Induction of glioblastoma multiforme in nonhuman primates after therapeutic doses of fractionated whole-brain radiation therapy

OBJECT: To determine the acute and long-term effects of a therapeutic dose of brain radiation in a primate model, the authors studied the clinical, laboratory, neuroimaging, molecular, and histological outcomes in rhesus monkeys that had received fractionated whole-brain radiation therapy (WBRT). METHODS: Twelve 3-year-old male primates (Macaca mulatta) underwent fractionated WBRT (350 cGy for 5 days/week for 2 weeks, total dose 3500 cGy). Animals were followed clinically and with laboratory studies and serial magnetic resonance (MR) imaging. They were killed when they developed medical problems or neurological symptoms, lesions appeared on MR imaging, or at study completion. Gross, histological, and molecular analyses were then performed. Nine (82%) of 11 animals that underwent long-term follow up (> 2.5 years) developed neurological symptoms and/or enhancing lesions on MR imaging, which were defined as glioblastoma multiforme (GBM), 2.9 to 8.3 years after radiation therapy. The GBMs were categorized as either unifocal (three) or multifocal (six), and were located in the supratentorial (six), infratentorial (two), or both (one) cranial regions. Histological examination revealed distant, noncontiguous tumor invasion within the white matter of all nine animals harboring GBMs. Novel interspecies comparative genomic hybridization (three animals) uniformly showed deletions in the GBMs that corresponded to chromosome 9 in humans. CONCLUSIONS: The high rate of GBM formation (82%) following a therapeutic dose of WBRT in nonhuman primates indicates that radioinduction of these neoplasms as a late complication of this therapy may occur more frequently than is currently recognized in human patients. The development of these tumors while monitoring the monkeys' conditions with clinical and serial MR imaging studies, and access to the tumor and the entire brain for histological and molecular analyses offers an opportunity to gather unique insights into the nature and development of GBMs.     

Prevalence, identification and distribution of various species of enterococci isolated from clinical specimens with special reference to urinary tract infection in catheterized patients

Various clinical specimens were processed to find the prevalence rate of enterococci and to identify the species of clinical isolates of enterococci. Screening of various clinical specimens revealed that enterococci were prevalent in 22.19% of the total specimens, with Foley's catheters and burn wounds to be the major site of isolation. High rate of colonization was noted as opposed to infection. Conventional test scheme proposed by Facklam and Collins were successfully used to speciate enterococcal strains. Seven species of enterococci were identified in the study from a set of 202 cultures, with E.faecalis (49.50%) and E. faecium (35.64%) predominating. E. avium (9.40%), E. hirae (2.47%), E. raffinosus (1.98%) and one isolate each of E.gallinarum and E. casseliflavus were the other members of Enterococcus species identified. Urinary tract infection (UTI) by enterococci due to catherisation was found in 8.92% of the patients and is probably the result of high rate of colonization of Foley's catheters and use of broad-spectrum antibiotics.     

Helicobacter pylori in duodenal ulcer disease and its eradication

Antral biopsy specimens were processed for Helicobacter pylori by Gram staining, rapid urease test (RUT) and culture from 25 patients with symptoms of duodenal ulcer, amongst whom the positivity rate was 84%. Follow up of 16 patients after appropriate therapy showed complete regression of the disease in 87.5% of cases whereas in 12.5% of cases a decrease in the extent of duodenal ulceration was noted.     

Vascular endothelial growth factor (vascular permeability factor) expression in injured rat brain

We investigated the expression of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) in stab and freeze brain injury models in rats. Immunohistochemical staining with anti-VEGF antibodies demonstrated an increase in VEGF-positive cells in and around both lesions. Morphologically, the injury-induced VEGF-positive cells resembled astrocytes. Double immunofluorescent staining for the astrocytic marker glial fibrillary acidic protein (GFAP) and VEGF demonstrated directly that VEGF-positive cells which appeared in response to these injuries were astrocytes. VEGF expression in astrocytes was maximal on days 3 and 4 after injury in terms of both cell number and affected area. The increase in VEGF-positive cells was more widespread in the freeze lesion than in the stab wound, and occurred in both the lesioned and nonlesioned hemispheres. VEGF-positive cells were still present 3 weeks after both injuries, but their numbers were reduced and their distribution became limited to the immediate vicinity of the lesions. These observations indicate that astrocytes react to injury by increasing VEGF expression, suggesting that VEGF might participate in the central nervous system response to injury. J. Neurosci. Res. 49:451–460, 1997. © 1997 Wiley-Liss, Inc.     

Cost of pediatric cataract surgery in Maharashtra, India

AIM: To calculate the direct cost of pediatric cataract surgery, from the provider's perspective. METHODS: The direct cost was calculated using standard costing methods in a pediatric ophthalmology department of a comprehensive community eye care center in western India. Fixed costs included those of the building, interior decoration, out patient department's equipment, operation theater equipment, personnel, administration and hospital maintenance. The consumable costs included materials used during surgery. Only direct costs were considered. RESULTS: The average direct costs were Indian rupees (Rs.) 69 ($1.77) for an outpatient department consultation, Rs.606 ($15.53) for operation theater equipment use, and Rs. 2 427($62.23) for personnel. The consumable costs ranged from Rs.1 452 ($37.23) to 15 267 ($391.46), depending on the protocol used. The net average cost of pediatric cataract surgery ranged from Rs. 4 722 ($122) to Rs. 18 537 ($475) per eye. CONCLUSION: Cataract surgery is cost intensive for children with cataract. Pediatric ophthalmologists should decide about most cost effective standards of care to rationalize consumable cost.     

N-(Acyloxyalkoxycarbonyl) derivatives as potential prodrugs of amines. I. kinetics and mechanism of degradation in aqueous solutions

Four acetoxyethoxycarbonyl derivatives of closely related primary and secondary amines were synthesized as model prodrugs. The degradation kinetics of these compounds were studied in aqueous solutions as a function of pH and temperature to determine their stability and to assess their suitability as potential prodrugs of amines. At pH 相似文献   

Study of photic versus non-photic cues as entrainers of circadian running activity in rats

Though relative dominance of photic/non-photic cues on rodent circadian running activity is known, the exclusive role of non-photic entrainers in rats deprived of photic entrainers is not demonstrated and hence present work using retino-hypothalamic pathway blocked male rats (n = 10) was initiated. Blocking is done by enucleation of eyeballs. Circadian running activity is studied before enucleation and after enucleation towards instinctual social cues, food, water and sexual cues provided in activity cage. Twenty four hour activity of rats was recorded kymographically for a fifteen day period before enucleation and for a similar period after enucleation. Analysis of the records revealed that eight animals had predominant diurnal rhythm whereas two animals had predominant nocturnal rhythm. Enucleation of diurnal rats neither altered total running activity pattern nor caused any significant change in the goal compartments thus showing absence of entrainment by photic cues. In contrast nocturnal rats showed gradual shift of activity towards day time on enucleation thus indicating that nocturnal animals were entrained by photic cues. The overriding influence of non-photic entrainers on photic entrainers is discussed.     

CT features with pathologic correlation of acute gastrointestinal graft-versus-host disease after bone marrow transplantation in adults

OBJECTIVE: This study was conducted to describe the CT features of acute gastrointestinal graft-versus-host disease in adults and to correlate these findings with the pathologic grades of disease severity. MATERIALS AND METHODS: Patients (n = 22) with a history of allogeneic bone marrow transplantation and pathologically confirmed acute gastrointestinal graft-versus-host disease underwent contrast-enhanced (n = 13) and unenhanced (n = 9) CT. CT scans were retrospectively evaluated for intestinal and extraintestinal abnormalities by two radiologists who were unaware of the biopsy results. The CT findings were correlated with the pathologic grade of disease severity using the Pearson's correlation coefficient and the two-tailed nonparametric Spearman's rank correlation coefficient. RESULTS: CT features included small-bowel wall thickening (22/22), engorgement of the vasa recta adjacent to affected bowel segments (20/22), stranding of the mesenteric fat (16/22), large-bowel wall thickening (13/22), bowel dilatation proximal to thickened wall segments (5/22), ascites (10/22), periportal edema (8/22), mucosal enhancement (7/13), and serosal enhancement (4/13). The wall thickening had a discontinuous distribution in nine patients (41%). Bowel wall thickening was associated with high-grade graft-versus-host disease in patients in whom the distal esophagus (p = 0.015), ileum (p = 0.034), or ascending colon (p = 0.05) was involved. Increasing numbers of thickened bowel segments correlated with high-grade graft-versus-host disease (r = 0.548, p = 0.008). Increasing numbers of abnormal CT findings did not correlate with high-grade graft-versus-host disease (r = 0.117, p = 0.604). CONCLUSION: A variety of bowel abnormalities can be seen on CT in patients with acute graft-versus-host disease. CT findings associated with high-grade graft-versus-host disease are thickening of the distal esophagus, ileum, or ascending colon, as well as increasing numbers of thickened bowel wall segments.