Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease--the Indian Atherosclerosis Research Study

Inflammation plays a major role in coronary artery disease (CAD). We investigated the polymorphisms in the interleukin 6 (IL6) gene and their effect on the expression of acute-phase proteins in premature CAD in Asian Indian families. One hundred and ninety affected sibling pairs (ASPs) were genotyped for three tag single nucleotide polymorphisms (SNPs) in the IL6 gene for linkage analysis. We observed suggestive logarithm of odds (LOD) score for one SNP (rs2066992) in a subset of 62 ASPs with the age at onset less than 45 years (LOD score=1.114, p=0.011 in linkage analysis; pi=0.55, p=0.008 in identity by descent; LOD score=1.06, p=0.014 in quantitative trait locus for plasma levels of high sensitivity C-reactive protein, hsCRP). This was followed by sequencing of the promoter region and haplotype analysis in 46 probands and 40 controls. Five out of the eight previously reported promoter SNPs were found to be polymorphic (rs1800797, rs1800796, rs7802307, rs7802308, rs1800795). Two novel sequence variants were also found. One promoter haplotype (GGAAG) was detected with an odds ratio (OR) of 3.676 (p=0.0017, 95% confidence interval [CI]: 1.68-8.045) and population attributable risk of 21.1% (95%CI: 9.2%-31.5%). The plasma levels of both hsCRP and fibrinogen exhibited significant association with these promoter SNP genotypes (p<0.001). In conclusion, IL6 gene polymorphisms appear to be important genetic factors in premature CAD, and in the regulation of key atherogenic markers in Asian Indian families.     

Concomitant cervical and lumbar intradural intramedullary lipoma

BACKGROUND: Lipomas of the spinal cord are often a component of spinal dysraphic states. Nondysraphic intramedullary spinal cord lipomas are rare, and concomitant isolated cervical and lumbar intradural intramedullary lipomata are very rare. One patient with concomitant isolated nondysraphic cervical and lumbar spinal cord lipomata has been reported and management options discussed. CASE DESCRIPTION: A young girl presented with insidious-onset diffuse neck pain and early myelopathic signs. Conventional radiographs were normal. Magnetic resonance imaging of the whole neuraxis revealed concomitant cervical and lumbar intradural intramedullary lipoma. Subtotal resection of the lesion was performed at both levels, after which the patient improved symptomatically and was ambulant independently. CONCLUSION: Concomitant intradural lipomas at 2 different locations unassociated with a dysraphic state is very rare. Magnetic resonance imaging with fat suppression study is the investigation of choice. Adequate decompression with subtotal removal is the treatment of choice.     

Cardiovascular diseases display etiological and seasonal trend in human population: Evidence from seasonal cardiovascular comorbid diseases (SCCD) index

Seasonal changes in the human cardiovascular system are known to play an important role in the onset of many diseases. Confounding variables include behavioral and environmental factors; failing to address such variables makes measuring the true temporal impact of these diseases difficult. On the other hand, numerous clinical studies imply that only specific groups of people are more seasonal sensitive and that their maladaptation might contribute to various illnesses. As a result, it is critical to evaluate the etiological and seasonal sensitive patterns of cardiovascular diseases (CVD), which impact the majority of the human population. The hypothesis for this study formulated that cardiovascular and associated illnesses had substantial connections with seasonal and etiological variations. Thus in the present study, 4519 systematic screen-eligible studies were analyzed using data mining to uncover 852 disease association relationships between cardiovascular and associated disorders. A disease ontology-based semantic similarity network (DSN) analysis was performed to narrow down the identified CVDs. Further, topological analysis was used to predict the seven CVDs, including myocardial infarction (MI), in three clusters. Following that, Mann–Kendall and Cox–Stuart analyses were used to investigate the seasonal sensitivity and temporal relationship of these seven CVDs. Finally, temporal relationships were confirmed using LOESS and TBATS, as well as seasonal breakdown utilizing autocorrelation and fast Fourier transform results. The study provides indirect evidence of a severe etiological association among the three cardiovascular diseases, including MI, atrial fibrillation, and atherosclerosis, which are winter season sensitive in most of the world population. Hypertension has two seasonal falls and peaks due to its seasonal nature, that is, summer and winter hypertension. While, heart failure was also identified, with minor temporal trends. Hence, all five diseases could be classified as seasonal cardiovascular comorbid diseases (SCCD). Furthermore, these diseases could be studied for potential common risk factors such as biochemical, genetic, and physiological factors.     

Effects of the CCK(B) antagonist CI-988 on responses to mCPP in generalized anxiety disorder.

In order to evaluate the effect of the CCK(B) antagonist CI-988 on behavioral, neuroendocrine, and physiologic responses to the mixed, post-synaptic serotonin (5-HT) agonist/antagonist mCPP, 16 patients with a principal DSM-III-R diagnosis of generalized anxiety disorder (GAD) were enrolled in a study that involved two challenge tests. On one day, patients received a single oral dose of CI-988 followed 30 min later by an i.v. infusion of 0.1 mg/kg mCPP. On a second test day patients received placebo CI-988 followed 30 min later by active i.v. mCPP. The sequence of CI-988 was randomly assigned and the testing was conducted in double-blind fashion. In an initial dose-finding phase (N = 6) with a dose of CI-988 of 25 mg, there were no significant between-test differences in behavioral response to mCPP. Accordingly, the second phase of the study was conducted with a CI-988 dose of 100 mg in another of patients (N = 10). CI-988 (100 mg) was well tolerated and had no significant effects on pretest anticipatory anxiety. There was no significant blunting of the anxiety response to mCPP as a result of CI-988 administration, nor did CI-988 affect physiologic or neuroendocrine measures. Correlations between peak changes in plasma levels of CI-988 and mCPP-induced anxiety in the high-dose patient group were not significant. Overall, these findings did not provide evidence of anxiolytic effects of CI-988 in patients with GAD. The lack of effect of CI-988 on neuroendocrine and physiological measures further suggests that CI-988's pharmacological effects could be independent of 5-HT function. However, follow-up studies using higher doses of CI-988 are indicated to confirm this preliminary finding as are studies more closely evaluating the interrelationship between CCK and 5-HT function in GAD.     

Bone Mineral Density, Hip Axis Length and Risk of Hip Fracture in Men: Results from the Cornwall Hip Fracture Study

Bone mineral density (BMD) and hip axis length (HAL) are important determinants of fracture risk in women. There are, however, few data concerning their predictive risk in men. The aim of this study was to determine the relationship between BMD, HAL and the risk of hip fracture in men. A case–control design was used. Cases were men aged 50 years and over with a minimal-trauma hip fracture admitted to the Royal Cornwall Hospital, Truro, during 1995–1997. Controls were recruited from a large general practice within the catchment area of the hospital. Subjects were invited for assessment of BMD at the lumbar spine and proximal femur, using dual-energy X-ray absorptiometry. HAL was assessed using machine software. Data concerning BMD were available in 62 fracture cases and 100 controls. After adjusting for age, height and weight, a reduction in BMD was associated with a significant increase in the risk of hip fracture [odds ratio (OR) 1.8–4.0 per standard deviation (SD) reduction, depending on site]. HAL was similar in both fracture and control groups (12.0 cm vs 12.0 cm). After adjusting for height, there was no association between HAL and the risk of hip fracture (OR per 1 SD increase in HAL = 0.9; 95% confidence interval 0.6, 1.3). Compared with those with a cervical fracture (n= 31), those with an intertrochanteric fracture (n= 31) had lower BMD at all skeletal sites, though this was significant for the trochanteric site only. It is concluded that BMD though not hip axis length is a risk factor for low-trauma hip fracture in Caucasian men. Received: 28 September 1999 / Accepted: 21 April 2000     

Catastrophic payments for health care in Asia

Out-of-pocket (OOP) payments are the principal means of financing health care throughout much of Asia. We estimate the magnitude and distribution of OOP payments for health care in fourteen countries and territories accounting for 81% of the Asian population. We focus on payments that are catastrophic, in the sense of severely disrupting household living standards, and approximate such payments by those absorbing a large fraction of household resources. Bangladesh, China, India, Nepal and Vietnam rely most heavily on OOP financing and have the highest incidence of catastrophic payments. Sri Lanka, Thailand and Malaysia stand out as low to middle income countries that have constrained both the OOP share of health financing and the catastrophic impact of direct payments. In most low/middle-income countries, the better-off are more likely to spend a large fraction of total household resources on health care. This may reflect the inability of the poorest of the poor to divert resources from other basic needs and possibly the protection of the poor from user charges offered in some countries. But in China, Kyrgyz and Vietnam, where there are no exemptions of the poor from charges, they are as, or even more, likely to incur catastrophic payments.     

A calcified central venous fibrin sheath mimicking a fractured catheter

A 75-year-old female with end stage kidney failure had her tunneled central venous dialysis catheter (CVC) removed. A subsequent computed tomopgraphy (CT) scan of the chest reported a filling defect in the central vein that appeared to represent a fractured remnant of the CVC. The catheter had been retained for culture and was available for direct visualization, which showed it to be entirely intact. A subsequent venogram confirmed that the CT findings represented a retained calcified central venous fibrin sheath. As retained CVC fragments may require intervention, this diagnosis should be established carefully. A calcified fibrin sheath associated with a chronic CVC is a known, although rare, complication and should be considered in the differential diagnosis of an apparent CVC fracture prior to further interventions.