Biomedical subjects

S W Needleman

Publications and source records attributed to S W Needleman.

27 records · Page 2Linked to original sources

PubMed1982

Catechol estrogens and thrombosis: lack of a direct effect of 2-hydroxyestradiol on platelets.

Women who use the oral contraceptive pill are at risk for a variety of thromboembolic complications, but the precise mechanism is unclear. Since 2-hydroxyestradiol is a major metabolite of estradiol and possesses some of the structural and functional properties of catecholamines, we examined whether this compound might influence thrombogenesis, in particular whether it would exert an epinephrine-like effect on the platelet. In vitro, 2-hydroxyestradiol does not cause or potentiate aggregation or thromboxane release, nor does it prevent the rise in cyclic AMP caused by anti-aggregatory prostaglandins. While 2-hydroxyestradiol does not exert a direct effect on the platelet in vitro, it may play a role in thrombosis in women who take oral contraceptives through another mechanism.

Blood Platelets↗

PubMed1982

Catechol estrogens and thrombosis: differential effect of 2-hydroxyestradiol and estradiol on prostacyclin release.

High estrogen burden states, such as that seen in women who ingest oral contraceptive preparations, are associated with increased thrombosis. In other instances, however, estrogens decrease thrombogenicity. Variations in conversion to active metabolites could explain this paradox. Thus, we examined the influence of estradiol and a major metabolite, 2-hydroxyestradiol (catechol estrogen), on prostacyclin release from cultured human umbilical venous endothelium. In micromolar concentrations, both compounds inhibited prostacyclin (PGI2) release from bradykinin-, arachidonic acid-, and ionophore-stimulated, as well as unstimulated monolayers. However, when thrombin was used to stimulate release, estradiol enhanced, while 2-hydroxyestradiol inhibited, PGI2 formation. These sex steroids probably exert their influence at micromolar concentrations through a non-specific interaction with the cell membrane, and may be of importance in the predisposition to thrombosis suffered by those who use oral contraceptives.

Cells, Cultured↗

PubMed1982

Enrichment of human platelet phospholipids with linoleic acid diminishes thromboxane release.

We have investigated whether exposure of human platelets to elevated concentrations of linoleic acid, the principal dietary polyunsaturate, would influence platelet thromboxane A2 release. Platelets were incubated with albumin-bound linoleic acid at 30 degrees C for 24 h, with prostaglandin E1 added to prevent aggregation. The linoleic acid supplemented platelets released, on average, 50% less thromboxane A2 in response to stimulation with thrombin than corresponding control platelets. Other fatty acids were without appreciable effect. The inhibition of thrombin-stimulated thromboxane A2 release was dependent on the time and temperature of incubation, as well as on the concentration of added linoleic acid. Supplementation increased the amount of linoleic acid in the platelet phospholipids, but the arachidonic acid content of the phospholipids was reduced. [1-14C]Linoleic acid was not converted to arachidonic acid by the platelets. Linoleic acid was released exclusively from the inositol phosphoglycerides when the enriched platelets were stimulated with thrombin. The linoleate-enriched platelets converted less [1-14C]arachidonic acid to all prostaglandin products, suggesting that the platelet cyclooxygenase was partially inhibited.

Arachidonic Acid↗

PubMed1982

A comparative study of thromboxane and prostacyclin release from ex vivo and cultured bovine vascular endothelium.

Thromboxane B2, 6-keto-Prostaglandin F1 alpha, and Prostaglandin E2 release have been quantitated from cultured adult bovine endothelial cell monolayers and from ex Vivo vascular segments employing specific radioimmunoassays and thin layer chromatography. Release of all three prostaglandins was demonstrable from both endothelial cell systems under basal conditions and following exposure to the ionophore A23187 and arachidonic acid. In culture, the quantity of 6-keto-PGF1 alpha released was diminished compared to amounts released from the vessel segments while thromboxane B2 and prostaglandin E2 release were similar in the two endothelial model systems. However, the amount of thromboxane B2 assayed was small and the quantity of thromboxane A2 it represents is probably of little in vivo significance compared to prostacyclin.

6-Ketoprostaglandin F1 alpha↗

PubMed1982

Systemic lupus erythematosus complicated by disseminated sarcoidosis. Report of a case associated with circulating immune complexes.

The association of SLE with sarcoidosis has been reported infrequently. The case of a 47-year-old white woman who had the diagnosis of SLE made at our institution in October of 1979 is presented. In February 1980, the onset of bilateral hilar adenopathy prompted an investigation leading to the diagnosis of sarcoidosis. Circulating immune complexes were markedly elevated. The association of these two diseases has only recently been recognized and may be more widespread than previously suspected. Some animal and clinical data, in concert with our observations, suggest that humoral autoimmunity may give rise to both processes in the same patient.

Antigen-Antibody Complex↗

PubMed1981

Hypoplastic acute leukemia.

There have been few reports of acute leukemia presenting with a hypocellular bone marrow. All patients diagnosed as having acute leukemia were identified during a recent six-year interval who had blast cells plus promyelocytes of greater than 30% and marrow cellularity of needle biopsy less than or equal to 50%. Of 195 patients analyzed, 15 (7.7%) fulfilled the criteria. Ten patients were men and five women; the median age was 68 years with a range of 40-82. Seven complained of fatigue of 6-12 months duration, five were seen with occult infection, and three were asymptomatic. Hepatosplenomegaly was absent in 93% and none had lymphadenopathy. Fourteen patients were pancytopenic with median leukocyte count at presentation of 1.5 X 10(9)/liter, hemoglobin of 9.0 g/dl, and platelet count of 55 X 10(9)/liter. Circulating blast cells were not observed in ten patients; in the other five they were less than 0.7 X 10(9)/liter. The morphology of all cases appeared myeloid and Auer rods were seen in three patients; however, in one the peroxidase was negative. Classification according to FAB criteria revealed ten to be M1, three to be M2, one M4, and one L2. Median survival of the entire group was seven months. Of seven patients receiving no chemotherapy, two survived longer than 1 year (14, 24.5 months), one is alive at 7+ months, and the median survival was seven months. Eight patients with life-threatening complications received various combination regimens including an anthracycline, cytosine arabinoside, 6-thioguanine, vincristine, and prednisone. Five died of treatment complications; two achieved durable complete remission and are free of disease at 17 and 27 months. It can be concluded that hypoplastic acute leukemia is a distinct nosologic entity affecting primarily older patients with myeloid leukemia. Remission induction therapy in patients who are seriously ill has a low success rate, and in some patients prolonged survival is possible with supportive care alone.

Acute Disease↗

PubMed1981

Pulmonary embolism in patients with acute leukemia and severe thrombocytopenia.

While pulmonary thromboembolism has been reported in patients with acute leukemia complicated by severe thrombocytopenia, it has been studied infrequently and its pathogenesis remains imprecisely understood. Findings of 80 consecutive autopsies of patients with acute leukemia showed that three had pulmonary thromboembolism. All three patients had been severely thrombocytopenic and had received numerous platelet transfusions. Serial sections of thrombi were evaluated with electron microscopy. In no instance were platelet aggregates detected. However, Candida organisms were prominent in thrombotic specimens from each patient. These findings suggest that thromboembolism in such patients may involve occult fungal infection. Because pulmonary thromboembolism can complicate the course of acute leukemia and severe thrombocytopenia, it should be considered when clinical data suggest its occurrence.

Acute Disease↗

PubMedDate not supplied

Basic principles of chemotherapy in the treatment of metastatic head and neck cancer.

For patients who fail to achieve control of head and neck cancer with local therapy, chemotherapy offers limited benefit at present. Better understanding of the phenomena which surround tumor cell killing by active agents should allow for the rational design of more effective programs. For example, as tumors grow larger, many cells cease to engage in DNA synthesis and are refractory to drugs like methotrexate. In such a case, alkylating agents might be more effective. Tritiated thymidine uptake and nuclear DNA fluorescence studies can be exploited to analyze the kinetic and metabolic behavior of tumor cells, and are described. For animal models these studies have allowed the design of "kinetic" regimens of enhanced efficacy. Methotrexate, hydroxyurea, cyclophosphamide, vinblastine, and cis-platinum have appreciable antitumor activity in head and neck carcinoma. Combining active agents in a rational sequence could be facilitated by kinetic analysis of a patient's tumor, giving rise to specific regimens with more cytoreduction, less toxicity and resistance, and ultimately, better survival.

Antineoplastic Agents↗

PubMedDate not supplied

Effect of chemotherapy for the dysmyelopoietic syndrome.

Twenty patients are described who received chemotherapy for the diagnosis of acute myeloid leukemia but who were subsequently reclassified as having dysmyelopoietic syndrome using the French-American-British criteria. Thirteen patients had refractory anemia with excess blast cells (RAEB) (age range, 23-82 years; median, 68) and seven had chronic myelomonocytic leukemia (CMML) (age range, 44-79 years; median, 70). Three patients (two with RAEB and one with chronic myelomonocytic leukemia) had previously been treated with cytotoxic therapy for another malignancy. In 15 patients the antileukemic therapy was a chemotherapy regimen that was highly active in acute nonlymphoblastic leukemia (ie, containing daunorubicin and/or cytarabine). These patients achieved complete remission lasting 14, 34+, and 36+ months and survival times of 31, 35+, and 37+ months. All three patients were from a subgroup of four patients characterized by RAEB, younger age, no previous cytotoxic therapy, and treatment with an aggressive chemotherapy regimen. The median survival time of the patients not achieving remission was 1 month (range, less than 1-22). Our results suggest that while most patients with the dysmyelopoietic syndrome appear to have their life shortened by chemotherapy, there is a subgroup characterized by younger age, absence of previous cytotoxic therapy, and the morphologic picture of RAEB who can have a favorable response to aggressive treatment.

Adult↗