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Biomedical subjects

R Ginsberg

Publications and source records attributed to R Ginsberg.

At least 37 records · Page 2Linked to original sources
PubMed1995

A randomized trial of the activity and safety of Ro 24-7429 (Tat antagonist) versus nucleoside for human immunodeficiency virus infection. The AIDS Clinical Trials Group 213 Team.

Ro 24-7429, a Tat antagonist, dosed at 75, 150, or 300 mg/day, was compared with nucleoside analogue (zidovudine or didanosine) for 12 weeks in 96 human immunodeficiency virus (HIV)-infected patients to assess safety and activity. The primary adverse effect of Ro 24-7429 was rash, which necessitated treatment discontinuation in 6 of 71 patients. Nucleoside analogue treatment produced an average increase in CD4 cell count of 28 cells/mm3 at week 8 versus a decrease of 27 cells/mm3 in recipients of Ro 24-7429 (P < .001). Serum HIV p24 antigen levels decreased by an average of 111 pg/mL in nucleoside recipients at week 8 compared with an increase of 41 pg/mL in recipients of Ro 24-7429 (P = .007). Nucleoside-treated patients had a mean 0.66 log10 reduction in infectious peripheral blood mononuclear cells, while Ro 24-7429 recipients had a mean 0.02 log10 reduction (P = .02). No dose-response relationships were observed in the Ro 24-7429 groups. In this study, Ro 24-7429 treatment showed no evidence of antiviral activity.

Adult↗
PubMed1994

A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma.

PURPOSE: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy. PATIENTS AND METHODS: Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first. RESULTS: Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients). CONCLUSION: This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.

Aged↗
PubMed1993

Initial clinical (phase I) trial of TLC D-99 (doxorubicin encapsulated in liposomes).

A liposome-encapsulated form of doxorubicin (TLC D-99), which was shown in preclinical toxicology to be less toxic to the gastrointestinal tract and myocardium than free doxorubicin, was administered by constant infusion (1.00-1.80 h) to 38 patients in single doses of 20, 30, 45, 60, 75, and 90 mg/m2 every 3 weeks and daily for 3 days at doses of 20, 25, and 30 mg/m2/day. The dose-limiting toxicity was leucopenia: the maximum tolerated doses were one at 90 mg/m2 and three at 25 mg/m2/day. Nausea, vomiting, and stomatitis were minimal or absent at each dose; alopecia was minor. Fever and chills were noted at most of the doses, and malaise was seen in some patients, especially at the higher doses. No hepatic, renal, or other organ toxicities were observed. Clinical cardiac toxicity was not observed in any patient; however, the cumulative doxorubicin dose was greater than 400 mg/m2 in only one patient. There was large variation among patients in estimated pharmacokinetic parameters and profiles. Higher plasma levels and dose intensities were achieved with TLC D-99 than were predicted for free doxorubicin. Liposome-encapsulated doxorubicin was well tolerated and produced less nausea, vomiting, and stomatitis than would be expected with free doxorubicin administered at equally myelosuppressive doses.

Adult↗
PubMed1993

NR-LU-10 monoclonal antibody scanning. A helpful new adjunct to computed tomography in evaluating non-small-cell lung cancer.

UNLABELLED: Computed tomographic scanning has improved the noninvasive staging of lung cancer but has the deficiency of not distinguishing benign from malignant lesions. This prospective trial evaluated the usefulness of a new radiolabeled monoclonal antibody, NR-LU-10, as an adjunct to computed tomography by assessing its clinical applicability and accuracy in detecting malignancy in primary lung tumors and mediastinal nodes. NR-LU-10 is a technetium 99m-labeled Fab fragment of a murine immunoglobulin G2b monoclonal antibody that recognizes a 40 kD glycoprotein expressed in lung and other epithelial cancers. METHODS: (1) Patients with potentially resectable non-small-cell lung cancer were eligible; (2) all patients had computed tomographic scans of the chest; (3) whole body and single photon emission computed tomographic imaging were performed 14 to 17 hours after intravenous infusion of 20 to 30 mCi of NR-LU-10; (4) subsequent mediastinoscopy or thoracotomy with complete mediastinal nodal mapping provided pathologic correlation. RESULTS: Twenty-four patients were entered, 14 men and 10 women. No allergic reactions or other adverse effects were seen. Interference from a prior ventilation-perfusion scan precluded adequate imaging in 1 patient, but high-quality images were obtained in the other 23 patients. The 22 primary malignant tumors all had uptake and there was no uptake in 1 lung nodule found to be benign. In 21 patients who had surgical correlation of mediastinal nodal involvement, NR-LU-10 was false-positive in 5 and false-negative in 1; results of computed tomography were false-positive in 6 and false-negative in 1. In this preliminary study, NR-LU-10 antibody scanning was safe and easily performed, it produced high-quality images of the lung and mediastinum, and it was accurate in detecting primary non-small-cell lung cancers. Further evaluation of its value in staging the mediastinum is needed, in particular, its role as an adjunct to computed tomography to help distinguish benign from malignant lesions.

Antibodies, Monoclonal↗
PubMed1992

Preliminary observations of holmium:YAG laser tissue interaction using human uterus.

Preliminary observations of a pulsed Ho:YAG laser on human uterine tissue in-vitro are presented. The tissue effect on the uterine myometrium was demonstrated using fresh uteri which had been subjected to laser energy. The laser crater and surrounding zone of thermal necrosis (ZTN) was quantified. Measurements demonstrated a consistent narrow ZTN (0.8-1.8 mm) irrespective of power or pulse frequency used. The percentage forward transmission of laser energy through 1 mm of myometrium was investigated using a pyroelectric detector and found to be 0.41%. Finally, a visible and measureable photoacoustic component to the Ho:YAG laser was demonstrated using a water bath and needle hydrophone.

Biophysical Phenomena↗
PubMed1992

Nucleolar organiser regions (AgNORS) in anal intraepithelial neoplasia and invasive anal squamous cell carcinoma.

AIM: To evaluate the usefulness of counting nucleolar organiser region associated proteins (AgNORs) in the management of anal squamous neoplasia. METHOD: Using a silver staining technique for NOR associated proteins, 32 routinely processed paraffin wax embedded sections of anal epithelium were assessed. These consisted of normal anal epithelium (n = 9), anal intraepithelial neoplasia (AIN) grades I (n = 5), and III (n = 13), and invasive squamous neoplasia of the anus (n = 5). RESULTS: The median AgNOR counts for every 100 cells are as follows: normal anal epithelium 2.15 (95% CI 1.89-3.94); AIN I 3.21 (95% CI 2.89-7.14); AIN III 4.32 (95% CI 4.00-8.10); and invasive squamous cell carcinoma of the anus 5.51 (95% CI 2.48-10.62). There were significant differences between AgNOR counts in anal cancer and normal epithelium (p < 0.05; Mann-Whitney U test)), AIN III and normal anal epithelium (p < 0.005), and AIN III and AIN I (p < 0.05). No significant differences were observed between AIN I and normal anal epithelium, anal cancer and AIN I, and anal cancer and AIN III. There was a considerable degree of overlap among the different groups. CONCLUSIONS: Despite the strong association between AgNOR values and degree of dysplasia, the variability within pathological grade may preclude the adoption of this technique on its own as a prognostic indicator. It may, however, be useful in conjunction with other markers of neoplastic growth such as c-myc oncogene amplification or overexpression as a marker of disease progression in AIN and invasive anal squamous cell cancer.

Anus Neoplasms↗
PubMed1992

Identifying alterable patterns in employment success for highly successful adults with learning disabilities.

Adults with learning disabilities were studied to ascertain the patterns of successful functioning that promoted high levels of vocational success. This area of research has been neglected in the developing research base on adults with learning disabilities. In this study of 46 highly successful and 25 moderately successful adults with learning disabilities using ethnographic interviews, it was found that the overriding theme was control and that control was sought through the pursuit of two sets of themes--internal decisions and external manifestations. These themes transcended the entire sample, and the clear difference between the groups was the degree of attainment on the various elements the themes comprised. These elements and themes are discussed and a model of successful vocational functioning is developed and explained.

Achievement↗
PubMed1991

Endocervical carcinoma and precursor lesions: c-myc expression and the demonstration of field changes.

The monoclonal antibody Myc 1-6E10 was used in an immunocytochemical technique to examine the expression of the c-myc oncogene in normal endocervices and those with glandular intraepithelial neoplasia and invasive malignancy. Eleven of 14 normal endocervical biopsy specimens did not express the gene, while three showed nuclear, or light basal cytoplasmic localisation of the gene product, or both. All but one of 14 cases of low and high grade glandular intraepithelial neoplasia, and all 17 cases of invasive adenocarcinoma, showed a pan-cellular pattern of immunostaining. Of considerable additional interest was the demonstration of field changes in morphologically normal glandular epithelium in those biopsy specimens with concurrent cervical glandular intraepithelial neoplasia or adenocarcinoma. This was manifest as increased concentrations of myc proteins compared with normal tissues. These results further support the role of the c-myc gene in oncogenesis, and in the light of field changes, suggest possible difficulties in the clinical management of this group of patients.

Adenocarcinoma↗
PubMed1991

Is there ever a role for salvage operations in limited small-cell lung cancer?

Combined modality treatment with chemotherapy and radiation produces tumor regression in most patients with small-cell lung cancer, but the impact on survival has been small, and less than 20% of patients with limited disease survive 2 years. Survival time is extremely short after failure to respond or relapse after treatment. Local control remains a problem, with one third of patients having recurrence only at the primary site. In an attempt to prolong survival and perhaps achieve cure, we undertook surgical resection in 28 patients with limited small-cell lung cancer who did not have complete remission with standard treatment or who had only local recurrence after treatment. There were 28 patients, 22 male and six female, median age 61 years (range 41 to 76). All patients had been treated with chemotherapy and 13 had received preoperative radiotherapy to the primary site and mediastinum. Eight patients underwent an operation for relapse after complete remission. Five patients had had no response to treatment, three had had a slight response followed by progression during chemotherapy, and 12 had achieved partial response but had greater than 3 cm residual masses. Twelve patients required pneumonectomy, 15 lobectomy, one patient had unresectable disease, and two had bulky residual masses after the operation. Three others had microscopic residual disease. Pathologic examination showed only small-cell lung cancer in 18 patients, mixed small-cell and non-small-cell in four, and only non-small-cell lung cancer in six. There were only four patients with stage I disease, 10 with stage II, and 14 with stage III. The median survival from the date of diagnosis for the entire group is 105 weeks and from the date of operation, 74 weeks. The projected 5-year survival rate is 23%. The two patients with residual masses died with local progression, and distant metastatic disease developed in 17 others. One patient died at 6 years without recurrent disease. Eight patients are alive 2 to 5 years after diagnosis. Seven of these patients required only a lobectomy, four had stage I disease, two had stage II, and two had stage III disease. Five had pure small-cell lung cancer and three had mixed small-cell and non-small-cell tumors. All of the patients with pathologic stage I disease remain alive compared with one of 10 with stage II disease and two of 14 with stage III. In summary, relapse or failure to respond to chemotherapy may be due to non-small-cell lung cancer or a mixed tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Identification of somatostatin receptors in human small cell lung carcinoma.

Biopsy specimens obtained from eight patients with lung cancer were tested for content of somatostatin receptors by autoradiography. Somatostatin receptors were detected in two of three patients with small cell lung cancer (SCLC) but in none of five patients with non-small cell lung cancer (NSCLC) including adenocarcinoma (two), squamous cell carcinoma (two), and bronchoalveolar carcinoma (one). In those with SCLC, specific somatostatin receptor binding was evidenced only in tumor foci and not in surrounding stroma or normal lung parenchyma. Further tissue characterization by immunoperoxidase staining with the pancytokeratin monoclonal antibody, mAB-lu-5, revealed labeling to all of the NSCLC but to none of the SCLC specimen. Selective immunoreactivity was detected in both the SCLC and the NSCLC specimen to chromogranin and neuron-specific enolase (NSE) whereas none of the specimen had detectable immunostaining to somatostatin, bombesin, serotonin, adrenocorticotropic hormone, neurofilament, calcitonin, and synaptophysin. The identification of somatostatin receptors in primary human lung cancer may have a bearing on the biology of this disease and perhaps on the clinical application of somatostatin analogues in patients with SCLC.

Aged↗
PubMed1990

Nuclear and "cytoplasmic" estrogen and progesterone receptors in squamous cell carcinoma of the cervix.

Biopsies from 131 women with squamous cell carcinoma of the cervix diagnosed between May 1983 and July 1986 were assayed for nuclear and "cytoplasmic" estrogen receptors (NER and CER). Progesterone receptors (PR) were also assayed in 45 of these tumors. About a third of the tumors contained both CER and NER. One or the other fraction contained ER in 76.9% of cases and PR in 66.6%. Although there was a trend for those women whose tumors contained CER or NER to have a better prognosis, this was not significant. There was no evidence that PR status affected the prognosis.

Carcinoma, Squamous Cell↗
PubMed1990

Nucleolar organiser regions in adenocarcinoma in situ and invasive adenocarcinoma of the cervix.

Silver binding nucleolar regions (AgNORs) were evaluated in normal endocervix, adenocarcinoma, and its potential precursor, adenocarcinoma in situ (AIS), in an attempt to increase an understanding of the natural history of cervical adenocarcinoma and to identify a marker for abnormal endocervical (atypical glandular) cells which could aid diagnosis and follow up of endocervical lesions. For every 50 cells the mean AgNOR counts were as follows: normal endocervical cells (n = 15) 79.8 (95% Cl 68-91); AIS (n = 20) 200.7 (95% Cl 182-219); and invasive adenocarcinoma (n = 30) 299 (271-328). There was no overlap between the groups of normal endocervical cells and invasive adenocarcinoma, but there was significant overlap between cases of invasive adenocarcinoma and carcinoma in situ. In six out of 17 cases with AIS, NOR count in adjacent morphologically normal glandular cells ("internal" controls) was increased when compared with the "external" (normal endocervical) control group. This suggests the presence of wider field changes not previously identified using routine histological methods. The findings suggest that AIS is a potential premalignant precursor of invasive adenocarcinoma, but that assessment of NORs is of no practical use in discriminating between the histological types of cervical carcinoma.

Adenocarcinoma↗
PubMed1989

Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.

Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.

Adult↗