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Biomedical subjects

B H Cohen

Publications and source records attributed to B H Cohen.

At least 19 recordsLinked to original sources

Results of linear accelerator-based stereotactic radiosurgery for recurrent and newly diagnosed acoustic neuromas.

Stereotactic radiosurgery (SRS) is used to treat acoustic neuromas, but additional information is needed to firmly establish its safety and efficacy. We review our experience over 7 years treating 29 consecutive patients with a modified linear accelerator (linac) SRS system. Between August 1989 and October 1995, 29 patients with a median age of 67 years (range 26 to 83) underwent linac SRS treatment. Twenty-five patients had unilateral acoustic neuromas, and four patients with neurofibromatosis type II had bilateral vestibular schwannoma. Eligibility criteria for SRS were recurrent tumors (n = 9), age >65 (n = 16), or patient preference (n = 6). Follow-up magnetic resonance imaging scans were performed on all patients. The most common presenting symptoms were hearing impairment (18 patients) and gait difficulties (17 patients). Ten patients were deaf in the affected ear prior to treatment. Doses to the periphery of the tumor ranged from 800 to 2,400 cGy (median 1, 600 cGy) prescribed to the 50% to 80% isodose line (median 80%). After a median radiographic follow-up of 49 months (range 4 to 110 months), 11 tumors were smaller, 17 were stable, and one had evidence of progression (at 41 months). The 5-year local disease control rate (Kaplan-Meier estimate) was 94%. Acute complications were minimal, with only two patients experiencing nausea and vomiting after the procedure. Long-term complications included new or progressive trigeminal and facial nerve deficits with estimated 5-year incidences of 15% and 32%, respectively. Subjective hearing reduction or loss occurred in 14 (74%) of the 19 patients who had useful hearing prior to treatment. Five patients died from unrelated causes. These results suggest that linac SRS provides excellent short-term tumor control rates. Since there was a high risk of cranial nerve neuropathy, we do not recommend using only computed tomography-based planning and high prescription doses. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 145-151 (2000).

Adult↗

Multiple sleep latency test and polysomnography in diagnosing Kleine-Levin syndrome and periodic hypersomnia.

Kleine-Levin syndrome and periodic hypersomnia are often misdiagnosed initially because there is no objective test for these conditions. To determine the value of the Multiple Sleep Latency Test and polysomnography in this respect, the authors studied four patients with Kleine-Levin syndrome or periodic hypersomnia who had taken the Multiple Sleep Latency Test and undergone polysomnography during the symptomatic episode and/or during the asymptomatic interval. During but not between symptomatic episodes, the Multiple Sleep Latency Test revealed abnormal sleep latencies in all patients, and polysomnography revealed increased rapid eye movement propensity in one patient and a reduction in delta-sleep in two patients. In conclusion, the Multiple Sleep Latency Test and polysomnography are useful in diagnosing Kleine-Levin syndrome and periodic hypersomnia, especially when administered in a standardized fashion during and after the symptomatic period. The authors recommend that polysomnography and the Multiple Sleep Latency Test be performed no earlier than the second night after the onset of a symptomatic episode and the following day to reveal maximal hypersomnolence, and more than 2 weeks after a symptomatic episode to represent the asymptomatic interval.

Adolescent↗

Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas.

OBJECT: Craniopharyngiomas originate from the same cells as squamous cell skin carcinoma, which can be treated successfully with interferon-alpha (IFNalpha)-2a. The authors evaluated the activity and toxicity of systemic IFN in young patients with craniopharyngiomas. METHODS: Fifteen patients between the ages of 4.2 and 19.8 years who had progressive or recurrent craniopharyngiomas were enrolled in this study. Nine of these patients had never received external-beam radiation therapy. Therapy consisted of 8,000,000 U/m2 IFNalpha-2a administered daily for 16 weeks (induction phase) followed by the same dose three times per week for an additional 32 weeks (maintenance phase). Of the 12 patients who could be evaluated, radiological studies demonstrated a response to treatment in three with predominantly cystic tumors (one minor response, one partial response, and one complete response); one of these patients also showed improvement in visual fields. The size of the cystic component of the tumors often increased temporarily during the first several months of therapy. Three patients met the criteria for progressive disease during therapy. The median time to progression was 25 months. The need for radiation therapy in patients treated with IFN was delayed for 18 to 35 months (median 25 months) in six patients. All patients developed transient flulike symptoms shortly after receiving the first dose of IFN. Other toxicities (predominantly hepatic, neurological, and cutaneous) were seen in nine (60%) of the 15 patients during the first 8 weeks of treatment but resolved after temporary discontinuation and/or dose reduction. CONCLUSIONS: Interferon-alpha-2a is active against some childhood craniopharyngiomas; its toxicity precludes administration of high daily doses, and the optimum dose level and schedule remain to be defined.

Adolescent↗

Intracranial germ cell tumors.

Intracranial germ cell tumors are a heterogeneous group of lesions which occur in children and adults. Within the classification of intracranial germ cell tumors, there are a variety of different tumor types which carry different prognoses. The diagnosis of an intracranial germ cell tumor usually requires histological information, but a subgroup of tumors will secrete specific tumor markers, including alpha-fetoprotein and beta-human chorionic gonadotropin, which may obviate the need for surgical intervention. The management of intracranial germ cell tumors in both children and adults remains unsettled. Germinomas have a good prognosis, as over 90% of patients can be effectively treated with radiation therapy. The dose and volume of radiation therapy needed for disease control is not well established, and controversy exists concerning the need for whole brain or craniospinal radiation therapy for localized tumors. Germinomas are also chemosensitive and recent reports suggest that the dose and volume of radiation therapy required for disease control can be lessened with the addition of adjuvant chemotherapy. The outcome for patients with nongerminomatous germ cell tumors is less favorable. Radiation therapy alone will result in disease control in 40%-60% of patients. The addition of chemotherapy to radiation therapy may improve the rate of survival.

Adult↗

Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: A Children's Cancer Group Study.

PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% +/- 4% at 3 years and 79% +/- 7% at 5 years. Sites of relapse for the 14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Outcome in elderly patients undergoing definitive surgery and radiation therapy for supratentorial glioblastoma multiforme at a tertiary care institution.

PURPOSE: To determine the efficacy of definitive surgery and radiation in patients aged 70 years and older with supratentorial glioblastoma multiforme. METHODS AND MATERIALS: We selected elderly patients (> or = 70 years) who had primary treatment for glioblastoma multiforme at our tertiary care institution from 1977 through 1996. The study group (n = 102) included 58 patients treated with definitive radiation, 19 treated with palliative radiation, and 25 who received no radiation. To compare our results with published findings, we grouped our patients according to the applicable prognostic categories developed by the Radiation Therapy Oncology Group (RTOG): RTOG group IV (n = 6), V (n = 70), and VI (n = 26). Patients were retrospectively assigned to prognostic group IV, V, or VI based on age, performance status, extent of surgery, mental status, neurologic function, and radiation dose. Treatment included surgical resection and radiation (n = 49), biopsy alone (n = 25), and biopsy followed by radiation (n = 28). Patients were also stratified according to whether they were optimally treated (gross total or subtotal resection with postoperative definitive radiation) or suboptimally treated (biopsy, biopsy + radiation, surgery alone, or surgery + palliative radiation). Patients were considered to have a favorable prognosis (n = 39) if they were optimally treated and had a Karnofsky Performance Status (KPS) score of at least 70. RESULTS: The median survival for patients according to RTOG groups IV, V, and VI was 9.2, 6.6, and 3.1 months, respectively (log-rank, p < 0.0004). The median overall survival was 5.3 months. The definitive radiation group (n = 58) had a median survival of 7.3 months compared to 4.5 months in the palliative radiation group (n = 19) and 1.2 months in the biopsy-alone group (p < 0.0001). Optimally treated patients had a median survival of 7.4 months compared to 2.4 months in those suboptimally treated (p < 0.0001). The favorable prognosis group had an 8.4-month median survival compared to 2.4 months in the unfavorable group (p < 0.0001). On multivariate analysis, the KPS, RTOG group, favorable/unfavorable prognosis, and optimal treatment/suboptimal treatment were significant predictors of survival. CONCLUSION: Elderly patients with good performance status (> or = 70 KPS) when treated aggressively with maximal resection and definitive radiation had longer survival than those treated with palliative radiation and biopsy. Aggressive treatment in such patients should be considered.

Aged↗

Evidence for image-scanning eye movements during transitive inference.

Contrary to earlier work, recent studies have demonstrated a reduction in eye movements during the solution of tasks that seem to require visual imagery, relative to verbal tasks. The present study provides evidence that the nature of the visual imagery required by a task determines whether saccades are evoked and in which spatial pattern. In two experiments, subjects solved transitive inference problems with the relational terms left/right and above/below, while the horizontal and vertical EOG were recorded. Subjects made more horizontal and fewer vertical saccades while solving problems with the left/right terms than while solving identical problems with above/below. The results of silent counting tasks showed that the rate of subvocalization can also influence saccadic rate, especially in the horizontal plane, but cannot explain the eye-movement patterns observed during transitive inference. The results are discussed in terms of a motor theory of voluntary thinking.

Adult↗

Systemic T cell adoptive immunotherapy of malignant gliomas.

OBJECT: To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich source of tumor-immune T cells. METHODS: In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte macrophage-colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 x 10(8) to 1.5 x 10(11). There were no Grade 3 or 4 toxicities associated with the treatment. Following T-cell transfer therapy, radiographic regression that lasted at least 6 months was demonstrated in two patients with recurrent tumors. One patient demonstrated stable disease that has lasted for more than 17 months. The remaining patients had progressive disease; however, four of the eight patients with recurrent tumor remain alive more than 1 year after surgery for recurrence. Three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer. CONCLUSIONS: These intriguing clinical observations warrant further trials to determine whether this approach can provide therapeutic benefits and improve survival.

Adjuvants, Immunologic↗

Chemotherapy for medulloblastomas and primitive neuroectodermal tumors.

In the past two decades, chemotherapy has proven to be an increasingly more effective modality in the treatment of medulloblastoma. Current evidence suggests that chemotherapy be included as part of standard treatment for all patients with high-risk medulloblastoma. Ongoing multi-centre trials are determining whether chemotherapy should be added to reduced dose radiotherapy as a substitute therapy for standard-dose radiotherapy. The major randomized and non-randomized chemotherapy trials for newly diagnosed patients with medulloblastoma or for patients at recurrence are presented. It is hoped that the addition of chemotherapy will eventually lead to improved survival rates as well as the reduction in the craniospinal radiotherapy dose for patients with medulloblastoma.

Brain Neoplasms↗

Acute neurotoxicity of meperidine in an infant.

We report a 6-week-old boy with meperidine neurotoxicity. What distinguished our patient from those previously reported was his minimal exposure to therapeutic doses of meperidine in the setting of normal renal function, and no history of sickle cell anemia, cancer, hepatitis, or cirrhosis. In addition, our patient had no abnormal changes in the electroencephalogram during the event. After only 2 doses of meperidine, he exhibited acute orofacial dyskinesias consisting of tongue thrusting, lip pursing, and facial grimacing combined with prominent flexion of the arms and stiffening of his legs. However, a normal sucking response remained. His symptoms resolved over the next 36 hours and did not respond to naloxone. We believe that this unique presentation of meperidine-induced neurotoxicity may be due to changes in the basal ganglia resulting from perinatal hypoxemia.

Analgesics, Opioid↗

Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

PURPOSE: This study was designed to determine the toxicity, radiographic response rate, and outcome following high-dose thiotepa, etoposide, and autologous bone marrow rescue (ABMR) for young patients with recurrent malignant brain tumors. METHODS: Eligibility criteria required adequate renal, hepatic, and pulmonary function, and no bone marrow infiltration. Thiotepa 300 mg/m2 and etoposide 500 mg/ m2 were infused on 3 consecutive days, and autologous bone marrow was infused 72 hours following chemotherapy. RESULTS: Forty-five patients with recurrent high-grade brain tumors, aged 8 months to 36 years (median, 8 years), were treated. Seven patients (16%) died of treatment-related toxicities within 56 days of marrow reinfusion. Delayed platelet engraftment occurred in 44% of patients who survived beyond day 56. Of 35 patients with radiographically measurable disease who survived at least 28 days following ABMR, there were two complete responses (CRs) and six partial responses (PRs), for an overall response (CRs plus PRs) rate of 23% (SE = 7%). Objective responses were observed in four of 14 assessable patients with high-grade glioma and in two of six with primitive neuroectodermal tumors (PNETs)/ medulloblastoma. Survival was significantly improved in patients treated with minimal residual disease (P < .0005). Five of 18 patients (28%) with high-grade gliomas remain free of disease at 39+, 44+, 49+, 52+, and 59+ months post-ABMR. CONCLUSION: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors. These results merit further evaluation in children and young adults with both recurrent and newly diagnosed high-grade brain tumors.

Adolescent↗

Headaches as a symptom of neurological disease.

When a headache develops in a child or adolescent, both the patient and the parents may fear the presence of a brain tumor. However, most headaches are not a symptom of a serious neurological disease but are related to stress or migraine. In this article, headaches in relationship to neurological disorders are reviewed. The pathophysiology of head pain and increased intracranial pressure are reviewed. Methods used to evaluate patients suspected of harboring an intracranial abnormality include a thorough history, a carefully performed physical examination, and neuroimaging studies. This article reviews cerebrovascular disease, neoplasms, hydrocephalus, and other structural abnormalities that cause headaches.

Adolescent↗

The Burow's triangle scalp reduction. A new and improved technique for paramedian scalp reduction.

BACKGROUND: The paramedian incision for scalp reduction has many advantages over the median (midline-sagittal) incision. OBJECTIVE: This report describes a method by which the paramedian incision may be modified to provide even more advantages. METHODS: In 20 patients with male pattern alopecia, an anterior and posterior paramedian incision was performed along contralateral borders of the bald scalp. The two incisions were joined in the central scalp by a trans-coronal incision. The tissue movement that followed was similar to that of a Burow's triangle advancement flap. RESULTS: The new configuration provided maximal visual access with improved tissue mobilization and ease of handling. Because the tension-bearing vector was directed parallel to the transcoronal incision, there was little tendency for the scar to widen. Because posterior "slots" or "troughs" were not created, additional corrective procedures were not necessary. CONCLUSION: The Burow's triangle scalp reduction design is cosmetically and mechanically more advantageous than traditional median and unilateral paramedian designs of equivalent length.

Alopecia↗

Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial.

PURPOSE: To determine clinical characteristics and response to treatment for children with supratentorial primitive neuroectodermal tumors (S-PNETs). PATIENTS AND METHODS: After surgery and staging, 55 patients aged 1.5 to 19.3 years with S-PNETs were randomized to receive craniospinal radiotherapy (RT) followed by eight cycles of 1-(2-chloro-ethyl)-3-cyclohexylnitrosourea (CCNU), vincristine (VCR), and prednisone (standard treatment) or two cycles of 8-in-1 chemotherapy followed by RT and then eight additional cycles of 8-in-1. RESULTS: Three-year Kaplan-Meier estimates (estimate +/- SE) of survival and progression-free survival (PFS) rates for patients with confirmed diagnoses of S-PNET were 57% +/- 8% and 45% +/- 8%, respectively; survival and PFS rates for children with PNETs located in the pineal region were 73% +/- 12% and 61% +/- 13%, respectively, and were significantly different from the other S-PNETs (P < .03). The 8-in-1 arm had greater toxicity than the standard-treatment arm. Distributions of PFS between the two treatment groups were not significantly different (P > .5). Other univariate prognostic factors that influenced PFS included metastasis (M) stage (P < .03: M0 50% +/- 9% v M1-4 0%) and age (P < .02: 1.5 to 2 years 25% +/- 13% v > or = 3 years 53% +/- 9%). CONCLUSION: In this first randomized treatment trial for S-PNETs in children, no significant differences were detected between the two treatment groups. M0 and pineal site of involvement were independent predictors of a better outcome. However, survival was better than previously reported.

Antineoplastic Combined Chemotherapy Protocols↗

Decrease in skin-closing tension intraoperatively with suture tension adjustment reel, balloon expansion, and undermining.

BACKGROUND: The biomechanical and viscoelastic properties of the skin enable it to be significantly stretched within a relatively short period of time. This property, called mechanical creep, is exploited in various surgical maneuvers for intraoperative closure of large surgical defects. The recently introduced Miami Suture Tension Adjustment Reel (S.T.A.R.) device permits both the precise sutured attachment of a linear cycled load to approximate the edges of widened surgical defects, and the easy measurement of wound edge tension across the defects. OBJECTIVE: It was our purpose to compare the relative effects of linear load cycling with the S.T.A.R. device, spherical load cycling with balloon expander, and surgical undermining on the closing tension of surgical defects. METHOD: Surgical wounds were created on the flanks of six pigs and these defects were closed by various methods of repair. The combination of undermining and the S.T.A.R. device ws also evaluated. RESULTS: The average total decreases in skin closing tension were: undermining, 17.8 +/- 0.5%; balloon, 28.5 +/- 1.6%; S.T.A.R. device, 36.6 +/- 4.8%. CONCLUSION: Our data showed that all three techniques were effective in lowering the tension required to approximate surgically created defects, with the S.T.A.R. device proving to be most effective. Undermining and the S.T.A.R. device also worked synergistically to decrease skin-closing tension.

Animals↗

Medical and surgical management of acute disseminated encephalomyelitis.

Two children with a recent history of viral illness developed visual loss secondary to optic neuritis. Clinical findings and neuroimaging were consistent with acute disseminated encephalomyelitis (ADEM). Markedly elevated opening pressures were noted on lumbar puncture. The patients demonstrated an initial favorable response to high-dose corticosteroid administration. Both had recurrence of symptoms after being tapered off oral corticosteroids. High-dose corticosteroids were reinstituted and a bilateral optic nerve sheath decompression was performed on one patient who developed profound visual loss. A second patient underwent a lumboperitoneal shunt. Both children had resolution of their symptoms and had a recovery of normal visual acuity.

Brain↗