Concurrent carboplatin and iodine-125 brachytherapy for recurrent glioblastoma multiforme

Toxicity and safety study of concurrent carboplatin chemotherapy and iodine-125 (I-125) brachytherapy. I-125 brachy therapy has an established albeit limited role in surgically accessible recurrent gliomas. Carboplatin has anti-tumoral; activity against gliomas and demonstrated sensitization of tumor to radiotherapy. In 15 patients (age range 30-77 years; median 53) with recurrent glioblastoma multiforme, stereotactically placed catheters were afterloaded with I-125 sources. A median 50 Gy minimum treatment volume dose was delivered during a 100 h period in conjunction with continuous infusion carboplatin (100 mg/m(2)/20 h x 5). Tumor volumes ranged from 13 to 63 cm(3) (median, 32 cm(3)). Early complications included: headache (n=7), transient exacerbations of pre existing neurologic deficits (n=5), seizures (n=2), nausea/vomiting (n=2), myelosuppression (n=2) and a catheter site wound CSF leak (n=1). Late complications included: steroid dependency (n=10), carcinomatous meningitis in association with hydrocephalus (n=1) and radiation-induced necrosis requiring reoperation (n=6). All patients were evaluable with a median survival of 10 months. In 12 patients, best clinical and neuroradiographic response was stable disease all of whom died of recurrent tumor (local recurrence in 11; CSF dissemination in 1). In 3 patients best response was either complete (n=2) or partial (n=1) all of whom are alive with a median follow-up of 31 months. I-125 brachytherapy with concurrent carboplatin chemotherapy is associated with an acceptable level of toxicity, has anti-tumoral activity and warrants further investigation in carefully selected patients with recurrent gliomas.     

Measurement of initial N-acetyl aspartate concentration by magnetic resonance spectroscopy and initial infarct volume by MRI predicts outcome in patients with middle cerebral artery territory infarction.

BACKGROUND AND PURPOSE: (1)H MR spectroscopy can be used to study biochemical changes occurring in the brain in stroke. We used it to examine the relationship between metabolite concentration (N-acetyl aspartate [NAA], lactate, cholines and creatines), size of infarct, clinical deficit, and 3-month clinical outcome in patients with middle cerebral artery (MCA) territory infarction. METHODS: Thirty-one patients with acute MCA territory infarction were recruited within 72 hours of the onset of symptoms. Single-voxel short echo time stimulated echo acquistion mode spectroscopy was used to obtain metabolite data from the infarct core. Metabolite concentrations were determined with use of variable projection time domain-fitting analysis. Infarct size was determined with T2-weighted images. Patient outcome groups at 3 months were "independent," "dependent," or "dead." RESULTS: All patients (100%; 95% CI 75% to 100%) who had an infarct >70 mL did poorly. Eighteen of 20 patients (90%; 95% CI 68% to 99%) with a core NAA concentration <7 mmol/L did poorly at 3 months, whereas 7 of 11 patients (64%; 95% CI 31% to 89%) with an initial NAA concentration >7 mmol/L did well. Combining these results showed that all patients who had an initial infarct volume >70 mL did poorly, irrespective of the NAA concentration. Of those patients with infarcts <70 mL, those who had a core NAA concentration >7 mmol/L did well (88%; 95% CI 47% to 100%), whereas those with a lower NAA concentration did poorly (80%; 95% CI 44% to 97%). There was no association between other metabolite concentrations and outcome. CONCLUSIONS: Infarct volume and NAA concentration can together predict clinical outcome in MCA infarction in humans.     

Visual abnormalities in albino wallabies: a brief note

Abnormally reduced uncrossed retinofugal pathways and abnormally low retinal cell densities have been described in albinos of a number of species of eutherian mammal, but have not been studied in marsupials. The optic chiasm of marsupials differs from that of the eutherian brains that have been studied, with uncrossed fibres segregating from crossed fibres prechiasmatically in the marsupials, but not in the eutherians. We have examined the optic chiasm and the retina in albino and normally pigmented wallabies (Macropus rufogriseus) to determine whether the abnormalities found in eutherian albinos are also present in this marsupial. The uncrossed pathway of the albino wallaby is smaller than that of the pigmented animals and the cell density in the retinal ganglion cell layer is reduced at the area centralis. We conclude that the characteristic albino abnormalities are present in both groups of mammals in spite of the other known differences in the visual pathways. The albino mutation acts at the chiasm in a similar manner in both groups even though the determinants of the chiasmatic pathway differ.     

Risk factors for rape, physical assault, and posttraumatic stress disorder in women: examination of differential multivariate relationships

The National Women's Study, a 2-year, three-wave longitudinal investigation, employed a national probability sample of 3,006 adult women to: (a) identify separate risk factors for rape and physical assault, and (b) identify separate risk factors associated with post-rape posttraumatic stress disorder (PTSD) and post-physical assault PTSD. This investigation differed from previous studies in that it prospectively examined risk factors at the multivariate, as opposed to univariate level. Overall, past victimization, young age, and a diagnosis of active PTSD increased women's risk of being raped. By contrast, past victimization, minority ethnic status, active depression, and drug use were associated with increased risk of being physically assaulted. Risk factors for PTSD following rape included a history of depression, alcohol abuse, or experienced injury during the rape. However, risk factors for PTSD following physical assault included only a history of depression and lower education.     

Plasminogen activator inhibitor type 2 in human corneal epithelium

PURPOSE: To examine normal human corneal epithelium in vivo and in vitro for expression and status of plasniinogcn activ:ltor inhibitor type 2 (PAI-2). METHODS: Normal hiuman corneas were prepared for frozen sections and for culture of corneal keratinocytes. PAI-2 was analyzed by immunohistochemistry and western blot analysis uising antibodies that recognize all forms of PAI-2. RESULTS: In vivo and in vitro, PAI-2 was immunohistochemically localized to the superficial corneal keratinocytes. Immunostaining also revealed the presence of PAI-2 in its relaxed (i.e., cleaved) conformation. In vivo, the staining pattern of the relaxed form was identical with that of total PAI-2, but in vitro the relaxed form was detected in a smaller subpopulation of superficial cells. In vitro, the staining pattern indicated a cytoplasmic localization for PAI-2. Western blot analysis revealed that most of the PAI-2 was cell associated and functionally active. CONCLUSIONS: The present results are the first to show that PAI-2 is found in normal human corneal epithelium in vivo and in vitro, where it can be considered as a differentiation product. At least in vitro, all detectable PAI-2 is cell associated, with a cytoplasmic distribution. A subpopulation of keratinocytes also contains PAI-2 in its relaxed (i.e., cleaved) conformation. Cleavage by an as yet unidentified cytoplasmic proteinase may constitute a crucial aspect of the function of corneal epithelial PAI-2, which may be relevant to terminal differentiation and death of the corneal keratinocyte.     

Studies on the stability of trimelamol, a carbinolamine-containing antitumor drug

The stability of trimelamol (N2,N4,N6-trimethylol-N2,N4,N6-trimethylmelamine) a synthetic carbinolamine-containing antitumor drug, has been studied. Two major degradation pathways have been characterized and a unified mechanism proposed to rationalize the chemistry involved. One degradation pathway involves the consecutive loss of hydroxymethylene units by elimination of formaldehyde until the parent trimethylmelamine (4) results. An HPLC method was used to obtain kinetic data for the loss of trimelamol and to monitor the order of appearance of three degradation products. This pathway was shown to follow first-order kinetics at all pH values studied at both 18 and 37 degrees C. The second pathway involves the coupling of two trimelamol molecules via a methylene bridge to form bis(trimelamol) (6) which had been previously referred to in the literature as a "polymer". This reaction is acid catalyzed and temperature dependent. Bis(trimelamol) is virtually water insoluble and adheres strongly to glass surfaces. Finally, t1/2 values have been determined for trimelamol in aqueous solution at different temperatures, and the kinetics of formation of degradation products has been studied over a period of 30 h under a variety of conditions of pH and temperature. The data reported here are relevant to both the formulation and clinical administration of trimelamol, and may contribute to an understanding of mechanism of action and future analogue development studies.