Platelet polymorphisms: frequency distribution and association with coronary artery disease in an Indian population

Platelets play a critical role in normal blood hemostasis and thrombus formation in myocardial infarction (MI). Several polymorphisms of genes involved in platelet activation and fibrinolysis have been reported to be associated with MI. The aim of the present study was to determine the frequency distribution and association of polymorphisms in these genes with coronary artery disease (CAD) among Indians. A case-control genetic association study was performed for polymorphisms in platelet glycoprotein receptors (GPIIb/IIIa [HPA1a/1b], GPIb-IX-V [VNTR], and GPIa/IIa [C807T]), fibrinogen β-chain (BclI), α-chain (Aα312), tissue plasminogen activator (tPA) [I/D] and plasminogen activator inhibitor-I (PAI-1) [4G/5G] in 473 healthy controls and 446 patients with stable and unstable angina. Genotyping was either by PCR-based restriction endonuclease digestion or allele-specific primers. The I allele frequency of the tPA I/D polymorphism was significantly higher in our patients (χ(2)=7.33, P<0.01) and no other polymorphisms varied significantly between patients and controls. Also, none of the polymorphisms seemed to affect the severity of the disease, the only exception being the mutant alleles of β chain of fibrinogen gene, which were significantly elevated in single vessel disease. This is the first study to evaluate the role of gene polymorphisms in both the thrombotic and fibrinolytic pathway in the Indian population and suggests that tPA I/D polymorphism confers CAD risk in our population.     

Practices and views on fetal heart monitoring: a structured observation and interview study

OBJECTIVE: To assess and explain deviations from recommended practice in National Institute for Clinical Excellence (NICE) guidelines in relation to fetal heart monitoring. DESIGN: Qualitative study. SETTING: Large teaching hospital in the UK. SAMPLE: Sixty-six hours of observation of 25 labours and interviews with 20 midwives of varying grades. METHODS: Structured observations of labour and semistructured interviews with midwives. Interviews were undertaken using a prompt guide, audiotaped, and transcribed verbatim. Analysis was based on the constant comparative method, assisted by QSR N5 software. MAIN OUTCOME MEASURES: Deviations from recommended practice in relation to fetal monitoring and insights into why these occur. RESULTS: All babies involved in the study were safely delivered, but 243 deviations from recommended practice in relation to NICE guidelines on fetal monitoring were identified, with the majority (80%) of these occurring in relation to documentation. Other deviations from recommended practice included indications for use of electronic fetal heart monitoring and conduct of fetal heart monitoring. There is evidence of difficulties with availability and maintenance of equipment, and some deficits in staff knowledge and skill. Differing orientations towards fetal monitoring were reported by midwives, which were likely to have impacts on practice. The initiation, management, and interpretation of fetal heart monitoring is complex and distributed across time, space, and professional boundaries, and practices in relation to fetal heart monitoring need to be understood within an organisational and social context. CONCLUSION: Some deviations from best practice guidelines may be rectified through straightforward interventions including improved systems for managing equipment and training. Other deviations from recommended practice need to be understood as the outcomes of complex processes that are likely to defy easy resolution.     

Intraplaque haemorrhage mimicking carotid pseudoaneurysm on magnetic resonance angiography

Contrast-enhanced magnetic resonance angiography (CE-MRA) is a commonly used technique to assess the extracranial carotid arteries. We describe two patients (investigated for carotid artery atherosclerotic disease) who underwent CE-MRA. Results suggested pseudoaneurysms of the extracranial carotid arteries. Magnetic resonance direct thrombus imaging (MRDTI) showed that the appearances were due to intraplaque haemorrhage adjacent to the vessel, with the T1-shortening effect of methaemoglobin within the intraplaque haemorrhage mimicking blood flow on the CE-MRA sequence. The cases presented demonstrate this diagnostic pitfall and illustrate the contribution of simple magnetic resonance plaque imaging to establishing the correct diagnosis.     

Vertex epidural hematoma with bilateral abducent nerve palsy: case report and literature review

Epidural hematomas which are located at the vertex are rarely seen and form a small percentage of total epidural hematomas. Tearing in the superior sagittal sinus is the usual cause of an epidural hematoma located in the vertex. The clinical features of this entity are non-specific; hence, localization of the lesion is difficult. We report an adult who was hit by a motorcycle and was initially discharged from the hospital as a case of concussional head injury. He returned back with raised intracranial pressure symptoms, so a CT scan was done but was misinterpreted, and he reported one week later with bilateral abducent nerve palsy. Magnetic resonance imaging confirmed vertex EDH for which he was operated.These hematomas are seen rarely and can be interpreted as an artifact. Its recognition is important because it has an excellent prognosis. We concluded that all head injury patients should get high axial cuts on the CT scan, and any degree of suspicion should prompt a neurosurgeon to investigate further with coronal CT scan or MRI.     

Histological grading patterns in patients of cutaneous leishmaniasis

Objective: To determine the histological grading patterns in a cohort of hospitalized patients of cutaneous leishmaniasis. Design: Case series. Place and Duration of Study: The study was conducted at PNS Shifa Hospital, Karachi, from May 2004 to June 2006. Patients and Methods: One hundred patients of Cutaneous Leishmaniasis (CL), admitted in dermatology wards at PNS Shifa Hospital, Karachi, were examined. Only admitted patients of all ages and both sexes were included in the study. Patients of CL, who had received or were receiving systemic treatment were excluded. The lesions having marked secondary bacterial infection were also excluded. Initial diagnosis was clinical. History of being to an endemic area supported the diagnosis. The lesions were divided in two groups. Early, with duration less than 03 months and late, with duration between 3 and 12 months. The clinical lesions were noted as nodules, plaques, ulcers, crusted ulcers, lupoid lesions and plaques with scarring. Three types of skin smears (slit skin smear, saline aspirate smear and dab smear) were taken and examined with Giemsa stain. Cultures were performed on Nicolle-Novy-MacNeal (NNN) culture medium from Defense Scientific and Technology Organization (DESTO) Lab., Pakistan. Incisional skin biopsies were done. The biopsy specimens were examined by hemotoxylin and eosin stain (H & E stain). The number of Leishmania Tropica (LT) bodies was graded according to modified Ridley's parasitic index 1983. Clinical features were correlated with the histological patterns. Results: Five histological patterns were identified in current study: 1) diffuse dermal infiltration without necrosis, 2) patchy dermal infiltration, 3) diffuse dermal infiltration with necrosis, 4) early reactive granuloma formation and 5) established epithelioid granuloma formation. LT bodies were identified in 75% of cases. Epidermal features were non-specific. The early lesions presented with diffuse infiltrate and late lesions showed granuloma formation. Conclusion: Five distinct types of histological patterns of CL have been recognized in this study. The early lesions presented with diffuse infiltrate and late lesions showed granuloma formation but the mixed patterns were also seen. The yield of LT bodies is much higher with histopathology as compared to skin smears and hence is most diagnostic.     

Anti-inflammatory role of methotrexate in adjuvant arthritis: effect on substance p and calcitonin gene-related Peptide in thymus and spleen

Objective: To investigate the anti-inflammatory effect of methotrexate (MTX) in rats with adjuvant arthritis through its influence on the expression of proinflammatory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in immune organs, thymus and spleen. Design: Phase-I pre-clinical trial. Place and Duration of Study: The Aga Khan University, Karachi, from July to December 2003. Materials and Method: Adjuvant arthritis was induced in rats by inoculation with heat-killed mycobacteria. One group of arthritic rats (n=6) was treated with MTX (0.2 mg/kg body weight, subcutaneously) on every 4th day for a period of 18 weeks, while another group of arthritic rats (n=6) was treated with physiological saline served as control. At the end of experiment, animals were sacrificed and thymus and spleen were dissected and prepared for immunohistochemical analysis. The neuronal density of SP and CGRP immunoreactivity in thymus and spleen was assessed by semi-quantitative analysis. Results: There was a marked reduction in hind paw swelling and inflammation in the MTX-treated rats after 18 weeks of treatment. Restoration of joint spaces (tibiotalar and subtalar) was seen after 9 weeks of MTX treatment. CGRP-positive nerve fibres were significantly reduced (p=0.0001) in thymus of rats treated with MTX compared to control rats. SP-positive nerve fibers were also found to be decreased in thymus of rats treated with MTX compared to controls, however, the decrease was not statistically significant. The neuronal density of SP and CGRP-immunoreactivity in spleen was not significantly different in MTX-treated and placebo-treated rats. Conclusion: In arthritic rats, MTX significantly reduced CGRP expression in thymus. Suppression of pro-inflammatory neuropeptides, such as CGRP and probably SP could be another mechanism by which MTX produces its anti-inflammatory effect in adjuvant arthritis.     

Carotid intraplaque hemorrhage detected by magnetic resonance imaging predicts embolization during carotid endarterectomy

BACKGROUND: Microembolization detected during the dissection phase of carotid endarterectomy (CEA) is associated with plaque instability and might be associated with perioperative morbidity. Intraplaque hemorrhage is found in unstable plaques and is detectable using magnetic resonance imaging (MRI). We aimed to ascertain whether intraplaque hemorrhage as seen on carotid MRI predicts particulate embolization in the dissection phase of CEA. METHODS: Patients with high-grade symptomatic carotid stenosis undergoing CEA were prospectively enrolled. All underwent preoperative MRI assessment of the carotid arteries for intraplaque hemorrhage and transcranial Doppler scanning during the dissection phase of the CEA to assess the presence of microembolic signals. Associations between intraplaque hemorrhage and intraoperative microembolic signals were studied. RESULTS: Analysis was undertaken on 60 participants; of these, 36 (60%) showed ipsilateral carotid MRI intraplaque hemorrhage, and 24 (40%) did not. Microembolic signals were detected during the dissection phase in 23 (38.3%) participants, and 19 had MRI-detected intraplaque hemorrhage. The association between carotid intraplaque hemorrhage and the presence of dissection phase microembolic signals was significant (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.6 to 19.7, P = .007), even after controlling for age, sex, individual surgeon, degree of stenosis, and delay from symptom to CEA (adjusted OR, 5.8; 95% CI, 1.1 to 30.4, P = .037). CONCLUSION: Intraplaque hemorrhage as detected by carotid MRI predicts particulate embolization during the dissection phase of CEA. This imaging technique can be used to identify patients with increased intraoperative thromboembolic risk, and this could influence preventive strategies.     

Polymorphism rs7555523 in <Emphasis Type="Italic">transmembrane and coiled-coil domain 1</Emphasis> (<Emphasis Type="Italic">TMCO1</Emphasis>) is not a risk factor for primary open angle glaucoma in a Saudi cohort

Background

We investigated whether polymorphism rs7555523 (A?>?C) in human transmembrane and coiled-coil domain 1 (TMCO1) gene is a risk factor for primary open angle glaucoma (POAG) in a Saudi cohort.

Methods

A cohort of 87 unrelated POAG cases and 94 control subjects from Saudi Arabia were genotyped using Taq-Man® assay. The association of genotypes with POAG and other glaucoma specific clinical indices was investigated.

Results

The genotype and allele frequency of polymorphism rs7555523 at TMCO1 did not show any statistically significant association with POAG as compared to controls. The minor allele frequency was 0.103 in cases and 0.085 in controls. Except for awareness of glaucoma (p?=?0.036), no significant association of genotypes were seen with glaucoma specific clinical indices such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medications used. Binary logistic regression analysis (adjusted for age and gender) showed that age was a significant indicator for the development of glaucoma in this group (adjusted odds ratio?=?1.2; 95 % confidence interval?=?1.078–1.157; p?<?0.001).

Conclusion

Our study was unable to replicate the findings of previously reported association for polymorphism rs7555523 in TMCO1 with POAG and related clinical indices such as IOP and cup/disc ratio indicating that this variant is not a risk factor for POAG in the Saudi cohort.