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Biomedical subjects

D M Weber

Publications and source records attributed to D M Weber.

At least 19 recordsLinked to original sources

Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma.

PURPOSE: To assess the prognostic significance of magnetic resonance (MR) imaging in patients with newly diagnosed asymptomatic multiple myeloma. PATIENTS AND METHODS: Thirty-eight consecutive patients with asymptomatic myeloma of low tumor mass and negative skeletal surveys underwent MR imaging of the thoracic and lumbosacral spine. The presence and patterns of marrow involvement were correlated with standard laboratory parameters and time to disease progression. RESULTS: Nineteen patients (50%) had evidence of marrow involvement at spinal MR imaging. MR patterns of marrow involvement were classified as diffuse (five patients), variegated (nine), and focal (five). Patients with abnormal MR imaging studies required therapy after a median of 16 months, versus 43 months for those with normal MR studies (P < .01). CONCLUSION: Abnormal marrow patterns were present in half of patients with asymptomatic myeloma. An abnormal MR study of the spine identified asymptomatic patients who were likely to require treatment earlier than those with a normal MR study. A normal MR pattern provided additional justification to defer institution of chemotherapy. However, MR imaging remains an investigational tool to stage patients with multiple myeloma until more data are accumulated.

Adult

Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacter pylori.

Regression of low-grade B cell gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacter pylori with antibiotic therapy was recently shown in a small number of patients with low-volume tumors. A patient with a > 10 cm nodular gastric mucosa-associated lymphoid tissue lymphoma that caused hematemesis and weight loss is described. Antibiotic therapy of H. pylori resulted in full clinical recovery and resolution of the mass lesion and morphological features of lymphoma on routine histological examination. However, monotypic immunostaining of plasma cells persisted in a separate and grossly normal-appearing region of the stomach. Antibiotic therapy may be of benefit in patients with mucosa-associated lymphoid tissue lymphoma with mass lesions and significant signs and symptoms, but periodic search for residual lymphoma is needed.

Female

2Chlorodeoxyadenosine therapy of patients with Waldenström macroglobulinemia previously treated with fludarabine.

BACKGROUND: Fludarabine monophosphate and 2Chlorodeoxyadenosine are nucleoside analogues with activity against Waldenström macroglobulinemia. However, it is not clear whether prior exposure to one analogue precludes response to the other compound. PATIENTS AND METHODS: Fourteen patients with Waldenström's macroglobulinemia and prior exposure to fludarabine were treated with two courses of 2chlorodeoxyadenosine. RESULTS: Three out of four patients that had previously responded to fludarabine and were relapsing from unmaintained remission, achieved a partial response with 2chlorodeoxyadenosine therapy. However, only one out of 10 patients with disease resistant to fludarabine responded to 2chlorodeoxyadenosine. CONCLUSIONS: 2chlorodeoxyadenosine may be effective in patients with Waldenström macroglobulinemia sensitive to fludarabine. However, this compound has limited activity for patients with disease resistant to fludarabine.

Aged

Intensive sequential therapy for VAD-resistant multiple myeloma.

Few effective regimens are available for patients with advanced multiple myeloma resistant to alkylating agents and VAD. We treated 65 patients with advanced and refractory multiple myeloma with the combination of cyclophosphamide (3.0 gm/m2) and etoposide (900 mg/m2) followed by GM-CSF at a daily dose of 0.125 mg/m2. Thirty-five percent of patients responded with a 6% mortality rate. After a median of 2 months, 16 patients received myeloablative treatment supported by autologous bone marrow or blood stem cells. Four of ten previously resistant patients responded so that the overall response rate was 42%. The median survival for all patients was 10 months and the median remission was 8 months. The median survival for patients with both low serum lactate dehydrogenase and B2 microglobulin, or for those who received myeloablative treatment, was projected at 18 months. Our combination of cyclophosphamide and etoposide provided an effective rescue treatment for many patients with advanced multiple myeloma resistant to conventional therapies. This program allowed early blood stem cell collection in support of subsequent myeloablative therapy for selected patients.

Adult

A data adaptive reprojection technique for MR angiography.

Inability to detect vessel overlap and vascular loops can compromise the interpretation of magnetic resonance angiograms. A data-adaptive ray tracing (DART) technique was developed to produce the appropriate variations in signal intensity at points of vessel overlap in order to simulate the standard angiographic representation of vessels. In this technique a threshold is utilized to identify vessels in the image slices composing a 3D angiographic data set. A mask, which defines regions slightly larger than the vessel boundaries, is obtained by blurring the vessel information surviving the initial threshold. This mask is converted to binary form prior to multiplication by the original angiographic data set. Following application of an additional threshold to the masked data, line integrals through the regions defined by the mask are performed to obtain an angiographic signal proportional to the integrated vessel signal as in conventional angiography. This integrated reprojection is then uniquely combined with a maximum intensity pixel (MIP) reprojection to produce the final DART image. The application of the DART technique to 2D time-of-flight and 3D phase-contrast angiograms successfully enabled the identification of over-lapping vessels and vascular loops. DART was also found to produce less vessel narrowing than the MIP technique.

Algorithms

Peripheral MR angiography with variable velocity encoding. Work in progress.

An electrocardiographically triggered two-dimensional phase-contrast (PC) magnetic resonance angiographic pulse sequence was developed in which velocity encoding (VENC) was varied throughout an acquisition in response to changes in blood velocity during the cardiac cycle. This was done to better capture signal in the peripheral vasculature, where pulsatile flow degrades images. After reconstruction, a matched filter addition technique was applied to the cardiac phase images to obtain a single high-quality static image. Images were obtained of six healthy volunteers--with and without varying VENC--and contrast-to-noise ratio (C/N) calculations were performed for the added images. Varying VENC significantly improved vascular signal from small and large vessels (P less than .02), but it was most helpful for small vessels, for which the C/N increased by as much as 260% (average increase, 149%). These preliminary findings suggest that variable VENC can enhance the signal from the small and large peripheral blood vessels in cardiac-gated PC acquisitions.

Angiography

Spontaneous lymphocyte proliferation in HTLV-I/II infection reflects preferential activation of CD8 and CD16/56 cell subsets.

Previous studies have shown that lymphocytes from HTLV-infected persons spontaneously proliferate when cultured in vitro. We investigated which cell subsets become activated in this response. Mononuclear cells from 16 HTLV-seropositive former blood donors and 9 seronegative controls were cultured for 7 days; activation was then assessed by measuring DNA synthesis in cultured cells and by monitoring CD25 expression by CD3, CD4, CD8, CD19, and CD16/56 lymphocyte subsets. Of the 16 cultures of HTLV + donor cells, 10 showed spontaneous proliferation (Prol + group) and 6 did not (Prol - group). Cytofluorometric analysis revealed a significant increase in the fractions of CD8 cells and CD16/56 cells expressing CD25 for the Prol + group, compared to the Prol- and control groups. Similarly, the fractions of CD25 cells expressing CD8 or CD16/56 were significantly increased in the Prol + group. Although neither the fraction of CD4 cells expressing CD25 nor the fraction of CD25 cells expressing CD4 were increased for the Prol + group, the modal fluorescence intensity value for CD25 expression by CD4 cells was increased, suggesting some CD4 cell activation occurred as well. Blastoid cells were, on average, 79% CD25 +, whereas the sum of CD4 + CD25 + (27%), CD8 + CD25 + (30%), CD19 + CD25 + (3%), and CD16/56 + CD25 + (35%) subsets was 95%; the presence of 17% CD8 + CD16/56 + cells accounted for most of this discrepancy. These findings indicate that spontaneous lymphocyte proliferation in HTLV infection reflects preferential activation of CD8 and CD16/56 cell subsets, apparently including the minor CD8 + CD16/56 + subset.

Antigens, CD

Geometric quantitative coronary arteriography. A comparison of unsubtracted and dual energy-subtracted images.

The application of dual energy (DE) subtraction techniques to quantitative coronary arteriography (QCA) has the advantage of removing the tissue signal surrounding the vessel profile. We have compared the performance of two geometric QCA algorithms on DE-subtracted and -unsubtracted images to determine, for each, if DE subtraction is advantageous. The two algorithms under study were an edge detection algorithm and a Fourier analysis-based algorithm. For each algorithm, linear regression analysis was performed of measured cross-sectional area (CSA) versus actual CSA of coronary vessel phantoms. The edge detection algorithm was found to have improved precision (P less than .05) when applied to the DE-subtracted images. The Fourier analysis algorithm, however, was not effected by the DE subtraction. Among the unsubtracted image results, the Fourier measurements were more accurate (P less than .05) than the edge detection measurements. We conclude that the benefits to edge detection QCA of DE tissue subtraction outweigh the disadvantages of increased image noise and possible misregistration artifacts. However, the Fourier algorithm is relatively insensitive to tissue signal variations.

Algorithms

Quantitative dual-energy coronary arteriography.

Subtraction techniques for digital cardiac imaging have been hampered by misregistration artifacts. The use of dual-energy imaging is being evaluated as a means for reducing these artifacts. Results reported previously indicate that the dual-energy technique may be useful for applications such as exercise ventriculography and general quantification tasks. The purpose of the current study is to investigate the use of dual-energy subtraction imaging for quantitative coronary arteriography. In vivo coronary vessel phantoms (0.2 to 7 mm2 in cross-sectional area) were used to study the potential advantages of tissue suppressed energy subtracted images over unsubtracted images for quantification of absolute vessel cross-sectional area when cardiac motion is present. Estimates of lumen cross-sectional area (N = 20) were determined using videodensitometric analysis of selected energy subtracted and unsubtracted images. Linear regression analysis of measured and actual cross-sectional area showed energy subtracted image data (slope = 1.06, intercept = 0.48 mm2, r = 0.99) to have improved accuracy (P less than .05) and precision (P less than .05) over unsubtracted image data (slope = 1.24, intercept = 1.07 mm2, r = 0.95).

Angiography, Digital Subtraction

Functional differences between small and large luteal cells of the late-pregnant vs. nonpregnant cow.

This paper describes an in vitro model for the study of two types of steroidogenic luteal cells from cows in different physiological states. Two different populations of enzymatically dispersed bovine luteal cells were separated on the basis of size in a Cel-Sep Sedimentation Chamber. The separated small (12.5-23 micron in diameter) and large (greater than 23 micron in diameter) luteal cells of late-pregnant cows (Days 190-280) contained the distinct morphological characteristics previously defined for these two populations of cells. Cells were evaluated for progesterone (P4) production during a 3-h incubation with and without bovine luteinizing hormone (bLH, 10 ng/ml). Both small and large luteal cells from the late-pregnant cow were found to contain equal levels of P4 at Time 0 and increased but equal levels of P4 after a 3-h incubation. Neither cell type showed an increase in P4 production in response to the addition of bLH (p greater than 0.05). Since these results differed from earlier reports for luteal cells of the nonpregnant cow, small and large luteal cells of the mid-cycle (Day 14) were incubated, and the levels of P4 production were compared with P4 levels from the late pregnant cow. In agreement with previous reports for nonpregnant cows, progesterone content at Time 0 was 7-fold higher in large cells than in small cells (p less than 0.05), and after 3 h of incubation, 13-fold higher (p less than 0.05). Although the small cells responded to the presence of bLH in the incubation medium with a 4-fold increase in P4 production, this increase was not significant (p greater than 0.05). The large cell did not respond to bLH. However, the large cell type continued to contain and produce more P4 than did the small cells treated with bLH. This study indicates that both the small and large luteal cells of late-pregnancy are able to produce P4. However, the large luteal cell of the estrous cycle produces greater quantities of P4 than does the small luteal cell or the large luteal cell of late pregnancy.

Animals

Occlusive arterial disease in the lower leg and foot.

In approaching a patient suspected of peripheral vascular disease the following signs and symptoms are of key importance (16): 1) Pain in the extremity which is induced by exercise and relieved by rest; pain which is influenced by posture is localized to one digit, is unilateral or is paroxysmal. 2) Impaired pulsations of peripheral arteries. 3) Abnormal color of the skin, particularly when affected by raising or lowering the part. 4) Gangrene, ulceration, impaired nail and hair growth, excessive calluses, or paronychial infections. 5) Unusual warmth or coldness. 7) Swelling, atrophy, or difference in length of extremity. 8) Ausculatory evidence of arteriovenous fistula. 9) Cyanosis or unusual pallor of digits when immersed in cold water. 10) Peripheral neuritis.

Age Factors