Active Case Finding among Adults using an Individual's Vulnerability Score for Pulmonary Tuberculosis in a Rural Village of Goa: A Cross-sectional Study.

Background: "Detect-Treat-Prevent-Build" to achieve tuberculosis (TB)-free India is envisaged in the National Tuberculosis Elimination Program (NTEP). To be able to achieve this, it is important to address the fact that the most vulnerable and hard-to-reach groups need to undertake screening. The present review aimed to examine the vulnerability in connection with TB disparities faced by distinct sub-populations generally viewed as vulnerable and follow these for testing. Materials and Methods: The community-based cross-sectional study was conducted in the field practice area of sub-center Carambolim in a rural area of Goa for 3 months. The households were visited, and data collected via personal interviews were recorded on the questionnaire study tool. Based on the data, the participants' vulnerability mapping was done per the parameters identified. Results: Among 223 households, 528 persons were screened for vulnerability. The 47 highly vulnerable participants were advised sputum CBNAAT, of which 9 (19%) tested positive for pulmonary TB, while of the 86 moderately vulnerable participants, 4 (5%) tested positive for pulmonary TB. Among the 34 with symptoms suggestive of TB, 3 (9%) tested positive for pulmonary TB. Conclusions: The study detected 16 new TB patients from the population and found a higher incidence of pulmonary TB among the vulnerable group with no symptoms of Pulmonary TB. A further state-wide survey is recommended to diagnose such cases.

A switch-off fluorescence probe towards Pb(II) and cu(II) ions based on a calix[4]pyrrole bearing amino-quinoline group.

A new fluorescence receptor calix[4]pyrrole-N-(quinoline-8-yl) acetamide (CAMQ) containing a pyrrolic ring connected via the meso-position was synthesized, purified and characterized by elemental analysis, NMR and mass spectroscopy. This compound was examined for its fluorescence properties towards different metal ions e.g. Ag(I), Hg(II), Co(II), Ca(II), Ni(II), Zn(II), Cr(II), Ba(II), Fe(II), Cu(II), Pb(II)and Mg(II) ions by spectrophotometry and spectrofluorometry. It was concluded that the compound (CAMQ) possessed significantly enhanced selectivity for Pb(II) and Cu(II) ions in dimethyl sulfoxide (DMSO) even at very low concentrations (1 µM). It exhibit 'turn-on' fluorescence when exposed to Pb(II) and Cu(II) and did so in preference to other metal ions. The binding constants, stoichiometry and quantum yields have been determined. The quenching mechanism was assessed using the Stern-Volmer equation and was also discussed.

Recurrent meningeal sarcoma successfully treated with stereotactic radiosurgery.

Primary intracranial meningeal sarcoma is a rare neurological malignancy without strong evidence-based treatment guidelines. The authors describe a boy with primary meningeal sarcoma who symptomatically presented at 10 months of age and was treated with primary resection. The patient had multifocal recurrence approximately 2 years later. Given the location and rapid progression of the disease, the boy was treated with gamma knife surgery. He had a complete radiographic response 3 years posttreatment. He attends school full time and enjoys good quality of life. Based on local control and response to radiosurgery, the authors suggest that multifocal meningeal sarcomas not amenable to resection can be effectively managed with stereotactic radiosurgery.

Erythrocyte sedimentation rate (ESR) measured by the Streck ESR-Auto Plus is higher than with the Sediplast Westergren method: a validation study.

The erythrocyte sedimentation rate (ESR) is a nonspecific indicator of disease activity and is often used by clinicians in assisting diagnosis and follow-up of many inflammatory disorders. The Westergren method is considered the standard method for measuring ESR. Recently, many automated instruments have become available to address laboratory safety and time efficiency. We validated the Streck ESR-Auto Plus instrument (Streck, Omaha, NE) using the Sediplast (Polymedco, Cortlandt Manor, NY) Westergren method as the reference method. Blood samples collected in 113 EDTA tubes were transferred into Sediplast vials and Streck high-altitude vacuum tubes for measuring the ESR. There was good correlation between the Sediplast and Streck methods (0.95) using Pearson correlation. The y-intercept was at 6.5 using linear regression, indicating systematic bias with a mean difference of 7.13 using the t test (P < .0001). We modified our reference ranges to rectify the systematic bias found during validation.

Granulocytic sarcoma in a patient with myelodysplastic syndrome.

Granulocytic sarcomas (GS) are uncommon extramedullary tumors composed of immature cells of the granulocytic or myeloid series. Treatment for GS should be directed toward the underlying hematologic disorder. There is no standard treatment.

Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma.

OBJECT: The purpose of this study was to examine the results of using Gamma Knife surgery (GKS) for brain metastases from classically radioresistant malignancies. METHODS: The authors retrospectively reviewed the records of 76 patients with melanoma (50 patients), renal cell carcinoma (RCC; 23 patients), or sarcoma (3 patients) who underwent GKS between August 1998 and July 2007. Overall patient survival, intracranial progression, and local progression of individual lesions were analyzed. RESULTS: The median age of the patients was 57 years (range 18-85 years) and median Karnofsky Performance Scale (KPS) score was 80 (range 20-100). Sixty-two patients (81.6%) had uncontrolled extracranial disease. A total of 303 intracranial lesions (average 3.97 per patient, range 1-27 lesions) were treated using GKS. More than 3 lesions were treated in 30 patients (39.5%). Median GKS tumor margin dose was 18 Gy (range 8-30 Gy). Thirty-seven patients (48.7%) underwent whole brain radiation therapy. The actuarial 12-month rate for freedom from local progression for individual lesions was 77.7% and was significantly higher for RCC compared with melanoma (93.6 vs 63.0%; p = 0.001). The percentage of coverage of the prescribed dose to target volume was the only treatment-related variable associated with local control: 12-month actuarial rate of freedom from local progression was 71.4% for lesions receiving >or= 90% coverage versus 0.0% for lesions receiving < 90% (p = 0.00048). Median overall survival was 5.1 months after GKS and 8.4 months after the discovery of brain metastases. Univariate analysis revealed that KPS score (p = 0.000004), recursive partitioning analysis class (p = 0.00043), and single metastases (p = 0.028), but not more than 3 metastases, to be prognostic factors of overall survival. The KPS score remained significant after multivariate analysis. Overall survival for patients with a KPS score >or= 70 was 7.1 months compared with 1.3 months for a KPS score 3 metastases. Higher rates of local tumor control were achieved for RCC in comparison with melanoma, and this may have an effect on survival in some patients. Although outcomes generally remained poor in this study population, these results suggest that GKS can be considered as a treatment option for many patients with radioresistant brain metastases, even if these patients have multiple lesions.

Doses greater than 85 Gy and two isocenters in Gamma Knife surgery for trigeminal neuralgia: updated results.

OBJECT: The purpose of this study was to assess the efficacy of Gamma Knife surgery (GKS) in treating patients with trigeminal neuralgia (TN). Preliminary results of this study were previously reported. The updated results are reported in this paper. METHODS: Ninety seven patients with TN refractory to medical or surgical management underwent GKS between September 1998 and October 2005. Fifteen patients had multiple sclerosis (MS). The radiation dose was escalated from 70 to 99 Gy. The Barrow Neurological Institute Pain Scale (BNIPS) was used to assess pain before and after GKS. Eighty-four patients were available for evaluation with a mean follow up of 8.9 months. The overall response and complete response rates were 70.2% and 36.9%, respectively. At 12 months, there was a greater improvement in BNIPS scores for patients who were treated with two isocenters compared with those treated with a single isocenter. The mean percentage of pain decrease was 56.26% compared with 11.53% (p < 0.001). Patients treated with two isocenters rather than one and patients receiving greater than 85 Gy compared with lower doses had a longer duration of response. Only nine patients (11%) had mild numbness attributable to the GKS. Five of the nine patients experienced complete resolution of facial numbness on follow up. Patients with MS have a shorter duration of response compared with those without MS (p = 0.35). CONCLUSIONS: These updated results show that GKS continues to be an effective therapy for TN. It appears there is an enhanced response with doses 85 Gy or more and with two isocenters without increased complications.

Brain: the common site of relapse in patients with pancoast or superior sulcus tumors.

PURPOSE: We conducted a retrospective analysis to determine the occurrence of brain metastasis with superior sulcus tumors. METHODS AND MATERIALS: We reviewed 685 charts of patients treated for upper lobe lung cancer between 1997 and 2003. Twenty-nine out of 685 patients (4%) had a diagnosis of Pancoast or superior sulcus tumor. The histology includes 11 patients with adenocarcinoma, seven with non-small cell lung cancer (NSCLC), six with squamous cell carcinoma, four with large cell carcinoma, and one with anaplastic carcinoma. Regarding stage at presentation: seven patients had stage IIB, two had stage IIIA, 16 had stage IIIB, and four had stage IV. RESULTS: The median follow-up is 14 months (range 6-70 months). The total occurrence of brain metastasis is seven out of 29 patients (24%). Two patients (stage IV) had brain metastasis at the time of presentation and five patients (stage IIB-III) developed brain metastasis at a median time of 10 months after the diagnosis. Stage associated with brain metastasis after diagnosis is two patients for stage IIB, two for stage IIIA, and one for stage IIIB. For the 25 patients with stage IIB to stage III disease, nine (36%) developed distant metastasis after definitive therapy. Out of these nine patients, five (55%) developed brain metastasis. It was the most common site of distant failure. Histology for seven patients with brain metastasis was four of seven with adenocarcinoma, two of seven with squamous cell carcinoma, and one of seven with NSCLC. CONCLUSION: Brain metatasis may be relatively common at diagnosis. The brain is the frequent site of failure for superior sulcus tumors. We recommend careful surveillance for brain metastasis during and after the therapy. We also recommend obtaining brain imaging prior to surgery in patients receiving induction therapy for the primary tumor.

Effects of interleukins 2 and 12 on the levels of granzyme B and perforin and their mRNAs in tributyltin-exposed human natural killer cells.

Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells and antibody coated cells. Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as: slime control in paper mills, disinfection of circulating industrial cooling waters, anti-fouling agents, and the preservation of wood. TBT can be found in edible items such as fish. A previous study showed that a 1 h exposure of NK cells to TBT caused persistent inhibition of NK-cell ability to destroy tumor cells in the 24 and 48 h periods following exposure and that this loss of function could be significantly prevented and/or reversed if the NK-stimulatory interleukins (IL) 2 or 12 were present during the 24 and 48 h periods. We had also shown that TBT exposure was able to significantly decrease the protein and mRNA levels of the cytotoxic proteins, granzyme B and perforin, and the phosphorylation of cAMP-response-element-binding protein (CREB) under these conditions. In this study we address the effects of IL-2 and IL-12 on the TBT-induced decreases in NK-cell levels of the cytotoxic proteins, their mRNAs, and CREB phosphorylation. IL-2 appeared to prevent/reverse TBT-induced declines in perforin protein levels and the mRNA for perforin seen in the 24 h period following a 1 h exposure to 300 nM TBT. However, the TBT-induced decreases in the levels of perforin and perforin mRNA seen in the 48 h period following a 1 h exposure to TBT were not statistically significantly prevented/reversed by IL-2. Additionally, the TBT-induced decreases in granzyme B, granzyme B mRNA, and CREB phosphorylation were not statistically significantly reversed by either IL-2 or IL-12 after 24 or 48 h.

Dose-intensive thoracic radiation therapy for patients at high risk with early-stage non-small-cell lung cancer.

Recent studies suggest that radiation therapy (RT) dose escalation in early-stage non-small-cell lung cancer (NSCLC) is feasible when 3-dimensional therapy is used. However, the accompanying prolongation of the treatment course when standard fractionation is used could be suboptimal from a practical and biologic standpoint. We report results of a compressed course of RT for patients with pathologically documented clinical stage 1 NSCLC who were unsuitable for curative surgery because of pulmonary dysfunction or other medical comorbidities. Thirty-one lesions were treated with dose-intensive RT (eg, fraction>or=2.25 Gy and nominal total dose>or=60 Gy) and have been followed up for >or=6 months from the completion of treatment. All patients completed therapy without interruption. Three patients developed grade 3 pulmonary toxicity 1-3 months after therapy. The overall tumor response rate was 88% (35% complete response and 53% partial response), whereas in-field tumor progression was documented for 5 of 31 lesions. Actuarial median survival was 38 months and 3-year overall survival was 60%, and most deaths were secondary to intercurrent disease. Moderately accelerated single daily fractionated RT is feasible for high-risk patients with early-stage NSCLC and merits further investigation.

Dibutyltin exposure decreases granzyme B and perforin in human natural killer cells.

Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor and virally-infected cells. Dibutyltin (DBT) is a catalyst in the production of PVC plastics and a breakdown product of tributyltin (TBT). DBT is a significant environmental contaminant. This study investigates the mechanism by which DBT exposure decreases the immune function of human NK cells. NK cells destroy their target cells by releasing cytotoxic proteins, perforin, and granzyme B. We examined the effect of DBT exposures on the levels of cytotoxic proteins and their mRNAs. Exposure of NK cells to DBT for 1h caused significant decreases in the mRNAs for granzyme B and perforin but not in protein levels. A 24h exposure to DBT decreased mRNAs as well as protein levels for both granzyme B and perforin. Exposure to DBT for 1h followed by either a 24 or 48h period in DBT-free media, decreased levels of granzyme B and perforin. The results indicate that decreases in granzyme B and perforin levels in NK cells are consequences of DBT exposure. Additionally, DBT causes rapid decreases in mRNAs for perforin and granzyme B, suggesting decreases in transcription and/or increases in mRNA degradation.

Primary presentation of glioblastoma multiforme with leptomeningeal metastasis in the absence of previous craniotomy: a case report.

Glioblastoma multiforme is a highly malignant glioma with a well-known tendency for intracranial spread but rarely for extracranial spread. We report a case of an adult woman who presented with symptoms of leptomeningeal metastasis from an intracranial glioblastoma multiforme located adjacent to the lateral ventricle. There have been very few cases of glioblastoma multiforme presenting with leptomeningeal metastasis in the absence of previous therapeutic intervention.

Tributyltin exposure causes decreased granzyme B and perforin levels in human natural killer cells.

Natural Killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells and antibody coated cells. Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as: slime control in paper mills, disinfection of circulating industrial cooling waters, anti-fouling agents in shower curtains and the preservation of wood. TBT can be found in edible items such as dairy products and fish. This study investigates the mechanism by which TBT exposure decreases the immune function of human NK cells, in vitro. Cytotoxic function, the expression of the cytotoxic proteins (granzyme B and perforin), and cAMP response element binding protein (CREB) phosphorylation were examined. NK cells exposed to 300 nM TBT for 1 h showed no significant decrease in cytotoxic function, levels of granzyme B and perforin, or phosphorylation of CREB. However, mRNA levels for the cytotoxic proteins were significantly decreased. A 24 h exposure to 200 nM TBT caused significant decreases in cytotoxic function, levels of granzyme B and perforin, and levels of granzyme B and perforin mRNA. When NK cells were exposed to 300 nM TBT for 1h followed by a 24 h period in TBT-free media, again there were significant decreases in NK cell cytotoxic function, levels of granzyme B and perforin and their mRNA. A 1h exposure to 300 nM TBT followed by a 48 h period in TBT-free media showed similar changes in cytotoxic function and levels of granzyme B and perforin as seen after 24 h in TBT-free media. Additionally, both of these exposures showed significant decreases in phosphorylation of CREB. These results indicate that TBT exposures can disrupt the transcription of granzyme B and perforin and that this disruption cannot be entirely accounted for by a decrease in phosphorylated CREB (phosphoCREB) levels.

Markers of inflammation, proteolysis, and apoptosis in ESRD.

BACKGROUND: Hemodialysis (HD) is associated with protein catabolism and augmented apoptosis. Although the effect of metabolic acidosis and inflammatory cytokines on activation of the ubiquitin-proteasome pathway and branched-chain keto acid dehydrogenase (BCKAD) is well known, the effect of HD on these pathways remains unexplored. METHODS: Twelve patients with end-stage renal disease were studied before and during HD. Eight controls also were studied. Plasma levels of complement components and cytokines, interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured. Messenger RNA (mRNA) levels of caspase-3, a mediator of apoptosis; ubiquitin, a marker of proteolysis; and BCKAD-E2, an enzyme regulating branched-chain amino acid oxidation, were estimated in skeletal muscle biopsy specimens by means of reverse-transcriptase polymerase chain reaction. Annexin-V expression was quantified by DNA array. Before the study, participants were placed on a 1.2-g/kg/d protein diet, and metabolic acidosis was corrected. RESULTS: During HD, plasma IL-6 levels increased from 7.54 +/- 2.24 to 27.86 +/- 4.94 pg/dL (P < 0.001). Complement component, IL-1, and TNF-alpha levels did not change significantly during HD. mRNA levels of caspase-3 (0.50 +/- 0.01 versus 0.81 +/- 0.04), annexin-V (0.94 +/- 0.06 versus 1.48 +/- 0.05; P < 0.001), ubiquitin (1.10 +/- 0.03 versus 1.44 +/- 0.03), and BCKAD-E2 (0.47 +/- 0.01 versus 0.81 +/- 0.04) increased in muscle during HD compared with pre-HD values (P < 0.001). mRNA levels of ubiquitin (0.62 +/- 0.03) and BCKAD-E2 (0.58 +/- 0.02) were greater in controls than pre-HD values (P < 0.05). There were significant positive correlations between plasma IL-6 levels and expression of caspase-3, ubiquitin, and BCKAD-E2 genes. CONCLUSION: HD causes activation of cytokines, which may mediate the increase in gene expression of caspase-3, ubiquitin, and BCKAD-E2 in skeletal muscles.

The mevalonate pathway during acute tubular injury: selected determinants and consequences.

Renal injury evokes tubular cholesterol accumulation, mediated in part by increased HMG CoA reductase (HMGCR) levels. The present study was undertaken to define potential molecular determinants of these changes and to ascertain the relative importance of increased cholesterol production versus mevalonate pathway-driven protein prenylation, on the emergence of the so-called postrenal injury "cytoresistant state." Cultured proximal tubule (HK-2) cells were subjected to Fe or ATP depletion injury, followed 1 to 24 hours later by assessments of: 1) sterol transcription factor expression (SREBP)-1 and -2); 2) HMGCR mRNA levels; and 3) Ras/Rho prenylation. HMGCR mRNA and Ras/Rho prenylation were also assessed after in vivo ischemic and Fe-mediated renal damage. Using specific inhibitors, the relative importance of protein prenylation versus terminal cholesterol synthesis on HK-2 cell susceptibility to injury was also assessed. Acute injury induced HK-2 cell SREBP disruption and reductions in HMGCR mRNA. Renal cortical HMGCR mRNA also fell in response to either in vivo ischemic or Fe-mediated oxidant damage. At 24 hours after in vitro/in vivo injury, a time of cholesterol buildup, no increase in Ras/Rho prenylation was observed. Prenylation inhibitors did not sensitize HK-2 cells to injury. Conversely, squalene synthase (terminal cholesterol synthesis) blockade sensitized HK-2 cells to both Fe and ATP depletion attack. We concluded that: 1) acute tubular cell injury can destroy SREBPs and lower HMGCR mRNA. This suggests that posttranscriptional/translational events are responsible for HMGCR enzyme and cholesterol accumulation after renal damage. 2) Injury-induced cholesterol accumulation appears dissociated from increased protein prenylation. 3) Cholesterol accumulation, per se, seems to be the dominant mechanism by which the mevalonate pathway contributes to the postrenal injury cytoresistant state.