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.

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.

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.

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.

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.

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.

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.

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.

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.

Predictive value of maximal stress test in patients showing atypical or no symptoms of ischaemic heart disease.

A study was carried out on 76 patients attending outpatients' department of medicine, Government Medical College, Nagpur. These patients had either (a) atypical angina or (b) no symptoms but certain factors for ischaemic heart disease. All cases were subjected to maximal stress test. Thirty-five cases (46.05%) showed a positive result on the basis of 'ST' segment depression of 2 mm or more. In the absence of facilities for coronary angiography, treadmill test is an important diagnostic tool for ischaemic heart disease.

Spectrum of renal cortical necrosis in acute renal failure in eastern India.

Renal cortical necrosis is an uncommon cause of acute renal failure. We report 23 cases of biopsy-proven renal cortical necrosis which constituted 6.3% (23/363) of all cases of acute renal failure studied over a period of seven years (1985-92). The patients were divided into two groups: obstetric and non-obstetric. Obstetric complications were responsible for renal cortical necrosis in 15 (65.2%) patients while non-obstetric conditions accounted for the remaining eight (34.8%) cases. The overall incidence of cortical necrosis in obstetric acute renal failure was 15/63 (23.8%) patients, the incidence being nearly equal in early (20.5%) and late (29%) pregnancy. Post-abortum renal failure was the sole cause of cortical necrosis in early pregnancy in the obstetric group. Haemolytic uraemic syndrome (three patients) and septicaemia (two patients) were the main cause of necrosis in the non-obstetric group. The cortical necrosis was diffuse and patchy in 17 and six patients, respectively. The disease had a fatal prognosis in 20 (87%) patients; mortality was due to uraemic complications and infections in the majority of patients. The high frequency of post-abortum renal cortical necrosis in our patients is similar to the experience of other Indian workers.

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.

Glutamate in the mammalian CNS.

The excitatory amino acid glutamate plays an important role in the mammalian CNS. Studies conducted from 1940 to 1950 suggested that oral administration of glutamate could have a beneficial effect on normal and retardate intelligence. The neurotoxic nature of glutamate resulting in excitotoxic lesions (neuronal death) is thought possibly to underlie several neurological diseases including Huntington's disease, status epilepticus. Alzheimer's dementia and olivopontocerebellar atrophy. This neurodegenerative effect of glutamate also appears to regulate the formation, modulation and degeneration of brain cytoarchitecture during normal development and adult plasticity, by altering neuronal outgrowth and synaptogenesis. In addition to its function as a neurotransmitter in several regions of the CNS, glutamate seems to be specifically implicated in the memory process. Long-term potentiation (LTP) and long-term depression (LTD), two forms of synaptic plasticity associated with learning and memory, both involve glutamate receptors. Studies with antagonists of glutamate receptors reveal a highly selective dependency of LTP and LTD on the N-methyl-D-aspartate and quisqualate receptors respectively. The therapeutic value of glutamate receptor antagonists is being actively investigated. The most promising results have been obtained in epilepsy and to some extent in ischaemia and stroke. The major drawback remains the inability of antagonists to permeate the blood-brain barrier when administered systemically. Efforts should be directed towards finding antagonists that are lipid soluble and able to cross the blood-brain barrier and to find precursors that would yield the antagonist intracerebrally.

Changes in gill structure induced by BHC, lindane and endosulfan in the fresh-water teleost Puntius ticto (Ham.).

The effect of three organochlorinated pesticides on the gill structure of Puntius ticto, a freshwater teleost, was investigated. Fish exposed to sublethal concentrations of BHC (0.17 ppm), lindane (0.19 ppm) and endosulfan (0.20 ppm) were studied. The pesticides were detected qualitatively in the gill tissue by thin-layer chromatography (TLC). The results showed that they could be detected after 15 days' exposure, but not after 96 h exposure. Histopathological examination revealed several structural and functional changes in the gills. Exposure to BHC was followed by an inflammatory reaction and complete dystrophy of the lamellar structure of the gills. Lindane-treated fish showed disruption of the epithelial covering of the gills and excessive haemorrhage in the blood vessels. In exposure to endosulfan the gill lamellae shrank and became thinner.

The yolk nucleus in the freshwater teleost Garra gotyla gotyla (Gray).

The structure and functional significance of the yolk nucleus in Garra are described. The study shows that the yolk nucleus appears in the cytoplasm of the early perinucleolus stage of the oocyte. It is present as a deeply stained structure enclosed in a vesicle. It disappears in the yolk vesicle stage and vitellogenesis begins soon afterwards. This probably indicates that it plays a role in the initiation of vitellogenesis. When yolk formation starts, the yolk nucleus disappears; this also suggests that it is of functional significance in yolk synthesis.

Genesis and systematization of cardiovascular anomalies and analysis of skeletal malformations in murine trisomy 16 and 19. Two animal models for human trisomies.

On account of genetic homologies, trisomy 16 in the mouse is generally regarded as a direct animal model of Down's syndrome. Mouse trisomy 19, on the other hand, can be seen as a general model of human trisomies. A detailed evaluation of the cardiovascular system and skeleton in 109 fetuses with trisomy 16 and 422 balanced siblings was carried out in order to systematize the cardiovascular anomalies and the pathogenetic mechanisms responsible for their formation according to (1) general retardation, (2) genetically determined impairment of neural-crest cell migration, and (3) direct gene action on organogenesis. Skeletal malformations in the form of a rib-vertebra syndrome encountered in Ts 16 are described here for the first time. In 108 fetuses and 219 neonates resulting from cross-breeding to induce trisomy 19, we found no significant increase in the frequency of the foregoing anomalies. These results are discussed with regard to a chromosome-specific genetic influence as opposed to a general effect of chromosome imbalance. The specificity of the Ts16 syndrome is compared with that of individual organ anomalies as can be induced by teratogenic agents. Our investigation shows that specific malformation patterns of a particular type can be produced by a variety of methods. However, the overall patterns of the two syndromes are highly chromosome-specific. On detailed examination, the malformation pattern of mouse trisomy 16 shows significant similarities with that of human trisomy 21.