosarcomas (5 of 10). CCK-A and CCK-B receptors were not frequently found in these tumors, except for leiomyosarcomas. These data suggest that gastrin and CCK may play a previously unrecognized role in this group of human stem cell tumors. If the increased gastrin mRNA indeed translates into increased gastrin production, measurement of gastrinemia may have a diagnostic significance in the early detection of these tumors. As these two hormones have been reported to act as potent growth factors, they may be of pathophysiological relevance for patients with such stem cell tumors.     

Apolipoprotein E and B alleles in Parkinson's patients

Parkinson's patients were genotyped for the apolipoprotein E alleles as well as polymorphisms at the apolipoprotein B loci to determine whether they were at risk for late onset Alzheimer's disease or coronary disease. The Parkinson's patients were at no greater risk for either disease than were the control spouses. The frequency for the APOE4 allele was 11% compared with the spouses, 10%. Interestingly, 20% of the patients had the 2/3 genotype which may have a protective effect from late onset Alzheimer's disease.     

Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese

Hyperhomocyst(e)inemia has been identified as an independent risk factor for atherosclerotic and thromboembolic diseases such as coronary artery disease, cerebral artery disease, and venous thrombosis. Recently, the alanine/valine (A/V) gene polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes that catalyzes the remethylation of homocysteine, was reported. The VV genotype is correlated with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the association between the V allele of the MTHFR gene and ischemic stroke in an elderly Japanese population. The diagnosis of cerebral infarction of all study patients was confirmed by CT of the brain. The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. In 256 stroke patients and 325 control subjects, the frequencies of the V allele were 0.45 and 0.32, respectively. The odds ratios and 95% confidence intervals adjusted for the other risk factors were, respectively, 1.51 (1.02 to 2.23) for the AV genotype and 3.35 (1.94 to 5.77) for the VV genotype compared with the AA genotype. Both of these effects were statistically significant (P=0.041 and P<0.001, respectively). In patients with multiple infarcts in particular, the allele frequency of the V mutation was 0.56, and the association between the V allele and stroke was highly significant. Plasma homocyst(e)ine levels were significantly higher in patients with the VV genotype than in patients with the AA or AV genotype, especially those with low plasma folate levels. The V allele of the MTHFR gene was significantly associated with cerebral infarction in an elderly Japanese population in a codominant manner. The VV genotype may contribute to risk for ischemic stroke through a predisposition to increased plasma homocyst(e)ine levels, and dietary folate supplementation may be of benefit, particularly to patients with this genotype.     

Asymptomatic cerebral infarctions in patients with ischemic stroke

We studied 383 consecutive patients with stroke and ischemic lesions on CT scan for the presence of symptomatic cerebral infarction (SCI) and asymptomatic cerebral infarction (ACI). We evaluated risk factors as well as volume, site and number of the lesions. ACIs occurred in 34% of the cases (130/383); 88% of ACIs were lacunes and internal borderzone infarctions, with a volume of less than 2 ml. Larger infarctions were asymptomatic in 27 patients (20.8%); 114 (68.7%) out of 166 patients with two or more SCIs (68.7%) had one or more ACIs. Infarctions in the lateral middle cerebral artery (MCA) territory were SCIs, in the medial MCA territory ACIs. Independent risk factors for ACI were age above 70 years and smoking; cardioembolism prevailed in SCI, small vessel disease in ACI; high levels of disability prevailed in SCIs.     

Thrombocyte lactate dehydrogenase isoenzymes in patients with ischemic stroke

It was established that in the acute period of the ischemic stroke in the maiority of cases a change of isoenzyme structure of LDG thrombocytes was due to a decrease of LDG3 activity. In a number of patients the dominant change in the spectrum was determined by LDG and LDG4 fractions. The changes were of a stable character up to 10 weeks. LDG4 increase was characteristic of the isoenzymes spectrum in the patients with a severe development of the disease and in the patients in the remote period of the stroke. The obtained data can serve as a criterion for evaluating the adaptive changes in acute brain ischemia.     

Apolipoprotein E and A-IV polymorphisms in the Estonian population

A 41-year-old man was admitted to our hospital with chief complaints of painless tumor in the left scrotal contents and loss of body weight. As the tumor was suspected of being a neoplastic lesion, left radical inguinal orchiectomy was carried out. Histopathological examination showed metastatic adenocarcinoma of the bile duct. Metastatic carcinoma to the testicle, epididymis, and their tunics is unusual and testicular metastases from adenocarcinoma of the bile duct is extremely rare. A case of testicular metastases from carcinoma of the bile duct is reported and the literature reviewed.     

Atrial fibrillation in older stroke patients: association with recurrence and mortality after first ischemic stroke

Oxidation of dichlorofluorescin and dihydrofluorescin and transport of their oxidation products were studied in Saccharomyces cerevisiae cells given diacetates of these compounds. It was found that addition of peroxidase significantly accelerates the formation of dichlorofluorescein and fluorescein, indicating that peroxidase activity may be a limiting factor in studies of cellular oxidation using these probes. A significant leakage of dichlorofluorescin and dihydrofluorescin, and of their oxidized forms from the yeast cells, was found, without any apparent lag period. This phenomenon complicates interpretation of data obtained with the fluorescent precursors used but, on the other hand, points to the possibility of using measurements of dichlorofluorescein or fluorescein in the extracellular medium for studies of cellular oxidation processes.     

Apolipoprotein B genetic variability in Brazilian Indians

We analyzed tissue samples from bottlenose dolphins (Tursiops truncatus) that had stranded on beaches in Texas and Florida over a 1-year period starting in September 1991. The concentrations of 10 elements plus methyl mercury (MeHg) were determined in brain, kidney, and liver, and we examined these results for differences based upon age, site, sex, and tissue type. A strong inverse relationship between total mercury (Hg) and the percentage that was MeHg was found in liver, kidney, and brain tissue, presumably due to demethylation of MeHg. A threshold concentration was found for total Hg in brain tissue, indicating that most Hg was present as MeHg up to about 8 years of age. Increases in total Hg after this age were accompanied by an increase in the ratio of total Hg to MeHg, indicating demethylation. Strong relationships were found between total Hg in liver and age and between total Hg and selenium in liver, which have been observed before in many fish- and squid-eating marine mammals. The only difference based on sex of the animals was observed for MeHg, which was higher in females and contrary to the pattern often observed for organic contaminants. Several elements (copper, Hg, lead, zinc) exhibited intersite differences, which were not consistent. Bottlenose dolphin from Florida exhibited the highest levels of MeHg and total Hg, while animals from Texas exhibited the highest levels of lead, copper, and zinc. The essential elements copper and zinc were expected to be the same for the Texas and Florida animals; however, observed differences may indicate population differences in basic physiological levels, dietary intake, or health status.     

Evaluation of treatment outcome after nicergoline and pentoxifylline in patients with ischemic stroke

In this 4-year follow-up in vivo controlled study, 112 human permanent first molars from children between 6 and 11 years old were used to investigate the viability of the carbon dioxide (CO2) laser in promoting caries-free occlusal surfaces in permanent molars as an isolated form of treatment or associated with conventional fissure sealants. The findings suggest that occlusal caries prevention only by means of CO2 laser irradiation is not effective; that the utilization of photoactivated sealants, as well as its association with CO2 laser, applied over the occlusal fissures, are effective means of preventing occlusal caries, and that the application of CO2 laser over occlusal fissures prior to the application of a photoactivated fissure sealant improves the retention of the sealant.     

Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack

To evaluate the additional value of transesophageal (TEE) compared with transthoracic (TTE) echocardiography and the role of patent foramen ovale (PFO) and deep vein thrombosis in the work-up of embolic events, patients with presumed cardiac embolic stroke or transient ischemic attack (neurovascular etiology was excluded) were prospectively studied by transthoracic and transesophageal contrast echocardiography. If PFO was detected echocardiographically, PFO size was assessed semiquantitatively and phlebography of both legs was performed. Two hundred forty-two consecutive patients (153 men, 60 +/- 15 years) were studied. In 197 patients, neuroimaging showed evidence of embolic infarction. TEE identified 138 potential cardiac sources of embolism in 111 patients, compared with 69 by TTE (p <0.01) in 59 patients. TEE detected potential cardiac sources in 52 patients with negative TTE examination and was significantly superior compared with TTE for identifying left atrial thrombi, spontaneous echo contrast, PFO, atrial septal aneurysm, and atheroma of the ascending aorta. In patients with a positive TTE, additional diagnostic information by TEE was found in only 6 patients and did not change therapy. Phlebography was performed in 53 patients with PFO and revealed deep vein thrombosis in 5 patients (9.5%); all had medium or large PFOs. Thus, in patients with cerebral ischemia of suspected cardiogenic origin and a normal TTE examination, TEE detects potential causes of embolism in 31% of patients and is therefore of diagnostic relevance. Conversely, in the presence of a diagnostic TTE an additional TEE confers only marginal diagnostic benefit. Deep venous thrombosis was detected in nearly 10% of patients with PFO as the sole identifiable cardiac risk factor. Given that in 4 of 5 patients deep vein thrombosis was clinically silent, phlebography should be performed in patients with medium or large interatrial shunts if paradoxical embolism is suspected.     

Neuro-ultrasonographic evaluation of ischemic stroke

INTRODUCTION AND DEVELOPMENT: The development of new management strategies for acute stroke demands better understanding of the ischemic mechanism, cerebrovascular anatomy, and cerebral hemodynamics for individual patients. The use of carotid duplex sonography, transcranial Doppler sonography, and echocardiography allows evaluation of the key areas of interest in a prompt, safe, accurate, and cost effective manner. CONCLUSIONS: Knowledge of these methods is essential for neurologist caring for patients with stroke.     

Local intra-arterial thrombolysis in acute ischemic stroke

BACKGROUND AND PURPOSE: We performed a retrospective analysis of the prognostic factors in patients treated with local intra-arterial thrombolysis (LIT). The purpose of this study was to evaluate the safety and efficacy of LIT using urokinase in patients with acute ischemic stroke of the anterior or posterior circulation and to determine the influence of clinical and radiological parameters on outcome. METHODS: Forty-three patients were treated with LIT using urokinase (median dose, 0.75x10(6) IU). The median National Institutes of Health Stroke Scale (NIHSS) score at hospital admission was 18 (range, 9 to 36). Nine patients had occlusions of the internal carotid artery (ICA), 23 of the middle cerebral artery (MCA), 1 of the anterior cerebral artery, and 10 of the basilar artery (BA). Outcome was assessed after 3 months and classified as good for Rankin Scale (RS) scores of 0 to 3 and poor for RS scores of 4 or 5 and death. RESULTS: Nine patients (21%) recovered to RS scores 0 or 1, 17 (40%) to scores of 2 or 3, and 7 (16%) to scores of 4 or 5. Ten patients (23%) died. Outcome was good in 17 patients (80%) with MCA occlusions, in 3 patients (33%) with ICA, and in 5 patients (50%) with BA occlusions. Good outcome was associated with an initial NIHSS score of <20 (P<0.001), improvement by 4 or more points on NIHSS score within 24 hours (P=0.001), and vessel recanalization (P=0.02). Recanalization was more likely if LIT was started within 4 hours (P=0.01). Symptomatic cerebral hemorrhage occurred in 2 patients (4.7%). CONCLUSIONS: LIT was most efficacious in patients with MCA and BA occlusions when the initial NIHSS score was less than 20 and when treated within 4 hours. It is of limited value in patients with distal ICA occlusions.     

Role thrombocytes in etiopathogenesis of ischemic stroke

This paper presents the most essential problems concerning the role of platelets in the genesis of ischaemic brain disease and their role in spreading of ischaemic focus. The role of platelets in atherogenesis and development of vascular abnormalities in arterial hypertension and diabetes mellitus was considered, and attention was paid to conditions concerned with the pathogenesis of ischaemic stroke such as presence of antiphospholipid antibodies and presence of large volume platelets, in which platelet activation plays essential role. Then it was shown that platelet hyperactivation occurs in acute phase of ischaemic stroke and mechanisms of destructive action of activated platelets on recent ischaemic focus in brain such as secretion of neurotoxins and blocking of microcirculation by platelet aggregates were discussed.