PubMed Health⌕ Search

Biomedical subjects

J Mealey

Publications and source records attributed to J Mealey.

At least 19 recordsLinked to original sources

Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative Group trial 8420A.

PURPOSE: To test the efficacy of intra-arterial (IA) cisplatin versus intravenous (IV) PCNU for treating primary brain tumors, in a randomized trial (Brain Tumor Cooperative Group [BTCG] Trial 8420A). METHODS: 311 adult patients (ages 19-79 years; median 45) with supratentorial tumors (confirmed histologically) were randomized by nine participating institutions. Patients were required to have completed radiotherapy (4500-6020 cGy to the tumor bed) before randomization. Patients were stratified as either nonprogressive (clinically and radiologically stable) or progressive. Results were analyzed for the 311 patients in the randomized population (RP), and for the 281 patients in the Valid Study Group (VSG) meeting protocol eligibility requirements. 56% of patients in the VSG had glioblastoma multiforme, 33% had other malignant glioma, and 11% had low-grade glioma. 64% were stratified as progressive. 12% had received prior chemotherapy. RESULTS: The group randomized to PCNU had the longer survival (p = 0.06 for the RP, p = 0.07 for the VSG). In the VSG, median survival was 10 months for the cisplatin group, 13 months for the PCNU group. The difference between treatment groups was significant (p < or = 0.02) when adjusted for important prognostic factors. PCNU lead to greater hematotoxicity; cisplatin lead to greater renal toxicity and some ototoxicity. Some cisplatin patients experienced complications associated with IA administration, including six cases of encephalopathy. CONCLUSION: The trial showed a survival advantage to the group randomized to PCNU, although the difference was modest. Coupled with previous BTCG results, these trails suggest that PCNU is an active drug for brain tumors.

Adult↗

A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma.

This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.

Adolescent↗

Percutaneous lumbar discectomy: a new adjunct to open surgery.

Percutaneous automated lumbar discectomy is a new and alternative method to open operations for lumbar disc disease. The procedure and indications for the procedure are explained in this article. The results of the first 24 such procedures performed at the Indiana University Medical Center will be examined and discussed.

Humans↗

Multimodal treatment of adult intracranial gliomas.

Recent advances, experimental treatments and future protocols of adult intracranial gliomas are discussed in this article. Adult intracranial gliomas are not benign, and most are incurable with poor prognosis, despite aggressive treatment. Breakthroughs will be found only through well-designed, experimental protocol evaluation on patients with intracranial gliomas.

Adult↗

Results of a randomized trial comparing BCNU plus radiotherapy, streptozotocin plus radiotherapy, BCNU plus hyperfractionated radiotherapy, and BCNU following misonidazole plus radiotherapy in the postoperative treatment of malignant glioma.

In Brain Tumor Cooperative Group Study 77-02, eleven institutions randomized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery: conventional radiotherapy (6000 cGy in 30-35 fractions) + BCNU, conventional radiotherapy + streptozotocin, hyperfractionated (twice daily) radiotherapy (6600 cGy in 60 fractions) + BCNU, and conventional radiotherapy with misonidazole followed by BCNU. Data were analyzed for the total randomized population and for the 557 patients (86% with glioblastoma multiforme) who met protocol eligibility specifications (including confirmed histopathology on central review). Median survival was approximately 10 months following randomization. Overall there was no statistically significant difference in survival among the four groups. Among non-glioblastoma patients, the misonidazole group appeared to have poor survival. Peripheral neuropathy was a dose-limiting toxicity with misonidazole. It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma.

Adolescent↗

Late anaplastic gliomas in children previously treated for acute lymphoblastic leukemia.

At least 33 cases of late anaplastic gliomas in children previously treated for acute lymphoblastic leukemia have been discussed in the literature including 20 well-documented cases. The frequency of this second malignancy is much greater than expected and may represent a 'new syndrome' with some genetic predisposition. Additionally, CNS prophylaxis which includes both radiation and intrathecal methotrexate appears to work synergistically in increasing the incidence of glial tumors especially multifocal tumors in these patients. The prognosis for these children is dismal but an aggressive treatment approach including surgery, interstitial radiation, and chemotherapy appears to improve survival.

Adolescent↗

Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001.

Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.

Antineoplastic Combined Chemotherapy Protocols↗

Radiation-induced intracranial malignant gliomas.

The authors present seven cases of malignant gliomas that occurred after radiation therapy administered for diseases different from the subsequent glial tumor. Included among these seven are three patients who were treated with interstitial brachytherapy. Previously reported cases of radiation-induced glioma are reviewed and analyzed for common characteristics. Children receiving central nervous system irradiation appear particularly susceptible to induction of malignant gliomas by radiation. Interstitial brachytherapy may be used successfully instead of external beam radiotherapy in previously irradiated, tumor-free brain, and thus may reduce the risk of radiation necrosis.

Adult↗

Candida albicans shunt infection.

Seven cases of successfully treated Candida albicans cerebrospinal fluid shunt infections are reported. Treatment consisted of shunt removal and intravenous Amphotericin B in all cases and intraventricular Amphotericin B in 4 cases. Serious underlying medical illness, recent antibiotic therapy, indwelling intravascular and/or Foley catheters, coincident candidiasis and low birth weight prematurity are major risk factors for candida shunt infection. Candida shunt infection appears to occur by either contamination at the time of shunt placement or by hematogenous dissemination.

Adolescent↗

Differential silver staining in lymphocytes and lymphoblastoid cell cultures.

An analysis of the patterns of silver-stained nucleolar organizer regions (AgNORs), an indication of rDNA transcriptional activity, was carried out in metaphases from peripheral lymphocytes and young lymphoblastoid cell cultures (LCL) transformed by Epstein-Barr virus. Four individuals previously shown to carry a double NOR (dNOR) were studied. The dNOR varied in staining frequency and showed intra-individual variation in appearance in both cell types. For each individual a significantly greater mean number of AgNORs was observed in LCL (7.0-8.04) when compared with lymphocytes (5.8-6.4). To control for possible serum stimulation effects, lymphocytes from one individual were cultured in 20% serum as was the LCL of all subjects. The mean number of AgNORs in these lymphocytes remained significantly lower than in the LCL, as did the mean size of the dNOR, based on a relative score. Our results suggest that LCL have increased expression of rDNA, as evidenced by silver staining.

Cells, Cultured↗

Origin of organisms infecting ventricular shunts.

Results of skin cultures obtained before 413 of 505 operations for cerebrospinal fluid-diverting ventricular shunt placement or revision in a pediatric population from April 1980 to May 1983 are analyzed and compared to results of cultures from 20 subsequent shunt infections. Sensitivities to 11 different antibiotics were determined for each isolate cultured. The total operative infection rate was 20 of 505 (4%). Gram-negative bacilli alone accounted for 3 of 20 (15%) shunt infections. One gram-negative bacillus/Staphylococcus aureus infection occurred. Factors predisposing for gram-negative bacillus shunt infection were found in all 4 cases. The majority of shunt infections were caused by typical resident skin organisms: Staphylococcus epidermidis alone, 9/20 (45%); Staphylococcus aureus alone, 4/20 (20%); Corynebacterium sp., 1/20 (5%); alpha-Streptococcus with S. epidermidis, 1/20 (5%); and Micrococcus with S. epidermidis, 1/20 (5%). Only 4 (20%) of the 20 shunt infections were due to organisms identical to those originally grown from the skin. Another 4 (20%) seemed to be infected with a strain of organism different from that initially recovered from the skin. The remaining skin organism shunt infections may or may not have come from the patient's skin. The data suggest that not all skin organism shunt infections arise from contamination by resident skin bacteria at the incision sites at the time of operation. Alternate sources for the infecting organisms are discussed. The antibiotic sensitivity data on skin isolates and shunt isolates suggest that vancomycin is the antibiotic best suited for prophylaxis against shunt infection at our institution.

Adolescent↗

Metrizamide-enhanced computed tomography as an adjunct to metrizamide myelography in the evaluation of lumbar disc herniation and spondylosis.

Eighty patients with operatively proven lumbar disc herniation or lumbar spondylosis were preoperatively evaluated with metrizamide myelography followed by metrizamide-enhanced computed tomography (CT). The x-ray films were reviewed without knowledge of the operative findings, and the patients were subdivided into those with disc extrusions, spondylosis, or recurrent abnormalities. For the group as a whole, CT was correct in 82% and myelography was correct in 77%. Both CT and myelography together were accurate in 91%, a significant improvement (P less than 0.02). The authors conclude that, if both studies are performed, the percentage of cases correctly diagnosed is increased. Therefore, both metrizamide myelography and metrizamide-enhanced CT should be obtained in selected cases. A review of the literature is included.

Adult↗

Medulloblastoma. Period of risk reviewed.

Collins postulated that patients with Wilms' tumor surviving for a period equal to their age at diagnosis plus 9 months were no longer at risk for a recurrence. Although this no longer holds for Wilms' tumor, it has been applied to patients with medulloblastoma. Case histories of patients who survived a period of risk designated by Collins' rule and later developed a histologically confirmed recurrent medulloblastoma are discussed. Reported cases violating Collins' rule constitute less than 2% of all medulloblastomas. The continued use of Collins' rule is advocated. Patients who have survived this period of risk, are neurologically stable, and have a negative computerized tomography (CT) head scan are exceedingly unlikely to develop a recurrent medulloblastoma.

Age Factors↗

Cerebrospinal fluid ascites complicating ventriculoperitoneal shunting. Report of four cases.

Four cases of cerebrospinal fluid (CSF) ascites secondary to ventriculoperitoneal shunting are described. It is possible to differentiate CSF ascites from a CSF-filled pseudocyst by the characteristic bowel gas pattern on films of the abdomen and by the presence of shifting dullness. Two of the patients had active shunt infections, and had ascitic fluid with a protein level greater than 3 gm% and a white blood cell (WBC) count greater than 1000/cu mm. Both were treated successfully with antibiotics and removal of the shunt from the peritoneum. Two other patients had no evidence of infection, protein levels of less than 2 gm%, and WBC count less than 100 cu mm. These disorders resolved spontaneously. A review of 18 cases reported in the literature shows that the etiology of CSF ascites in the absence of shunt infection is multifactorial, and no features are consistently present in all cases. Ascites without infection may resolve spontaneously without surgical intervention.

Adult↗

Multiple fusiform intracranial aneurysms following curative radiation therapy for suprasellar germinoma. Case report.

A 17-year-old girl died from the rupture of a large fusiform aneurysm of the terminal internal carotid artery. Autopsy revealed three other fusiform aneurysms originating from major cerebral arteries clearly within the ports of previously administered telecobalt radiation therapy. Five years prior to her death, a suprasellar germinoma was partially removed and the area was treated by radiation therapy via three ports. The original arteriograms showed a normal vascular tree. Repeat arteriograms, 3 years and 8 months before her death, demonstrated the aneurysms. The development of aneurysms following radiation damage of the arteries has been reported previously, but not in intracranial vessels.

Adolescent↗

Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma.

Within 3 weeks of definitive surgery, 609 patients with histologically demonstrated, supratentorial malignant glioma were randomized to receive, in addition to 6000 rads of radiotherapy, one of four treatment regimens: carmustine (BCNU), high-dose methylprednisolone, procarbazine, or BCNU plus high-dose methylprednisolone. We analyzed the data for the total randomized population and for the 527 patients (87% with glioblastoma multiforme) in whom the initial protocol specifications were met (the valid study group). Significantly longer survival was experienced by patients receiving procarbazine or BCNU alone compared to those receiving only high-dose methylprednisolone. No other pairwise comparisons demonstrated differences significant at the 0.05 level. However, the combination of BCNU plus high-dose methylprednisolone tended to be less effective than BCNU alone in patients with poor prognosis. This study indicates that BCNU and procarbazine are moderately useful agents in conjunction with radiotherapy for patients with malignant glioma. In addition, future protocols may allow use of corticosteroids in conventional dosages for treating cerebral edema and controlling symptoms; conclusions based on survival as the endpoint are unlikely to be affected by administering steroids at somewhat greater than the usual dose. More effective regimens for the treatment of malignant glioma should be sought.

Adolescent↗

Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery.

Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significiant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.

Aged↗

Optic chiasmatic glioma in children.

We reviewed the records of 29 patients with optic nerve or chiasm glioma, or both, seen from 1955 to 1966. Sixteen patients were girls and 13 were boys. At the time of diagnosis, 14 patients were less than 2 years old. Optic atrophy was the most frequently seen physical finding, present in 26 of 29 patients. Twelve patients had diencephalic syndrome (41%). Proptosis was seen in eight. Eleven patients (38%) had associated neurofibromatosis. Pneumoencaphalogram was done on 26 patients and was abnormal in 23. The diagnosis was confirmed at surgery in 27 patients. All tumors were astrocytomas. Eighteen patients underwent radiotherapy. Surgery and radiotherapy were used as treatment for optic-chiasmatic glioma with diencephalic syndrome.

Age Factors↗