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.

Antibodies to bovine beta-casein in diabetes and other autoimmune diseases.

Cow's milk is thought to be an environmental trigger for autoimmune response in Type 1 diabetes. In the present study, our aim was to investigate the antibody response to bovine beta-casein in different immune- and non-immune-mediated diseases and to establish whether such an antibody response is specific to Type 1 diabetes. We measured antibodies to bovine beta-casein using an enzyme-linked immunosorbent assay in a total of 519 sera from subjects as follows: 71 patients with Type 1 diabetes, 33 patients with coeliac disease, 100 patients with latent autoimmune diabetes in adults (LADA), 50 patients with autoimmune thyroid disease (ATD), 50 patients with Type 2 diabetes, 24 patients with multiple sclerosis (MS), and 3 different groups of controls (n = 191). Significantly increased levels of antibodies to beta-casein were found in patients with Type 1 diabetes, coeliac disease and in LADA compared to age-matched controls (p = 0.01, p = 0.02 and p = 0.01, respectively). No differences were observed in beta-casein antibody titres between patients with other disease conditions (MS, and ATD) and age-matched controls. The highest antibody response to beta-casein in Type 1 diabetic patients and in patients with coeliac disease could reflect the gut mucosal immune disorders common to Type 1 diabetes and coeliac disease. Furthermore, the elevated beta-casein antibody levels found in LADA patients suggest that the antibody response to this protein may be relevant in autoimmune diabetes.

Chinese hamster ovary cells with reduced hexokinase activity maintain normal GDP-mannose levels.

Parental Chinese hamster ovary (CHO) cells were mutagenized and subjected first to a mannose suicide selection technique and second to a screen of individual colonies grown on polyester discs for reduced mannose incorporation into protein. The incorporation of radioactivity for the selection and the screen was conducted at 41.5 degrees C instead of the normal growth temperature of 34 degrees C in order to allow for the isolation of temperature-sensitive lesions. This selection/screening procedure resulted in the isolation of M15-4 cells, which had three- to five-fold lower incorporation of [2-3H]mannose into mannose 6-phosphate, mannose 1-phosphate, GDP-mannose, oligosaccharide-lipid, and glycoprotein at 41.5 degrees C. We detected no difference in the qualitative pattern of mannose-labeled lipid-linked oligosaccharides compared to parental cells. M15-4 cells synthesized dolichol. The defect of M15-4 cells was determined to be in hexokinase activity; crude cytosolic extracts were eight- to nine-fold lower in hexokinase activity in M15-4 cells compared to parental cells. As a result of this defect, incorporation of labeled mannose from the medium was significantly decreased. However, the level of GDP-mannose in M15-4 cells was 70% of normal. The phenotype of M15-4 was a lower specific activity of labeled GDP-mannose, not a substantial reduction in the level of GDP-mannose. Consistent with these results, no alterations in the glycosylation of a model glycoprotein, G protein of vesicular stomatitis virus, were observed. These cells grew slower than parental cells, especially in low-glucose medium.

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.

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.

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.

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.

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.

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.

Combination of vindesine and prednisone in malignant lymphoma and acute leukemia.

Nineteen patients with advanced refractory lymphoma and 12 patients with acute leukemia, including seven in blastic crisis of chronic myelogenous leukemia (CML), were treated with vindesine in combination with prednisone. Of 16 evaluable patients with lymphocytic or histiocytic lymphoma, one achieved complete remission (6%) and eight achieved partial remissions (50%). Median duration of response was 12 weeks (range, 4-72+). Four of six evaluable patients in blastic crisis of CML showed definite improvement in blood cell counts and symptoms. The major dose-limiting toxic effect was bone marrow suppression, while neurotoxicity was seldom cause for dose modification. The study shows vindesine and prednisone to be active in heavily pretreated patients with non-Hodgkin's lymphoma and blastic phase of CML.

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.

Phase II study of vindesine in patients with advanced breast cancer.

Vindesine, a new vinca alkaloid, was administered to 20 patients with advanced refractory breast cancer in a phase II trial. The drug was given at a dose of 3 mg/m2 by iv bolus each week for 6 consecutive weeks, and responding patients were maintained on a dose of 4 mg/m2 every 2 weeks. Nineteen patients were evaluable for disease response; partial remissions were obtained in five patients, for a response rate of 26%. Leukopenia was the major dose-limiting toxic reaction, but most patients were able to tolerate this schedule without difficulty. Neurotoxicity was mild and did not require dose reduction.

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.

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.

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.

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.

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.