Biomedical subjects
Publications and source records attributed to P Mehta.
This case represents leukemia and retinoblastoma in two separate children of a patient with retinoblastoma. This occurrence of retinoblastoma and acute lymphoblastic leukemia in the same sibship is uncommon and emphasizes multiple occurrence of some tumors.
Abnormalities of thromboxane (TXA2)-prostacyclin (PGI2) balance have been described in patients with coronary artery disease. Whether these abnormalities precede or follow an acute coronary event is debated. We report a patient in whom spontaneous acute right coronary artery occlusion was observed during coronary angiography. Measurements of arachidonic acid metabolites demonstrated imbalance in TXA2-PGI2 equilibrium preceding coronary occlusion. Marked increase in TXA2 in coronary sinus but not in the aortic blood suggested intracoronary release. Absence of PGI2 in the coronary venous blood at baseline and during tachycardia stress was evidence for failure of atherosclerotic coronary vessels to generate PGI2.
Vinca alkaloids are effective anticancer agents. Vindesine is a recent vinca alkaloid derivative with anti-tumor effects shown in in vitro systems and in patients with acute lymphocytic leukemia (ALL). The present study was designed to investigate the therapeutic effectiveness and toxicity of vindesine in combination with prednisone for remission induction in late stage ALL in children. Sixteen children with late-stage ALL were treated with vindesine 4.0 mg/m2/week intravenously and prednisone 60 mg/m2/day orally in four divided doses for minimum of three weeks. Thirteen children were evaluable. Of these patients, four had complete remission and four had partial response. Toxicity was well tolerated and consisted of bone pain, paresthesias, loss of deep tendon reflexes, leukopenia, and thrombocytopenia primarily. Abnormal liver function tests and fever were also noted in some patients. All patients had received vincristine and prednisone prior to vindesine prednisone combination. All patients had been resistant to vincristine prednisone combination prior to vindesine prednisone treatment. This study suggests effectiveness of vindesine in late stage ALL and lack of cross-resistance of vindesine and vincristine.
The hemodynamic effects of intravenous and intracoronary prostacyclin (PGI2) were evaluated in anesthetized, open-chest instrumented dogs. Coronary artery and aortic blood flows, aortic and left ventricular (LV) diastolic pressure, and heart rate were measured continuously. With intravenous PGI2 both left anterior descending (LAD) and circumflex (LCX) coronary artery blood flows remained unchanged; both arterial and LV diastolic pressures declined; coronary resistance declined progressively with increasing PGI2; peak reactive hyperemic flow following 10-second coronary artery occlusion declined progressively with increased PGI2; heart rate responses were variable at low doses but increased at high dose; and aortic blood flow increased consistently. With intracoronary PGI2 both LAD and LCX coronary blood flows increased promptly in dose-related manner. In dogs with critical coronary artery narrowing (loss of reactive hyperemia) created by an external plastic occluder, intravenous prostacyclin (0.5 microgram/kg/min) did not alter flow in narrowed coronary artery, but increased flow in the non-narrowed coronary artery (p less than 0.02) as both systemic arterial and LV diastolic pressure declined. These results show that PGI2 has potent direct coronary and systemic vasodilator actions.
To evaluate the effects of dipyridamole on blood platelet function in patients with coronary artery disease, platelet counts and aggregation were examined in aortic and coronary venous blood. Before administration of dipyridamole, platelet counts and aggregation in response to adenosine diphosphate were less (p less than 0.02) in coronary venous than in aortic blood. Dipyridamole administration (100 mg) resulted in an increase in platelet counts and platelet aggregation in coronary venous blood so that the differences in aortic and coronary venous blood values were eliminated. These phenomena were probably related to inhibitory actions of dipyridamole on platelet adhesion to atherosclerotic vessels. To further study the mechanism of action, the direct effects of dipyridamole on in vitro platelet aggregation were evaluated. Although dipyridamole, in the concentrations used, had no effect on in vitro platelet aggregation, it greatly potentiated the aggregation inhibitory actions of exogenous prostacyclin. In vivo potentiation of endogenous prostacyclin and inhibitory actions on platelet adhesion are the most likely mechanisms of the potentially beneficial actions of dipyridamole.
Platelet function was evaluated in 10 hypertensive and 11 normal subjects. In the placebo phase, the plasma beta thromboglobulin level (an index of platelet activation in vivo) was significantly (p less than 0.01) higher in the hypertensive than in the normal subjects; other tests of platelet function gave similar results in the two groups. After control of blood pressure with lofexidine (a centrally acting imidazoline derivative), plasma beta thromboglobulin levels decreased in 9 of the 10 hypertensive patients, but increased in one who showed no change in blood pressure. These studies suggest that enhanced platelet activation in primary hypertension may be associated with increased vascular resistance.
In the last decade, several studies evaluating blood platelet function in patients with coronary heart disease have been reported. Although several platelet function abnormalities such as enhanced platelet aggregation, decreased platelet survival and increase in platelet release reaction in the stable condition and during stress in patients with myocardial ischemia have been recognized, the mechanism of these abnormalities is just beginning to be understood. Discovery of certain platelet and endothelium-generated prostaglandins has provided some information as to the possible mechanism of platelet dysfunction. Abnormalities of prostaglandin production and platelet sensitivity to various prostaglandins may have an important bearing on the enhanced platelet aggregation in vivo, genesis of atherosclerosis and probably precipitation of acute ischemic events. Since the discovery of these prostaglandins, the precise mode of action of several commonly used platelet-active drugs has been clarified. Development of new drugs acting at selective steps in the prostaglandin pathways may provide some exciting novel therapeutic procedures in patients with coronary heart disease.
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In 12 nonpregnant women, total iodine, protein-bound iodine, inorganic iodine, and thyroxine values were measured in serum before and 15, 30, 45 or 60 minutes after a two-minute vaginal disinfection with povidone-iodine (Betadine). Only 15 minutes after application, serum iodine levels were raised and remained significantly elevated 30, 45 and 60 minutes after disinfection. Serum concentrations of total iodine and inorganic iodine were increased up to fivefold to 15-fold, respectively; during the relative short period of observation, thyroxine levels were not altered. An overload of iodine can suppress thyroid hormonogenesis, and the fetal and neonatal thyroid glands are especially sensitive. In pregnant women, vaginitis should not be treated with povidone-iodine because of the possible development of iodine-induced goiter and hypothyroidism in the fetus and newborn. The risk is especially high when povidone-iodine is used repeatedly.
Platelet prostaglandin generation (malondialdehyde production) and platelet sensitivity to prostacyclin (a vasodilator and platelet aggregation inhibitor) and to epoxymethanodienoic acid (EMA) (a vasoconstrictor and platelet aggregation stimulant endoperoxide analog) were studied in patients with angina pectoris and in control subjects. Platelet malondialdehyde production was higher in patients than in control subjects (mean +/- standard error of the mean 2.50 +/- 0.30 versus 1.70 +/- 0.13 nmol/10(9) platelets, p < 0.02). Platelets from patients were significantly less sensitive to prostacyclin's antiaggregatory effects than were those from control subjects (amount of prostacyclin required for 50 percent platelet aggregation inhibition 1.90 +/- 0.35 versus 0.68 +/- 0.05 ng, p < 0.02). Furthermore, less EMA was required to induce 50 percent platelet aggregation in patients with angina pectoris than in the normal subjects (133 +/- 8 versus 194 +/- 16 ng, p < 0.001). These observations suggest that increased platelet prostaglandin generation and abnormal platelet sensitivity to prostacyclin and endoperoxide analog in certain patients with coronary artery disease are important potential mechanisms in the pathogenesis of myocardial ischemia.
The effects of orally administered aspirin (650 mg) on platelet aggregation patterns and counts in aortic and coronary venous blood were evaluated in patients with coronary artery disease. Studies were conducted at rest and during the stress of tachycardia. Before administration of aspirin, platelet aggregation and counts were lower (p less than 0.01) in coronary venous blood than in aortic blood. The stress of tachycardia resulted in increased (p less than 0.01) platelet aggregation only in coronary venous blood. After administration of aspirin, differences in platelet aggregation and counts between coronary venous and aortic blood at rest were eliminated, and the tachycardia-associated increase in coronary venous blood platelet aggregation was significantly reduced. These observations suggest that aspirin influences and abolishes the changes that occur in blood platelet function as platelets traverse the atherosclerotic myocardial vascular bed. The absence of an increase in platelet aggregation during the stress of tachycardia after administration of aspirin may have important pathophysiologic and therapeutic implications.
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One-hundred twenty-nine high-risk infants with thrombocytopenia and 238 control infants without thrombocytopenia were evaluated. Mothers of thrombocytopenic babies had similar history to those of nonthrombocytopenic babies, although fewer chronic narcotic abusers were found among mothers of thrombocytopenic babies. Thrombocytopenia was more common in babies less than 37 weeks' gestation and in sick babies compared to healthy babies. Sixty percent of infants had no recognizable cause of thrombocytopenia. Features associated with thrombocytopenia included umbilical line placement, respiratory assistance, hyperbilirubinemia, phototherapy, prematurity, respiratory distress syndrome, low Apgar score, sepsis, meconium aspiration, and necrotizing entercolitis. Thrombocytopenic babies had Apgar score, sepsis, meconium aspiration, and necrotizing entercolitis. Thrombocytopenic babies had more complications, more hemorrhage, and greater mortality than nonthrombocytopenic babies. Platelet size was increased in two babies with immune thrombocytopenia and in none of the others. This study shows that neonatal thrombocytopenia is often associated with high-risk factors and with increased hemorrhage, morbidity, and mortality. This relationship suggests an important prognostic value to platelet size was increased in two babies with immune thrombocytopenia and in none of the others. This study shows that neonatal thrombocytopenia is often associated with high-risk factors and with increased hemorrhage, morbidity, and mortality. This relationship suggests an important prognostic value to platelet counts, although the extent to which the thrombocytopenia contributed directly to morbidity and mortality is not clear.
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In vitro platelet aggregation responses to epinephrine and ADP were significantly lower in patients with sickle cell disease when compared to age- and sex-matched normal subjects. Platelet aggregation responses were reduced in all patients regardless of clinical status. Measurement of circulating platelet aggregates showed normal values in patients with sickle cell disease in steady state or with infection alone, but a significant increase in others with acute vaso-occlusive crises. Recovery from vaso-occlusion was associated with a decline in circulating platelet aggregates. This study suggests that in vivo platelet activation may result in "tired" platelets which are refractory to epinephrine and ADP stimulation in vitro.