Plasma infusion for thrombotic thrombocytopenic purpura during pregnancy.

Thrombotic thrombocytopenic purpura (TTP), a disease of unknown cause, has been reported relatively frequently during pregnancy. The disorder typically runs a fulminant course with a high mortality, and survival of both mother and fetus has been exceedingly rare. We report here the fourth case of TTP during pregnancy in which both the mother and fetus survived. Therapeutic approaches to TTP have included corticosteroids, antiplatelet agents, splenectomy, and, more recently, exchange plasmapheresis, exchange transfusion, and plasma infusion. The patient described herein was refractory to corticosteroids, antiplatelet agents, and only transiently responsive to exchange transfusion. The administration of plasma infusions achieved a sustained partial remission that allowed full gestation of the developing fetus. The patient attained full remission following cesarean section and simultaneous splenectomy.

Noncardiogenic pulmonary edema associated with hydrochlorothiazide therapy.

We describe a patient with the sudden onset of pulmonary edema on two separate occasions immediately after the ingestion of hydrochlorothiazide. Although this adverse reaction to hydrochlorothiazide has been reported previously in six patients, the cause of the pulmonary sensitivity remains obscure. A noncardiogenic etiology has been suggested, but prior cases have failed to document cardiopulmonary hemodynamic measurements. A Swan-Ganz balloon flotation catheter demonstrated cardiopulmonary pressures in our patient consistent with a noncardiac origin of the pulmonary edema.

Effect of total parenteral nutrition on hepatic histology.

We evaluated the effect of total parenteral nutrition (TPN) on abnormalities of hepatic histology. Liver biopsies of 93 patients who were concurrently receiving TPN were compared with a control group of 35 patients. The control patients were matched for extent of preexisting liver disease and degree of illness. The liver biopsy specimens were blindly graded on 19 histopathologic findings, including fatty change, portal inflammation, and cholestasis. Twenty-seven clinical variables, such as preexisting liver disease, the presence or absence of sepsis or shock, and number of days receiving TPN before biopsy, were recorded. Individual and partial correlations were established between the clinical variables and histopathologic findings. The control and TPN groups proved to have been closely matched regarding the extent of risk factors for hepatic histopathologic features. Positive correlations were repeatedly found between abnormal hepatic histologic features and preexisting liver disease, abdominal sepsis, renal failure, and blood transfusion but not with the administration of TPN. We conclude that clinical phenomena, such as existing liver disease, renal failure, and abdominal sepsis, rather than administration of TPN, had a predominant effect on histopathologic features in this group of patients.

Urinary retention in sickle cell syndromes.

Four patients with sickle cell disease noted the development of urinary retention during an acute painful crisis. The acute urinary retention resolved with improvement in the painful sickle cell crisis. No evidence of anatomic urologic defect, systemic neurologic abnormality, or infection was documented in these patients. Patients with sickle cell disease in painful crisis should be observed for signs of acute urinary retention.

Globin synthesis studies in a person heterozygous for alpha-thalassemia-2, Hb S and Hb G Philadelphia.

A 21-year-old American black female with mild anemia was found to be triply heterozygous for alpha-thalassemia-2, hemoglobin S and hemoglobin G Philadelphia. Hemoglobin A comprised 39% of her total hemoglobin. The alpha-thalassemia gene was expressed by an alpha/non-alpha synthesis of ratio of 0.79 +/- 0.09 and was equally unbalanced in the peripheral blood and the bone marrow. Globin synthesis studies indicated that the percentage of Hb G and Hb S in the peripheral blood is about 32% and 31% respectively. These values are due to the coexistent alpha-thalassemia-2 gene with the following most likely genotype: --alpha G/alpha alpha, beta A/beta S (or --alpha/alpha G alpha, beta A beta S).

FAM chemotherapy +/- aminoglutethimide in the treatment of pancreatic carcinoma.

Human pancreas contains receptors for estrogens and androgens as well as aromatase activity. FAM chemotherapy was administered to 14 patients with pancreatic cancer (seven at Stage IV). The median survival of these patients was 24.4 +/- 4.8 weeks. FAM chemotherapy plus aminoglutethimide/hydrocortisone (AG/HC) (250 mg bid AG + 20 mg bid HC) was administered to 14 patients (seven at stage IV). The median survival of this group was 17.3 +/- 2.9 weeks (P = 0.74 vs FAM alone). We conclude that addition of AG/HC does not add to the survival of patients with carcinoma of the pancreas treated with chemotherapy.

A randomized trial of aminoglutethimide +/- estrogen before chemotherapy in advanced breast cancer.

Recent reports have suggested that the sensitivity to chemotherapy of endocrine-dependent breast cancer may be enhanced by transient exposure to hormonal stimulation. To test this concept, 39 postmenopausal women with proven metastatic breast carcinoma and measurable disease were entered into this prospective, double-blind trial; 35 are currently evaluable. All patients were continuously treated with aminoglutethimide and hydrocortisone to lower estrogen production, plus cyclic chemotherapy. Patients in the "stimulation" arm received in addition, Estrace 2 mg b.i.d. sublingually for 3 days before and on the day of chemotherapy. Estrace administration appeared to accelerate tumor growth as demonstrated by increased bone pain, hypercalcemia, and growth of skin lesions. Response rates, response duration, and survival were similar in the stimulation and control groups.

Elevated sedimentation on coral reefs adjacent to a beach nourishment project.

An increasingly common method to restore eroding beaches is nourishment, a process by which lost sand is replaced with terrestrial or offshore sediments to widen beaches. The southeastern Florida coastline contains shore-parallel coral reef communities adjacent to eroding beaches. Scleractinian corals and other reef-associated organisms are known to demonstrate sensitivity to elevated sedimentation levels. Sediment traps were used to examine spatio-temporal sedimentation patterns and assess the effects of nourishment (dredge and fill) activities. Several environmental variables correlated with among-site spatial variability of sediment parameters. Intra-annual variability correlated with wind velocity and direction. Nourishment activities showed localized effects, with sites in close proximity to dredging areas exhibiting significantly higher collection rates and lower percent fines than control sites. A regional increase in sedimentation occurred while nourishment activities were ongoing. Due to concurrent impacts of hurricanes, only one during-construction sampling interval revealed substantially higher collection rates relative to corresponding pre-construction sampling intervals.

Agranulocytosis and hepatitis as a result of Mexican drug therapy.

A 26-year-old woman with debilitating juvenile rheumatoid arthritis was treated at a Mexican arthritis clinic with two unknown medications. She subsequently developed agranulocytosis and cholestatic hepatitis as an adverse reaction to these drugs, later identified as oxyphenbutazone and diazepam. The etiology of these drug-induced problems is reviewed, and the dangers of this unorthodox form of medical therapy are discussed.

Extensive tissue necrosis associated with warfarin sodium therapy.

Skin and soft tissue necrosis is an uncommon but increasingly recognized complication of coumarin anticoagulant therapy. A patient is described with extensive involvement of all four extremities and the nose, requiring amputation of three extremities. The characteristic clinical features of the disorder are reviewed, with a discussion of the pathology, pathogenesis, and possible treatment modalities.

A functional link between N-linked glycosylation and apoptosis in Chinese hamster ovary cells.

Seven different Chinese hamster ovary (CHO) cell mutants, isolated in different ways and having biochemical defects that were expressed at 34 degrees C, were found to be temperature sensitive for growth at 40.5 degrees C. Six of the mutants had five different lesions in N-linked glycosylation; two mutants were in the same complementation group. The temperature-sensitive phenotype in three mutants appeared by cell fusion studies to be linked to the glycosylation phenotype. In some of the glycosylation mutants [B4-2-1 (Lec15.1), Lec9, Lec1, and Lec24], but not in all of them (MI5-4 and MI8-5), incubation at 40.5 degrees C induced apoptosis, as determined by appearance of DNA fragmentation. Tunicamycin (TM) also induced apoptosis in both parental and Lec9 cells. There was a direct correlation between inhibition of glycosylation by TM treatment and induction of apoptosis. Induction of apoptosis by TM was inhibited by cycloheximide. These studies suggest that specific alterations in N-linked glycosylation in CHO cells are endogenous inducers of apoptosis.

Interaction of alpha-thalassemia genes with each other and with HbC in an American black family.

The relative rates of in vitro synthesis of hemoglobin chains have been studied in an American black family in which the mother is doubly heterozygous for alpha-thalassemia and HbC and the father is heterozygous for alpha-thalassemia. The alpha/non-alpha synthetic ratio was equally unbalanced in both the bone marrow and the peripheral blood of the mother. Although HbC comprised 35% of her hemoglobin (compared to 42.2 +/- 2.2 in individuals with HbC trait and balanced globin synthesis), synthetic data showed that the newly synthesized beta C chain was 44% of the total newly synthesized beta chains. Isolated membranes contained more newly synthesized beta C than beta A chains. Three of the offspring were within the normal range, and the remaining three had alpha-thalassemia. There were two spontaneous abortions during the second trimester of pregnancy. Hydrops fetalis did not occur, and none of the children had HbH disease or HbC trait.

The diagnosis of pulmonary thromboembolism in sickle cell disease.

The symptoms of thromboembolism in sickle cell anemia patients with acute chest syndromes are difficult to differentiate from the similar symptoms of painful thoracic crises and infectious pulmonary episodes. Furthermore, the chronic pulmonary abnormalities in sickle cell disease frequently contribute to the confusing results of noninvasive diagnostic procedures usually employed in evaluating pulmonary thromboembolism. In this study the chronic pulmonary status of asymptomatic sickle cell patients was defined, and this information was used in the evaluation of patients with acute chest syndromes suggestive of pulmonary thromembolism. Sixteen asymptomatic sickle cell patients were prospectively studied by chest roentgenography, spirometry, arterial gas analyses, and radioisotopic lung scans. There was an appreciable degree of preexisting chronic restrictive lung disease with mild to moderate arterial hypoxemia and abnormal lung scans in more than half of the patients. These prospective baseline data were incorporated into the diagnostic evaluation of four of these patients who later developed an acute chest syndrome suggestive of pulmonary thromboembolism. Determination of the cause of the chest pain was greatly faciliated by the existence of the baseline pulmonary data. In another patient persistence of abnormal studies following a presumed thromboembolic episode aided diagnostic evaluation when another episode of chest pain occurred. The findings indicate that comprehensive pulmonary studies in sickle cell patients while in an asymptomatic state will provide baseline data which aid the evaluation of possible pulmonary thromboembolism in acute chest syndromes without resorting to high-risk invasive studies.

Studies of the terminal stages of hemoglobin synthesis. II. Lack of effect of alpha and beta hemoglobin chains on the rate of globin synthesis in a human cell-free system.

The influence of heme containing alpha A and beta S globin chains on the rate of synthesis of globin subunits has been studied in a human cell-free system derived from sickle reticulocytes. The autologous lysate system produced measurable amounts of nascent protein as equal amounts of alpha and nonalpha chains, which were released as soluble globin. The addition of either alpha A or beta S hemoglobin chains in concentrations between 10(-5)M and 10(-8)M did not alter either the rate of total globin synthesis or the alpha/beta synthesis ratio. The results suggest that the presence of free hemoglobin chains within the cell does not in itself affect the rate of globin chain synthesis and that other mechanisms within the cell are more important in coordinating the synthesis of equal amounts of alpha and nonalpha globin chains. One cannot conclude that there is no effect on chain initiation, since in the mammalian systems very littl chain initiation occurs.

Effect of cancer chemotherapeutic agents on the chemiluminescence of human granulocytes.

21 unilateral breast cancer patients taking different combinations of chemotherapeutic agents (cyclophosphamide, methotrexate, 6-fluorouracil, vincristine, and prednisone) were studied to determine how chemotherapy affected their granulocytes. It is widely believed that in cancer patients chemotherapeutic agents increase susceptibility to infection. Therefore, luminol-enhanced chemiluminescence was used to evaluate leukocyte function since the chemiluminescence response has been correlated to bacterial killing. the chemiluminescence response in cancer patients (6-week treatment) was significantly reduced (approximately 50%; p less than 0.01) compared to nontreated volunteers. Preliminary studies using 3H-formyl-methionyl-leucyl-phenyl alanine binding showed similar decreases. We postulate that chemotherapy for 6 weeks may affect granulocyte precursor cells in bone marrow, thereby weakening peripheral granulocytes and reducing both their bactericidal capacity and 3H-formyl-methionyl-leucyl-phenyl alanine receptors.

Erythroid aplasia in juvenile rheumatoid arthritis.

A 9-year old girl had clinical manifestations of juvenile rheumatoid arthritis that were further complicated by severe anemia. Subsequent studies showed the anemia to be due to erythroid aplasia. Hematologic remission was induced with prednisone, 60 mg/day.

Evidence for a second chemotactic system in the cellular slime mold, Dictyostelium discoideum.

An unknown substance found in bacteria (Escherichia coli) is especially effective in attracting the vegetative amoebae of the cellular slime mold, Dictyostelium discoideum. However, the aggregating amoebae are not attracted to it at all. On the other hand, the vegetative amoebae show very little chemotactic response to cyclic adenosine monophosphate (cyclic AMP), whereas the aggregating amoebae are exceptionally responsive to it. It is suggested that the new factor may be used in food seeking, whereas cyclic AMP, the chemotactic substance responsible for aggregation, is the acrasin of this species. The important point is that the amoebae are differentially stage-specific in their responses to these two chemotactic agents.

The self-tuning controller: comparison with human performance in the control of arterial pressure.

A self-tuning controller was implemented for the automated infusion of sodium nitroprusside to lower mean arterial pressure in anesthetized dogs. The system incorporated a recursive least-squares parameter identifier and a modified minimum-variance controller. The onset delay was estimated on-line, the performance criterion included the cost of control, and requested step-changes were automatically translated into five successive smaller steps to reduce overshoot. The performance of the system in lowering mean arterial pressure was quantitatively compared with that of a well-trained anesthesiologist. In 10 runs in four animals, the automated system performed as well as the physician who devoted 100% of his attention to the task. Since the stability of the self-tuning controller cannot be guaranteed, such a system should be operated only in the presence of appropriate supervisory algorithms.