Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders.

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times.

Etoposide differentially affects bone marrow and dermal derived endothelial cells.

Chemotherapy alteration of the bone marrow microenvironment has the potential to influence hematopoietic recovery following transplantation. To discern the effect of specific drugs on components of the complex marrow microenvironment, in vitro models have significant utility. In the current study we sought to determine whether dermal (HMEC-1) and marrow derived endothelial cells (BMEC-1) respond differently to identical chemotherapy exposure. BMEC-1 cells were consistently more sensitive to etoposide exposure than HMEC-1 cells, measured as reduced viability. BMEC-1 also had reduced focal adhesion kinase (FAK) and VCAM-1 protein expression following chemotherapy, in contrast to dermal derived endothelial cells in which neither protein was influenced dramatically by etoposide. The two endothelial cell lines had markedly different levels of baseline VE-Cadherin protein, which was modestly altered by treatment. These data indicate that marrow derived endothelial cells have disruption of specific proteins following chemotherapy that may influence their ability to facilitate hematopoietic cell entry or egress from the marrow. In addition, these observations suggest that while BMEC-1 and HMEC-1 share a variety of characteristics, they differ significantly in their response to stress and should be incorporated into specific models with this consideration.

Intra-tibial injection of human prostate cancer cell line CWR22 elicits osteoblastic response in immunodeficient rats.

We investigated the utility of CWR22 human prostate cancer cells for modeling human metastatic prostate cancer, specifically their ability to induce bone formation following intra-tibial injections in the nude rat. Prostate cancer is unique in regard to its tropism for bone and ability to induce new bone formation. In contrast to humans, other mammalian species rarely develop prostatic cancer spontaneously upon aging and do not have the propensity for bone metastasis that is the hallmark of cancer malignancy in men. We chose human prostate cancer cell line CWR22 based on its properties, which closely resemble all of the features that characterize the early stages of prostatic cancer in human patients including slow growth rate, hormone dependence/independence and secretion of prostate-specific antigen. When CWR22 cells were injected directly into the proximal tibia of immunodeficient male rats, both osteoblastic and osteolytic features became evident after 4 to 6 weeks, with elevated levels of serum prostate-specific antigen. However, osteosclerosis dominates the skeletal response to tumor burden. Radiological and histological evidence revealed osteosclerotic lesions with trabeculae of newly formed bone lined by active osteoblasts and surrounded by tumor cells. Toward the end of the 7-week study, osteolytic bone lesions become more evident on X-rays. Paraffin and immunohistochemical evaluations revealed mature bone matrix resorption as evidenced by the presence of many tartrate resistant acid phosphatase positive multinucleated osteoclasts. We conclude that the CWR22 human prostate cell line used in an intra-tibial nude rat model provides a useful system to study mechanisms involved in osteoblastic and osteolytic bony metastases. This type of in vivo model that closely mimics all major features of metastatic disease in humans may provide a critical tool for drug development efforts focused on developing integrated systemic therapy targeting the tumor in its specific primary or/and metastatic microenvironments. In addition to targeting bone marrow stroma, this strategy will help to overcome classical drug resistance seen at the sites of prostate cancer metastasis to bones.

Reduction in caregiver-identified problem behaviors in patients with Alzheimer disease post-hearing-aid fitting.

Studies and clinical procedures related to patients with Alzheimer disease (AD) largely have ignored the hearing ability of either the patient or caregiver. Yet the majority of treatment and investigation depends on or presupposes communication ability. Further, caregiver complaints often center around communication-based issues. Hearing deficits may be the most frequently unrecognized condition in patients with AD because patients either communicate adequately in quiet or the impairment is masked by other behavioral symptoms of AD. The current investigation identified individuals with AD with perceived and measured hearing impairment, provided amplification management, and evaluated the impact of treatment on caregiver-identified problem behaviors believed to be related to hearing status. Specifically, treatment compliance (hearing-aid use) and treatment efficacy (reduction in perceived hearing handicap and problem behaviors) were measured in the current investigation. A multiple-baseline design across individuals with multiple dependent variables was used to evaluate the reduction of problem behaviors post-hearing-aid treatment. Eight participants were included and 1 to 4 problem behaviors were significantly reduced for each patient after hearing-aid treatment. All participants were able to complete the necessary evaluation for hearing-aid fitting and wore their hearing aids between 5 and 15 hours per day by the end of the study. This investigation employed novel methodology in the areas of on-site hearing evaluation and hearing-aid selection, advanced hearing-aid technology, and primary data recording of caregiver-identified problem behaviors by caregivers.

[Metastatic breast carcinoma with neuroendocrine differentiation--its combined therapy with tamoxifen and the somatostatin analog octreotide]. / Metastasiertes Mamma-Karzinom neuroendokriner Differenzierung--kombinierte Therapie mit Tamoxifen und dem Somatostatin-Analogon Octreotid.

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman with histologically confirmed liver metastases from an undiagnosed primary tumor was admitted for further diagnosis and treatment. She had no symptoms and was in a very good general condition. The physical examination was unremarkable. INVESTIGATIONS: The liver enzymes GOT and GPT were slightly elevated. The carcinoembryonic antigen (CEA) and the erythrocyte sedimentation rate (ESR) were markedly raised. Repeat analysis of the liver biopsies revealed a carcinoma with neuroendocrine differentiation (carcinoid). TREATMENT AND COURSE: Chemoembolization of the advanced liver metastases was undertaken. Subsequently the breast tumor was resected. Histological analysis revealed a mammary carcinoma with neuroendocrine differentiation. Postoperative radiotherapy to the breast was instituted and she was started on tamoxifen (30 mg daily). But despite repeat chemoembolization the liver metastases continued to grow. Administration of octreotide, a somatostatin analogue, was begun (200 micrograms twice daily). There were no side effects; the tumor markers showed definite reduction and scintigraphy demonstrated almost complete regression. Computed tomography indicated a dissociated response of the liver metastases to the treatment (some got smaller, one had grown and several new ones had appeared). CONCLUSION: Combined tamoxifen and octreotide treatment of a metastasizing carcinoma of the breast with neuroendocrine differentiation may give effective palliation.

Managing hearing loss in a patient with Alzheimer disease.

This case study reports the management of hearing loss in a patient with Alzheimer disease (AD) living at home with a spouse care giver. The report highlights the interaction between symptoms associated with AD and hearing loss and the lack of data regarding remediation of hearing loss in this population. Specifically, the case illustrates the modifications in evaluation and verification of the hearing aid fitting that may be advisable when working with patients with AD. The data for this patient illustrate some novel measurement techniques that may assist the professional in documenting the impact of treatment in this population.

Gene therapy for leukemia and lymphoma.

Gene therapy of malignant diseases can be divided into four basic approaches: gene interference, gene insertion, immunopotentiation, and suicide gene approaches. This article reviews the application of these approaches in the therapy of leukemias and lymphomas.

Using comparative clinical information to understand practice patterns and affect organizational change.

The University Hospital Consortium is collecting clinical, administrative and financial data from its members to develop a Clinical Information Network. The value of this collective data lies in how comparative information about peer hospitals and physicians in the same specialty can be used to influence practice. The raw data from each hospital is analyzed, classified, normalized and stored in a data repository which is easily accessible. This data becomes information when it is presented in a variety of ways, and is supported by a knowledge-base of health care rules. The "drilling down" technique to progressive levels of detail serves the needs of all levels in the organization--executives, managers, and analysts. The system combines the power of a mainframe for the data repository with the ease of use of a PC-based workstation. With an open-ended approach, the users can ask a variety of questions of the data, as well as perform statistical analysis, create graphical presentations and generate explanations of the analysis techniques.

A national contributory elder care exchange program.

The state of the United States health care provision system is discussed; special attention is given to issues of eldercare. A new contributory health care concept is described which would reduce need for health care, and would supply labor to care for the fast-growing elderly population for the present and the future. The role of industry in provision of health care today and in this plan are discussed. Potential obstacles are suggested. Further research and areas of exploration are discussed for development of this concept.

Characterization of envelope proteins of alcelaphine herpesvirus 1.

Alcelaphine herpesvirus 1 is a gammaherpesvirus which causes malignant catarrhal fever, an acute lymphoproliferative disorder of cattle and other susceptible Bovidae, which is almost invariably fatal. A preliminary analysis of proteins induced by the virus indicated that as many as six glycoproteins and one nonglycosylated molecule might be present in the virus envelope. Monoclonal antibodies selected for recognition of virion envelope proteins included two that recognized a complex of infected cell proteins, designated the gp115 complex, and neutralized virus infectivity in the absence of complement. The gp115 complex consisted of five glycoproteins of 115, 110, 105, 78, and 48 kilodaltons (kDa), and all except the 48-kDa species reacted with antibody in Western blots (immunoblots). Pulse-chase experiments analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions suggested that the 110-kDa protein was the precursor molecule which was processed by addition of sugars to 115 kDa. The 115-kDa protein was cleaved to form a disulfide-linked heterodimer of 78 and 48 kDa, which was the mature form of the molecule incorporated into the virion envelope. The glycoprotein contained N-linked sugars, but little or no O-linked sugar was present. The relative abundance of the mature protein and its ability to induce neutralizing antibodies suggest that it will prove useful to studies aimed at elucidating the biology and pathogenesis of alcelaphine herpesvirus 1.

Proteins specified by bovine herpesvirus-2.

Polypeptides synthesized in bovine testes cells infected with bovine herpesvirus type 2 were labeled with [35S]methionine and were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Thirty-eight virus-induced proteins, ranging in molecular weight from 32,000 to 149,000, were detectable by analysis of whole cell lysates between postinfection hours 2 and 36. A similar number was immunoprecipitated by rabbit antiserum to bovine herpesvirus type 2. Twelve proteins incorporated [3H]glucosamine. On the basis of their temporal characteristics and their pattern of synthesis in the presence of cycloheximide and dactinomycin, 3 proteins, including at least one that was nondetectable in the absence of drugs, were classified as alpha proteins, 4 as beta proteins, 1 as a beta/gamma protein, and 27 as gamma proteins. Host cell protein synthesis was not reduced substantially until postinfection hours 22 to 28.