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Biomedical subjects

H S Greenberg

Publications and source records attributed to H S Greenberg.

At least 19 recordsLinked to original sources
PubMed1992

Clinical outcome in aggressively treated meningeal gliomatosis.

We reviewed 11 consecutive patients with an antemortem cytologic diagnosis of meningeal gliomatosis. In three patients, meningeal gliomatosis was diagnosed before surgical resection of the glioma. Three of five patients with anaplastic astrocytoma and one with oligodendroglioma improved with treatment. Patients with glioblastoma multiforme did not respond and had a median survival from the diagnosis of meningeal gliomatosis of only 8 weeks. Meningeal gliomatosis can be an early finding in gliomas. Treatment response is probably related to tumor histology and grade.

Adolescent↗
PubMed1991

Variability of 5-bromo-2'-deoxyuridine incorporation into DNA of human glioma cell lines and modulation with fluoropyrimidines.

Human glioma-derived cell lines were found to vary in their ability to incorporate the radiosensitizer 5-bromo-2'-deoxyuridine (BrdUrd) into DNA after one cell doubling. The U-251 cell line was the best incorporator of BrdUrd, whereas U-118 and D-54 demonstrated poor incorporation with respective C50 (BrdUrd concentration required for 50% of the maximum amount of BrdUrd incorporation into DNA) values of 2.8- and 6-fold greater than that of U-251 (P less than 0.001). Modulation of radiosensitizer uptake into DNA could be achieved using the thymidylate synthase inhibitors 5-fluorouracil or 5-fluoro-2'-deoxyuridine (FdUrd). Incorporation into U-251 cells increased only slightly in the presence of the fluoropyrimidines. The BrdUrd concentration required for 50% of the maximum amount of BrdUrd incorporation into DNA changed (P less than 0.001) from 1.8 +/- 0.11 microM (SD) in the absence of a modulator to 1.1 +/- 0.09 or 1.1 +/- 0.16 microM in the presence of 10 microM 5-fluorouracil or 5 nM FdUrd, respectively. The D-54 cell line, which was the worst incorporator of BrdUrd, was found to have an extensive amount of BrdUrd into DNA following biomodulation. The C50 in the absence of modulation was 7.3 +/- 1.3 microM, which was reduced (P less than 0.001) to 0.62 +/- 0.04 and 0.32 +/- 0.13 microM, respectively, in the presence of 10 microM 5-fluorouracil and 5 nM FdUrd. This represents a 12- to 22-fold reduction in the concentration of radiosensitizer required to achieve the same level of BrdUrd incorporation into DNA. Furthermore, this enhancement of BrdUrd DNA incorporation seen in the presence of the fluoropyrimidines is observed at clinically achievable concentrations. The degree of radiosensitization was solely dependent upon the amount of BrdUrd incorporated into DNA. D-54 cells grown in the presence of 0.18 microM BrdUrd plus 5 nM FdUrd or 2.8 microM BrdUrd alone yielded a similar level of BrdUrd incorporation into DNA and radiosensitization, though a 15-fold lower BrdUrd concentration was used in the presence of FdUrd. The combined use of a radiosensitizer with a fluoropyrimidine may overcome poor incorporation of BrdUrd into DNA that may exist among resistant subpopulations of cells within malignant glioma.

Bromodeoxyuridine↗
PubMed1991

Protracted Lhermitte's sign following head and neck irradiation.

Lhermitte's sign is a rare complication of head and neck irradiation involving the delivery of dose to the cervical spinal cord. Although uncommon, symptoms of lightning-like electric sensations spreading into both arms, down the dorsal spine, and into both legs on neck flexion following head and neck irradiation, causes great concern in both the patient and the physician. This spontaneously reversible phenomenon is important for the otolaryngologist and radiation oncologist to recognize and discuss. A particularly severe and protracted case of Lhermitte's sign involving a patient recently completing a radical course of radiation for nasopharyngeal carcinoma is described in detail, including a review of the literature surrounding the cause and management of this condition.

Carcinoma, Squamous Cell↗
PubMed1991

Three-dimensional treatment planning of astrocytomas: a dosimetric study of cerebral irradiation.

To demonstrate that 3-dimensional planning is both practical and applicable to the treatment of high-grade astrocytomas, 50 patients over a 2-year period have received cerebral irradiation delivered in focussed, non-axial techniques employing from 2 to 5 beams. Astrocytomas have been planned using rapid, practical incorporation of CT data to define appropriate tumor volumes. Tumor + 3.0 cm and tumor + 1.5 cm volumes have been treated to conventional doses of 4500 cGy and 5940 cGy, respectively, using beam orientations that maximally spared normal remaining parenchyma. Analyses of 3-dimensionally calculated plans have been performed using integral dose-volume histograms (DVH) to help select treatment techniques. Using identical CT-based volumetric data as input for generation of Beam's Eye View (BEV) designed blocks, DVH curves demonstrate dosimetric advantages of non-axial techniques over conventional parallel-opposed orientations. Assessment of the non-axial techniques in selected cases indicates that uniform target volume coverage could be maintained with a typical reduction of 30% in the total amount of brain tissue treated to high dose (95% isodose line).

Astrocytoma↗
PubMed1991

Malignant astrocytomas: focal tumor recurrence after focal external beam radiation therapy.

Hochberg and Pruitt have reported glioblastomas recurring within 2 cm of the primary site in 90% of patients after whole-brain radiation therapy. They suggested that computerized tomography (CT) scan accuracy would permit smaller radiation fields. A treatment protocol with smaller-field focal brain irradiation following surgical resection is reported. The first 4500 cGy of radiation is focused to within a 3-cm margin around the tumor, with a 1500-cGy boost within a 1.5-cm margin. Forty-two patients with grade III or IV astrocytoma, treated with focal brain radiation therapy were reviewed retrospectively to assess patterns of tumor recurrence. Thirty patients received intra-arterial bromodeoxyuridine (BUdR) radiosensitization with focal brain radiation therapy, and 12 patients underwent conventional focal brain radiation therapy. Tumor margin was defined on preoperative and recurrence CT scans as the contrast-enhanced area; these were traced on acetate templates and compared with each other and with the actual scans. In all 42 patients, the lesion recurred within a 2-cm margin of the original tumor. Four patients had two recurrent areas: the second area was within the 2-cm margin in two, and outside this margin in two. These results are similar to those of Hochberg and Pruitt. It is suggested that focal irradiation is now the optimal treatment for malignant astrocytoma. Since recurrences continue to be within the irradiated volumes, it appears that higher focal doses of radiation are appropriate for clinical treatment trials of malignant astrocytomas.

Brain Neoplasms↗
PubMed1991

Metastatic epidural spinal cord compression.

It is important to remember that ESCC is a complication of systemic malignancy and usually denotes disseminated disease with poor survival rates. Early diagnosis is crucial. The initial symptom is almost always back pain, which is local, radicular, or both. Following neurologic examination and radiography, MRI scanning or myelography/CT is immediately indicated if radiculopathy or myelopathy is present or if the radiographs of the spine are abnormal. In cancer patients with local back pain and normal findings on neurologic examination and radiography of the spine, there is still a probability of 0.1 of significant ESCC. Therefore, urgent CT/MRI scanning is justified. At present, the best treatment for ESCC remains unknown. In the majority of patients, radiotherapy is the most readily available and appropriate option because it is equal in effect to posterior decompressive laminectomy in both radiosensitive and radioresistant tumors. In patients with posterior epidural disease without tissue diagnosis, laminectomy with or without stabilization should be performed. Posterior decompressive laminectomy alone is contraindicated in patients with vertebral collapse. In selected instances of anterior epidural compression without tissue diagnosis or after failure of radiotherapy, an anterior surgical approach or synchronous vertebral decompression with posterior stabilization may be indicated. In the future, after appropriate clinical trials, vertebral body resection may be the optimal approach in de novo selected patients with ESCC with radioresistant tumors and limited systemic spread of the disease.

Combined Modality Therapy↗
PubMed1990

Random sampling by glitter drop method.

In the course of a study on glioblastoma tissue and cultured cell lines, a glitter drop technique for random sampling was introduced (1). Here, we report the initial description of the details of this procedure and its application to cell counts from explant slides and to determining bromodeoxyuridine (BUdR) labeling indices (LI) in tissues. The method is without bias, easy to perform and takes only a short time. It compares well with three other generally used random sampling procedures.

Bromodeoxyuridine↗
PubMed1990

The ocular effects of intracarotid bromodeoxyuridine and radiation therapy in the treatment of malignant glioma.

Since July 1985, 23 patients have been entered into a phase I/II clinical trial using intraarterial 5-bromodeoxyuridine (BUdR) (400-600 mg/m2 daily for 8.5 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy daily in 6.5 weeks) in the treatment of malignant gliomas (Kernohan grades 3 and 4). The side effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Mucopurulent conjunctivitis and exposure keratitis developed in several patients and spontaneous corneal perforation developed in one. Eyes from two individuals examined at autopsy showed significant changes. Animal studies that predated clinical trials using rhesus monkeys did not predict the ophthalmologic complications seen in human subjects.

Adult↗
PubMed1990

Nuclear parameters as prognostic indicators in glioblastoma patients.

The objective of this study was to determine whether nuclear parameters were associated with prognosis in glioblastoma multiforme. DNA indices, cell cycle parameters, and nuclear population densities were compared with patient survival. Selection criteria included the pathologic diagnosis of a cerebral glioblastoma multiforme, absence of therapy before surgery, and adequate tissue to measure each nuclear parameter studied. Nine cases accrued over a two year period. The amount of DNA per nucleus was quantified in fresh tissue specimens by nuclear-isolation flow cytometry in Vindelov's solution. One particular association was significant when tested by Cox models: The percentage of nuclei with S-phase amounts of nuclear DNA was a significant predictor of decreased survival (regression coefficient = 0.20, p = 0.04). The percentage of nuclei in the G0/G1 peak was marginally associated with longer survival. These data are evidence of an association between nuclei in certain phases of the DNA cell cycle and postoperative survival.

Adolescent↗
PubMed1990

Procarbazine chemotherapy in the treatment of recurrent malignant astrocytomas after radiation and nitrosourea failure.

The Brain Tumor Study Group has shown procarbazine (PCB) to be as effective an adjuvant treatment as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). We treated 35 patients with recurrent malignant astrocytomas after radiation and nitrosourea failure with successive courses of PCB 150 mg/m2/d for 28 days every 8 weeks. After 2 courses, 2 patients had complete responses, 7 had partial responses, 11 had stable disease, and 15 had progression. Significantly more patients receiving PCB had complete or partial responses or stable disease than a similar group of patients in a previous trial who received intra-arterial (IA) cisplatin (DDP). There is a significant advantage in time to disease progression for those receiving PCB compared with those receiving IA diaziquone (AZQ). Our results suggest that PCB is a more effective 2nd agent than IA DDP or AZQ following radiation and nitrosourea failure.

Adult↗
PubMed1989

Intra-arterial cisplatin for the treatment of malignant gliomas.

Cisplatin (DDP) is a chemotherapeutic agent that has shown efficacy against primary CNS malignancies. Intra-arterial (IA) administration of DDP to patients with brain tumors should produce higher peak levels of drug than intravenous (IV) administration of an identical dose and reduce systemic toxicity. Twelve patients with malignant glioma were entered into the study. All had failed irradiation, 11 had failed IA BCNU. Each patient received IA DDP, 58-100 mg/m2, into the internal carotid artery at four to six week intervals. One of 12 patients had a partial response of 6 months. The remaining 11 patients had progressive disease or severe complications. Toxicity included seizures in four patients, weakness and/or aphasia in four patients, coma in two patients, and visual deterioration in two patients. IA DDP has very limited efficacy in patients with malignant gliomas after failure of nitrosoureas and is associated with an unacceptable level of toxicity. IA DDP may be more effective when used as initial chemotherapy of malignant gliomas.

Adolescent↗
PubMed1989

Psychologic functioning in 8- to 16-year-old cancer survivors and their parents.

This study presents data on psychologic adjustment (self-concept, depression, locus of control, family environment, and parental distress) for a sample of 8- to 16-year-old long-term cancer survivors (n = 138) and their mothers, and for a sample consisting of a matched group of healthy children (n = 92) and their mothers. The null hypothesis of no group differences between survivors and control subjects was tested with respect to these variables. It was hypothesized that survivors with severe late effects would have poorer self-concepts, a more external locus of control, and more depressive symptoms than children with no or mild-to-moderate late effects. The children completed the Piers-Harris Self-Concept Scale, the Nowicki-Strickland Locus of Control Scale, and the Children's Depression Inventory. Mothers completed the Family Environment Scale and the Derogatis Stress Profile. The majority of former patients are functioning within normative limits on these standardized measures, although their scores were lower than those in the comparison group. One-way analyses of variance on the dependent measures indicate that the children with severe medical late effects have a poorer total self-concept, more depressive symptoms, and a more external locus of control than those with no or mild-to-moderate late effects. Therapies for childhood cancer are now well standardized and many long-term deleterious effects are known, so children at risk can be identified readily and steps taken early in treatment to prevent or mitigate future psychologic problems.

Adolescent↗
PubMed1989

Mucocutaneous complications of intraarterial 5-bromodeoxyuridine and radiation.

5-Bromodeoxyuridine (BUDR), a halopyrimidine thymidine analogue, is incorporated into the DNA of dividing cells and causes photoradiosensitization. Twenty-five patients with malignant astrocytomas were treated with continuous intracarotid BUDR radiosensitization and radiotherapy for 8 1/2 weeks. Unique dose-limiting mucocutaneous complications were encountered. Ipsilateral facial dermatitis with epilation of eyebrows and eyelashes, ocular irritation, and bilateral nail dystrophy developed in all patients. Less common reactions included oral ulceration in six patients, body exanthem on the trunk in five, and atypical erythema multiforme major in one.

Alopecia↗
PubMed1989

Mixing in the human carotid artery during carotid drug infusion studied with PET.

The safety and efficacy of drug infusion into the carotid artery require adequate mixing of the infused solution with carotid blood. Using positron emission tomography (PET), we studied the mixing of solutions infused into the human carotid artery in seven patients by analyzing the distribution of [15O]H2O infused into the carotid artery and by vein. At four infusion rates ranging from 0.5 to 10 ml/min, the variability in distribution averaged 16.5-17.8% among the pixels in a large volume of interest, without dependence on the infusion rate. The overall correlation between [15O]H2O influx with arterial infusion and [15O]H2O influx with venous injection was 0.78-0.82 at the four infusion rates, with no trend toward higher correlations at the faster infusion rates. The distribution into the anterior, middle, and posterior cerebral artery territories differed from distribution throughout the entire carotid territory by an average of 6.2-9.6% at the four infusion rates, with no trend toward smaller differences at the faster infusion rates. Infusions performed into a vinyl tube simulating the carotid artery indicated that at 0.5 ml/min, the velocity of fluid exiting the catheter makes no apparent contribution to mixing. We conclude that with infusions at the carotid bifurcation, mixing in the human carotid artery is complete or nearly complete over a wide range of infusion rates. The mixing appears to result from the patterns of blood flow within the artery, and not from jet effects at the catheter tip.

Adult↗
PubMed1989

Double-blind comparison of alprazolam and adinazolam for panic and phobic disorders.

Subjects primarily suffering from DSM-III panic disorders (agoraphobia with panic attacks, 13 subjects; panic disorder, one subject) were tested with two drug treatments after a baseline was established using single-blind placebo capsules three times daily for 1 week. Double-blind, 4-week crossover treatments were given with alprazolam, 0.5-6.0 mg/day, and adinazolam mesylate, 10-120 mg/day. Mean final doses in mg/day were 3.1 for alprazolam and 95.5 for adinazolam mesylate. Both were broadly effective in comparison with the baseline condition. Measures included self-rated symptoms and global impressions, physician-rated global impressions, and two forms of challenges, agoraphobic and noradrenergic. The two active drugs were highly similar in overall efficacy across the sample, but alprazolam was favored globally in six subjects, and adinazolam was favored globally in another six subjects. Only two subjects obtained maximal improvement ratings without side effects with both drugs. No diagnostic or demographic factor correlated with the differential in responses to the two active treatments. No clinically significant laboratory abnormalities occurred with either drug.

Adult↗
PubMed1988

Intracerebral hemorrhage complicating intravenous tissue plasminogen activator treatment.

Tissue plasminogen activator's thrombolytic action is relatively specific for fibrin; however, systemic bleeding can occur in patients, especially when heparin is simultaneously administered. We describe two cases of intracerebral hemorrhage from a cohort of 450 patients (0.44%) treated at one institution with tissue plasminogen activator and heparin for acute myocardial infarction. A pooled worldwide review of 5258 cases from several clinical protocols for treatment of acute myocardial infarction, using tissue plasminogen activator from one source, revealed a similar overall incidence of 0.68%. The incidence of intracerebral hemorrhage may be reduced by lowering the total dose of tissue plasminogen activator or by reducing the infusion rate and duration. The incidence of central nervous system hemorrhage with tissue plasminogen activator is within the range reported with streptokinase, but because equal coronary artery thrombolytic doses are not known, no definitive comparison is possible.

Aphasia↗
PubMed1988

Intra-arterial 5-bromo-2-deoxyuridine (BUdR) radiosensitization with external beam radiation in rhesus monkeys: toxicity study.

A primate toxicity study was performed to test the hypothesis that BUdR does not increase the likelihood of unilateral or bilateral central nervous system damage secondary to radiation therapy. BUdR, a halogenated pyrimidine analog is incorporated into DNA of dividing cells and sensitizes them to radiation. It is best given unilaterally, intra-arterially by continuous infusion because of its regional advantage (Rd) estimated to be between 11 and 16. Six rhesus monkeys were implanted with a Model 400 Infusaid pump perfusing the right internal carotid artery. Three of the six monkeys received intra-arterial (IA) BUdR infusion plus whole brain external beam radiation (6,000 R over 6 weeks) and three received radiation alone. The two BUdR treated animals completing radiation developed symmetric bilateral high signal aberrations on MRI in the frontal, parietal, and occipital centrum semiovale and corona radiata at nine months. At autopsy, confluent microinfarcts were found to correspond topographically to the MRI abnormalities. In the radiation alone group, two animals had normal MRI and autopsy while the third animal had bilateral MRI high signal aberrations develop sequentially with corresponding microinfarcts at autopsy. These changes were greater in severity than those seen in the BUdR treated animals. We support previous evidence that there is differential intraspecies sensitivity to radiation. We find that BUdR produces no unilateral potentiation of radiation toxicity.

Animals↗