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Biomedical subjects

B Webber

Publications and source records attributed to B Webber.

At least 37 records · Page 2Linked to original sources

Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasms. Results of an Intergroup Rhabdomyosarcoma study project.

The authors assessed a panel of immunohistochemical stains against 109 pediatric solid tumors, primarily rhabdomyosarcomas, under the auspices of the Intergroup Rhabdomyosarcoma Study. Fresh tumor tissue received from participating organizations was divided into portions that were either frozen or fixed in formalin, alcohol, or B5. Immunostaining was performed by the avidin-biotin complex method using monoclonal antibodies to desmin, neurofilaments, vimentin, cytokeratin, and leukocyte common antigen on cryostat sections. Tissue was also embedded in paraffin and stained with antimuscle-specific actin (MSA) and polyclonal antibodies to desmin, creatine kinase M subunit (CKM), myoglobin, and neuron-specific enolase (NSE). Antidesmin staining of cryostat sections was the most sensitive indicator of rhabdomyosarcoma (58 of 62 specimens positive). Results with this reagent in alcohol-fixed and formalin-fixed tissue were similar (46 of 56 positive versus 43 of 56 positive, respectively) and comparable with results with anti-MSA in formalin-fixed tissue (43 of 55 positive). However, the proportion of cells stained by antidesmin was higher in alcohol-fixed tissue than in formalin-fixed tissue. Staining with antimyoglobin and anti-CKM was much less satisfactory, with positivity rates of 17 of 37 and 11 of 57, respectively, in formalin-fixed rhabdomyosarcomas. Immunostaining of muscle markers revealed evidence of myogenesis in six undifferentiated sarcomas and in two sarcomas with inadequate histologic study on hematoxylin-eosin-stained sections. However, positivity was also noticed in samples of fibromatosis, Wilms' tumor, ectomesenchyoma, peripheral primitive neuroectodermal tumor, renal rhabdoid tumor, myositis ossificans, malignant fibrous histiocytoma, and embryonal sarcoma of the liver. The authors conclude that combined use of antidesmin and anti-MSA enhances the diagnosis of childhood sarcomas, especially when employed with other techniques such as electron microscopic study.

Actins↗

Clinical features and results of therapy for children with paraspinal soft tissue sarcoma: a report of the Intergroup Rhabdomyosarcoma Study.

Soft tissue sarcomas of the paraspinal region comprised 3.3% (56 of 1,688) of the patients entered and eligible on Intergroup Rhabdomyosarcoma Studies I (IRS-I) and II (IRS-II) (1972 to 1984). These lesions tended to be greater than 5 cm in diameter at diagnosis, invaded the spinal extradural space, and were of the extraosseous Ewing's sarcoma or undifferentiated sarcoma subtype in 55% (30 of 56) of the cases. Patients with tumors in clinical groups II, III, and IV were treated with radiotherapy (XRT) and vincristine-dactinomycin (VA) or VA plus cyclophosphamide (VAC) +/- doxorubicin. Clinical group I patients treated on IRS-II did not receive XRT, while those on IRS-I were randomized to receive VAC +/- XRT. Forty-four of the paraspinal patients (79%) achieved a complete response (CR) compared with 77% (1,260 of 1,632) for patients with disease in other sites. Twenty-seven patients (55%) subsequently relapsed (five local, three regional, four local and distant, and 14 distant). The proportion of patients surviving 5 years by clinical group (stage) from I to IV were 50%, 50%, 62%, and 27%, respectively. Paraspinal patients had somewhat poorer survival than patients with disease in other sites, both in IRS-I and IRS-II; the percentage of paraspinal patients surviving 5 years was 50% and 52% for IRS-I and IRS-II, respectively, whereas these percentages were 55% and 63% for patients with disease in other sites. Histology did not influence the CR rate, but unexpectedly, patients who had embryonal rhabdomyosarcoma (RMS) had the poorest overall survival rate. We concluded that patients with paraspinal lesions may require extended-field radiation therapy to reduce the high local failure rate and more intensive chemotherapy to achieve better local and systemic tumor control.

Child↗

Secondary surgical procedures to evaluate primary tumor status in patients with chemotherapy-responsive stage III and IV sarcomas: a report from the Intergroup Rhabdomyosarcoma Study.

Fifty children with clinical group III (localized, but unresected) or clinical group IV (disseminated) soft tissue sarcomas were entered in a trial to determine if the addition of etoposide and cisplatin to standard chemotherapy regimens and irradiation (4,000 cGy) would be tolerated by pediatric patients. Responding patients had a secondary surgical procedure performed after approximately 20 weeks of therapy for the purpose of establishing histological response, determining its extent, and removing residual tumor tissue, when feasible. Such procedures were performed in 29 of 50 (58%) of these patients, ie, 20 of 31 (65%) of those in group III, and nine of 19 (47%) of those in group IV. Surgical procedures consisted of exploration of the site and biopsy (only) in 16 patients; grossly complete tumor excision in nine; and subtotal tumor excision in four. In nine patients (six in group III, three in group IV) apparent total excision of a previously unresected primary tumor mass was accomplished at second surgery. One distant but no local relapse has occurred in this group, and eight of nine have survived (five of six with identified tumor in the specimen) for a duration of 232 to 348 weeks (six greater than 260 wks), suggesting that among patients with primary tumors in selected sites, with either stage III or stage IV disease, excision of residual masses following intensive chemotherapy/radiotherapy regimens may favorably influence outcome. Local relapse subsequently occurred in seven of 18 patients in whom tumor tissue could not be identified in biopsy specimens or in excised masses taken from the primary site at second surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Partial cystectomy in the management of rhabdomyosarcoma of the bladder: a report from the Intergroup Rhabdomyosarcoma Study.

Among 154 children with primary vesical rhabdomyosarcoma entered in the IRS (1972 to 1986), tumor excision constituting a partial cystectomy was performed in 33. These procedures were performed in the following situations (1) as an initial operation for localized disease (22); (2) as a secondary procedure for localized disease following chemotherapy (CT) or CT/irradiation response (6); and (3) as an initial operation in the presence of disseminated abdominal disease (5). Partial cystectomy included full-thickness resection of 15% to 80% of the bladder wall. Ureters were reimplanted or revised in two patients. The 33 patients undergoing partial cystectomy were in the following clinical groups: I, total excision (10); II, gross excision with "microscopic residual" or positive nodes (8); III, subtotal excision (10); and IV, tumor dissemination (5). Patients in clinical groups I and II received vincristine and actinomycin-D (VA) or VA + cyclophosphamide (VAC) +/- adriamycin (ADR). Patients in groups III and IV received the same agents +/- cisplatin. Irradiation (2,000 to 5,000 cGy) was administered to 18 patients (55%) in groups II to IV. Six relapses occurred among 28 patients with localized disease, and one among five patients with dissemination; all resulting in progressive disease and/or death. Estimated 3-year survival following partial cystectomy (79%) is similar to that for all patients with primary bladder tumors (78%). In contrast with the total group, in which the majority of survivors have eventually required total cystectomy; 25 of 26 survivors of partial cystectomy have functional bladders from 146 to 686 weeks (median, 356 weeks) from study entry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee.

Prestudy patient characteristics and specific therapy of all eligible patients with rhabdomyosarcoma entered into Intergroup Rhabdomyosarcoma (RMS) Studies I (IRS-I) (1972 to 1978, n = 686) or II (IRS-II) (1978 to 1984, n = 1,002) were examined for their relationship to survival within each of the four clinical groups using univariate and multivariate analyses. The estimated survival at 5 years from the start of treatment was 56% in IRS-I and 62% in IRS-II (P = .006). The largest survival difference between studies was in patients with group III tumors (52% v 65%). The clinical group was the most important patient characteristic related to survival in both studies. Survival progressively decreased for patients from clinical group I (localized disease, completely resected) to group IV (metastatic disease at the onset). In clinical group I, the only patient characteristic consistently related to survival was histology. Patients with alveolar tumors had the poorest survival, while those with botryoid/embryonal lesions had the best survival. In clinical group II, no characteristic was consistently related to survival. In clinical group III, an orbital primary site was associated with a favorable survival. In clinical group IV, patients with genitourinary tumors had a significant survival advantage. Use of disease-free survival as an end point gave very similar results. This information, from the largest available data base on prognostic indicators in childhood RMS in the context of aggressive multimodal therapies, is being used to plan therapy in the forthcoming study (IRS-IV).

Adolescent↗

Ovarian stimulation for in-vitro fertilization: clomiphene and HMG.

Details of the problems and successes obtained after various forms of hormonal stimulation in an IVF programme are presented. The endocrine conditions normally existing in the natural menstrual cycle are discussed first, followed by analyses of the types of responses to clomiphene, clomiphene and HMG, HMG alone and LHRH agonists. Clomiphene produces fewer embryos than other treatments but gives a good control of follicle growth and ovulation. Clomiphene and HMG increases the number of available oocytes, and this raises the chance of pregnancy, but there is a greater heterogeneity in the follicular population. HMG alone is suitable for most conditions except for those with PCO syndrome and gives an average of six oocytes per treatment cycle. The problems associated with premature rises in levels of LH are overcome by using LHRH agonists with HMG, and this results in satisfactory numbers of oocytes but requires endocrine support in the luteal phase. The need for luteal phase support after various therapies remains unclear, and a calculation of the ratios between various steroids may help to clarify the need for it.

Clomiphene↗

Intensive chemotherapy including cisplatin with or without etoposide for children with soft-tissue sarcomas.

Forty-two children, 6 months to 17 years of age with newly diagnosed soft-tissue sarcomas (gross residual or metastatic), were treated according to either of two pilot protocols that included intensive chemotherapy before irradiation. Vincristine, actinomycin D, cyclophosphamide, and doxorubicin were used in various combinations with cisplatin alone (regimen 35) or with cisplatin plus etoposide (regimen 36) in a 20-week induction treatment; irradiation (4,000 cGy) was delayed until week 6. Fourteen (82%) of the 17 patients on regimen 35 and 15 (60%) of the 25 on regimen 36 had a complete response. Although severe leukopenia was frequent in both groups (88% and 84% of patients), there were only two fatal infections and no early deaths. Other potentially serious toxicity included a greater than 10% weight loss in 52% of the patients and hypomagnesemia in 74%. An average of 75-100% of the prescribed drug doses were administered during the induction phase of therapy. We conclude that this intensified treatment is toxic but feasible to deliver. The higher overall response rate compared to that in the preceding Intergroup Rhabdomyosarcoma Study (69% vs 53%) suggests improved therapeutic efficacy that warrants further evaluation of both regimens.

Adolescent↗

Hyperdiploidy and chromosomal rearrangements define the anaplastic variant of Wilms' tumor.

Flow cytometric measurement of the DNA content of Wilms' tumor cells revealed a striking correspondence with the histologic subtype and treatment outcome. In the 48 cases studied, a hyperdiploid DNA content ranging from 1.7 to 3.2 times the result for normal diploid cells distinguished all but one of the ten anaplastic tumors. Lower values, from 1.0 to 1.4 times the diploid DNA content, characterized the nonanaplastic specimens. By Kaplan-Meier analysis, the probability of achieving 3 years of relapse-free survival was significantly lower in the group with higher DNA content (0.42 v 0.87, P less than .01). Analysis of banded chromosomes for a subset of 22 patients contributed important information beyond the flow cytometric study. Cases of anaplasia associated with poorer responses to therapy showed numerous complex translocations, whereas all others lacked such changes. By combining flow cytometric techniques and conventional methods of chromosome analysis, it should be possible to identify those patients with Wilms' tumor who are most likely to fail therapy. The biologic implication of these findings is that the development of clinical drug resistance in Wilms' tumor is a result of the genetic instability of the malignant clone.

Antineoplastic Combined Chemotherapy Protocols↗

Assessment of percussion, vibratory-shaking and breathing exercises in chest physiotherapy.

While gravity-assisted positions (postural drainage) and the forced expiratory technique are known to promote sputum clearance, the additional value of percussion, vibratory-shaking and breathing exercises individually in chest physiotherapy is uncertain. These modalities have been evaluated in 8 patients with copious sputum production (mean: 44 g/day), using an inhaled radioaerosol technique. Tracheobronchial clearance was unaffected by the addition of either vibratory-shaking or percussion with and without breathing exercises to postural drainage. There was however a significant (p less than 0.01) increase in the dry weight of sputum produced during each of these treatments. The combination of postural drainage used in conjunction with the forced expiration technique is responsible for the majority of mucus mobilisation and should form the basis of routine chest physiotherapy programmes; the other modes appear to be of lesser value.

Breathing Exercises↗

Relapsed Wilms' tumor. Factors affecting survival and cure.

To identify factors contributing to extended survival among patients with relapsed Wilms' tumor, we assessed 10 clinical and biologic variables thought to have predictive value. With a median follow-up of 6 years, 32 (20%) of 156 patients who achieved complete remission have relapsed. Twenty-four have died with recurrent tumor, and eight are surviving for 2 to 12 years from diagnosis. Only time to relapse, or length of initial complete remission, had a significant influence on survival. Of 11 patients with complete remissions lasting longer than 12 months, six have died--compared with seven of 10 having remissions of 6 to 12 months and 11 of 11 with shorter remissions (p = 0.014). Surgery alone was the curative therapy in three of the eight surviving patients. Until more effective chemotherapy regimens are developed, an aggressive surgical approach may be indicated in selected patients with relapsed Wilms' tumor.

Child, Preschool↗

The response of Ewing's sarcoma to sequential cyclophosphamide and adriamycin induction therapy.

Twenty-four consecutive patients with Ewing's sarcoma were treated in a protocol designed to deliver induction chemotherapy with postinduction surgical-pathologic evaluation of the primary tumor site. This was followed by delayed radiotherapy, the dose and port of which was dependent on the response to induction chemotherapy. All patients received 5 courses of sequential cyclophosphamide and adriamycin during the 3-mo induction period. Nineteen of 23 evaluable patients had no gross residual tumor following this therapy. Of the remaining 4, 2 had complete surgical excision of residual gross disease. Of the 22 patients who were free of gross tumor following induction chemotherapy and surgery, 5 received no radiotherapy, 16 received moderate-dose limited port radiotherapy (3000-3500 R), and 1 received high-dose limited port radiotherapy (5000 R). All 14 patients with localized disease attained remission and are surviving 9-41+ mo (median 21+) with 2 local recurrences occurring after 10 and 33 mo of remission. Of the 10 patients presenting with metastatic disease, 8 attained complete remission with 4 of the 8 remaining disease-free 12-34+ mo from diagnosis. This study indicates that Ewing's sarcoma is very sensitive to moderate-dose 2 drug chemotherapy of low toxicity and that it is possible to delay radiotherapy and any extensive surgical procedure until remission is induced.

Adolescent↗

The percentages of Hb F and of G gamma and A gamma chains in the Hb F synthesized by reticulocytes and BFUe-derived colonies of patients with sickle cell anemia.

The synthesis of Hb F was studied in the BFUe-derived colonies of 20 SS patients after incubation with 35S methionine for 24 hours, 13 days after the start of the experiments. Similar analyses were made for isolated reticulocytes from 28 SS patients; these cells were incubated for 2 hours and occasionally for 24 hours. The G gamma and A gamma percentages were determined in these two Hb F preparations and in the Hb F of circulating red cells using two different HPL chromatographic procedures. The data show an increased production of Hb F in the colonies mainly of patients with low blood Hb F values. A close correlation was present between the % G gamma chain in peripheral red cells and the G gamma percentages observed for the Hb F synthesized in the BFUe-derived colonies and that in reticulocytes. However, the values for the reticulocytes were significantly higher than those for the colonies. These data indicate a considerable variability among SS patients in their ability to produce Hb F in in vitro colonies which may in part be due to differences in the numbers of BFUe types in circulation. The variation in G gamma and A gamma levels in Hb F synthesized in reticulocytes and BFUe-derived colonies could be the result of slight differences in the stability of the corresponding mRNA's.

Adolescent↗

[Effects of ethinyloestradiol sulphonate in soft-gelatin capsules on coagulation parameters of weaning women (author's transl)].

Two groups of 16 puerperae each with and without low doses of ethinyloestradiol sulphonate in soft-gelatin capsules were involved in studies into coagulation parameters as well as into basophilic leucocytes and antithrombin III.--No statistically significant difference was found to exist between the two groups. Both the basophils and antithrombin III were strongly reduced in the two groups.

Blood Coagulation↗