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Biomedical subjects

K J Murray

Publications and source records attributed to K J Murray.

At least 55 records · Page 3Linked to original sources
PubMed1996

Immunohistological characteristics of T cell infiltrates in different forms of childhood onset chronic arthritis.

OBJECTIVE: To characterize synovial T cell infiltrate, in terms of CD4/CD8 ratio and level of activation of T cells, in juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy(JSpA), to correlate these findings with clinical outcomes of the different forms of disease, and to compare them with findings in adult RA synovium. METHODS: We studied synovial tissue specimens from 22 individuals with childhood onset of chronic arthritis (12 polyarticular JRA, 5 pauciarticular JRA, 5 JSpA) and 4 with adult RA. Specimens were selected from an initial bank from 40 patients on the basis of significant inflammation on hematoxylin and eosin and CD3 and CD68 monoclonal antibody staining (T cells and macrophages, respectively). Indirect immunohistochemistry was used with monoclonal antibodies to CD3, CD4, CD8, and interleukin 2 receptor alpha to determine CD4/CD8 ratios and the levels of activation within the T cell subsets. The distribution of gamma delta T cells was also studied. RESULTS: Two patterns of T cell infiltration were seen. The majority of patients had lymphocytic aggregates associated with diffuse infiltrates; a few tissue specimens had diffuse infiltrates without aggregates. The CD4/CD8 ratio was significantly lower in pauciarticular course JRA than polyarticular JRA (p < 0.01) and RA (p < 0.05). Similarly patients with JSpA had a significantly lower CD4/CD8 ratio than patients with polyarticular JRA (P < 0.05). The level of T cell activation (CD3+IL-2R+) was significantly higher in pauciarticular compared with both polyarticular JRA (P < 0.01) and RA (p < 0.05). In general, higher levels of activation of CD8 cells than CD4 cells were seen, particularly in the pauciarticular JRA and JSpA groups. gamma delta T cells were prominent in 2 patients. CONCLUSION: Demonstrated differences in T cell subset distribution between types of childhood chronic arthritis at a histopathological level may reflect different pathogenic mechanisms.

Adolescent↗
PubMed1995

Central pathology review in clinical trials for patients with malignant glioma. A Report of Radiation Therapy Oncology Group 83-02.

BACKGROUND: Confounding biologic factors, including histologic grade, may influence the outcome of adult patients with malignant gliomas more than may modifications in therapeutic approach. Any clinical trial design for malignant gliomas in adults must account for such biologic factors, including the accurate identification of the two histologic subgroups astrocytoma with anaplastic foci (AAF) or glioblastoma multiforme (GBM), which are associated with distinctly different survival outcomes. This paper examines the need for a central pathology review before entry of patients in cooperative group clinical trials stratified by histologic grade. METHODS: Pathology slides from Radiation Therapy Oncology Group (RTOG) trial 83-02, a randomized Phase II study of hyperfractionated and accelerated hyperfractionated radiation therapy and carmustine for malignant gliomas, provided 747 analyzable cases, with 680 (91%) available for central pathology review. This review was performed by a single pathologist according to RTOG/Eastern Cooperative Oncology Group histopathologic criteria. The kappa statistic was used to measure agreement between the institutional and central classification of AAF and GBM. The influence of misclassification was examined using computer simulation of varying clinical trial sizes (n = 25, 50, or 200). The effect on the statistical power of trials (n = 200) with varying mixtures of AAF and GBM tumors was investigated using computer simulations. RESULTS: Of 159 tumors classified as AAF by institutional pathology review, only 66% (105) were classified as AAF (AAF/AAF) by central review, and 54 of these cases (34%) were classified as GBM (GBM/AAF), whereas 96% (501) of 521 institutionally classified as GBM (GBM/GBM) were similarly classified by central review. Computer simulations demonstrated a 59% underestimation in the median survival (1.82 vs. 4.49 years) for trials of patients with institutionally defined AAF compared to patients with centrally defined AAF in studies of 200 patients, resulting from the addition of poor prognosis of GBM in the trial. Misclassification can also substantially reduce the statistical power of a clinical trial. In one of the simulation studies, statistical power was reduced from 65% to 14% if 50% of the patients were to receive an inaccurate histologic classification. Even greater losses in power are possible in many plausible clinical settings. CONCLUSIONS: This examination of a central versus an institutional pathology review demonstrates a low level of agreement on AAF classification and a high level of concordance on GBM classification. The results indicate the need to adjust sample size for trials of both AAF and GBM tumors to have adequate statistical power. A central pathology review remains essential for trial entry for patients with AAF and could be omitted for trials enrolling patients with GBM only.

Adult↗
PubMed1995

Echographic monitoring of response of extraocular muscles to irradiation in Graves' ophthalmopathy.

PURPOSE: Confirmation of the efficacy of orbital irradiation in Graves' ophthalmopathy is needed due to the unpredictable natural history of the disease, the variation in individual clinical presentations, the contribution of other simultaneous treatments, and the lack of controlled studies using objective criteria to classify and assess response over time. Orbital echography before and at select intervals following orbital irradiation is proposed as an objective parameter of tissue response to orbital irradiation over time. METHODS AND MATERIALS: From January, 1983 to September, 1993, 55 patients with progressive Graves' ophthalmopathy underwent 20 Gy retrobulbar irradiation. On retrospective review, standardized orbital echography was performed randomly prior to irradiation in 37 of the 55 patients to assess the acoustic characteristics of the extraocular muscles and to quantitate their individual and summed diameters. Twenty-one patients had at least one follow-up echographic evaluation at random intervals of 0 to 27.5 months following completion of irradiation. Twelve patients received steroids before or during irradiation, which were tapered in proximity to completion of radiation. Follow-up ranged from 2 to 65 months with the majority followed at least 6 months (18 patients). RESULTS: Of the 21 patients with serial studies, 18 showed an interval decrease in individual and summed muscle size over time and return of symmetry. Interval improvement was documented as early as the 1 month follow-up study, with continued improvement seen during the 3-9-month studies, with stability typically achieved within 12 months. One patient had further changes between the 21 and 27.5 month follow-up studies. Exacerbation of disease was, however, echographically demonstrated in three patients at 6.5, 8.5, and 13 months. Follow-up studies in two of these patients again revealed improvement, one following tapered steroids. The third patient required orbital decompression. CONCLUSION: Objective parameters of response are needed to document both the immediate and long-term outcome of orbital irradiation on the course of Graves' ophthalmopathy and confirm its efficacy. Serial echography is proposed as a new technique for providing parameters to judge response.

Follow-Up Studies↗
PubMed1995

Quality-adjusted survival analysis of malignant glioma. Patients treated with twice-daily radiation (RT) and carmustine: a report of Radiation Therapy Oncology Group (RTOG) 83-02.

PURPOSE: To quantify the quality of life of malignant glioma patients treated on a randomized Phase I/II trial of twice-daily radiation therapy (RT) and carmustine, using a modified quality adjusted survival (QAS) model, and to compare the QAS among assigned treatment arms. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) accrued 786 malignant glioma patients to a Phase I/II randomized dose escalation trial of twice-daily RT with carmustine from 1983 to 1989. Patients were randomized to one of four arms of hyperfractionated RT in 1.2 Gy twice daily (BID) fractions (64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.6 Gy) or to either of two accelerated hyperfractionated RT arms in 1.6 Gy BID fractions (48.0 or 54.4 Gy). Although preliminary toxicity and survival data have been published, little information is available regarding the quality of these patients' lives during and following such therapy. QAS is a refinement of the methodology for assessing survival quality among breast cancer patients receiving adjuvant chemotherapy. The QAS method allows for inclusion of both improvement and decline in neurologic functional status. Patients were scored by the presence or absence of 15 neurologic signs and symptoms at on-study and at every follow-up. Within each category were gradations of severity, with the quality survival time (Q-TIME) adjusted according to any changes in these neurologic findings. The summation of all changes in signs and symptoms were weighted by 1/15th and incorporated into the QAS model as QAS = Q-TIME-TOX-RRX. TOX was the time spent with treatment-related toxicities, and RRX was the time spent in recovery from subsequent therapy. RESULTS: Of 747 evaluable patients, the average QAS time was 18.5 months. The average QAS for the hyperfractionated arms of 64.8 Gy, 72.0 Gy, 76.8 Gy, and 81.6 Gy were 15.6, 20.8, 10.0, and 13.7 months, respectively. For the accelerated hyperfractionated RT arms of 48.0 and 54.4 Gy, the average QAS times were 13.1 and 13.4 months. The QAS time of the 72.0 Gy arm was significantly longer than that of all other groups, except the 64.8 Gy arm. As expected, the QAS times were strongly discriminated by both age and Karnofsky Performance Scores (KPS) (p < 0.001). Younger patients and patients with high KPS benefited most from assignment to the 72.0 Gy arm; QAS time was not significantly longer in any treatment arm among patients over age 50 or with KPS scores of 80 or less. CONCLUSIONS: This quality-adjusted survival methodology can be successfully applied to malignant glioma patients and permits a quantitative assessment of the influence of investigational therapies on patient quality of life. This analysis confirms the potential benefit of intermediate dose (72.0 Gy) hyperfractionated RT for selected malignant glioma patients.

Adult↗
PubMed1995

Functional measures in children with rheumatic diseases.

The measurement of function in children with rheumatic diseases is an intimate part of not only the initial diagnostic work-up, but also of every clinic visit during the course of these chronic diseases. This article focuses on the development of specific and general instruments used to systematically measure function and thus, outcome of the rheumatic diseases and their treatments. Reference is made to instruments developed for use in the general pediatric and adult rheumatology population as a basis for the discussion of the instruments in use in pediatric rheumatology. Specifically, the dimensions of physical function, psychosocial impact, economic impact and quality of life are addressed.

Activities of Daily Living↗
PubMed1995

Pediatric sensorineural hearing loss after temporal bone radiation.

In adults, sensorineural hearing loss (SNHL) resulting from megavoltage temporal bone radiation therapy (RT) is dose dependent. A review of the literature reveals only two cases of pediatric SNHL after RT without chemotherapy. This report presents four cases of late onset, asymmetric SNHL after RT in children treated for posterior fossa tumors. The children were treated with surgical resection of the tumor, followed by RT of 50 to 54 gray and no chemotherapy. These children, without evidence of tumor recurrence, developed severe SNHL 18 to 36 months after the completion of RT. Although no definite audiometric pattern was seen, most of the patients had a predominately high frequency SNHL in the poorer hearing ear, and fluctuant hearing in the better ear, without evidence of osteoradionecrosis or otitic infection. A review of the literature suggests that injury to the outer hair cells and cochlear neurons of the basal turn of the cochlea are possible sources for the hearing loss. Pretreatment audiologic evaluation as well as a minimum of 3 years of evaluations following RT would be prudent.

Brain Neoplasms↗
PubMed1994

Inhibition of cyclic nucleotide phosphodiesterase by derivatives of 1,3-bis(cyclopropylmethyl)xanthine.

Alkylation of the selective type IV phosphodiesterase inhibitor, 8-amino-1,3-bis(cyclopropylmethyl)-xanthine (1, BRL 61063), led exclusively to the N-7 substituted derivatives 2-9, which showed varying selectivities for the PDE type IV isoenzyme relative to PDE Va. The 4-methoxybenzyl derivative 6 in particular was a highly potent PDE Va inhibitor (IC50 0.14 microM) and showed a 24-fold selectivity for this isoenzyme relative to PDE IV. Sulfonation of 1 was more complex, with the product profile being highly dependent on the reaction conditions. As with alkylation, sulfonation at N-7 generally increased potency against PDE Va, especially in the aryl-containing moieties lacking strongly electron-withdrawing substituents (12, 15-17, 19). Bis-arylsulfonation at the exocyclic amino group generally reduced inhibitory potency against both PDE IV and Va. An 8-amidino compound 33, formed by the unusual reaction of 1 with N-methylpyrrolidinone in the presence of benzenesulfonyl chloride, had an IC50 value of 0.05 microM against PDE Va and is believed to be the most potent inhibitor of this isoenzyme reported. No correlation of PDE IV inhibition with displacement of [3H]rolipram from its high-affinity binding site was demonstrated. This suggests that either the catalytic site and the rolipram binding site are not the same or that PDE IV can exist in two conformations, only one of which binds to rolipram with high affinity, and that the compounds described vary in their selectivity for this isoform.

Adenosine↗
PubMed1994

Continuous split course irradiation for stage I and II Hodgkin's disease: 20 year experience at the Medical College of Wisconsin.

Between January 1970 and December 1989, 153 consecutive patients with stage I or II Hodgkin's disease were treated at the Medical College of Wisconsin Affiliated Hospitals. Eighty-eight patients were clinically staged and 65 patients underwent staging laparotomy. Ninety-nine patients were treated using continuous split course irradiation (CSCI) technique. Overall survival (OS) at 5, 10, and 15 years was 89%, 79%, and 68%, respectively. Disease-free survival (DFS) at 5, 10, and 15 years was 75%, 72%, and 68%, respectively. No significant differences were found in OS or DFS when comparing pathologically and clinically staged patients or when comparing patients treated using CSCI with those treated with the standard technique. Patients treated using CSCI tended to complete therapy in a shorter time, without increased morbidity.

Adolescent↗
PubMed1994

Relaxation of guinea-pig trachea by cyclic AMP phosphodiesterase inhibitors and their enhancement by sodium nitroprusside.

1. The effects of agents that elevate either cyclic AMP (the phosphodiesterase (PDE) III inhibitor siguazodan, salbutamol) or cyclic GMP (sodium nitroprusside (SNP)) on the relaxant activity of the PDE IV inhibitor, rolipram, were investigated in carbachol (0.1 microM) precontracted guinea-pig tracheal sheets. 2. Rolipram, siguazodan and SNP caused concentration-related reductions in tone of tissues precontracted with 0.1 microM carbachol (EC50 values 12.5; 2.73 and 0.35 microM respectively). Whilst the concentration-response relationship for the PDE III inhibitor, siguazodan, was monophasic that of the PDE IV inhibitor, rolipram, was biphasic. 3. The relaxant activity of rolipram was markedly enhanced in the presence of 10 microM siguazodan (EC50 < 0.01 microM), 0.1 microM salbutamol (EC50 0.03 microM) and 0.3 microM SNP (EC50 0.03 microM). In contrast, the relaxant activity of siguazodan was unaffected by SNP and only modestly enhanced by rolipram (10 microM) and salbutamol (0.1 microM). 4. The relaxant activity of SNP was enhanced by the PDE V inhibitor SK&F 96231 (30 microM: EC50 0.06 microM) and rolipram (30 microM, EC50 0.08 microM) but was unaffected by 30 microM siguazodan. 5. At concentrations up to 10 microM, neither siguazodan nor rolipram elevated tracheal cyclic AMP levels. However, the combination of 10 microM rolipram and siguazodan caused a two fold increase in the cyclic AMP content (from 2.19 to 4.36 pmol cyclic AMP mg-1 protein). SNP (0.1-10 microM) failed to produce a significant increase in tracheal cyclic AMP levels. At 0.1 microM the effect of SNP on tracheal cyclic AMP levels was significantly (P < 0.05) increased in the presence of rolipram but not siguadozan. 6. The results indicate that the relaxant effects of rolipram are markedly enhanced by agents that inhibit PDE III activity or elevate cyclic GMP. They support the hypothesis that SNP potentiates the effects of rolipram via the inhibitory action of cyclic GMP on hydrolysis of cyclic AMP by PDE III. The findings also suggest that whilst PDE III may be more significant in regulating basal smooth muscle tone in the absence of any exogenous stimulus to cyclic AMP accumulation, PDE IV activity may be more tightly coupled to the pool of adenylyl cyclase stimulated by beta2-adrenoceptor agonists.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Pulmonary effects of type V cyclic GMP specific phosphodiesterase inhibition in the anaesthetized guinea-pig.

1. We have investigated the bronchodilator potential of type V phosphodiesterase (PDE V) inhibitors in anaesthetized ventilated guinea-pigs using the potent and selective PDE V inhibitor, SK&F 96231. We have compared its activity to that of salbutamol, the PDE III inhibitors, siguazodan and SK&F 95654 and to the PDE IV inhibitor rolipram. 2. Administered as an i.v. infusion SK&F 96231 (0.6 and 1 mg kg-1 min-1, i.v.) caused a slowly developing inhibition of histamine (100 nmol kg-1, i.v.)-induced bronchoconstriction and elevated tracheal cyclic GMP levels in the anaesthetized guinea-pig. SK&F 96231 (0.1 and 0.3 mg kg-1 min-1, i.v.) was without effect on histamine-induced bronchoconstriction. In the presence of a sub-threshold infusion of SNP (0.1 mumol kg-1 min-1, i.v.) there was a marked enhancement of SK&F 96231-induced inhibition of histamine responses such that at infusion rates that were ineffective alone, SK&F 96231 caused a > 50% inhibition of histamine responses. The stimulation of tracheal cyclic GMP accumulation by SK&F 96231 was also potentiated. 3. Administered directly into the airway, SK&F 96231 (300 micrograms in 5 mg lactose carrier) was largely without effect on histamine-induced bronchoconstriction (4.9 +/- 1.9% inhibition). In the presence of SNP (0.1 mumol kg-1 min-1, i.v.) or isosorbide dinitrate (200 micrograms administered by insufflation into the trachea) there was a marked potentiation of the inhibitory activity of SK&F 96231 (40 +/- 4% and 62 +/- 1.8% respectively). 4. Salbutamol and rolipram (3-300 microg by insufflation) caused a dose-related inhibition of histamine responses with a maximum of 91 +/- 2% and 59 +/- 10% respectively. The PDE III inhibitor, siguazodan,was without effect on histamine responses but they were reduced (27.7 +/- 4.8% at 300 microg) by SK&F95654. There was a marked enhancement of the inhibitory activity of rolipram in the presence of SK&F 95654.5. We conclude that SK&F 96231 has weak anti-spasmogenic activity in the guinea-pig in vivo, we suggest that this is primarily a consequence of a low endogenous guanylate cyclase activity in the airway. The potentiation of the anti-spasmogenic activity of SK&F 96231 by SNP suggests that a combination of PDE V inhibitor and guanylate cyclase agonist might provide significant bronchodilator activity.6. We have established that PDE IV inhibitors are bronchodilators when administered directly into the airway of anaesthetized guinea-pigs but that PDE III inhibitors are only weakly active. The marked enhancement of the inhibitory activity of rolipram by the PDE III inhibitor, SK&F 95654, indicates that inhibitors of both PDE III and PDE IV might offer greater potential as bronchodilators than inhibitors of either isoenzyme alone.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Prostate cancer: are racial differences in clinical stage and survival explained by differences in symptoms?

PURPOSE: To better understand racial differences in data for patients referred for definitive treatment of biopsy-proved adenocarcinoma of the prostate gland. MATERIALS AND METHODS: Two groups of patients were defined for further analysis. Group 1 comprised all patients who received definitive external beam irradiation of prostatic carcinoma; group 2 comprised all patients with prostatic carcinoma referred between January 1988 and December 1992 for examination at the first clinical indication of adenocarcinoma of the prostate. All patients were evaluated for age, race (black vs white), differentiation of tumor, date of diagnosis, and clinical stage. RESULTS: In group 1, black patients were significantly younger and presented with disease at higher clinical stage but equivalent grade and survival compared with white patients. In group 2, black patients were significantly younger and had similar differentiation of tumor but with significantly higher clinical stage compared with white patients and more often had obstructive symptoms and less often had been screened for elevated prostate-specific antigen levels. CONCLUSION: Black patients should undergo earlier screening for prostate cancer.

Adenocarcinoma↗
PubMed1994

Pancreatitis associated with brain tumor therapy.

PURPOSE: Four children with prolonged emesis during brain tumor therapy were diagnosed with pancreatitis. PATIENTS AND METHODS: All were exposed to medications or radiotherapy that potentially contributed to pancreatitis. CONCLUSIONS: Because recognition of pancreatitis may necessitate changes in supportive care, pancreatitis should be included in the differential diagnosis of vomiting in this population.

Adolescent↗
PubMed1993

Comparison of the effect of isobutylmethylxanthine and phosphodiesterase-selective inhibitors on cAMP levels in SH-SY5Y neuroblastoma cells.

A comparison of the effects of various phosphodiesterase (PDE) inhibitors upon cellular cAMP levels was undertaken in human neuroblastoma SH-SY5Y cells. When inhibitors such as rolipram and Ro 20 1724 (selective for the low Km cAMP-specific PDE) were used, cAMP levels were seen to rise dramatically under basal (< or = 60 fold) or forskolin-stimulated (< or = 200 fold) conditions. However, the non-selective PDE inhibitor isobutylmethylxanthine (IBMX) was 7-18% as effective as these other agents even at 1 mM. The poor efficacy of IBMX was not attributable to concomitant increases in cGMP, to alterations in cAMP egress or to a lack of sensitivity of the cellular PDEs to IBMX inhibition. In additivity experiments, IBMX potently and rapidly reduced cAMP that had accumulated after rolipram treatment. The fact that the agonist 2-chloroadenosine can enhance cAMP accumulation in these cells, and that cAMP elevated by rolipram or forskolin can be reduced by adenosine deaminase and theophylline suggest that cell-derived adenosine enhances cAMP in these cells in an autocrine fashion. Since IBMX is an adenosine receptor antagonist, it is suggested that its blockade of endogenous adenosine effects is at least partly responsible for its poor response when compared to other PDE inhibitors which are weaker adenosine receptor antagonists. These results forewarn against assuming that similar levels of cAMP accumulate after application of PDE inhibitors in these cells.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Central lymphatic irradiation for stage III nodular malignant lymphoma: long-term results.

PURPOSE: To report the long-term results of central lymphatic irradiation for stage III nodular malignant lymphoma. PATIENTS AND METHODS: Between 1969 and 1985, 34 patients (26 with nodular poorly differentiated lymphoma, four with nodular mixed lymphocytic/histiocytic lymphoma, and four with nodular histiocytic lymphoma) were treated with central lymphatic irradiation. Median age of the group was 51 years (range, 30 to 73). There were 15 men and 19 women. Staging work-up included a physical examination and bone marrow biopsy in all patients. Seventy-four percent had a lymphangiogram (LAG) and 44% a laparotomy (LAP). Eighty-two percent had either a LAP or a LAG. Thirty-two patients were Ann Arbor stage IIIA and two were stage IIIB. All patients received lymphatic irradiation that encompassed cervical, supraclavicular, axillary, mediastinal, paraaortic, mesenteric, pelvic, and femoral lymphatics to total doses ranging from 20 to 30 Gy in 1.0- to 1.8-Gy fractions. Waldeyer's ring was initially treated in 17 patients. Follow-up information is available on all 34 patients. Median follow-up is 9 years, 8 months (range, 15 to 244 months). RESULTS: Life-table actuarial overall, disease-free, and cause-specific survival rates at 15 years are 28%, 40%, and 46%, respectively. Only one relapse was observed after 9 years. Disease-free survival was significantly improved in patients with five or fewer sites of involvement (P = .02). Age, sex, B symptoms, histology, and technique of irradiation were not prognostically significant. Salvage therapy, including further irradiation and/or chemotherapy, was delivered to 20 patients. Ten percent of these patients remain alive without evidence of disease. Toxicity data were available for the patients treated at the Medical College of Wisconsin (MCW). Radiation Therapy Oncology Group (RTOG) acute hematologic, gastrointestinal, and salivary toxicity scores were < or = 2 in 83% of patients. Late toxicity scores were < or = 2 in 96%. Persistent xerostomia was noted in 23% of patients who received initial treatment to Waldeyer's ring. CONCLUSION: These results suggest that initial comprehensive central lymphatic irradiation may be the preferred approach to achieve a durable relapse-free interval for this group of patients.

Adult↗
PubMed1993

Vertebral artery injury during anterior decompression of the cervical spine. A retrospective review of ten patients.

Ten patients who suffered iatrogenic injury to a vertebral artery during anterior cervical decompression were reviewed to assess the mechanisms of injury, their operative management, and the subsequent outcome. All had been undergoing a partial vertebral body resection for spondylitic radiculopathy or myelopathy (4), tumour (2), ossification of the posterior longitudinal ligament (1), nonunion of a fracture (2), or osteomyelitis (1). The use of an air drill had been responsible for most injuries. The final control of haemorrhage had been by tamponade (3), direct exposure and electrocoagulation (1), transosseous suture (2), open suture (1), or open placement of a haemostatic clip (3). Five patients had postoperative neurological deficits, but most of them resolved. We found direct arterial exposure and control to be safe, quick and reliable. Careful use of the air drill, particularly in pathologically weakened bone, as in infection or tumour, is essential. Arterial injury is best avoided by a thorough knowledge of the anatomical relationships of the artery, the spinal canal, and the vertebral body.

Adult↗
PubMed1993

The role of photodynamic therapy in posterior fossa brain tumors. A preclinical study in a canine glioma model.

Photodynamic therapy was studied in dogs with and without posterior fossa glioblastomas. This mode of therapy consisted of intravenous administration of Photofrin-II at doses ranging from 0.75 to 4 mg/kg 24 hours prior to laser light irradiation in the posterior fossa. Tissue levels of Photofrin-II were four times greater in the tumor than in the surrounding normal brain. Irradiation was performed using 1 hour of 500 mW laser light at a wavelength of 630 nm delivered through a fiberoptic catheter directly into the tumor bed via a burr hole. All animals receiving a high dose (4 or 2 mg/kg) of Photofrin-II developed serious brain-stem neurotoxicity resulting in death or significant residual neurological deficits. A lower dose (0.75 mg/kg) of Photofrin-II produced tumor kill without significant permanent brain-stem toxicity in either the control animals or the animals with cerebellar brain tumors receiving photodynamic therapy.

Animals↗