Dismantling the ability of CT and MRI to identify the target mismatch profile in patients with anterior circulation large vessel occlusion beyond six hours from symptom onset.

PURPOSE: Patients with large vessel occlusion and target mismatch on imaging may be thrombectomy candidates in the extended time window. However, the ability of imaging modalities including non-contrast CT Alberta Stroke Program Early Computed Tomographic Scoring (CT ASPECTS), CT angiography collateral score (CTA-CS), diffusion-weighted MRI ASPECTS (DWI ASPECTS), DWI lesion volume, and DWI volume with clinical deficit (DWI + NIHSS), to identify mismatch is unknown. METHODS: We defined target mismatch as core infarct (DWI volume) of < 70 mL, mismatch volume (tissue with TMax > 6 s) of ≥ 15 mL, and mismatch ratio of ≥ 1.8. Using experimental dismantling design, ability to identify this profile was determined for each imaging modality independently (phase 1) and then with knowledge from preceding modalities (phase 2). We used a generalized mixed model assuming binary distribution with PROC GLIMMIX/SAS for analysis. RESULTS: We identified 32 patients with anterior circulation occlusions, presenting > 6 h from symptom onset, with National Institute of Health Stroke Scale of ≥ 6, who had CT and MR before thrombectomy. Sensitivities for identifying target mismatch increased modestly from 88% for NCCT to 91% with the addition of CTA-CS, and up to 100% for all MR-based modalities. Significant gains in specificity were observed from successive tests (29, 19, and 16% increase for DWI ASPECTS, DWI volume, and DWI + NIHSS, respectively). CONCLUSIONS: The combination of NCCT ASPECTS and CTA-CS has high sensitivity for identifying the target mismatch in the extended time window. However, there are gains in specificity with MRI-based imaging, potentially identifying treatment candidates who may have been excluded based on CT imaging alone.

Genetic selection pressure in TLR9 gene may enforce risk for SLE in Indian Tamils.

Objectives Lupus is a classical systemic autoimmune disease with genetics as one of the well known causative factors for the disease pathogenesis. Toll-like receptors are the major pattern recognition receptors associated with innate immunity and also act as an interface with the adaptive immunity. Genetic polymorphisms in genes encoding TLRs were implicated in the development of infections, malignancies and autoimmune diseases. TLR9 is a member of TLR family, and recognizes the CpG DNA motifs of pathogens. Though the incidence rate of lupus in Asians was reported to be low (30 - 50/100,000 population), poor disease prognosis due to higher incidence of renal complications and aggressive disease worsens the scenario. The ability of TLR9 to detect and elicit an immune response against double-stranded DNA makes TLR9 a relevant factor to be tested for its association with the clinical and serological phenotypes of lupus. However, lack of relevant genetic data on normative frequencies of the TLR9 (rs187084) polymorphism may serve as a constraint to derive the sample size to conduct case control association studies. Hence this study was conducted to establish the normative frequency of TLR9 (rs187084) polymorphism in Indian Tamils. Materials and methods The TLR9 (rs187084) polymorphism was screened in South Indian Tamils ( n = 208) by PCR-RFLP. Results and discussion We observed a higher occurrence of the mutant allele (65%) in South Indian Tamils. No gender disparity with respect to the mutant allele frequency was observed. The higher incidence of mutant allele in both genders suggests that this population had undergone a genetic selection pressure as an evolutionary genetic measure to withstand the prevailing endemic infections like TB and malaria. Though the enhanced expression of TLR9 was protective against infections, it may also influence the development of autoimmune diseases. Conclusion The higher incidence of theTLR9 (rs187084) over-expression mutation in Indian Tamils is suggestive of a genetic adaptation or selection pressure to withstand the prevailing endemic infectious and parasitic diseases. However, this genetic adaptation poses a greater risk to develop autoimmune diseases like SLE etc through complex gene environment interactions. The normative frequency of the TLR9 (rs187084) polymorphism established in our population could now be used to define the sample size for future case control studies.

Chemical constituents and larvicidal potential of Feronia limonia leaf essential oil against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus.

In the present investigation, the leaf essential oil of Feronia limonia was evaluated for chemical constituents and mosquito larvicidal activity against the larvae of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus. GC and GC-MS analyses revealed that the essential oil contain 51 compounds. Estragole (34.69 %) and ß-pinene(23.59 %) were identified as the major constituents followed by methyl (Z)-caryophyllene (11.05 %), eugenol (6.50 %), linalool (3.97 %), phytol (3.27 %), sabinene (2.41 %) and limonene (2.27 %). Larval mortality was observed after 12 and 24 h of exposure period. The oil showed remarkable larvicidal activity against A. stephensi (LC(50) = 38.93 and LC(90) = 108.64 ppm (after 12 h); LC(50) = 15.03 and LC(90) = 36.69 ppm (after 24 h)), A. aegypti (LC(50) = 37.60 and LC(90) = 104.69 ppm (after 12 h); LC(50) = 11.59 and LC(90) = 42.95 ppm (after 24 h)) and C. quinquefasciatus (LC(50) = 52.08 and LC(90) = 124.33 ppm (after 12 h); LC(50) = 22.49 and LC(90) = 60.90 ppm (after 24 h)). Based on the results, the essential oil of F. limonia can be considered as a new source of larvicide for the control of vector mosquitoes.

Clinical stroke penumbra: use of National Institutes of Health stroke scale as a surrogate for CT perfusion in patient triage for intra-arterial middle cerebral artery stroke therapy.

BACKGROUND AND PURPOSE: CTP may help triage acute stroke patients for IAT, but requires additional contrast agent, radiation, and imaging time. Our aim was to determine whether clinical examination (NIHSS) with NCCT and CTA can substitute for CTP without significantly affecting IAT triage of patients with acute MCA stroke. MATERIALS AND METHODS: We reviewed NCCT, CTA, and CTP imaging performed within 8 hours of symptom onset in 36 patients presenting with MCA territory stroke (September 2007-October 2009). Two neuroradiologists reviewed, independently and by consensus, NCCT, CTA, and CTP (CTP group), and 2 different neuroradiologists blinded to CTP reviewed NCCT, CTA, and NIHSS (stroke scale group) to determine IAT eligibility: M1 or proximal M2 occlusion; infarct core <1/3 MCA territory; and ischemic penumbra >20% infarct core. The stroke scale group estimated infarct core from NCCT and CTA source images and ischemic penumbra from core size relative to NIHSS score and re-evaluated patients after unblinding to CTP. We computed intragroup and intergroup κ scores for IAT treatment recommendation and used the McNemar test to determine whether CTP significantly affected the stroke scale group's decisions. RESULTS: IAT was recommended in 16/36 (44%) and 17/36 (47%) patients by the CTP and stroke scale groups, respectively, with intragroup κ scores of 0.78 ± 0.11 versus 0.83 ± 0.09. The intergroup κ score was 0.83 ± 0.09. When unblinded to CTP, the stroke scale group revised 2/36 (5.6%) decisions, which was insignificant (P = .48, McNemar test). CONCLUSIONS: NIHSS interpreted with NCCT and CTA may be an effective substitute for CTP-derived measures in the IAT triage of patients with acute MCA stroke. Replacing CTP may potentially reduce radiation and contrast dose and time to treatment.

Endovascular therapy of acute ischemic stroke: report of the Standards of Practice Committee of the Society of NeuroInterventional Surgery.

OBJECTIVE: To summarize and classify the evidence for the use of endovascular techniques in the treatment of patients with acute ischemic stroke. METHODS: Recommendations previously published by the American Heart Association (AHA) (Guidelines for the early management of adults with ischemic stroke (Circulation 2007) and Scientific statement indications for the performance of intracranial endovascular neurointerventional procedures (Circulation 2009)) were vetted and used as a foundation for the current process. Building on this foundation, a critical review of the literature was performed to evaluate evidence supporting the endovascular treatment of acute ischemic stroke. The assessment was based on guidelines for evidence based medicine proposed by the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM). Procedural safety, technical efficacy and impact on patient outcomes were specifically examined.

Cerebellar pial arteriovenous malformations presenting with medullary venous hypertension: imaging and endovascular treatment.

A patient in their 60s presented with headache and progressive lower extremity weakness over 1 week. Initial MRI was thought to represent venous hypertension secondary to a dural arteriovenous fistula. However, angiography revealed a cerebellar pial arteriovenous malformation with medullary venous hypertension. The imaging and endovascular treatment of this unusual case of a pial cerebellar arteriovenous malformation presenting in that manner is presented.

An easily identifiable anatomic landmark for fluoroscopically guided sacroplasty: anatomic description and validation with treatment in 13 patients.

BACKGROUND AND PURPOSE: Percutaneous sacroplasty has recently gained attention as a potential treatment for sacral insufficiency fractures. We describe a readily identifiable fluoroscopic landmark that facilitates needle placement and validate this with virtual needle placement by using CT data and fluoroscopically guided treatment in 13 patients. MATERIALS AND METHODS: From CTs of 100 consecutive patients, the optimal target zone for needle placement in the sacral ala was defined at the intersection of lines from each of the corners of the first sacral segment, which is readily identifiable on lateral fluoroscopy. We then measured the distance from that virtual target point to the anterior sacral cortex by using the CT data for 3 specific trajectories: 1) parallel to the L5-S1 disk, 2) axial with respect to the patient, and 3) along the long axis of the sacrum. Case records of 13 consecutive patients treated by using this technique were also reviewed. RESULTS: The mean distances for the 3 trajectories were 11.3 mm, 11.2 mm, and 12.8 mm, respectively. Needle placement would have been outside the anterior sacral cortex in 3 patients. Review of preprocedure imaging easily identified this potential breach. During treatment, needle placement by using the landmark was successful in all patients, and there were no complications. CONCLUSIONS: A safe target for sacroplasty needle placement in the superolateral sacral ala can be defined by using the intersection of lines drawn from the corners of the first sacral segment. We validated this landmark by using it for treatment in 13 patients. Further studies evaluating clinical outcomes following sacroplasty will be necessary.

Safety of intravenous heparin administration after endovascular treatment for ruptured intracranial aneurysms.

INTRODUCTION: Thromboembolic events are the primary complications encountered during endovascular treatment (EVT) of intracranial aneurysms. Intraprocedural heparinization is common during EVT but is less common post-procedure. The safety of heparinization following EVT is unknown, especially for ruptured aneurysms. MATERIALS AND METHODS: The records of 138 consecutive patients at our institution from 1 January 2000 to 30 June 2007 who were treated with EVT for 140 ruptured intracranial aneurysms were reviewed. All patients were treated with low dose intravenous heparin post-procedure for 24 h as per the departmental protocol. Cases of worsening hemorrhage requiring surgical evacuation were considered significant hemorrhages. Prior surgical exploration and external ventricular drain (EVD) placement were also noted. RESULTS: There were two cases (1.4%) of significant worsening hemorrhage during post-procedure heparin administration. Among 13 patients who underwent craniotomy (for hematoma evacuation or attempted surgical clipping) prior to EVT, there was one (7.7%) case of significant hemorrhage. Among the 60 patients who underwent EVD placement prior to EVT, there was one (1.7%) case of significant hemorrhage. CONCLUSION: Administration of systemic heparinization may be safe during the first 24 h post-EVT of a ruptured intracranial aneurysm in patients without recent craniotomy. Further study in determining the benefit of this protocol in reducing post-embolization thromboembolic complications may be warranted.

CT of the duodenum: an overlooked segment gets its due.

Abdominal computed tomography (CT) is frequently performed to evaluate gastrointestinal pathologic conditions, and the majority of the gastrointestinal radiology literature has concentrated on the colon, stomach, and distal small bowel. In a description of CT findings of duodenal pathologic conditions, congenital, traumatic, inflammatory, and neoplastic diseases are presented. Congenital duodenal anomalies such as duplications and diverticula are usually asymptomatic, while annular pancreas and malrotation may manifest in the 1st decade of life. CT plays a vital role in the diagnosis of traumatic duodenal injury. Primary inflammatory processes of the duodenum such as ulcers and secondary involvement from pancreatitis can reliably be diagnosed at CT. Infectious diseases of the duodenum are difficult to diagnose, as the findings are not specific. While small bowel malignancies are relatively rare, lipoma, adenoma, and adenocarcinoma, as well as local extension from adjacent malignancies, can be diagnosed at CT. Careful CT technique and attention to the duodenum can result in reliable prospective diagnoses.

Tufted angioma in a case of neurofibromatosis type I.

Tufted angiomas are rare benign tumours with a characteristic histopathological appearance. Their occurrence in neurofibromatosis type 1, a genodermatosis in which vascular malformations are not uncommon, has hitherto not been reported. Some of the characteristic features of tufted angiomas are discussed.

Synthesis of new indeno[1,2-c]isoquinolines: cytotoxic non-camptothecin topoisomerase I inhibitors.

In an attempt to design and synthesize potential anticancer agents acting by inhibition of topoisomerase I (top1), a new series of indenoisoquinolines was prepared and tested for cytotoxicity in human cancer cell cultures and for activity against top1. The synthesis relied on the condensation of substituted Schiff bases with homophthalic anhydrides to produce cis-3-aryl-4-carboxyisoquinolones that were cyclized to indenoisoquinolines in the presence of thionyl chloride. Both top1 inhibitory activity and cytotoxicity maximized in a single compound, 6-[3-(2-hydroxyethyl)aminopropyl]-5,6-dihydro-2,3-dimethoxy-8, 9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride (19a), which proved to be a very potent top1 inhibitor having a 110 nM mean graph midpoint (MGM) when tested for cytotoxicity in 55 human cancer cell cultures. A number of structurally related indenoisoquinolines were also obtained that had both potent cytotoxicity as well as top1 inhibitory activity. The key feature of the more potent compounds was the presence of an aminoalkyl side chain on the indenoisoquinoline nitrogen atom. The DNA cleavage patterns induced by top1 in the presence of the indenoisoquinolines were different from those seen with camptothecin. Some of the cleavage sites induced by the indenoisoquinolines were different from those seen with camptothecin, and conversely, camptothecin induced unique cleavage sites not apparent with the indenoisoquinolines. However, both camptothecin and the indenoisoquinolines also induced DNA cleavage sites that were the same in both series but varied in intensity. In addition, some of the DNA cleavages seen with the free base of 19a (compound 18c) in the presence of top1 were inhibited at higher drug concentrations, suggesting either a direct inhibition of the enzyme or an alternative mechanism involving DNA intercalation. Consistent with intercalation, compound 18c did unwind DNA.

Synthesis of cytotoxic indenoisoquinoline topoisomerase I poisons.

A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs topoisomerase 1 (top1). The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (21) and cis-6-allyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (22), both of which displayed submicromolar mean graph midpoints when tested in 55 human cancer cell cultures. Two of the most potent top1 inhibitors were 6-(3-carboxy-1-propyl)-5,6-dihydro-5, 11-dioxo-11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2, 3-dimethoxy-8,9-(methylenedioxy)-11H-indeno[1,2-c]isoquinolinium chloride (27), both of which also inhibited top2, unwound DNA, and are assumed to be DNA intercalators. However, two additional potent top1 inhibitors, 6-allyl-5,6-dihydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (13c) and 5,6-dihydro-6-(4-hydroxybut-1-yl)-2,3-dimethoxy-8, 9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (19a), did not unwind DNA and did not affect top2. Some of the DNA cleavage sites detected in the presence of the indenoisoquinolines were different from those seen with the camptothecins. The cleavage sites induced by the indenoisoquinolines were reversed by salt treatment, which is consistent with the reversible trapping of top1 cleavable complexes by the indenoisoquinolines. In general, the potencies of the indenoisoquinolines as top1 inhibitors did not correlate with their potencies as cytotoxic agents, as some of the most cytotoxic agents had little if any effect on top1. On the other hand, the most potent of the indenoisoquinolines vs top1 were not the most cytotoxic. In several cases, moderate activity was observed for both cytotoxicity and activity vs top1.

Cardio vascular morbidity in proteinuric south Indian NIDDM patients.

Proteinuria is a well known risk factor for cardiovascular morbidity. There has been no report on cardiovascular morbidity in Indian NIDDM patients with proteinuria. Hence this study has been undertaken to estimate the prevalence of cardiovascular diseases (CVD) in South Indian NIDDM with proteinuria. We studied two groups of NIDDM patients with diabetes for > or = 5 years: group PR with persistent proteinuria of > 500 mg/day (n = 297) and group NPR with normoalbuminuria (albuminuria < or = 30 micrograms/mg creatinine)(n = 296), who reported for review during the study period. They were matched for age, duration of diabetes and BMI. The prevalence of cardiovascular diseases, namely myocardial infarction, the presence of ischaemic heart disease and the history of coronary bypass surgery were compared in the two groups. The prevalence of hypertension was higher among the PR than the NPR patients (56.5 vs 24.7%, chi 2 = 61.3, P < 0.01). CVD were detected in 39.2% (n = 116) of the PR and 13.2% (n = 39) of the NPR groups. (chi 2 = 54.85, P < 0.001). The risk was thus three-fold higher in the PR group. Univariate analysis showed that in the proteinuric group, the prevalence of complications was higher in association with hypertension (45.8% vs 30.2%, chi 2 = 6.82, P = 0.009). Multiple logistic regression analysis showed that the factors associated with CVD were proteinuria (odds ratio 5.03), age (OR 1.08) and BMI (OR 1.07) while sex, age at onset of diabetes, duration of diabetes, hypertension, smoking, HbA1, serum creatinine, cholesterol and triglycerides did not show independent contribution. The study, highlights the high risk conferred by macroproteinuria in Indian NIDDM patients. This risk is found to be independent of the presence of associated hypertension.

Postpemphigus acanthomata: a sign of clinical activity?

BACKGROUND: Pemphigus is a group of vesiculobullous disorders in which the blisters usually heal with hyper or hypopigmentation. The appearance of acanthomata at sites of previous blisters has been noted in some cases. METHODS: All cases of pemphigus admitted to the Madras Medical College hospitals during a 2-year period from March 1993 to March 1995 were taken into the study and screened for the presence of acanthomata. RESULTS: Fifty-two cases of pemphigus were identified, 47 of pemphigus vulgaris and five of pemphigus foliaceus; and of these 13 developed acanthomata when the blisters healed. Ten of these cases were of pemphigus vulgaris and three were of pemphigus foliaceus; biopsy of these lesions showed hyperkeratosis, acanthosis, papillomatosis, and intraepidermal clefting. Immunofluorescence carried out in two of these acanthomata also showed intercellular fluorescence. CONCLUSIONS: The occurrence of acanthomata in healed lesions of pemphigus is not uncommon; because histopathologic and immunofluorescence evidence of disease activity is present, cases of this sort require careful follow-up.

Neurofibroma occurring in patients with rheumatoid arthritis.

Two female patients suffering from rheumatoid arthritis presented with the complaint of papular skin lesions over the dorsal aspect of hands. Histopathological examination of papules showed the features of neurofibroma.

Acantholytic dyskeratotic epidermal naevus.

A 43-year old male presented with unilateral warty papular eruptions of 20 years duration, involving the left side of trunk, left upper and lower limbs. There were also whitish macules intermingled with them. Histological features were compatible with Darier's disease. There was no evidence of any family history or palmar pits and nail changes typical of Darier's disease. We are reporting this case as acantholytic dyskeratotic epidermal naevus representing a mosaic form of Darier's disease.

Malignant blue nevus.

Blue nevus represents an aberrant collection of functioning benign dermal melanocytes. Its malignant degeneration is rare and is regarded as a form of malignant melanoma. We report a case of 35-year old male with this rare condition whose primary lesion over left foot ulcerated and patient later succumbed to multiple metastases.

Darier's disease with warty dyskeratoma and basal cell epithelioma.

A 48-year old man with warty dirty papules over the seborrhoeic areas, also had a nodule with a central keratotic crater over the right cheek. Biopsy of this nodule revealed features of Darier's disease, warty dyskeratoma and basal cell epithelioma. Even though Darier's disease and warty dyskeratoma are considered as a distinct entities, the presence in the same lesion emphasizes the need for further studies on this association.