Nitrite plasma levels in normolipemic and hypercholesterolemic patients with peripheral occlusive arteriopathy

BACKGROUND: The authors studied the nitrite plasma levels in a group of patients with peripheral obstructive arteriopathy. METHODS: The series consisted of 63 subjects (43 males, 20 females, mean age 64 +/- 9 years) suffering from peripheral arterial occlusive disease of the lower limbs, at II (55 cases) and III (8 cases) Fontaine stage; 21 subjects with total cholesterol (TC) lower than 200 mg/dl were considered as normolipemics, 24 subjects with TC values between 200 and 240 as mild hypercholesterolemics, 18 subjects with TC above 240 mg/dl as severe hypercholesterolemics. For each subject the determination of nitrite plasma levels was carried out, by the Gutman and Hollywood colorimetric method. RESULTS: In the normolipemic arteriopathics the basal value of nitrites was sharply reduced (p < 0.05) compared to the controls; in the mild hypercholesterolemics the mean basal value of nitrites was markedly higher compared to the controls; in the severe hypercholesterolemics the mean basal value of nitrites was statistically (p < 0.05) higher than that of the controls. In the arteriopathic patients, globally considered, the mean basal value of nitrites was superimposable on that of the normal control subjects. CONCLUSIONS: This study, carried out on the nitrite plasma levels in a group of arteriopathic patients allowed us to show the enhanced levels of nitric oxide due to the increase of LDL; this effect, previously observed in hypercholesterolemic diabetic and coronaropathic patients, leads us to the hypothesis of a stimulating effect of LDL upon NO endothelial synthesis; this would be a compensatory response to the damaging and vasoconstricting action of LDL.     

Nitrite plasma levels in normolipemic and hypercholesterolemic arteriopathics after vasoactive and lipid-lowering treatment

BACKGROUND: The authors studied the plasmatic levels of nitrites, stable end-products of nitric oxide in arteriopathic patients before and after vasoactive and lipid-lowering treatment. METHODS: The series consisted of 63 subjects (mean age 64 +/- 9) suffering from peripheral arterial occlusive disease; 21 subjects with total cholesterol (TC) lower than 200 mg/dl were considered as normolipemic (group A); 24 subjects with TC ranging between 200 and 240 mg/dl were considered as mild hypercholesterolemic (group B); 18 subjects with TC higher than 240 mg/dl were consider as severe hypercholesterolemic (group C). All the patients were examined before and after 15 and 30 days of a vasoactive treatment (calciparine, aspirin, buflomedil and pentoxiphylline); group B after vasoactive and diet (NCEP phase 1) treatment and group C after vasoactive, diet and drug (simvastatin) treatment. Nitrite plasma levels were determined by the Gutman and Hollywood colorimetric method. RESULTS: In group A the basal value of nitrites was sharply (p < 0.05) lower than controls; after vasoactive treatment a significant increase (p < 0.05), was observed after 15 and 30 days; in group B the basal value was higher than controls; after 15 days a significant increase (p < 0.5) was noted, but a regression was found after 30 days. Also in group C the basal value of nitrites was higher (p < 0.05) than controls; after treatment significant changes were not found. CONCLUSIONS: The increase of nitrites in group A may be due to an improved endothelial function; this phenomenon, less appreciable in group B and no longer evident in group C may depend on the lipid-lowering treatment.     

Pharmacokinetics and protein binding of cis-dichlorodiammine platinum (II) administered as a one hour or as a twenty hour infusion

Summary The pharmacokinetics of cis-dichlorodiamminoplatinum (II) (cisplatin) have been studied in seven patients, of whom four received the drug as a one hour infusion and three received it as a 20 h infusion. The patients receiving the drug over one hour exhibited biphasic clearance of total platinum with a rapid initial phase (8.7–22.5 min) and a prolonged second phase (30.5–106 h). Free (ultrafilterable) cisplatin was readily detectable in this group and was rapidly cleared (half-life about 22 min). The volume of distribution of the drug was 50.3–65.6 liters and it was 26.6–50% excreted in the urine in 48h. In the patients receiving the 20 h infusion, a more complex plasma elimination curve was seen, with the appearance of a secondary peak. Free drug was not detectable in these patients and they showed less urinary excretion (21.4–25.9% at 48 h) than the one hour group. Cisplatin was bound to several plasma proteins, including albumin, transferrin, and -globulin. The data indicate that cisplatin is retained in the body more extensively after a 20 h infusion than after a one hour infusion.     

Phase II trial of extended indications for resection is small cell carcinoma of the lung

Surgical resection offers distinct theoretical advantages as the "local" modality in treatment of Stage I and II small cell carcinoma of the lung. We have treated 10 such patients by initial resection since 1975; all survivors but one received adjuvant chemotherapy for the full course thereafter. One patient died of a pulmonary embolus; the other nine remain without evidence of disease from 7 to 69 months after resection. A trial was undertaken of extended indications for resection in selected patients with Stage III-M0 disease. Criteria for patient selection have been developed gradually; these exclude patients for reasons of refusal, physiological inadequacy, disease unsuited to gross total eradication, or lack of adequate initial response to chemotherapy. Of six patients who survived the exclusion criteria and underwent resection, one has had a relapse at 26 months. All others remain without evidence of disease, 5 to 25 months after the start of treatment. We believe that systematic patient selection on the basis of defined criteria will identify a subset of patients having markedly improved chances for disease control. This group may represent as many as half of the patients first presenting with localized or MO disease. Patients excluded as candidates for resection have continued to receive standard nonsurgical combined-modality therapy.