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Between 1967 and 1987, 26 patients with bronchogenic cysts were treated in our institution: 15 females and 11 males, ranging in age from 2 months to 14 years (average 6 years, 4 months). Only four patients (15%) were 1 year old or less. Seven patients presented with asymptomatic lesions discovered on chest film. Nineteen patients presented with respiratory symptoms. Of note are the four patients aged 1 year or less, who presented with dyspnea and cyanotic spells. Only one of them presented with dysphagia. All patients underwent routine chest films and tomography and, later, computed tomography (CT) scan of the thorax once the study became available. Barium esophagogram and bronchoscopy were performed as required. Contrary to what has been published concerning the intraparenchymal location of bronchogenic cysts, the majority of the cysts (65%) were located in the mediastinum, usually in close proximity to the carina, mainstem bronchi, trachea, esophagus, or pericardium. Only 27% (7 of 26) were intraparenchymal, and 8% (2 of 26) were situated in the inferior pulmonary ligament. A correct preoperative diagnosis was made in 19 patients (73%). Intrapulmonary lesions were removed by segmentectomy or lobectomy. Cysts located elsewhere were simply excised. Among the cysts adhering to the trachea, 50% (two of four) required suture of the membranous trachea after excision. Postoperative complications included one pneumonia, which responded to antibiotics, and one transient paresis of the right phrenic nerve. Follow-up averaged 17 months (range, 0 to 17 years). No sequelae were noted and all patients were cured.

We have utilized HPLC to develop optimal conditions for assaying the transformation of arachidonic acid in thrombin-treated human platelets. In the presence of increasing amounts of albumin, the total amount of radioactivity released from thrombin-treated platelets pre-labeled with 3H-arachidonic acid is first enhanced and then inhibited. Maximal release, reflecting primarily enhanced amounts of free labeled arachidonic acid, occurs at a final albumin concentration of 0.5 mg/ml. Calcium promoted the release of all radiolabeled metabolites, but it specifically enhanced HETE formation and release. Magnesium was without effect. Cyclo-oxygenase derived products constituted the bulk of released label at short time intervals, but after ten minutes exposure to thrombin in the presence of albumin (0.5 mg/ml) and 3 mM calcium, radioactivity in the released products was equally distributed among cyclo-oxygenase derived products (TXB2 + PGD2 + HHT), HETE and free arachidonic acid.

It has been suggested that inhibition of platelet cyclooxygenase by chronic low dose aspirin may spare vascular prostacyclin production. Conventional doses of aspirin (greater than 5 mg/kg) have been shown to inhibit the generation of both thromboxane A2 and prostacyclin. Low dose aspirin inhibits prostacyclin production by excised human venous tissue, thus questioning the selectivity of such regimens. However, many clinical and surgical conditions requiring platelet inhibition involve the arterial system. We have studied the effects of various aspirin regimens on platelet, venous, and arterial cyclooxygenase activity in a nonhuman primate (Macaca fascicularis). We determined the lowest chronic dose of oral aspirin required to effectively inhibit platelet cyclooxygenase and aggregation to be 1 mg/kg. After 14 days of 0, 1, or 2 mg/kg aspirin, intact veins and arteries were surgically removed and perfused, and luminal prostacyclin (6-keto-PGF1 alpha) generation was assessed. Levels of 6-keto-PGF1 alpha in venous perfusates were reduced by 89% and 86% (p less than 0.05) after 1 and 2 mg/kg, respectively. Arterial 6-keto-PGF1 alpha levels were unchanged by 1 mg/kg aspirin, but after 2 mg/kg were reduced by 66% (p less than 0.05). Preferential inhibition of platelet over arterial cyclooxygenase is thus achievable, but only over a narrow dose range.

Enteric coated aspirin (ECA) at doses of 325-1300 mg is an effective alternative to regular aspirin for inhibition of platelet activity while avoiding gastric irritation. The objectives of this study were to determine: (1) the lowest chronic dose of ECA providing effective inhibition of platelet activities, (2) the time course of the inhibition, and (3) the reappearance of platelet cyclo-oxygenase activity. Seven subjects were studied before and after seven daily doses of 40-325 mg ECA. Serum thromboxane (TX) B2 levels indicated that the lowest dose of ECA resulting in greater than 90% inhibition of platelet cyclo-oxygenase was 80 mg/d. Platelet aggregation and ATP release in response to collagen (1 microgram/ml) and arachidonic acid (1 mM) were abolished and bleeding times were prolonged from 6.1 +/- 1.5 min to 9.7 +/- 2.8 min (mean +/- SD, P less than 0.01). Examination of platelet cyclo-oxygenase activity on a daily basis revealed that 24 h after the first 80 mg dose serum TXB2 had decreased by approximately 60% and was suppressed by more than 90% after four doses. Recovery of platelet cyclo-oxygenase activity after a single 80 mg dose of ECA was delayed for 48-72 h indicating that aspirin reached the systemic circulation. We conclude that chronic inhibition of platelet activity may be achieved in a cumulative manner with 80 mg ECA/d.

Thirteen asymptomatic women taking oral contraceptives (OCs) were compared with normal subjects. Platelet aggregation and serotonin (tagged with carbon 14) release with adenosine diphosphate, epinephrine, and collagen did not differ from controls. Activation of the intrinsic coagulation pathway was evaluated by measurements of factor XII, prekallikrein, and kallikrein inhibitors. Women taking OCs had normal factor XII levels, moderately elevated prekallikrein levels, and decreased kallikrein inhibitor levels, a pattern not consistent with activation of the intrinsic pathway. The concentration of heavy molecular weight fibrinogen derivatives (HMWFD) was significantly elevated (P less than .001). In contrast, fibrin and fibrinogen degradation products in serum were lower than normal (P less than .05). The increased HMWFD concentration may reflect activation of the coagulation system not mediated by factor XII activation nor potentiated by decreased antithrombin III. Thus, plasma coagulation abnormalities rather than platelet changes may be the factor that predisposes women taking OCs to thromboembolic disorders.

Ethanol partitions into cellular membranes and alters membrane-associated phenomena in numerous cell types. Since platelet aggregation and its inhibition by prostacyclin are mediated by membrane-associated receptors and enzymes, we examined the interaction of ethanol, prostacyclin, and aspirin on human platelet reactivity. Using platelet-rich plasma, we examined the effect of increasing concentrations of ethanol (0.05% to 1.0%) on the platelet-inhibitory effects of a submaximal dose (5 x 10(-10) M) of prostacyclin, the concomitant production of cyclic 3',5'-adenosine monophosphate (AMP), and the release of thromboxane A2. Ethanol alone had little effect on platelet aggregation induced by 5 micrograms/ml collagen; however, it potentiated the inhibitory effect of prostacyclin on platelet aggregation in a dose-dependent manner in the range of 0.05% to 1.0% ethanol. Whereas prostacyclin increased platelet cyclic AMP levels, ethanol had no further effect on cyclic AMP levels. Ethanol alone reduced thromboxane A2 generation, but this effect could not totally account for the observed interaction of ethanol and prostacyclin on aggregation, since aspirin did not totally abolish the interaction. The dose range in which the ethanol/prostacyclin/aspirin interactions occur encompasses the plasma levels of ethanol that may be achieved by the consumption of alcoholic beverages. The results may, in part, explain the dose-related physiological and pathological consequences of chronic alcohol consumption on the cardiovascular system.

Pseudo-differential operators of order -M and type rho, delta(1), delta(2) are shown to be bounded in L(2) provided that 0