Meta-analysis of cardiovascular toxicity risks in cancer patients on selected targeted agents.

PURPOSE: The purpose was to estimate the risk and severity of cardiovascular toxicities associated with selected targeted agents. METHODS: We searched English-language literature for randomized clinical trials published between January 1, 2000 and November 30, 2013 of targeted cancer therapy drugs approved by the FDA by November 2010. One hundred ten studies were eligible. Using meta-analytic methods, we calculated the relative risks of several cardiovascular toxicities [congestive heart failure (CHF), decreased left ventricular ejection fraction (DLVEF), myocardial infarction (MI), arrhythmia, and hypertension (HTN)], adjusting for sample size using the inverse-variance technique. For each targeted agent and side effect, we calculated the number needed to harm. RESULTS: Regarding CHF, trastuzumab showed significantly greater risk of all-grade and high-grade CHF. There was significant increased risk of all-grade DLVEF with sorafenib, sunitinib, and trastuzumab and high-grade DLVEF with bevacizumab and trastuzumab. Sorafenib was associated with significant increased all-grade risk of MI based on one study. None was associated with high-grade risk of MI or increased risk of arrhythmia. Bevacizumab, sorafenib, and sunitinib had significant increased risk of all-grade and high-grade HTN. CONCLUSIONS: Several of the targeted agents were significantly associated with increased risk of specific cardiovascular toxicities, CHF, DLVEF, and HTN. Several had significant increased risk for high-grade cardiovascular toxicities (CHF, DLVEF, and HTN). Patients receiving such therapy should be closely monitored for these toxicities and early and aggressive treatment should occur. However, clinical experience has demonstrated that some of these toxicities may be reversible and due to secondary effects.

Chemical characteristics of aerosols and trace gas distribution over North and Central India.

A field campaign on aerosol chemical properties and trace gases measurements was carried out along the Delhi-Hyderabad-Delhi road corridor (spanning about 3,200 km) in India, during February 1-29, 2004. Aerosol particles were collected on quartz and cellulose filters using high volume (PM(10)) sampler at various locations along the route (i.e., urban, semi-urban, rural, and forest areas) and have been characterized for major cations (Na(+), Ca(2+), Mg(2+), K(+), and NH (4) (+)), anions (Cl(-), NO (3)(-), and SO (4)(2-)), and heavy metals (Cu, Cd, Fe, Zn, Mn, and Pb). Simultaneously, we measured NO(2) and SO(2) gases. These species show large spatial and temporal variations. The ambient PM(10) concentration has been observed to be the highest (55 ± 4 µg m(-3)) near semi-urban areas followed by forest areas (48 ± 2 µg m(-3)) and in rural areas (44 ± 22 µg m(-3)). The concentrations of NO( x ) (NO(2)+NO) and SO(2) ranged from 16 to 69 µg m(-3) and 4 to 11 µg m(-3), respectively. Among anions, NO(3)(-) and SO(4) (2-) are the major constituents of PM(10). The urban and semi-urban sites showed enhanced concentrations of Fe, Zn, Mn, Cd, and Pb. This study provide information about atmospheric concentrations of various species in the northern to central India, which may be important for policy makers to better understand the air quality of the region.

Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets.

Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10-16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Efficacy and safety of kanamycin, ethionamide, PAS and cycloserine in multidrug-resistant pulmonary tuberculosis patients.

BACKGROUND: We carried out this study to determine the efficacy and safety of a regimen containing kanamycin, ethionamide, isoniazid, para-aminosalicylic acid (PAS) and cycloserine in the treatment of multidrug-resistant tuberculosis (MDR-TB). METHODS: A prospective, uncontrolled study of 39 pulmonary tuberculosis patients, who had received adequate first-line antituberculosis treatment including supervised category II retreatment regimen, and were still sputum smear positive for acid-fast bacilli (AFB) in whom sputum culture revealed isolates of M. tuberculosis resistant to rifampicin and isoniazid with and without resistance to other antituberculosis drugs. They received kanamycin (initial 4-6 months), ethionamide, isoniazid, PAS and cycloserine for a minimum period of two years. RESULTS: Out of 39 patients, 29 (74.3%) achieved sputum conversion within six months and remained so at the end of two years. Two (5.1%) patients died, six (20.6%) patients were lost to follow up, and two (5.1%) patients remained sputum smear-positive for AFB through out the period of study. Twenty-nine patients, declared cured, were followed for an average period of 16 months (3-48 months), during which two (6.9%) patients relapsed, four (13.8%) patients were lost to follow-up and remaining 23 remained sputum smear-negative. Eight (21.1%) patients developed major side effects which required stoppage/change of drugs. CONCLUSION: In MDR-TB patients, regimen consisting of ethionamide, isoniazid, PAS and cycloserine and kanamycin appears to be effective and safe.

Platelet monoamine oxidase. I: Effect of temperature, anticoagulant, and centrifugation technique.

Platelet yield and monoamine oxidase (MAO) activity per platelet in platelets obtained by the method of Corash, which isolates essentially all platelets from whole blood, and by a single differential centrifugation of whole blood, were compared. Platelets recovered by one spin in a swinging bucket rotor appeared to be a homogeneous population containing a reliable representation of the platelet population obtained by the Corash method since the MAO specific activity yielded by the two methods was not significantly different. The effect of the anticoagulant, temperature, and type of rotor on platelet recovery from blood and MAO activity/platelet were also studied. The MAO and plasma amine oxidaze (PAO) activities obtained from blood anticoagulated with ethylenediaminetetracetate (EDTA) were significantly greater than those found when acid-citrate-dextrose was the anticoagulant. Blood centrifuged in a swinging bucket rotor at room temperature yielded 80-90% of total platelets as compared to the 45-65% recovered with a fixed-angle rotor at 0-4 C. The most efficient method of platelet isolation was found to be a 2 1/2-min room-temperature spin at 600 X g with a swinging bucket rotor using EDTA as anticoagulant.

2-Amino-4-phosphonobutyric acid selectively blocks two-way avoidance learning in the mouse.

There seems to be ample evidence supporting the view that glutamate plays a significant role in the mammalian brain as a neurotransmitter. It is considered to be a likely transmitter candidate in one or more hippocampal pathways. Recently it has been visualized in excitatory, possibly glutamatergic, neurons in the hippocampus. Glutamate has been proposed to mediate memory formation. We wanted to see if blocking glutamate action by a specific glutamate antagonist could result in reduction of learning ability. 2-Amino-4-phosphonobutyric acid (APB) is an analogue of glutamic acid and has been used as a glutamate antagonist in electrophysiological studies on invertebrate neuromuscular junction, retina and hippocampus. We tested the influence of APB on the acquisition of two way avoidance learning in the shuttle box and on learning in the water maze. Our results show that intraperitoneal injection of APB led to a reduction in avoidance learning, whereas learning in the water maze was unaffected.

Comparison of PathVysion and INFORM fluorescence in situ hybridization kits for assessment of HER-2/neu status in breast carcinoma.

BACKGROUND: Fluorescence in situ hybridization is advocated for precise assessment of HER-2/neu status in breast carcinoma; however, few objective data compare available kits for clinical laboratories contemplating development of the test. METHODS AND RESULTS: Thirty breast carcinomas were analyzed for HER-2/neu amplification with the PathVysion kit (Vysis, Downers Grove, IL) and INFORM kit (Ventana Medical Systems, Tucson, AZ). Each kit was evaluated for morphology, background staining, technical and interpretation time, and cost. PathVysion detected amplification in seven of 30 cases (23.3%); INFORM detected six of 30 cases (20%). A greater percentage of PathVysion cases showed good morphology and lower background staining than INFORM. Technical and interpretation times, as well as cost, were less with PathVysion than INFORM. CONCLUSION: PathVysion is superior to INFORM because it produces better morphology and less background staining and is faster and less expensive than the INFORM kit. It also includes a chromosome 17 probe that serves as an internal control and enables correction for chromosome 17 aneuploidy.

HER-2/neu assessment in breast cancer by immunohistochemistry and fluorescence in situ hybridization: comparison of results and correlation with survival.

BACKGROUND: HER-2/neu immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results guide breast cancer therapy; however, few studies compared the results and no published studies have correlated them with patient outcome. METHODS AND RESULTS: We compared results, cost, and turnaround time in 117 archival, invasive breast carcinomas and compared 50-month survival in 65 of these cases using commercial HER-2/neu IHC and FISH assays. Twenty-one of 112 FISH (19%) and 33 of 117 IHC cases (28%) were positive. Concordance was high overall (88%; 98 of 112 cases) and in IHC 3+ cases (88%; 14 of 16 cases) but low in IHC 2+ cases (35%; six of 17 cases). Survival correlated with IHC results in 3+ cases (P =.02) and FISH cases with signal ratio greater than 4.0 (P =.03), but not in IHC 2+ cases (P=.7). Cost and turnaround time were greater for FISH. CONCLUSION: IHC is appropriate for initial HER-2/neu assessment; however, patients with tumors scored less than 3+, particularly those interpreted as 2+, would benefit from FISH to more accurately assess HER-2/neu status and avoid inaccurate prognostication and inappropriate treatment.

Correlation between MAO activity in blood platelets obtained by single and multiple centrifugations.

Monoamine oxidase (MAO) activity in human blood platelets isolated by a single centrifugation at 600g for 2 1/2 minutes, which isolates only 45-65% of total platelets, was highly correlated with the MAO activity in platelets isolated by a method which isolates essentially 100% of platelets (r = 0.95, p less than 0.01). These results indicate that the single centrifugation method, which isolates only a portion of platelets, gives a reliable estimate of MAO activity in the entire platelet population.

Effect of chlorpromazine treatment on monoamine oxidase activity in platelets isolated by the Corash method.

The effect of chlorpromazine treatment on platelet monoamine oxidase (MAO) activity was compared in platelets isolated by the Corash method, which harvests essentially all the platelets in a blood sample, and a single centrifugation method, which yields 45-65% of the platelets. A highly significant decrease in platelet MAO activity following chlorpromazine was found in platelets obtained from the same subjects by both methods. The decrease observed by the two methods was significantly correlated. These results indicate the degree of decrease in MAO activity associated with chlorpromazine is not due to isolation of a subpopulation of platelets with low MAO activity by the single centrifugation method.

Sinusitis and carotid artery stroke.

The relationship between sinusitis and ischemic stroke is unexplored. The anatomic proximity between the paranasal sinuses and the internal carotid artery suggests that inflammation of the sinuses could easily extend to the intracranial vasculature. We report 4 patients with acute ischemic stroke and extensive disease of the paranasal sinuses. All patients had large vessel stroke involving the internal carotid artery territory. All patients had extensive disease of the sphenoid and other sinuses. The sinus disease was demonstrated by magnetic resonance imaging. These case report observations suggest a relationship between inflammation of the paranasal sinuses, particularly sphenoid sinusitis, and ischemic stroke.

Childhood bacterial meningitis in Pondicherry, South India.

OBJECTIVE: To identify causative bacteria from cerebrospinal fluid (CSF) of children with meningitis and analyse various clinical and laboratory parameters. METHODS: Over a 20 month period, September 1994 to April 1996, one hundred episodes of acute bacterial meningitis in children aged 1 month-12 years were studied in a tertiary urban hospital in South India. Organisms were isolated from the cerebrospinal fluid (CSF) in 35% of cases. Among infants and children, the two major pathogens were H. influenzae (17%) and S. pneumoniae (12%). RESULTS: The illness at presentation was mild in 13% and severe in 36% of cases. The association of subdural effusion in children with Salmonella Gp B meningitis merits attention. The overall case fatality rate was 25%. S. pneumoniae had a higher case fatality rate than Salmonella Gp B and H. influenzae (50% vs 17% vs 12%). All the three infants below 3 months of age with S. pneumoniae meningitis died. On analysis of selected clinical and laboratory features by discriminant analysis, CSF culture was the significant (P = 0.02) variable in relation to outcome. In pneumococcal meningitis, CSF WBC count was a highly significant variable in relation to outcome (Wilk's Lambda 0.15, F = 24.64, P = 0.0002). CONCLUSION: Prevention of infections due to H. influenzae and S. pneumoniae should be given higher priority.

Norms for renal parenchymal volume in Indian children.

Seventy-seven clinically normal children with kidneys of normal size were examined sonographically. Renal parenchymal volumes were calculated and related to age, height, body weight and body surface area; growth charts were constructed. A significant correlation was found between the renal parenchymal volume and the body somatometric parameters. The present report thus provides norms for renal parenchymal volume in Indian children.

Congenital infiltrating lipomatosis of the face with exophytic temporomandibular joint ankylosis: a case report and review of the literature.

Congenital infiltrating lipomatosis of the face (CIL-F) is a rare lipomatous lesion with diffuse fatty infiltration of tissues and hyperplasia of underlying bone. We report clinical and CT findings in an unusual case of CIL-F presenting with progressive hemifacial asymmetry, manifesting as severely restricted mouth opening owing to exophytic temporomandibular joint ankylosis. The role of imaging in diagnosis is presented with a review of the literature. Differential diagnosis of CIL-F and its exclusion as a cause of hemifacial hyperplasia are also discussed.

Primary hyperparathyroidism presenting as an exophytic mandibular mass.

A 36-year-old female patient presented with a massive painless swelling in the left mandible. The patient's medical history was unremarkable. The initial clinical and radiological evaluation indicated an aggressive odontogenic neoplasm or a metastasis from an unknown primary; the suspicion of a systemic metabolic or endocrine disorder lay low on the list of differential diagnoses. Further investigations revealed gross skeletal changes and a hypoechoic right parathyroid mass. The total serum parathyroid hormone levels and ultrasound-guided fine needle aspiration cytology (FNAC) of the mandibular and parathyroid lesions provided the diagnosis of primary hyperparathyroidism presenting as a mandibular brown tumour. This case thus highlights the importance of a thorough diagnostic work-up for all lesions in the maxillofacial region and also serves to add another facet to the myriad of presentations associated with primary hyperparathyroidism.