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Biomedical subjects

J Casper

Publications and source records attributed to J Casper.

At least 73 records · Page 4Linked to original sources
PubMed1994

Aerodynamic and stroboscopic findings before and after microlaryngeal phonosurgery.

Acoustic, aerodynamic, and laryngo-video-stroboscopy (LVS) studies were done on 50 patients before and after microlaryngeal surgery for benign vocal fold lesions. Perceptual pre- and postratings were also obtained. After microlaryngeal surgery, statistically significant differences between pre- and posttreatment conditions included postoperative findings of (a) a lowering of mean flow rate, (b) an increase in glottal efficiency, and (c) an increase in maximum sound pressure level. There was no significant improvement in maximum phonation time. Stroboscopy findings showed changes of glottal configuration, linearity of the vocal fold edge, amplitude of vocal fold vibration, excursion of the mucosal wave, and periodicity. Acceptable perceptual voice quality appeared to depend on a straight vocal fold edge, good vibratory amplitude, and good mucosal wave. Improved understanding of vocal function after phonosurgery should help us refine surgical principles and techniques. The combined use of LVS and phonatory function measures is advocated.

Glottis↗
PubMed1994

The anti-tumour activity of ifosfamide on heterotransplanted testicular cancer cell lines remains unaltered by the uroprotector mesna.

Ifosfamide is clinically used in combination chemotherapy regimens for the treatment of patients with high-grade lymphomas, sarcomas and metastatic germ cell tumours. In order to reduce the oxazophosphorine-related urothelial toxicity, sodium mercaptoethane sulphonate (mesna) is used in different schedules following the administration of ifosfamide. The proposed mechanism of mesna activity is the binding of toxic oxazaphosphorine metabolites such as acrolein in the urine of the patients. Since an influence of mesna on ifosfamide anti-tumour activity is controversial, the current study has used xenografts from two human testicular cancer cell lines heterotransplanted into nude mice to study the anti-tumour activity of ifosfamide in combination with different dosages and schedules of mesna. In both human testicular cancer cell lines, H 12.1 and 2102 EP, ifosfamide demonstrated anti-tumour activity as a single agent. No reduction in ifosfamide activity was observed with the application of mesna at a dose range from 50% to 200% of the ifosfamide dose. Furthermore, the application of mesna before and 3 h after ifosfamide, a schedule used in many clinical protocols because of the short half life of mesna, not only maintained high ifosfamide anti-tumour activity but also seemed to be associated with the lower systemic and urothelial toxicity of ifosfamide therapy compared with ifosfamide given alone. In conclusion, the experimental in vivo system using human heterotransplanted testicular cancer cell lines confirms the significant anti-tumour activity of ifosfamide in malignant germ cell tumours and demonstrates that mesna does not impair ifosfamide anti-tumour activity in this model. These results are most likely transferable to the use of mesna in patients with metastatic testicular cancer.

Animals↗
PubMed1994

Diagnosis and treatment of persistent dysphonia after laryngeal surgery: a retrospective analysis of 62 patients.

Sixty-two patients with persistent or recurrent dysphonia after laryngeal surgery underwent interdisciplinary voice evaluation, laryngostroboscopy, and objective measurements of vocal function. The causes of persistent dysphonia were attributed to vocal fold scarring (n = 22), residual mass lesion (n = 8), residual inflammation (n = 13), recurrent mass (n = 4), and hyperfunctional voice disorder (n = 7). Laryngoscopy often showed excessive ventricular compression and anterior-to-posterior laryngeal compression. Ventricular dysphonia was often a compensatory gesture in response to poorly mobile vocal fold membranes. Stroboscopy was able to document a number of abnormalities which included abnormalities of laryngeal configuration, vibratory asymmetry, reduction of amplitude, and mucosal wave. Using a diversified approach consisting of medical therapy, voice therapy, and repeat surgery, better vocal function was able to be restored in the majority of patients. An interdisciplinary approach to the dysphonic patient after laryngeal surgery was most useful in defining the pathology and refining a treatment rehabilitation program.

Adult↗
PubMed1994

Treatment of poor marrow graft function with allogeneic CD34+ cells immunoselected from G-CSF-mobilized peripheral blood progenitor cells of the marrow donor.

The treatment effect of immunoselected allogeneic CD34+ blood cells was evaluated in two patients with poor graft function following BMT without evidence for immune-mediated rejection. Patient A had no signs of hematopoietic recovery up to day +34 post-BMT and patient B had normal leukocyte counts only with G-CSF support and remained platelet transfusion-dependent for > 200 days post-BMT. PBPC from the HLA-identical sibling BM donors were mobilized with G-CSF (2 x 5 micrograms/kg sc daily) for 5 days. Aphereses were performed on days 4 and 5 of G-CSF administration. CD34+ cells were separated from the pooled PBPC concentrates by immunoadsorption with the anti-CD34 moAb 12.8 in a biotin-avidin system. Patient A received 0.4 x 10(6) CD34+ and 4.3 x 10(5) CD3+ cells/kg body weight and patient B 3.4 x 10(6) CD34+ and 1.4 x 10(5) CD3+ cells/kg body weight. The trilineage repopulation of BM and the rapid improvement of peripheral blood parameters correlated with CD34+ cell infusion. Patients' blood and BM cell analyses proved the donor origin. Patient A died from CMV pneumonitis and multiorgan failure 27 days after CD34+ cell infusion (day +61 post-BMT). Patient B is still stable and in remission 260 days after CD34+ cell infusion (day +478 post-BMT). Neither patient suffered further exacerbation of GVHD). Thus, immunoselected allogeneic CD34+ blood cells might be appropriate for treatment of post-BMT graft failure.

Adult↗
PubMed1992

A phase II study of high dose tamoxifen in progressive, metastatic renal cell carcinoma.

Thirty-four patients with progressive advanced renal cell carcinoma (RCC) were treated with high-dose tamoxifen (HD-TAM) 100 mg/m2 p.o. daily until progression. The overall remission rate was 12%, including 1 complete remission. Seventeen of the thirty-four (50%) patients had minor remission or no change. Taking into consideration the documented progression prior to tamoxifen therapy, further tumour growth could be arrested in 62% (1 CR, 3 PR, 17 MR/NC) of the patients. Median response duration for CR/PR was 20 months (range 6-21+) and median progression-free survival for MR/NC was 6 months (range 2-15). The one-year survival rate was 41%. Patients with only pulmonary metastases, good performance status and prior nephrectomy seemed to have a better survival. Side effects were comparable to those of conventional doses of tamoxifen (20-30 mg p.o. daily). These data suggest that HD-TAM may be a useful therapeutic approach with low toxicity, considering that, in metastatic RCC, the treatment intent is at best palliative.

Adult↗
PubMed1992

The predictive value of HLA-DR oligotyping for MLC responses.

Comparison of HLA proteins between a patient and potential unrelated marrow donors is difficult because many similar, but not identical, HLA proteins are expressed in the human population. A reliable and practical method to detect these subtle differences is provided by oligotyping, a new technique that identifies polymorphic sequences in the genes encoding the HLA proteins. Oligotyping was used to compare polymorphic HLA-DR sequences in 286 pairs of samples from patients and potential unrelated donors who were serologically matched for HLA-DR specificities. Oligotyping detected HLA-DR differences in 53% of these pairs and all mismatched pairs were reactive in primary mixed lymphocyte cultures. Where HLA-DR disparity was not detected by oligotyping, 37% of the pairs were nonreactive in MLC. The remaining 63% often contained an allele associated with the HLA-DRw11 serological specificity. In the absence of HLA-DRB1*11, oligotyping was predictive of MLC reactivity for samples with HLA-DR2, -DR4, and DRw52. In clinical settings, the ability to predict MLC reactivity on the basis of precise HLA typing provides an alternative to MLC. Further, the relationship between specific polymorphic sequences and reactivity in MLC may lead to more fundamental insights into the mechanisms involved in alloreactive responses.

Amino Acid Sequence↗
PubMed1992

Dysphonia in the aging: physiology versus disease.

A chart review from 151 dysphonic patients over the age of 60 was done to define aging related voice disorders. Overwhelmingly, patients suffered from dysphonia due to disease processes associated with aging rather than to physiologic aging alone. These include: 1. central neurological disorders affecting laryngeal function (e.g., stroke, Parkinson's disease, essential tremor, Alzheimer's disease); 2. benign vocal fold lesions (e.g., Reinke's edema, benign and dysplastic epithelial lesions); 3. inflammatory disorders (e.g., laryngitis sicca, medication effect); 4. laryngeal neoplasia; and 5. laryngeal paralysis. Typical laryngeal findings of vocal fold bowing and breathiness consistent with presbylarynges were present in only six patients. Presbylarynges is not a common disorder and should be a diagnosis of exclusion made only after careful medical and speech evaluation.

Aged↗
PubMed1992

Pancreatitis associated with bone marrow transplantation in children.

Vomiting, abdominal pain and distension, common findings in children who receive bone marrow transplants (BMT), are usually attributed to chemo-irradiation and mucositis, universally found in these patients. We report seven children, 3.5% of BMT patients at our institutions, with these symptoms who were found to have mild to severe pancreatitis during conditioning for or after receiving BMT. All patients were receiving drugs known to cause pancreatitis, such as adrenocorticosteroids and sulfonamides as well as numerous putative pancreatotoxins such as cyclosporin A and cytosine arabinoside. Five of the seven patients had suffered from graft-versus-host disease. In patients who have received BMT, upper gastrointestinal symptoms should not be attributed to mucositis or chemo-irradiation without first testing for pancreatitis.

Adolescent↗
PubMed1991

Functional staging for vocal cord paralysis.

Phonatory function can be reliably tested after vocal paralysis. After a review of 116 cases, 55 patients underwent objective testing. The clinical history of vocal ability and aspiration were found to be significantly correlated with measurements of phonatory mean flow rate (MFR), maximum phonation time (MPT), and maximum decibel output (SPL). A four-stage classification system, based on clinical and objective measurements, has been formulated. In stage I, measures of vocal parameters approached those of normals with MFR = 155 cc/sec, MPT = 12 sec, and SPL = 92 dB. Patients with stage IV disability have high MFR (480 cc/sec), but low MPTs (less than 3 sec) and low SPL values (76 dB). Factors such as sex, age, weight loss, and the presence of malignancy affect the degree of vocal function deficit. Post-therapy recordings indicated an improvement in vocal function by an increase in MPT and SPL, with a decrease in MFR. Measurements of MFR, PT, and SPL are good objective indicators available to the clinician. Functional staging can be applied to assessment and treatment of vocal cord paralysis.

Adult↗
PubMed1991

High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study.

We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.

Adolescent↗
PubMed1991

Cisplatin, etoposide, and ifosfamide salvage therapy for refractory or relapsing germ cell carcinoma.

Thirty patients with metastatic progressive germ cell carcinoma who failed to be cured with first-line cisplatin chemotherapy were treated with a salvage regimen consisting of cisplatin 20 mg/m2, etoposide 100 mg/m2, and ifosfamide 1.2 g/m2 (PEI) intravenously (IV), days 1 to 5 every 3 weeks. Ten patients (33%) were tumor-free at the end of therapy. Complete response (CR) was achieved with chemotherapy alone in four patients and with additional surgery in six patients (two necroses, two mature teratomas, two carcinomas). Six patients (20%) had normalization of tumor markers but unresectable residual disease (Rm-), and the remaining 14 patients (46%) failed to respond. Of 10 patients with CR, nine (90%) relapsed again (eight carcinomas, one mature teratoma). The median duration of CR was 3.5 months. The median survival of the whole group was 311 days (range, 110 to 996+). Currently, seven of 30 patients are alive, and five of them are without signs of progressive tumor. The response to prior cisplatin therapy predicted for response and survival after PEI salvage therapy. Of 14 patients with prior CR, eight (57%) achieved a second CR compared with one of 11 (9%) with prior unfavorable response (P = .039). The median survival for patients with prior favorable response was 400 days, compared with 251 days for patients with prior unfavorable response (P less than .001). Myelosuppression was dose-limiting, with leukopenia greater than grade 2 in 84% and thrombocytopenia greater than grade 2 in 51% of all cycles. This three-drug regimen can induce a second CR in one third of patients with relapsed or refractory germ cell carcinoma. Only those patients with prior favorable responses can expect to be cured by this salvage regimen, while patients with prior unfavorable response should be considered for alternative salvage approaches.

Adult↗
PubMed1990

Comparative activity of four anthracyclines against heterotransplanted germ cell tumor lines.

Though the majority of patients with metastatic nonseminomatous germ cell tumors can be cured by modern combination chemotherapy, for those patients who do not respond to standard therapy additional drugs are needed. The activity of three new anthracycline derivatives, 4-epidoxorubicin, THP-doxorubicin and mitoxantrone against two established human testicular cancer cell lines in comparison to doxorubicin and to cisplatin, vinblastine, bleomycin and ifosfamide was studied in a xenograft model. All drugs were given at equitoxic doses. There were no differences in antitumor activity between the four anthracycline derivatives. In line H 12.1, which is very sensitive to the standard drugs cisplatin, vinblastine, bleomycin and ifosfamide, all four anthracycline derivatives were inferior to these agents. In contrast, in line H 23.1, where all four standard agents showed a significant lower antitumor activity when compared to line H 12.1, the anthracyclines preserved their activity, indicating a lack of cross resistance. Thus the anthracycline derivatives seem to be inferior to the standard drugs as first line treatment but because of apparent lack of cross resistance they deserve further evaluation in refractory germ cell tumors.

Animals↗
PubMed1990

Interaction of human embryonal carcinoma cells and differentiated derivatives in vitro with simian virus 40, human adenovirus type 7, or PARA.

Polyclonal antibodies were used to assay human embryonal carcinoma (EC), differentiating EC, yolk sac carcinoma, and teratoma cells for expression of viral early antigen (T-Ag) after infection with simian virus 40 (SV40). Cells of four EC lines were induced to differentiate by cultivation at low density or by exposure to retinoic acid or dimethyl sulfoxide. After infection with SV40, T-Ag was expressed by 1%, or less, of the cells (presumed to be differentiated derivatives) in only some EC cultures whereas the antigen was synthesized by a significant percentage of the yolk sac carcinoma, teratoma, and differentiating EC cells. Also, viral late proteins were produced by EC cells infected with human adenovirus type 7 (Ad7), and SV40 T-Ag was expressed by EC cells after infection with PARA, which is an Ad7-SV40 hybrid virus containing the SV40 T-Ag sequence controlled by Ad7 late regulatory sequences. Thus, T-Ag is not synthesized by the parental EC cells infected with SV40, but it is expressed in cultures of infected differentiated derivatives. The EC cells produce T-Ag, however, when expression of the viral protein is controlled by the Ad7 regulatory sequences in PARA particles. These results demonstrate that expression of T-Ag after infection with SV40 is an indicator of EC cell differentiation and also raise the possibility that, as in mouse EC cells infected with the virus, the SV40 regulatory sequences controlling T-Ag synthesis are not active in human EC cells.

Adenoviruses, Human↗