Thrombospondin levels in patients with malignancy.

Thrombospondin (TSP), a large glycoprotein present in platelets, and various normal and tumor tissues, has recently been shown to promote cell adhesion and platelet aggregation. Most importantly because TSP has been shown to promote metastasis of melanoma tumor cells to the lung in a murine model (1) and since thromboembolic events commonly occur in patients afflicted with metastatic tumors, we explored the role of TSP in human cancer by measuring TSP blood levels in patients with various malignant neoplasms. Blood TSP levels were measured by indirect enzyme-linked immunoadsorbent assay (ELISA) from 20 control subjects, 22 patients with gastrointestinal (GI) cancer, 18 patients with breast cancer, and 17 patients with lung cancer. Control subjects consisted both of healthy subjects and acutely ill patients with no malignancies. TSP levels of both healthy and acutely ill controls were found to range between 245-440 ng/ml with a mean of 365 ng/ml. In contrast, elevated levels of TSP greater than the mean value of 400 ng/ml for controls ranging between 590-3,650 ng/ml were found in 20/22 (91%) patients with GI malignancies, 13/18 (72%) patients with breast cancer, and 15/17 (88%) with lung cancer. Mean TSP levels of GI, breast, and lung cancer patients were 3, 2, and 3 fold greater than controls, respectively. Increased blood TSP levels in patients were not due to increased levels of platelets since both control and patient groups had platelet counts within the normal range. These results suggest that TSP may play a role in tumor cell metastasis in man and could serve as a blood marker for metastasis.     

Heart failure in 2001: a prophecy.

Understanding of heart failure has developed through 3 paradigms involving organ, cell, and gene. The first views heart failure as an abnormality of organ (pump) function leading to salt and water retention and vasoconstriction. Therapy to correct these circulatory abnormalities is well accepted and effective. The second considers heart failure as a disordered cellular function, mainly impaired contraction and relaxation. Efforts to correct the biochemical and biophysical abnormalities responsible for these disorders of myocardial performance have, however, been less successful. Recent emphasis on efforts to improve prognosis as well as symptoms in patients with chronic heart failure demonstrates that it is a lethal disease with problems of survival similar to those in malignancies. The third paradigm of abnormal gene expression, which in the failing heart represents a cardiomyopathy of overload, appears to be a major cause of poor prognosis in these patients. Evidence that the angiotensin-converting enzyme inhibitors have important effects on cell growth, as well as on vascular tone, suggests that their ability to prolong survival in patients with heart failure may be due largely to the inhibition of detrimental effects of angiotensin II on cardiac gene expression. Thus, it seems likely that work focused on the third paradigm will uncover specific abnormalities of gene expression that are responsible for poor survival of patients with heart failure. By 2001, I predict that heart failure will be viewed as an abnormality of cell growth and this will lead to the development of therapies to retard, if not reverse, the clinical deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identifying persistent adverse effects of anticholinergic drugs in the elderly

Investigations on the symptoms associated with the use of anticholinergic medications by elderly patients demonstrated that these medications are frequently associated with persistent adverse effects that may go unrecognized by both patients and physicians. An increase in autonomic symptoms was readily demonstrated in a group of elderly outpatients taking anticholinergics. Cognitive effects, however, were not apparent, possibly due to the heterogeneity of the populations studied. A parallel study did, however, demonstrate an association between anticholinergic medications and slowing of EEG background frequency. Findings on the relationship between EEG background frequency and cognitive measures suggest the possible value of the combined use of psychological and electrophysiological measures for identifying patients who require further evaluation of their medication regimen.     

Evaluation of peripheral blood involvement of mantle cell lymphoma by fluorescence in situ hybridization in comparison with immunophenotypic and morphologic findings.

Mantle cell lymphoma is non-Hodgkin's B-cell lymphoma characterized by the t(11;14)(q13;q32) translocation. Peripheral blood involvement of mantle cell lymphoma is usually associated with a poor prognosis and therefore, its identification is clinically important. In this study, we performed cyclin D1/IgH-probe fusion fluorescence in situ hybridization analysis on 223 peripheral blood samples: 185 from 125 mantle cell lymphoma patients, and 38 normal controls. The cutoff values for the test were established using normal controls. Flow cytometry on peripheral blood and corresponding bone marrow samples was used to evaluate this test. In all, 26% of the 185 peripheral blood samples and 27% of the 161 corresponding bone marrow samples were flow cytometry positive for mantle cell lymphoma. The mean numbers of single and- double-fusion signals and the mean number of CD5/CD19-positive cells, absolute blood lymphocyte count, and white blood cell count were significantly higher in peripheral blood and corresponding bone marrow samples with mantle cell lymphoma-positive flow cytometry. Double-fusion signals were more specific than single-fusion ones. Fluorescence in situ hybridization was far more likely to be positive for mantle cell lymphoma when the peripheral blood and the corresponding bone marrow samples had positive flow cytometry results or morphology (P<0.01). Our study indicates that cyclin D1/IgH-fusion fluorescence in situ hybridization analysis could be used to determine the presence and character of circulating mantle cell lymphoma cells in peripheral blood, thus enhancing our ability to evaluate leukemic mantle cell lymphoma and minimum residual disease.     

Ultrasound biomicroscopy and management of late posterior migration of a ripcord suture after glaucoma drainage implant surgery.

Three years after receiving a Baerveldt tube implant for neovascular glaucoma, a 50-year-old man presented to the Wills Eye Hospital Glaucoma Service with pain and decreased vision in his left eye. On examination, a 4-0 nylon ripcord suture was seen to have migrated posteriorly through the pupil and in front of the intraocular lens. The distal end of the suture was not seen on dilated indirect ophthalmoscopic examination or by standard B-scan ultrasonography. Ultrasound biomicroscopy examination was performed, and the distal end of the suture was found to lie just anterior to the pars plana. Careful removal of the suture was performed intraoperatively through two paracentesis incisions using Kelman forceps. Posterior ripcord migration is a rare complication after glaucoma drainage implant surgery, and ultrasound biomicroscopy imaging may be helpful in determining its proper management.     

Work life of persons with asthma, rhinitis, and COPD: A study using a national, population-based sample

Objective  

To estimate the duration of work life among persons reporting a physician's diagnosis of COPD, asthma, or rhinitis compared to those with select non-respiratory conditions or none and to delineate the factors associated with continuance of employment.     

Asynchronous blepharospasm, facial and cervical dystonia, and bilateral asynchronous hemifacial spasm.

We present a patient with a facial movement disorder that has characteristics of both blepharospasm and bilateral asynchronous hemifacial spasm. Because of the increased incidence of blepharospasm in patients with hemifacial spasm, our patient's clinical presentation is probably not a chance occurrence, but rather a manifestation of some predisposition for these two movement disorders. This unusual constellation of signs and symptoms challenges the current diagnostic criteria and suggests that some of these facial movement disorders may lie on a spectrum, rather than represent distinct entities.