Variation in the isocentre of a Philips linear accelerator (SL-20) used for stereotactic radiosurgery/stereotactic radiotherapy

Stereotactic irradiation, either in the form of stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) of brain lesions requires high precision and submillimetre accuracy in the isocentre, the main determinants being gantry and couch rotations. It is thus necessary to evaluate the isocentre variation due to gantry and couch rotations in the particular setup for SRS/SRT. This paper describes variation in the isocentre of a Philips (now Elekta) SL-20 linear accelerator modified for adapting a couch-mounted radiosurgery system. By considering the isocentre as defined by a mechanical index as the standard, the variations in the isocentre of the linear accelerator were independently measured for the gantry and for couch rotations. The variation in the isocentre for gantry rotation was found to be between 0.1 mm and 0.9 mm, conforming to the submillimetre accuracy required for SRS/SRT. However, the isocentre variation due to couch rotation varied considerably, possibly because the couch is of the RAM type. The isocentre variation due to couch rotation is rectified by microadjusting the couch mount at the time of treatment using a laser target localizing frame. It is our conclusion that a modified linear accelerator can be used for performing SRS/SRT after careful and separate evaluation of the isocentre stability due to gantry and couch rotations.     

Survival signaling and selective neuroprotection through glutamatergic transmission

In the brain, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate glutamatergic neurotransmission and, when intensely activated, can induce excitotoxic cell death. In addition to their ionotropic properties, however, AMPA receptors have been functionally coupled to a variety of signal transduction events involving Src-family kinases, G-proteins, and the mitogen-activated protein kinase (MAPK). In the present study, we tested whether AMPA receptors are linked to appropriate signaling events in order to prevent neuronal injury and/or enhance recovery. AMPA stimulation in hippocampal slice cultures caused the selective activation of MAPK through the upstream activator MAPK kinase (MEK). Inhibition of either component of the AMPA receptor--MAPK pathway potentiated cellular damage due to serum deprivation, suggesting that this pathway facilitates compensatory signals in response to injury. Correspondingly, positive modulation of AMPA receptors with the Ampakine 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516) enhanced MAPK activation and reduced the extent of synaptic and neuronal degeneration resulting from excitotoxic episodes. CX516 was neuroprotective when infused into slices either before or after the insult. The Ampakine derivative also elicited neuroprotection in an in vivo model of excitotoxicity as evidenced by reduction in lesion size and preservation of two different types of neurons. Interestingly, the AMPA receptor--MAPK pathway selectively protects against excitotoxicity since enhancing the pathway did not protect against the nonexcitotoxic, slow pathology initiated by lysosomal dysfunction. The results indicate that glutamatergic communication is important for cellular maintenance and that AMPA receptors activate survival signals to counterpoise their own excitotoxic potential.     

Differential effects of organic calcium-channel blockers on diastolic SR calcium-handling in the frog heart

1. Gradual loss of sarcoplasmic reticular (SR) calcium during a rest-period is responsible for the rest-induced decay (RID) of force in mammalian myocardium. Effect of verapamil and diltiazem on a similar RID in the frog myocardium suggests a new mechanism of action of these drugs. 2. Strips of frog-ventricle were paced at 0.2 Hz and the rhythm was interrupted by varying rest-periods ranging from 10 to 180 s. In control conditions, the amplitude of the post-rest beat was significantly lower than that of the pre-rest beat for rest-periods more than 40 s (RID). 3. Verapamil and diltiazem (which are organic calcium-channel blockers (OCCB)) changed the pattern of RID in the control solution to a 'rest-induced potentiation' (RIP) in the same preparation while another OCCB nifedipine and the inorganic calcium-channel blocker cadmium did not alter the post-rest phenomenon. 4. We propose that verapamil and diltiazem produce an RIP due to either blockade of SR calcium-leak during rest or enhancement of SR calcium-uptake during rest.     

Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium

Background  

Helicobacter pylori (H. pylori) causes gastritis and intestinal metaplasia (IM) that may evolve to gastric carcinoma. The objective of this study was to compare the profile of mucins in the progressive stages of H. pylori infected pre-neoplastic and neoplastic human gastric epithelium. We used a panel of monoclonal antibodies with well-defined specificities of MUC2, MUC5AC and MUC6 to characterize the expression pattern of mucins by immunohistochemistry.     

Yield of pulmonary tuberculosis cases by employing two screening methods in a community survey.

OBJECTIVE: To compare the yield of tuberculosis (TB) cases by two screening methods. SETTING: Two disease surveys conducted in Tiruvallur, south India. RESULTS: Of bacteriologically confirmed cases, 60% were identified by symptom inquiry alone whereas 82% were identified using chest radiography (CXR). CONCLUSION: The prevalence of TB was underestimated by both methods. The total cases in this community can be estimated by multiplying the number of identified cases by a correction factor (CF) of 1.7 when symptom inquiry alone is used or 1.2 when CXR is used. The CF may be different in other settings.     

Organization of inhibitory feed-forward synapses from the dorsal to the ventral cochlear nucleus in the cat: a quantitative analysis of endings by vesicle morphology

The main ascending, excitatory pathway from the cochlea undergoes synaptic interruption in the dorsal and ventral cochlear nuclei. The dorsal cochlear nucleus also forms a feed-forward circuit, which receives cochlear input and projects to the ventral cochlear nucleus by a tuberculo-ventral tract. This circuit may provide an inhibitory fringe (side bands) surrounding the center bands of the main ascending pathway. Biotinylated dextran injections into the dorsal cochlear nucleus anterogradely labeled the tuberculo-ventral tract and its endings in the anteroventral cochlear nucleus but also retrogradely filled cochlear nerve fibers and their terminals in the same regions. To distinguish tuberculo-ventral from cochlear nerve terminals, we used electron microscopy of the immunolabeled endings. Images were digitized and filter-enhanced, and the sizes and shapes of synaptic vesicles were used to construct quantitative profiles of the terminal types. The cochlear nerve endbulbs mapped to the same iso-frequency band of the injection site (main band). Flanking the main band were smaller labeled endings. About 45% of labeled terminals were pleomorphic and equally represented in the main band and side bands. Therefore, if there is an inhibitory fringe in the main projection pathway, it was not selective for tuberculo-ventral tract endings. Surprisingly, an excitatory category of round vesicles of intermediate size was labeled in the main band but not in the side bands. These intermediate endings may balance the feed-forward inhibition from the tuberculo-ventral tract. The quantitative method devised for classification of ending types by their vesicle profiles should be a generally useful tool for analysis.     

Morphogenesis of the mitochondrial alterations in muscle diseases

In this paper we present sequential morphologic changes produced in rat muscle mitochondria. Respiratory toxins such as crotoxin (rattle-snake venom) and 2,4-dinitrophenol (DNP-an uncoupler of oxidative phosphorylation) were injected in rat quadriceps muscle and the mitochondrial aterations were studied at various time intervals. The series of mitochondrial changes consisted of rounding and swelling of mitochondria, unfolding of the cristae as straight lines, formation of the concentric rings, appearance of paracrystalline inclusions, formation of multiple vesicles and finally vacuole formation. These changes were comparable to the range of mitochondrial alterations seen in the human material examined. Similarity of the timerelated mitochondrial changes in the rat to the spectrum of changes observed in human muscle biopsies suggests that the mitochondrial alteration in the human muscle disorders is a stepwise process in which respiratory alterations and calcium ion may play a role.     

Selected biological and behavioural risk factors associated with pulmonary tuberculosis.

OBJECTIVES: To measure the independent association of risk factors age, sex, smoking and alcoholism with pulmonary tuberculosis (TB) in terms of prevalence odds ratio (POR). METHOD: A community-based cross-sectional survey was conducted from June 2001 to December 2003. A total of 93945 individuals aged > or = 15 years selected from a random sample of villages in a district from South India were screened for pulmonary TB by chest symptoms and chest X-ray (MMR). Two sputum samples were collected (one spot and one early morning) from patients with chest symptoms and those with abnormal X-rays for examination by microscopy for acid-fast bacilli and by culture for Mycobacterium tuberculosis. Bacillary cases are bacteriologically positive cases diagnosed by either sputum smear or culture examination. In addition, data on exposure to tobacco smoking and alcohol consumption were collected from the male population only. All females were considered non-smokers and non-alcoholics. RESULTS: A total of 429 bacteriologically positive cases were detected during the survey. The adjusted PORs (with 95%CI) for age, sex, smoking and alcoholism were 3.3 (2.7-4.1), 2.5 (1.9-3.3), 2.1 (1.7-2.7) and 1.5 (1.2-2.0), respectively. CONCLUSION: Risk factors such as age, sex, smoking and alcoholism are independently associated with pulmonary TB. Risk factors age and sex show a stronger association than smoking and alcoholism.