Motor neuron disease and serum monoclonal proteins: poor response to treatment of the paraproteinemia.

An association between motor neuron disease (MND) and paraproteinemia has been previously reported. In a retrospective study, we found that 13 of 117 (11%) patients with MND who had serum protein electrophoresis studies were found to have a serum M-protem. Eleven of 13 patients had probable or definite amyotrophic lateral sclerosis (ALS), Of the 11 patients with ALS, six were treated with immunotherapy or chemotherapy. Subjective or objective neurologic improvement was not identified in any. Our data support an association between MND and paraproteinemia, but response to treatment of the paraproteinemia was disappointing. Searching for an M-protein in probable or definite ALS may not be therapeutically relevant.

Atherosclerosis and unstable angina in Bernard-Soulier syndrome.

Platelets and von Willebrand factor play pathogenetic roles in atherosclerosis and acute coronary artery ischemic syndromes. Patients with Bernard-Soulier Syndrome are deficient in several platelet membrane glycoproteins, including glycoprotein Ib (GpIb). Glycoprotein Ib is the primary platelet receptor for von Willebrand factor and plays a critical role in the initiation of thrombus formation. Glycoprotein Ib, but also GpIIb/IIIa, mediates the adhesion of platelets to damaged endothelium, particularly at the high shear stresses found in small or diseased arteries. A patient with Bernard-Soulier syndrome is described who developed coronary artery atherosclerosis and unstable angina requiring coronary artery bypass grafting. The implications of this experiment in nature on the contribution of platelets and platelet GpIb and GpIIb/IIIa receptors to the development of atherosclerosis and unstable angina are discussed.

Biotechnology-derived foods from animals.

American agriculture is being challenged to produce food in a way that is environmentally sound, that enhances human health, is safe, and whose cost is competitive internationally. The tools of biotechnology offer new techniques for modifying biological traits in a much more directed way than is possible with conventional animal breeding and enables us to ask questions and find answers in a way that was not possible in the past. The new tools facilitate disease diagnosis and prevention, help design foods with improved nutritional characteristics, and increase production efficiency. Full realization of the potential of biotechnology will depend upon our ability to deal with public perceptions of "genetic engineering", support for research, and policy issues such as patenting of animals.

Acute promyelocytic leukemia: impact of hemorrhagic complications on response to induction chemotherapy and survival.

From 1976 to 1989, 21 adult patients with previously untreated acute promyelocytic leukemia were seen at the University of Virginia Hospital. We reviewed their cases retrospectively to determine the impact of hemorrhagic complications and other factors on treatment outcome. We observed a complete remission rate of 35%; the median survival in complete responders was 15 months. Evidence of disseminated intravascular coagulation was found in 13 (62%) of the 21 cases at diagnosis. Fatal intracranial hemorrhage was the leading cause of death, occurring in eight (40%) of the 20 patients evaluated. Initial leukocyte count greater than 4.0 x 10(9)/L and platelet count less than 20 x 10(9)/L were significantly associated with an increased risk of intracranial hemorrhage. In patients with disseminated intravascular coagulation, the rate of intracranial hemorrhage was reduced by treatment with heparin. The high mortality of 40% (8/20) due to intracranial hemorrhage during induction was a major contributor to the low complete remission rate of 35% (7/20) in this series of consecutive unselected patients with newly diagnosed acute promyelocytic leukemia.

ATLL complicated by strongyloidiasis and isosporiasis: case report.

In summary, we present this as the first reported case of both isosporiasis and strongyloidiasis complicating HTLV-I-associated ATLL. Prompt diagnosis and treatment of these parasites in the immunocompromised host are necessary to prevent severe wasting and dehydration. This should also prevent the significant morbidity and mortality associated with dissemination well-described for Strongyloides, and recently seen at autopsy in a patient with isosporiasis. Recurrent infections are common with both organisms, therefore chronic suppressive therapy and prophylactic treatment prior to chemotherapy or steroid administration is warranted.

Splenectomy in hematologic disorders. The ever-changing indications.

A comparison between a series of splenectomies performed at the University of Virginia Medical Center for hematologic disorders between 1946 and 1962 (Series I) and 1963 and 1982 (Series II) is presented. Four hundred splenectomies (20 per year) were performed between 1963 and 1982 compared with 94 (5.5 per year) between 1946 and 1962. Also noted in Series II was a sharp decline in the number performed each year between 1974 and 1983. The major factor responsible for these observations was the evolution of the staging laparotomy for malignant lymphomas, particularly Hodgkin's disease, and the decline in the average annual incidence of staging laparotomies since 1974. Staging laparotomy currently is rarely done for non-Hodgkin's lymphomas. Also contributing to the changes noted was an increase in the total number but subsequent fall in the annual incidence of splenectomy for hereditary spherocytosis, idiopathic hypersplenism, and myeloproliferative disorders in Series II. The average number of splenectomies for idiopathic thrombocytopenic purpura increased from 1.1 per year in Series I to 3.6 per year in Series II; the annual incidence during the study period of Series II, however, remained constant. The total number of splenectomies for hairy cell leukemia and Felty's syndrome increased from zero in Series I to 12 and 17, respectively, in Series II, whereas the number of miscellaneous reasons dropped from 29 (1.7 per year) in Series I to 15 (0.75 per year) in Series II. The mortality rate in Series I was 6.3% compared with 4.0% in Series II. No deaths occurred in Series II after 1979. Indications for splenectomy in Series II were for diagnostic purposes in 3.2%, therapeutic in 56.5%, staging in 39.5%, and restaging in 0.8%. Accessory spleens were found in 49 (12.5%) in Series II.

Nodular sclerosing Hodgkin's disease with giant Reed-Sternberg cells.

A 70-year-old woman with multiple symptoms and extensive lymphadenopathy had a lymph node biopsy specimen that contained highly pleomorphic, giant Reed-Sternberg cells that resembled cells from other malignant giant cell neoplasms. The cells were strongly positive for Leu-M1, alpha 1-antitrypsin, S-100 protein, kappa light chain, and lambda light chain. With five courses of chemotherapy for pathologic stage IV-B Hodgkin's disease, the patient achieved a complete remission, and remains free of disease 85 months after diagnosis.

Promyelocyte morphology. Differentiation of acute promyelocytic leukemia from benign myeloid proliferations.

Bone marrow aspirates from patients with acute agranulocytosis or a marked left shift in myeloid maturation can mimic acute leukemia, particularly acute hypergranular promyelocytic leukemia. Bone marrow aspirates from 16 cases of apparent acute promyelocytic leukemia, 4 cases of acute agranulocytosis, and 1 case of a marked myeloid left shift were studied for the presence or absence of differentiating features. Normal or reactive promyelocytes were characterized by prominent paranuclear clear Golgi zones, whereas promyelocytes from true leukemic cases all had heavy azurophilic granules dispersed diffusely throughout the cytoplasm. Prominent Golgi zones in promyelocytes were associated only with benign myeloid conditions and were not observed in acute promyelocytic leukemia. The presence of prominent clear Golgi zones in promyelocytes is an important feature assisting in the distinction between leukemic and benign promyelocytes.

T-immunoblastic lymphoma mimicking B-immunoblastic lymphoma.

A T-cell immunoblastic lymphoma having plasmacytoid features that mimic B-cell immunoblastic lymphoma, is described. The lesion was composed of sheets of pleomorphic plasmacytoid cells that displayed a helper T-cell immunophenotype (Leu-1+, Leu-3+, Leu-4+, Leu-5+, Leu-9-, Leu-2-). Ultrastructural features were consistent with a T-cell lymphoma. Flow cytometric analysis revealed that the cells were DNA triploid and had a high proliferative activity. Although the histology of immunoblastic lymphomas alone may suggest either a T- or B-cell phenotype, immunophenotyping is essential in making this distinction.

Lymphocyte subsets in normal bone marrow.

Bone marrow aspirates and biopsies from ten normal donors were stained directly with monoclonal antibodies specific for lymphocyte, monocyte, and myeloid antigens, and were analyzed by flow cytometry. To avoid cell loss, lymphocytes were not specifically isolated prior to staining. T cells comprised 46% of aspirate lymphocytes and 22% of biopsy lymphocytes. Further, the Leu-3:Leu-2 ratio of bone marrow T cells was below 1.0. B cells comprised 8% to 11% of bone marrow lymphocytes in both aspirates and biopsies, and there was a substantial percentage of cells in the lymphocyte window that was negative for all B and T cell markers. The lymphocyte window had very little myeloid contamination; however, when the myeloid window was examined, staining was greater than 90%.

A controlled study of ticarcillin plus clavulanic acid versus piperacillin as empiric therapy for fever in the immunocompromised host.

Clavulanic acid, a potent beta-lactamase inhibitor, was studied in fixed combination with ticarcillin and used with tobramycin as empiric therapy for fever in the immunocompromised host. Fifty febrile episodes were evaluated in patients with hematologic malignancy and/or neutropenia. Eighty-one percent of evaluable infections treated with the study regimen of ticarcillin, clavulanic acid, and tobramycin responded. Seventy-four percent of evaluable infections treated with the control regimen of piperacillin, tobramycin, and vancomycin responded (p = 0.4). Resistance to piperacillin and ticarcillin were noted in 23.8 percent of 21 isolated organisms. Resistance to ticarcillin and clavulanic acid was noted in only one (4.7 percent) of the isolated organisms (p = 0.092). Untoward reactions, including rash, nephrotoxicity, and superinfection, were unusual and occurred with equal frequency in the study and control groups. Clavulanic acid in combination with ticarcillin was effective and safe in treating fever in the immunocompromised host.

Adult respiratory distress syndrome due to malignant histiocytosis.

While a 23-year-old man was being evaluated for a two-month history of night sweats, fever, and weight loss, he had the typical clinical, radiologic, and laboratory findings of adult respiratory distress syndrome (ARDS). After a diagnosis of malignant histiocytosis (MH) was established by lymph node biopsy, review of an earlier lung biopsy initially interpreted as nonspecific revealed malignant histiocytes. He failed to respond to combination chemotherapy and died as a result of progressive respiratory failure.