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Biomedical subjects

J Isakov

Publications and source records attributed to J Isakov.

18 recordsLinked to original sources
PubMed2002

The use of surgery and yttrium 90 in the management of extensive and diffuse pigmented villonodular synovitis of large joints.

OBJECTIVE: The surgical treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints alone is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of yttrium 90 (90Y) yielded better results. We report our experience with 10 cases treated with debulking surgery followed by intra-articular injection of 90Y. PATIENTS AND METHODS: Between January 1989 and June 1998, 10 patients (eight males and two females aged 15-49 yr) with extensive diffuse PVNS were treated. In six patients the knee joint, in three patients the ankle joint, and in one patient the hip joint were involved. The 10 patients underwent 15 operations, one patient had three surgical procedures, and three patients underwent two surgeries (the intervals between re-operations for local recurrence were 2-4 yr). All patients had an intra-articular injection of 15-25 mCi (555-925 MBq) 90Y, 6-8 weeks after the last surgery. RESULTS: Mean follow-up time was 6 yr (range 2.5-12 yr). All patients were followed using repeated computerized tomography (CT) scans, magnetic resonance imaging (MRI), plain X-ray films and bone scans semi-annually. In nine patients, neither evidence of disease nor progression of bone or articular destruction were noted. In one patient, stabilization of disease was achieved with no further evidence of bony or articular damage. No complications were noticed after surgery or after the intra-articular 90Y injection. CONCLUSION: A combination of debulking surgery with intra-articular injection of 90Y for extensive diffuse PVNS of major joints is a reliable treatment method, with good results.

Adolescent↗
PubMed2000

Internal hemipelvectomy for bone sarcomas in children and young adults: surgical considerations.

AIMS: Pelvic bone sarcomas in children and young adults are rare, and associated with a poor prognosis and a high rate of local recurrence. Primary goals of treatment include prevention of local recurrence and distant metastases. A secondary goal is maintenance of quality of life by avoiding major amputative surgery. This is why internal hemipelvectomy (a limb-sparing surgery) is advocated whenever possible. The focus of our presentation is surgical issues in the context of resection and reconstruction of the pelvis in the first two decades of life. MATERIALS AND METHODS: Between January 1988 and June 1998, 27 patients were treated and operated on (follow-up time 1.5-12 years). There were 17 males and 10 females. Their age ranged between 2 and 22 years. There were 24 patients with Ewing's sarcoma (ES) and three with other bone sarcomas. In 19 patients the tumour involved the entire or part of the iliac bone (in some cases with extension to the sacrum). In five patients the tumour involved the pubis and/or ischium. In three patients the tumour involved the sacrum with some extension to the posterior iliac bone. All patients received neoadjuvant and adjuvant chemotherapy and radiotherapy with different protocols (related to the origin of referral). RESULTS: Twenty-seven patients underwent internal hemipelvectomy. According to Enneking's classification there were: type I-10; type II-one; type III-six; type IV-five (including one localized sacrectomy); type I+IV-five patients. In 15 patients some kind of reconstruction was needed and in 12 no reconstruction was done. Four wound infections occurred that were managed successfully by surgical debridement, antibiotics and local wound care. In one case removal of the 'implant' was needed. No primary or secondary amputations were performed in the series. The rate of local recurrence was 22%. Functional status at the last follow-up visit or before death, according to the AMSTS functional rating system: excellent-six; good-17; fair-three and poor-one. All patients except the one poor result maintained their walking ability during the follow-up time. CONCLUSIONS: Internal hemipelvectomy is achievable in most cases and justified for better quality of life in children, adolescents and young adults with sarcomas. Further efforts are needed to improve the reconstructive options in the pelvis.

Adolescent↗
PubMed2000

Gastrointestinal autonomic nerve (GAN) tumor of the rectum.

Gastrointestinal autonomic nerve (GAN) tumor is a relatively newly defined member of the gastrointestinal stromal tumor family, which is a rare group of mesenchymal neoplasms originating in the bowel wall throughout the entire gastrointestinal tract. A thorough search of the literature revealed only one brief mention of this tumor arising in the rectum. We present a full description of such a tumor and summarize the clinical characteristics, therapeutic measures used, biological behavior, and outcome of this unique case.

Autonomic Nervous System Diseases↗
PubMed1999

Isolated limb perfusion with high-dose tumor necrosis factor alpha and melphalan for Kaposi sarcoma.

BACKGROUND: Although the classic form of Kaposi sarcoma is considered indolent and benign, at times its evolution is more severe, with an acute onset and debilitating complications necessitating aggressive treatment and even amputation. OBJECTIVE: To evaluate the efficacy of hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan as a limb-sparing modality for extensive regional Kaposi sarcoma. SETTING: University hospital and national referral center. PATIENTS: Five patients, aged 60 to 82 years, with extensive, symptomatic, classic Kaposi sarcoma of the lower limb were operated on. All were candidates for amputation owing to debilitating symptoms. INTERVENTIONS: Patients underwent ILP through the iliac (n = 2), femoral (n = 2), and popliteal (n = 1) vessels. Tumor necrosis factor alpha, 4 mg, and melphalan, 1.5 mg/kg body weight, were perfused for an overall time of 90 minutes. The limb was heated to 40 degrees C. Clinical and pathological responses were recorded for all patients after 6 to 8 weeks. RESULTS: The overall response rate was 100%: 1 of 5 patients had complete response and 4 of 5 had partial response. Two patients had progression of disease 2 months after ILP but one of them was asymptomatic and did not require any further treatment. The second patient underwent amputation. Thus, limb preservation was achieved in 80% (4 of 5 patients). Median follow-up was 24 months. There were no deaths associated with treatment or major system complications. Local complications were all reversible. CONCLUSION: These findings suggest that hyperthermic ILP with tumor necrosis factor alpha and melphalan can be considered an effective palliative and limb-sparing treatment modality for extensive Kaposi sarcoma.

Aged↗
PubMed1999

Multifocal soft tissue sarcoma: limb salvage following hyperthermic isolated limb perfusion with high-dose tumor necrosis factor and melphalan.

BACKGROUND AND OBJECTIVES: The prognosis for recurrent multifocal limb soft tissue sarcoma (STS) is dismal due to systemic spread. However, many of these patients undergo amputation due to ineffective local control. The purpose of the present study was to determine whether isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and melphalan permits limb salvage and palliation for such patients. METHODS: Of 53 STS patients treated with hyperthermic ILP with TNF (3-4 mg) and melphalan (1-1.5 mg/kg), 13 (25%) had multifocal STS and were candidates for amputation. RESULTS: The overall response rate was 92% (12/13) with 38% complete response and 54% partial response. Two patients died during the early postoperative period. Limb salvage was achieved in 85% of patients. One patient (8%) had only stable disease and underwent amputation. Local recurrence occurred in 38% but did not result in amputation. CONCLUSIONS: Although the number of patients in this study is too small to allow definitive conclusions, it seems that ILP/TNF offer limb salvage and palliation for recurrent multifocal STS patients.

Adult↗
PubMed1999

[Elastofibroma, a rare cause of snapping scapula syndrome].

Scapular pain is a common complaint in daily orthopedic practice. A different type of scapular discomfort, the snapping scapula syndrome that occurs when smooth gliding motion of the scapula upon the chest wall is interfered with is much less common. We studied the syndrome of periscapular pain and discomfort, and present a rare etiology: elastofibroma dorsi, a unique, benign, soft tissue-tumor with unique characteristics. Elastofibroma appears deep to the lower scapular pole, is often bilateral, and consists of a mixture of collagen, elastic fibers and fibroblasts. We present 6 cases, in 3 men and 3 women aged 51-65.

Aged↗
PubMed1997

Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) is a syndrome of profoundly impaired cellular and humoral immunity. In humans, SCID is most commonly caused by mutations in the X-linked gene IL2RG, which encodes the common gamma chain, gamma c, of the leukocyte receptors for interleukin-2 and multiple other cytokines. To investigate the frequency and variety of IL2RG mutations that cause SCID, we analyzed DNA, RNA, and B-cell lines from a total of 103 unrelated SCID-affected males and their relatives using a combination of molecular and immunologic techniques. Sixty-two different mutations spanning all eight IL2RG exons were found in 87 cases, making possible correlations between mutation type and functional consequences. Although skewed maternal X chromosome inactivation, single-strand conformation polymorphism, mRNA expression, and cell surface staining with anti-gamma c antibodies were all helpful in establishing IL2RG defects as the cause of SCID, only dideoxy fingerprinting and DNA sequence determination each detected 100% of the IL2RG mutations in our series. Abnormal gamma c chains may be expressed in the lymphocytes of as many as two thirds of patients with X-linked SCID. Specific mutation diagnosis thus remains technically challenging, but it is important for genetic counseling and perhaps for helping to select appropriate subjects for retroviral gene therapy trials, This is a US government work. There are no restrictions on its use.

DNA Fingerprinting↗
PubMed1997

Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency.

Interleukin-4 (IL-4) is an important cytokine for B and T lymphocyte function and mediates its effects via a receptor that contains gammac. B cells derived from patients with X-linked severe combined immunodeficiency (X-SCID) are deficient in gammac and provide a useful model in which to dissect the role of this subunit in IL-4-mediated signaling. We found that although IL-4 stimulation of X-SCID B cells did not result in Janus tyrosine kinase-3 (JAK3) phosphorylation, other IL-4 substrates including JAK1 and IRS-1 were phosphorylated. Additionally, we detected signal transducers and activators of transcription 6 (STAT6) tyrosine phosphorylation and DNA binding activity in X-SCID B cells with a wide range of gammac mutations. However, reconstitution of these X-SCID B cells with gammac enhanced IL-4-mediated responses including STAT6 phosphorylation and DNA binding activity and resulted in increased CD23 expression. Thus, gammac is not necessary to trigger IL-4-mediated responses in B cells, but its presence is important for optimal IL-4-signaling. These results suggest that two distinct IL-4 signaling pathways exist.

B-Lymphocytes↗
PubMed1987

Evidence against ras activation in human ovarian carcinomas.

Activation of ras genes in human ovarian carcinomas and ovarian carcinoma cell lines was tested by transfection of NIH 3T3 cells with high molecular weight DNA extracted from fresh tumors or from cell lines. Of 18 ovarian tumors and tumor cell lines that were exhaustively tested, only one yielded DNA active in focus-induction in this assay. Southern blot analysis of DNA in serially transformed NIH 3T3 foci revealed restriction fragments that hybridized with a probe specific for the human N-ras oncogene and with human repetitive (Alu) sequences. Individually transformed foci contained N-ras hybridizing fragments of different sizes. Northern blots of RNA extracted from different transformants revealed the expression of different transcripts hybridizing with the N-ras probe. The transformants also expressed a 700 base RNA that hybridized with a human B-lym probe. The low prevalence of ras activation in ovarian tumors as measured by transforming capability suggests that ras activation does not play an important role in the development of most human ovarian tumors.

Animals↗
PubMedDate not supplied

Vascular invasion in high grade sarcoma of the extremity is associated with short overall survival.

Intravascular sarcoma thrombi were histologically evident in 2% of 470 patients with soft tissue or bone sarcoma treated during the last 3 years. Vascular invasion by sarcoma in our series was associated with an aggressive disease and short-term overall survival. In all the cases there was a large or locally advanced primary high grade sarcoma, and in all but one case, where preoperative chemotherapy was administered, the response was far from satisfactory. The post-operative course in 70% of the patients was characterized by early systemic spread, and a median overall survival of 9.5 months. The gloomy prognosis of our patients does not necessarily stem only from the presence of vascular invasion, but may also be related to other factors as histologic grade and tumor size. However, as compared to similar cases in our patient population, which did not show vascular invasion, the course here was more violent and short.

Adolescent↗
PubMedDate not supplied

Establishment of a reproducible transplantable sarcoma in a rat.

BACKGROUND: Animal models are valuable tools in cancer research. Mice are the most commonly used animals but for surgical procedures, such as bowel anastomosis and organ perfusions, larger animals (e.g. rats) are preferable. Unfortunately, rat cell-lines are scarce and rat strains are ample, so that adaptation of a cell-line to the specific strain used in individual laboratories is difficult. In this study we present a simple and reproducible model of rat carcinogenesis. MATERIAL AND METHODS: Carcinogenesis was induced by 7,12 dimethylbenzantracene dissolved in wax and paraffin at 60 degrees C. For matrix production, we used HTR polymers. The resulting particles were implanted subcutaneously (SC). RESULTS: Tumors occurred in all rats. The resulting tumors, designated GF, were locally invasive with low metastatic potential. In vitro doubling time was 7.5 hours. Injection of 5 x 10(6) cells or transplantation of a tumor fragment resulted in a visible tumor within six weeks. The histologic picture and immunohistochemical pattern were consistent with pleomorphic soft tissue sarcoma of myogenic origin. CONCLUSIONS: This method will enable an individual laboratory to create and maintain a sarcoma cell line that will effectively grow in its own rats.

Actins↗