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Biomedical subjects

G Rosen

Publications and source records attributed to G Rosen.

At least 55 records · Page 3Linked to original sources

Antibiotic prophylaxis and infection resistance of massive tumor endoprostheses during chemotherapy.

Fifty-five consecutively treated patients with malignant bone tumors had preoperative and postoperative chemotherapy by one oncologist. These same patients had massive bone resection and cemented endoprosthetic bone replacement by one orthopaedic oncologist. Despite 143 instances of documented fever and/or neutropenia in 45 of these 55 patients, no known deep periprosthetic infections developed in any patient during follow-up (mean, 29.4 months; median, 25 months; range, 5 months to 62 months). Broad spectrum antibiotics had been administered in at least 118 instances to these patients (intravenously in hospital, 9 times to 7 patients; intravenously at home, 38 times to 18 patients; and orally at home, 71 times to 26 patients). This study confirms the low infection rate of these massive endoprostheses, despite neutropenic and/or febrile episodes if the patient is given prophylactic broad spectrum antibiotics during the episodes. We support the continued use of massive endoprostheses for bone reconstruction in patients requiring chemotherapy.

Adolescent↗

Influence of methotrexate dose intensity on outcome of patients with high grade osteogenic osteosarcoma. Analysis of the literature.

BACKGROUND: The authors surveyed the published clinical trial literature on the subject of localized high grade osteosarcoma in order to develop new hypotheses dealing with drug-dose combinations in the treatment of this disease. METHODS: A computerized literature search was conducted to identify all available published reports of the clinical trials using high dose methotrexate (MTX) in multidrug protocols treating osteosarcoma. Thirty studies, including discussion of high dose MTX (> 7.5 g/m2 per course) and precise quantification of 5-year disease free survival (DFS), fulfilled the inclusion criteria of this dose-intensity analysis. The total number of patients treated in eligible studies was 1909. Correlation among the planned total doses, the dose intensities of the drugs, and the 5-year DFS were tested by regression analysis. RESULTS: No correlation of any other drug dose or dose intensity with DFS appeared as important as the MTX finding. In multivariate analysis, the dose intensity of MTX was found to be the one most correlated with DFS. This correlation appeared to hold for adjuvant and neoadjuvant trials. CONCLUSIONS: The dose intensity of MTX seems to be a major factor in predicting the outcome of patients with localized high grade osteosarcoma.

Adult↗

A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy.

Thrombocytopenia is a complication of cancer treatment that can limit dose intensity. Interleukin-11 (IL-11) is a growth factor that increases platelet production. We conducted a multicenter, randomized, placebo-controlled trial of recombinant human IL-11 (rhIL-11) in 93 patients with cancer who had already been transfused platelets for severe thrombocytopenia resulting from chemotherapy. The patients had received platelet transfusions for nadir platelet counts of < or = 20,000/microL during the chemotherapy cycle immediately preceding study entry. Chemotherapy was continued during the study without dose reduction. Patients were randomized to receive placebo or rhIL-11 at 50 or 25 micrograms/kg subcutaneously once daily for 14 to 21 days beginning 1 day after chemotherapy. Eight of 27 (30%) evaluable patients treated with rhIL-11 at a dose of 50 micrograms/kg did not require platelet transfusions versus 1 of 27 (4%) patients who received placebo (P < .05). Five of 23 (18%) patients treated with rhIL-11 at 25 micrograms/kg avoided platelet transfusions (P = .23). Side effects were fatigue and cardiovascular symptoms, including a low incidence of atrial arrhythmias and syncope. There were no differences among treatment groups in the incidence of neutropenic fever, days of hospitalization, or number of red blood cell transfusions. This study shows that rhIL-11 treatment of a dose of 50 micrograms/kg significantly increases the likelihood that patients who have already been transfused platelets for severe chemotherapy-induced thrombocytopenia will not require platelet transfusions during a subsequent chemotherapy cycle.

Adolescent↗

A comparison of partial inferior turbinectomy and cryosurgery for hypertrophic inferior turbinates.

A variety of surgical procedures are performed for treatment of hypertrophic inferior turbinates, but there is no completely effective therapy. We evaluated subjectively and objectively 52 patients who underwent one of two procedures: partial inferior turbinectomy (PIT) or cryosurgery of the inferior turbinates (CS). The results of PIT showed good functional results in 77 per cent of cases for long-term effectiveness. The results of CS showed that effectiveness was reduced from a 62 per cent success rate after one year to 35 per cent later, but CS was a simple procedure which was performed on an outpatient basis with no post-operative morbidity.

Adolescent↗

Hemifacial spasm associated with external carotid artery compression of the facial nerve.

We report a unique case of hemifacial spasm due to compression of the facial nerve by the main trunk of the external carotid artery within the parotid space. Decompression of the facial nerve as well as partial section of the proximal trunk of the nerve, caused the hemifacial spasm to disappear. Our case gives support to the theory that hemifacial spasm can be caused by pressure on the facial nerve along all its course and not only in its intra-cranial portion.

Carotid Artery, External↗

Surgical indications for Ewing's sarcoma of the pelvis.

BACKGROUND: Despite advances in adjuvant therapy, Ewing's sarcoma of the pelvis remains an anatomic site with a poor prognosis. This study evaluate the role of surgery in the management of patients with pelvic Ewing's sarcoma who also received conventional radiation therapy and chemotherapy. METHODS: From May 1978 to February 1994, 19 patients with Stage IIB Ewing's sarcoma of the pelvis were treated at the UCLA Medical Center (Los Angeles, CA). There were eight lesions of the ilium, two of the sacrum, and nine involving two adjoining regions of pelvis. All patients received conventional medical management. The 19 patients were divided into two groups according to treatment modality. A group of 12 patients (Group A) had surgical resection, and their results were compared with those of another group of 7 patients (Group B) who did not have surgery. RESULTS: The 5-year cumulative survival (Kaplan-Meier method) was 39% for all patients, 51% for Group A, and 18% for Group B. The 3-year cumulative survival was 59% for all patients, 72% for Group A, and 36% for Group B. Although the survival rate of Group A seemed better than that of Group B, the difference was not statistically significant (P = 0.093, log rank method). This study also suggested that, regardless of treatment modality, the outcome of patients with lesions involving two adjoining pelvic bones was poorer than that of those with a single lesion. In Group A, the 3-year cumulative survival rate for patients with single bone lesions (n = 8) was 86% and for patients with lesions involving two adjoining pelvic bones (n = 4) was 50% (P = 0.045, log rank method). Furthermore, the statistical analysis of the combined data of the single pelvic bone lesions in UCLA and that of Mayo Clinic series (n = 16 for surgery group and n = 15 for nonsurgery group) confirmed the better results for the surgical patients, which was consistent with the results from the Mayo Clinic with an even greater significance (P < 0.002). CONCLUSION: This study demonstrates that surgery plus chemotherapy and radiation therapy is helpful for treating patients with pelvic Ewing's sarcoma so long as the tumor is limited to a single pelvic bone.

Adolescent↗

High grade soft tissue sarcoma of the flexor fossae. Size rather than compartmental status determine prognosis.

BACKGROUND: High grade soft tissue sarcoma arising in the popliteal space, axilla, and antecubital fossae (flexor fossae tumors) have by convention been classified as extracompartmental tumors by the accepted staging and grading criteria of the Musculoskeletal Tumor Society (MSTS). Advances in neoadjuvant chemotherapy and radiation therapy have made surgical resection more feasible. The hypothesis to be tested is that compartmental status may not be of prognostic significance if the tumor is adjusted for size, histologic grade, and distant metastasis after undergoing adjuvant chemotherapy and radiation. METHODS: From June 1976 to December 1992, 22 patients with high grade soft tissue sarcomas of the flexor fossae (Group A) were treated at UCLA Medical Center. The histologic subtypes were liposarcoma (five), synovial cell sarcoma (eight), malignant fibrous histiocytoma (four), leiomyosarcoma (two), angiosarcoma (two), and rhabdomyosarcoma (one). The popliteal fossa was the location in 11, the axilla in 10, and the antecubital fossa in 1. Wide resection was attempted in all patients after preoperative chemotherapy and radiation therapy. Amputation was performed in 5 patients because of repeated or extensive recurrent tumor. A group of 77 patients (Group B) with high grade soft tissue sarcoma located within an extremity compartment were chosen to test the hypothesis that survival of patients with tumors in the flexor fossae is equal to that of patients with intracompartmental tumors of similar size and grade if both are given adjuvant therapy. This group was chosen so that histologic subtype, size, sex, and location would be similar in the two groups. The authors selected thigh and calf tumors for comparison with popliteal fossa tumors and periscapular, deltoid, and arm tumors for comparison with axilla and antecubital fossae tumors. All of these patients had similar treatment and follow-up protocols. The median follow-up of survivors in Group A was 104 months and for patients in Group B was 79 months. RESULTS: The 5-year cumulative survival rate (Kaplan-Meier method) of patients in Group A was 76%, and 67% for those in Group B. The difference was not significant. Three patients in Group A (14%) and 17 (22%) in Group B had local tumor recurrence. Eight patients in Group A (36%) and 27 (35%) in Group B had lung metastases. Age, sex, histologic subtype, and surgical margins did not affect survival outcomes, lung metastasis, and local recurrence. However, patients with larger tumors (maximum dimension > or = 8 cm or cross-sectional area > or = 40 cm2) had significantly poorer survival, more metastases, and local recurrences. CONCLUSION: Flexor fossae sarcomas do not have a poorer prognosis than extremity intracompartmental tumors when adjusted for size, distant metastasis, and histologic grade when they are treated with adjuvant radiation therapy, chemotherapy, and surgery.

Adolescent↗

Comparison of the proteins of middle ear effusion with human mast cell proteins.

In order to clarify the role of mast cells in the aetiology of secretory otitis media (SOM), we compared the protein components of middle ear effusion (MEE) with human mast cells using acrylamide gradient gel electrophoresis and electrofocusing methods. This first direct comparison between the proteins of MEE and human mast cells has been made possible by a method developed in our laboratory for cultivation of human mast cells in tissue culture. On electrophoresis, we found that out of 12 bands of MEE proteins that were different from the serum, seven (58 per cent) had a similar electrophoretic migration rate (Rx) to mast cells. On electrofocusing, three of the four bands of MEE had a similar Rx to the mast cells. We have shown that proteins of mast cells and MEE had similar Rxs. Therefore, our study supports previous studies which suggests that mast cells play an important role in the aetiology of SOM.

Basophils↗

Proteases of Treponema denticola outer sheath and extracellular vesicles.

Electron microscopical observations of the oral periodontopathogen Treponema denticola show the presence of extracellular vesicles bound to the bacterial surface or free in the surrounding medium. Extracellular vesicles from T. denticola ATCC 35404, 50 to 100 nm in diameter, were isolated and further characterized. Protein and proteolytic patterns of the vesicles were found to be very similar to those of isolated T. denticola outer sheaths. They were enriched with the major outer sheath polypeptides (molecular sizes, 113 to 234 kDa) and with outer sheath proteases of 91, 153, 173, and 228 kDa. These findings indicate that treponemal outer sheath vesicles contain the necessary adhesins and proteolytic arsenal for adherence to and damage of eucaryotic cells and mammalian matrix proteins. The major outer sheath- and vesicle-associated protease of T. denticola ATCC 35404 was purified and characterized. The purified enzyme had a molecular size of 91 kDa, and it dissociated into three polypeptides of 72, 38, and 35 kDa upon heating in the presence of sodium dodecyl sulfate with or without a reducing agent. The activity of the enzyme could be inhibited by diisopropylfluorophosphate, phenylmethylsulfonyl fluoride, and phenylboronic acid. The value of the second-order rate constant of the protease inactivation by phenylmethylsulfonyl fluoride was 0.48 x 10(4) M(-1) min-1. Inhibition of the enzyme by phenylboronic acid was rapid (< 1 min) and pH dependent. These data strongly suggest that this major surface proteolytic activity belongs to a family of serine proteases.

Amino Acid Sequence↗

Preoperative therapy for soft tissue sarcoma.

Soft tissue sarcomas appear to be an ideal tumor type for delivering preoperative therapy. The rationale for preoperative therapy is that it is delivered to undisturbed tissue planes with well-oxygenated tissue. This is of great benefit for radiation therapy, because with new computed tomography scan treatment planning it is possible to completely delineate the tumor without surgical clips or postoperative hematoma (or both) obscuring the tumor margin.

Antineoplastic Combined Chemotherapy Protocols↗

Synovial sarcoma. Uniform response of metastases to high dose ifosfamide.

BACKGROUND: This report describes the unusually high response rate of metastatic synovial sarcoma to high dose ifosfamide (14-18 g/m2) when that drug was used to treat 13 consecutive patients with recurrent metastatic synovial sarcoma before surgery (or thoracotomies) to provide optimal salvage therapy for these patients. PATIENTS AND METHODS: Thirteen patients with recurrent or pulmonary metastatic synovial sarcoma seen at the Cedars-Sinai Comprehensive Cancer Center (Los Angeles, CA) from April, 1989 through January, 1993 were treated with high dose ifosfamide (14-18 g/m2). Ifosfamide was infused at the dose of 2 g/m2 over a 4-hour bolus infusion, followed by 2-g/m2 24-hour continuous infusions of ifosfamide, for a total of 14 or 18 g/m2 (6-8 days). Mesna (Mesnex, Bristol-Myers Oncology, Princeton, NJ) was infused with the ifosfamide at equimolar doses. Supplemental sodium bicarbonate (180 mEq) was given daily to prevent severe acidosis. Nine of the thirteen patients were treated with prior chemotherapy for their primary tumors. Prior chemotherapy consisted of doxorubicin (Adriamycin, Adria Labs, Dublin, OH) in all patients and doxorubicin combined with cisplatin in eight of them. RESULTS: All 13 patients had objective responses to high dose ifosfamide chemotherapy. There were nine partial responses and four complete responses. Five of the patients died of disease at 20-40 months (median, 27 months) from initial therapy. Eight patients have survived from 2 to 43 months (median, 20 months) from initial therapy, and three of these patients are disease free. Those patients surviving disease free had successful surgical removal of their residual metastatic disease after chemotherapy. CONCLUSION: Metastatic synovial sarcoma appears to be particularly sensitive to high dose ifosfamide chemotherapy. This experience suggests that there is a role for high dose ifosfamide chemotherapy in preoperative and postoperative adjuvant chemotherapy for primary synovial sarcoma, which is usually always a high grade malignant lesion with a poor prognosis after surgery alone.

Adolescent↗

Characterization of fibrinolytic activities of Treponema denticola.

Several fibrinolytic activities of Treponema denticola, an oral spirochete associated with gingivitis and periodontal disease, were identified and characterized following phase partitioning with the nonionic detergent Triton X-114. The apparent molecular masses of the proteases ranged from 91 to 228 kDa when analyzed in sodium dodecyl sulfate-polyacrylamide gels containing fibrinogen as the protease substrate. A qualitative analysis of zymograms showed that the proteases were highly enriched in the detergent phase, although the 91-, 173-, and 228-kDa proteases were also found in the aqueous phase. Zymograms of crude outer sheaths prepared by repeated freezing-thawing revealed that the proteases may be associated with this subcellular compartment. The proteases displayed substrate specificity towards fibrinogen, were susceptible to sulfhydryl group reagents, and had a pH optimum between 7 and 8. The similarities in their sensitivity to inhibitors, temperature stability, pH optimum, and laddered protein profiles suggest that these hydrolytic enzymes may be part of a family of oligomeric proteases that may play an important role in the invasiveness of and tissue damage caused by the spirochete.

Endopeptidases↗

Treatment of a second bone osteosarcoma. 3 cases and an unusual MRI finding.

We report 3 patients with a second bone involved with osteosarcoma. They were found among approximately 200 cases of limb-sparing surgery with chemotherapy. 1 patient had the unusual finding of a positive MRI scan with all other routine tests negative. The first and then the second bone tumor were successfully removed with limb-sparing surgery. All 3 patients are doing well, with no evidence of disease.

Adolescent↗

Thoracotomy in the management of metastatic soft-tissue sarcomas in adults.

The multidisciplinary management of metastatic soft-tissue sarcomas in adults is capable of salvaging approximately half of the afflicted patients. This management includes preoperative chemotherapy for three months, thoracic surgery, continued chemotherapy, and the use of intrapleural mitoxantrone for once-present malignant pleural effusions or suspected pleural seeding of tumor. Thus, there is a definite role for the inclusion of thoracic surgery in the management of patients with soft-tissue sarcomas in whom pulmonary metastases develop.

Adolescent↗

The role of thoracic surgery in the management of metastatic osteogenic sarcoma.

Fifty percent of patients with osteogenic sarcoma who develop pulmonary metastases are salvageable with continued effective chemotherapy and thoracotomies, as long as good local control is achieved in the primary tumor. In patients presenting with simultaneous primary tumor and pulmonary metastatic disease, the cure rate is potentially as high as it is in those patients who present with primary tumor alone. However, in the latter patients, curative surgery must be done to obtain permanent local control for the primary tumor, and thoracotomy must be performed to remove residual disease to ensure against recurrent disease.

Adolescent↗