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Biomedical subjects

R P Moser

Publications and source records attributed to R P Moser.

At least 19 recordsLinked to original sources

Cytokine responses to intraventricular injection of interleukin 2 into patients with leptomeningeal carcinomatosis: rapid induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and soluble interleukin 2 receptor (Mr 55,000 protein).

Interleukin 2 (IL-2) is a potent immunostimulant that causes the release of secondary cytokines and the production of lymphokine-activated killer cells. We investigated the cellular and cytokine responses to injection of recombinant human IL-2 into the human cerebrospinal fluid of 11 patients with metastatic tumors involving the spinal or cerebral leptomeninges. After initial intraventricular IL-2 administration (1.25 x 10(5) to 2 x 10(6) Cetus units/injection), cerebrospinal fluid samples were collected at intervals from 0 to 24 h. Enzyme-linked immunosorbent assay results indicated that IL-2 levels gradually decreased during the first 24 h, with an average t1/2 between 4 and 8 h. Induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and interleukin 2 receptor (p55) was also assessed by enzyme-linked immunosorbent assay. Tumor necrosis factor alpha and interleukin 6 levels peaked at 2 to 4 h and 4 to 6 h, with concentrations between 71 to 1,714 pg/ml and 942 to 10,500 pg/ml, respectively. Interleukin 1 beta, gamma-interferon, and soluble IL-2 receptor peaked later, during 6 to 12 h; the levels achieved were 234 pg/ml, 25 NIH units/ml, and 207 units/ml, respectively. All cytokine concentrations returned to near baseline between 12 and 24 h; however, the soluble IL-2 receptor levels remained elevated. Additional observations included a rapid influx of neutrophilic leukocytes, followed by a prolonged presence of lymphocytes. These data indicate a broad and complex potential of the immune response in the central nervous system, as well as further define the cytokine cascade in response to IL-2 alone.

Adenocarcinoma

Oligoclonal expansion of V beta 8+ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma.

Oligoclonality was investigated in interleukin-2 (IL-2)-activated T cells (tumor-infiltrating lymphocytes, TILs) residing in metastatic melanomas using seven different monoclonal antibodies (mAbs) specific for T-cell receptor (TCR) V alpha or V beta regions and flow cytometry. IL-2-activated TILs from 25 of 42 metastatic melanomas (60%) displayed oligoclonal expansion, whereas IL-2-activated peripheral bllod mononuclear cells (PBMCs) from only 2 of 20 patients (10%) did so during 2-5 weeks in culture. Skin-derived lymphocytes from 20 patients were cultured; only four samples proliferated and none showed oligoclonal expansion. Preferential oligoclonal expansion of TILs was observed in V beta 8+ cells (10/42, P less than 0.05), V beta 6.7+ cells (7/42, P less than 0.05), and V alpha 2+ cells (7/42, not significant). Oligoclonal expansion of V beta 8+ cells was primarily found in T cells from subcutaneous metastases (8/20 cases, P less than 0.05), whereas that of V beta 6.7+ cells and V alpha 2+ cells was also found in T cells from lymph node or organ metastases. These mAbs to TCR V regions stimulated effector TILs to produce interferon-gamma, but not IL-2 or IL-4. Subcutaneous tumor-specific (V beta 8+ cells) and non-specific (V beta 6.7+ cells and V alpha 2+ cells) oligoclonalities were observed in IL-2-activated melanoma TILs, suggesting different immune responses among different sites of metastases.

Antibodies, Monoclonal

Case report 716. Soft-tissue metastasis in synovial sarcoma.

We describe the case of a 21-year-old woman with a synovial sarcoma of the thigh, who exhibited a soft-tissue metastasis to the shoulder approximately 3 months after her initial presentation. Due to its increasing availability and the recognized importance of MRI in the preoperative evaluation of patients with soft-tissue masses, it is important to be aware of even the uncommon manifestations of frequently encountered soft-tissue sarcomas.

Adult

Case report 722. Osteosarcomatosis in a skeletally immature girl.

We report a case of a clinically and radiographically dominant osteosarcoma of the proximal end of the tibia, in which the second skeletal focus of osteosarcoma was apparent on MRI, after having escaped detection on routine radiographs and scintigraphy. Detection of the second lesion significantly altered the subsequent treatment and prognosis. The improved sensitivity of MRI may increase the accuracy of the diagnosis of osteosarcomatosis. Although further study is needed, MRI study of long bones, especially T1-weighted images in the coronal plane, may be considered as a screening procedure to exclude occult skeletal involvement in patients with osteosarcoma and negative standard metastatic evaluation.

Adolescent

Case report 730. Malignant large cell lymphoma of tibial epiphysis.

We present a case of primary lymphoma of bone arising in the proximal tibial epiphysis of a 16-year-old boy. To the best of our knowledge, primary lymphoma of bone has not been described previously as a mimicker of chondroblastoma. This case report is intended to increase awareness among clinicians and radiologists that primary lymphoma of bone can present with a long clinical prodrome and initially benign radiographic appearance. Early recognition of this unusual presentation will (hopefully) increase the likelihood of cure. However, it is recognized that in children, primary lymphoma of bone is a rare diagnosis and associated with a poor prognosis unless aggressive treatment is utilized [8].

Adolescent

Differentiation of residual or recurrent tumors from post-treatment changes with F-18 FDG PET.

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) was used to differentiate recurrent or residual malignant disease from the effects of cancer treatment. Transaxial images were obtained after injection of 5-10 mCi (185-370 MBq) of F-18 FDG in 68 patients (including 33 with brain tumors) whose posttreatment computed tomographic (CT) or magnetic resonance (MR) imaging findings had been suggestive of malignant disease. PET findings were correlated with surgical results in 18 patients and with the outcomes of CT, MR imaging, clinical, and laboratory 9-month follow-up studies in 50 patients. There was good agreement between F-18 FDG uptake and presence or absence of malignant disease except in four cases of brain tumors in which histologic findings could not be correlated with biologic behavior. The putative sensitivity and specificity in the 33 cases of brain tumors were 80% and 94%, respectively. The authors conclude that PET with F-18 FDG is useful in detection of previously treated metabolically active tumors but is limited in diagnosis of recurrent microscopic or metabolically inactive tumors.

Abdominal Neoplasms

Giant cell tumor in skeletally immature patients.

The radiographs and clinical and surgical histories of 50 skeletally immature patients with histologically verified giant cell tumor (GCT) of the long and short tubular bones were retrospectively studied to determine the prevalence, location within bone (eg, epiphysis, metaphysis), skeletal distribution, radiographic appearance, and pathogenesis of GCTs. Skeletal immaturity was determined radiographically by the presence of open epiphyses. Patients were selected from a group of 876 patients who were seen in consultation with documented GCT of the tubular bones. Approximately 5.7% of all GCTs occurred in the skeletally immature (this rate must be viewed with caution due to the selection bias inherent in any referral population). The lesions almost invariably involved the metaphysis. The tibia was the most commonly affected site, representing approximately 26% of cases. All were geographic lytic lesions, with margins ranging from sclerotic to ill defined. An expanded (widened), remodeled bone contour was frequently encountered. Approximately 56% of lesions were solid or solid with cystic change; the remaining 44% were predominantly cystic.

Adolescent

Idiopathic dilatation of the thoracic venous system.

Isolated venous aneurysm is a rarely reported cause of a mediastinal mass. The authors describe a patient who demonstrated aneurysmal dilatation of the superior vena cava, the left innominate vein, the azygos and the hemiazygos veins and the left inferior pulmonary vein after blunt chest trauma. This case emphasizes the value of computed tomography in the diagnosis of this complex, presumably congenital entity.

Adult

Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease.

Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment.

Adult

Magnetic resonance appearance of peripheral nerve sheath tumors.

Magnetic resonance imaging (MRI) was used to evaluate 22 histologically proven peripheral nerve sheath tumors, approximately two-thirds of which arose in the lower extremity. The histologic distribution was as follows: 12 schwannomas, 7 neurofibromas, and 3 malignant peripheral nerve sheath tumors (2 of which occurred in patients with neurofibromatosis). Most lesions demonstrated an intermediate to moderately bright signal on T1-weighted images and were minimally inhomogeneous. All lesions were moderately bright on proton-density-weighted images and bright on T2-weighted images, again with variable inhomogeneity. The extent of the tumor was best assessed on proton-density- and T2-weighted images. Smooth margins were noted in 19 lesions. Of the 3 remaining lesions, 2 were malignant (but had been subjected to biopsy prior to MRI), and the other lesion was a plexiform neurofibroma. MRI accurately determined the relationship between the lesion and the adjacent neurovascular structures and muscles, thereby assisting surgical management. On MRI, 5 lesions demonstrated coexistent subtle muscle atrophy along the longitudinal axis of surrounding or distally innervated musculature. This latter finding, together with the presence of a tumor in the vicinity of a large nerve trunk, suggests a peripheral nerve sheath neoplasm.

Adult

Case report 649: Arteriovenous malformation (arteriovenous hemangioma) of the distal thigh with bone involvement.

The case discussed is that of a 31-year-old woman with long-standing hypertrophy and vascular symptoms of the right lower extremity. The etiology of these abnormalities remained undiagnosed, although the patient was treated symptomatically. Following presentation, both MR images and contrast-enhanced CT scans were adequate for diagnosis of the underlying arteriovenous malformation. This was confirmed by arteriography, and the patient received palliative treatment by sequential intra-arterial embolization.

Adult

Characterization of interleukin-2-initiated versus OKT3-initiated human tumor-infiltrating lymphocytes from glioblastoma multiforme: growth characteristics, cytolytic activity, and cell phenotype.

Outgrowth of tumor-infiltrating lymphocytes (TIL) from the human primary brain tumor glioblastoma multiforme was achieved by OKT3 initiation (10 ng/ml), followed by sustained expansion by interleukin-2 (IL-2; 200 U/ml). Tumor-infiltrating lymphocyte (TIL) initiation by this process was performed in parallel with the standard "IL-2-only" method. Of ten tumors, seven yielded TIL in response to OKT3/IL-2, whereas only three of these seven grew after initiation with IL-2 alone. On the basis of cell doubling times, at least 60 doublings, resulting in (hypothetically) up to 10(23) TIL from as few as 2 x 10(5) cells in tumor suspensions, could be achieved using OKT3/IL-2. OKT3-initiated TIL proliferated in culture for as long as 288 days, although senescence of some cultures occurred at as early as 73 days. Significant heterogeneity of lymphocytes infiltrating the fresh tumors and heterogeneity of resultant TIL phenotype and function were apparent, yet several common trends were noted. In all cases after OKT3 initiation, significant net growth was not apparent until approximately 14 days. In contrast, in the three samples that grew in response to IL-2 alone, log-phase growth was always observed earlier. During the early phase of the cultures, all TIL expressed some killing activity toward a broad spectrum of tumors, including the autologous tumor. No consistent preference of TIL for lysis of autologous tumor was observed. Glioblastoma multiforme TIL cultures contained a mixture of CD8+ and CD4+ cells, with few CD16+ or NKH-1+. Of the six TIL examined in detail for population phenotype in relationship to time in culture, four eventually became exclusively CD4+. Further analysis of these CD4+ TIL indicated that all were of the helper-inducer class, 4B4+ and 2H4-. Concurrent with the decline in CD8+ cells, a decline in the cytolytic activity of these TIL cultures occurred. Furthermore, in two TIL that remained CD8+, a decline in the cytolytic activity also occurred. Therefore, loss of killing activity was not merely a reflection of the major cell phenotype changes. These results indicate that the OKT3/IL-2 process provides an alternative to IL-2 alone for TIL initiation and growth, as well as providing a novel system for further analysis of tumor-derived lymphocyte and accessory cell functional potential.

Adult

Case report 653: Arthritis of the wrist due to Mycobacterium avium-intracellulare.

We present a case of arthritis of the wrist in an elderly man due to Mycobacterium avium-intracellulare. Prior steroid injections and a surgical procedure on the affected wrist were predisposing risk factors for subsequent mycobacterial involvement of the skeleton. Radiographs demonstrated findings characteristic of tuberculous arthritis: particularly, osteopenia with marginal erosions and diffuse lytic lesions involving the carpals, proximal metacarpals, and distal ends of the radius and ulna. MR scans showed soft-tissue involvement and extensive marrow replacement consistent with infection. It is to be reemphasized that the clinical and radiological findings in this case are very often indistinguishable from TB. The diagnosis depends on the results of tissue culture. Since radiologists are likely to be involved increasingly in interpreting images of immunocompromised patients afflicted with a variety of both typical and atypical infections, it is important occasionally to report rare infections such as that described herein.

Aged

Outcome and patterns of failure following limited-volume irradiation for malignant astrocytomas.

Between January 1982 and June 1986, 60 consecutive patients with high-grade astrocytomas [39 glioblastoma multiforme (GBM), 21 anaplastic astrocytoma (AA)] were treated with radiation therapy after biopsy (13 patients) or resection (47 patients). Fifty-three patients were treated with limited-volume irradiation, and seven patients received whole-brain irradiation. The mean tumor dose was 65.4 Gy. In 35 patients, chemotherapy was given as part of their initial treatment. The 1- and 2-year survivals for GBM patients were 40 and 14%, respectively. Survival figures for AA patients were 76 and 52% at 1 and 2 years, respectively. The progression-free rate at 1 year was 13% in GBM and 29% in AA patients. Thirty-four of 48 patients who received limited-volume irradiation had evidence of progression on postirradiation CT scans. Six patients (3 GBM, 3 AA) had evidence of a new intracranial metastatic site on CT scan. In three patients the metastasis was within the previously irradiated volume, and in the other three patients, it was outside this volume. All six had evidence of progression of their primary tumor at the original location on CT scan prior to the discovery of the metastatic site. Twenty-one patients (15 GBM, 6 AA) had at least one postirradiation reoperation for a recurrent mass. Nineteen patients had recurrent tumors in the primary site, and two patients had necrosis but no tumor. Patients who received limited-volume irradiation for high-grade astrocytomas achieved the same survival results as patients treated previously with whole brain irradiation. New intracranial metastases did not influence the outcome, since these were always antedated by tumor progression at the primary site.

Actuarial Analysis

Fat-containing soft-tissue masses of the extremities.

The authors review the radiologic spectrum of fat-containing soft-tissue masses of the extremities, with emphasis on computed tomography, magnetic resonance imaging, and pathologic correlation. These masses include both common and uncommon, benign and malignant lesions, such as lipoma, intramuscular and intermuscular lipoma, neural fibrolipoma, lipoblastoma, lipomatosis, hibernoma, hemangioma, elastofibroma, and liposarcoma, as well as lesions that may mimic fat-containing soft-tissue masses. Imaging studies of fat-containing lesions will often allow a specific presumptive diagnosis. When a specific diagnosis is not possible, however, knowledge of the spectrum of fat-containing lesions will allow a suitably ordered differential diagnosis.

Adolescent

Osteoid osteoma.

Osteoid osteoma is a benign skeletal neoplasm composed of osteoid and woven bone that rarely exceeds 1.5 cm in greatest dimension. The lesion is most commonly located in the cortex of long bones where it is associated with dense, fusiform, reactive sclerosis. Less often, it may be cancellous, where reactive osteosclerosis is usually less intense and may be distant from the lesion. Cancellous lesions are frequently intraarticular (most often in the hip) and may be associated with synovitis and joint effusion. Rarely, osteoid osteomas occur in a subperiosteal location. Patients are usually young, and there is a strong male predominance. Pain is the most common symptom. Radiographs of patients with cortical osteoid osteoma are often diagnostic. Intraarticular lesions, however, may be subtle, and scintigraphy may be required to locate the lesion for subsequent computed tomography (CT). CT is useful to identify and precisely locate the lesion and to provide guidance for percutaneous localization or treatment.

Adolescent

Extracolonic manifestations of the familial adenomatous polyposis syndromes.

The classic prototypes of the gastrointestinal polyposis syndromes are familial polyposis coli and Gardner syndrome. Extracolonic manifestations have been described in both diseases, and the distinction between them has become less clear. In fact, some authorities have suggested that familial polyposis coli and Gardner syndrome may represent a spectrum of the same disease. In both conditions, extracolonic expressions are the rule rather than the exception, and familiarity with them is essential for accurate diagnosis and correct patient management. In this pictorial essay, we discuss familial polyposis coli and Gardner syndrome together under the heading familial adenomatous polyposis syndromes. The colonic characteristics of these syndromes will be reviewed briefly, followed by examples of the most common extracolonic manifestations.

Adenomatous Polyposis Coli