Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more than 40 years age group: a transcranial Doppler study.

INTRODUCTION: Middle cerebral artery (MCA) disease is the most common vascular lesion in stroke. Transcranial Doppler (TCD) is a non-invasive bedside screening method for assessing cerebral blood flow. AIM: To investigate the prevalence of MCA stenosis in asymptomatic but high-risk individuals for stroke. MATERIALS AND METHODS: Prospective study between December 2011 and December 2013. Vascular risk factors considered included: hypertension (HTN), diabetes mellitus, smoking, alcohol consumption, coronary artery disease (CAD), peripheral vascular disease (PVD), hypercholesterolemia and obesity. TCD was performed with portable machine through the temporal windows by use of a standardized protocol. RESULTS: Of the 427 subjects, 374 were analyzed; males 264 (70.6%) and females 110 (29.4%). Mean age was 54.2 ± 7.6 years. The frequency of the risk factors was: HTN 287 (76.7%), diabetes 220 (58.8%), CAD 120 (32.1%), hypercholesterolemia 181 (48.4%), smoking 147 (39.3%), alcohol 99 (26.5%), obesity 198 (52.9%) and PVD 8 (2.1%). Of the 374 subjects, 27 (7.2%) had intracranial arterial stenosis and the rest had normal intracranial arteries. On univariate analysis, subjects with higher age, HTN, CAD, smoking and hypercholesterolemia had higher risk of having intracranial arterial stenosis (P < 0.05). Multivariate analysis showed HTN and CAD are independent risk factors for intracranial arterial stenosis. CONCLUSIONS: Overall prevalence of intracranial arterial stenosis is 7.2% in high-risk population sample from Hyderabad in South India. HTN and CAD are independent risk factors for the development of intracranial arterial stenosis.

Efficacy of locally-delivered doxycycline microspheres in chronic localized periodontitis and on Porphyromonas gingivalis.

AIM: This study aimed to assess the efficacy and effect of locally-delivered doxycycline microspheres with scaling and root planing in periodontal pocket therapy and on Porphyromonas gingivalis, respectively. METHODS: Twenty sites with a probing pocket depth of 4-6 mm were divided into two groups: a control group consisting of scaling and root planing, with one application of doxycycline microspheres only at baseline, and a test group consisting of scaling and root planing, with an application of doxycycline microspheres at baseline and 1 and 3 months. Clinical readings included the plaque index, gingival index, probing pocket depth, and relative attachment level. Rapid polymerase chain reaction method was used for the detection of P. gingivalis. RESULTS: A statistically-significant reduction in probing pocket depth and attachment gain was found in both groups; the test group showed a significant reduction in probing pocket depth and attachment gain compared with the control at 3 and 6 months. P. gingivalis cell count in the test group was significantly reduced at all the time periods, except from 1 to 3 months. CONCLUSION: Local drug delivery of doxycycline microspheres significantly improved the treatment outcomes in periodontal pocket therapy and reduced P. gingivalis in the periodontal pocket.

Role of lipid-soluble complexes in targeted tumor therapy.

UNLABELLED: Radionuclide therapy remains a promising arsenal against cancer. However, low tumor uptake, high radiation dose to normal organs, and subsequent adverse effects are challenging problems. This study assessed the therapeutic significance of lipid-soluble compounds of (111)In, which passively diffuse through the cell membrane, bind to cytoplasmic components, and remain cell bound until decay. METHODS: Athymic nude mice bearing human colorectal, prostate, or breast cancer received 11.1-14.8 MBq (300-400 micro Ci) (111)In-8-hydroxyquinoline ((111)In-oxine) or (111)In-mercaptopyridine-N-oxide ((111)In-Merc) in 200 micro L solution intratumorally through a multihole needle. Tumors in some mice were dissected, and 20- micro m-thick sections were autoradiographed. In additional mice, tumor diameter was measured daily, mice were imaged and weighed, and blood samples were drawn for determination of neutrophil counts for up to 28 d after injection. Some mice were sacrificed at predetermined times for quantitative tissue distribution of (111)In. Additionally, tumor cells were labeled with (111)In-oxine and homogenized, and (111)In associated with cell components was determined using polyacrylamide gel electrophoresis. Radiation dose that could be delivered to adjacent tissues was estimated. The (111)In absorbed dose as a function of radial position r in a 1-g tumor was theoretically compared with those of beta-emitting radionuclides (90)Y and (177)Lu. RESULTS: More than 85% of (111)In remained in tumors, bound to cell cytoplasmic components of apparent molecular weights 250 and 6 kDa. (111)In in tumors was uniformly distributed. Only 2% of the injected (111)In was in the liver, kidneys, and carcass. Statistical analysis showed that on day 28, control tumors grew >100%, whereas treated tumors either had growth arrest or grew only slowly (17%). The estimated radiation dose per megabecquerel (millicurie) injected was 90 Gy/g (9,000 rad/g), of which 64% was from conversion electrons, 16% from Auger electrons, 20% from gamma-photons and x-rays, respectively. Radiation dose to adjacent normal organs was 5%-10% of the radiation dose to the tumor and negligible to the liver and kidneys. Neutrophil counts remained unchanged. Mouse body weight was +/-10% of the initial weight. The radiation dosimetry for (111)In and (177)Lu compared favorably, but not that of (90)Y. CONCLUSION: Treatment is independent of receptor density, heterogeneity, or the hypoxic status of cells. It is applicable to treat all known and accessible tumor types, and it delivers a negligible radiation dose to vital organs and only 5%-10% of the radiation dose to organs adjacent to the tumor. Intratumoral administration of (111)In-oxine appears to be a feasible, effective, safe, and promising treatment for cancer.

Radiolabeled PNAs for imaging gene expression

Scintigraphic imaging of gene expression in vivo by non-invasive means could precisely direct physicians to appropriate intervention at the onset of disease and could contribute extensively to the management of patients. However, no method is currently available to image specific overexpressed oncogene mRNAs in vivo by scintigraphic imaging. Nevertheless, we have observed that Tc-99m-peptides can delineate tumors, and that PNA-peptides are specific for receptors on malignant cells and are taken up specifically and concentrated in nuclei. We hypothesize that antisense Tc-99m-PNA-peptides will be taken up by human breast cancer cells, hybridize to complementary mRNA targets, and permit imaging of oncogene mRNAs in human breast cancer xenografts in a mouse model, providing a proof-of-principle for non-invasive detection of precancerous and invasive breast cancer. Oncogenes cyclin D1, erbB-2, c-MYC, and tumor suppressor p53 will be probed. If successful, this technique will be useful for diagnostic imaging of other solid tumors as well