The importance of multidisciplinary teams in a large biomedical research program.

The formation of multidisciplinary teams is vital to modern biomedical research. These teams are important contributors to the advancement of scientific discovery as well as the translation of those discoveries into useful clinical practice. The issues involved in providing scientific and technical expertise in computational science and engineering to support a large biomedical research program are presented. The activities of the Division of Computational Bioscience (DCB) of the Center for Information Technology (CIT) at the National Institutes of Health (NIH) are highlighted. Professionals in this organization apply the concepts and technologies of computer science, engineering, physical science and mathematics to biomedical applications, making available this expertise to the NIH Intramural Research Program (IRP). The areas of application include imaging, informatics, instrumentation, telemedicine, structural biology and mathematical analysis. Examples where collaborative research and development teams containing DCB professionals have worked to produce significant results are presented. These examples are a chromosome microdissection instrument, a telemedicine system for radiation oncology, and a medical image archive.

Anaplastic large-cell lymphoma (Ki-1 lymphoma) and diffuse large-cell immunoblastic lymphoma: two diagnostic problem cases.

Electron microscopy can be used to establish diagnoses in some otherwise difficult cases of neoplasia, but it is not generally regarded as important in the diagnosis of lymphoma. However, in some cases of anaplastic tumors not initially recognized as lymphomas, electron microscopy can prove quite valuable. Two cases are reported in which lymphoma was not suspected on the basis of the histologic findings, but was diagnosed by electron microscopy. Case 1 involved a 60-year-old woman who presented with a retroperitoneal mass that was located primarily in the body of the psoas muscle. Nuclear pockets were seen with electron microscopy. Ultimately she was diagnosed with anaplastic large-cell lymphoma (Ki-1 lymphoma). Case 2 involved a 43-year-old male with retroperitoneal lymphadenopathy, renal failure, polyclonal gammopathy, and a febrile illness. Signet-ring cells without junctions were identified with electron microscopy. Immunoperoxidase stains confirmed diffuse large-cell immunoblastic lymphoma.

Phase II trial of low-dose N-(phosphonacetyl)-disodium L-aspartic acid and high-dose 24-hour infusional 5-fluorouracil in advanced gastric adenocarcinoma. A Southwest Oncology Group study.

N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an initial period of 8 weeks. No objective responses were noted. PALA and 5-FU is inactive against gastric adenocarcinoma at the doses and schedule used in this trial.

Parallel computing in biomedical research.

Scalable parallel computer architectures provide the computational performance needed for advanced biomedical computing problems. The National Institutes of Health have developed a number of parallel algorithms and techniques useful in determining biological structure and function. These applications include processing electron micrographs to determine the three-dimensional structure of viruses, calculating the solvent-accessible surface area of proteins to help predict the three-dimensional conformation of these molecules from their primary structures, and searching for homologous DNA or amino acid sequences in large biological databases. Timing results demonstrate substantial performance improvements with parallel implementations compared with conventional sequential systems.

Oerskovia xanthineolytica bacteremia in an immunocompromised patient with pneumonia.

Oerskovia species, which are Nocardia-like bacteria that have rarely been found to cause human disease, are usually found in association with a foreign body with removal of the infected focus being necessary for cure. We present a case of Oerskovia xanthineolytica bacteremia in a patient with metastatic breast cancer, community-acquired pneumonia, and a tunneled subcutaneous central venous catheter. Although the actual source of the bacteremia in this case is not proven, this patient's presentation with apparent lobar pneumonia and her improvement on antibiotics without catheter removal suggest that Oerskovia may be capable of causing primary pulmonary infection in the immunocompromised host.

Recurrent non-0:1 Vibrio cholerae bacteremia in a patient with multiple myeloma.

BACKGROUND: Episodes of bacteremia with non-0:1 Vibrio cholerae are rarely reported, even though the organism is endemic along the Gulf Coast of the United States. Recurrent episodes of bacteremia with non-0:1 V. cholerae are described even more rarely. A patient is reported who had multiple myeloma and experienced two episodes of bacteremia with non-0:1 V. cholerae. METHODS: Hospital records and the medical literature were reviewed, and the organism was serotyped by the Alabama State Laboratory. RESULTS: The patient had no prodromal illnesses or diarrhea with either episode of bacteremia. Treatment with empiric antibiotic therapy resulted in successful resolution of his bacteremia, which is fatal in almost 50% of reported cases in patients with malignant neoplasms. CONCLUSIONS: This is the first reported case of non-0:1 V. cholerae bacteremia occurring in a patient with multiple myeloma. Both his initial episode and a second episode of bacteremia responded to broad-spectrum antibiotics, which are used as empiric therapy for patients with hematologic malignancies and fever. Emphasis is placed on the paucity of clinical manifestations and the need for empiric therapy for non-0:1 V. cholerae infection in patients with hematologic malignancies.

Pituitary abscess after autologous bone marrow transplantation.

The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31-year-old man with a 9 month history of T-cell lymphoma died suddenly more than 60 days after successful treatment with high-dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.

Transient neurologic dysfunction following moderate-dose methotrexate for undifferentiated lymphoma.

Two patients, aged 24 and 19 years, who had undifferentiated lymphoma, developed the acute onset of focal neurologic deficits 10 days after treatment with moderate-dose methotrexate (2.76 g/m2 by 42-hour intravenous infusion) and 12.5 mg of intrathecal methotrexate. Prior chemotherapy also included intravenous cyclophosphamide, doxorubicin, vincristine, oral prednisone, and intrathecal cytosine arabinoside. Dysarthria with left hemiparesis was noted in one patient and inability to speak and quadriparesis in the other. Cerebrospinal fluid and cranial computerized tomography results were normal; however, EEGs showed focal abnormalities in both patients. Full neurologic recovery occurred within 48 hours. These symptoms developed early in the course of treatment and have not recurred in one patient who continued to receive the same regimen. The mechanism for this neurologic dysfunction is unclear. A similar picture has been reported in patients receiving high-dose methotrexate (8-10 g/m2) for osteogenic sarcoma.