Effects of a K+ATP channel opener, lemakalim, on systemic, coronary and regional vascular dynamics in conscious dogs: comparison with nifedipine, adenosine, nitroglycerin and acetylcholine

The systemic, coronary and regional vascular responses to the K+ATP channel opener lemakalim were compared to other potent vasodilators (i.e., nifedipine, adenosine, nitroglycerin and acetylcholine). Experiments were performed in 12 conscious dogs 2 to 4 weeks after implantation of aortic catheters and flow probes on the ascending aorta, left circumflex coronary, celiac, mesenteric, renal and iliac arteries, and solid-state miniature pressure gauges in the left ventricular cavity. Dose-response curves induced by bolus injection (i.v.) were examined. For doses that reduced total peripheral resistance by 22%, lemakalim reduced celiac (-28 +/- 2%), mesenteric (-24 +/- 3%), renal (-17 +/- 3%) and iliac (-18 +/- 3%) vascular resistances (i.e., by amounts similar to those observed with the other vasodilators, except for adenosine, which increased renal resistance). At these doses, lemakalim induced a greater decrease (-52 +/- 3%) (P < .05) in coronary resistance, as compared with nifedipine (-35 +/- 3%), adenosine (-38 +/- 3%), nitroglycerin (-25 +/- 2%) and acetylcholine (-32 +/- 3%). However, when near maximal vasodilation was elicited, adenosine elicited the greatest (P < .05) decrease in coronary resistance (-81 +/- 1%), as compared with lemakalim (-74 +/- 2%), nifedipine (-67 +/- 2%), nitroglycerin (-63 +/- 2%) and acetylcholine (-72 +/- 1%). Both the time to maximal increases in regional blood flow and the time for recovery in all vascular beds were significantly prolonged for lemakalim compared with the other vasodilators. Thus, the K+ATP channel opener lemakalim dilates the coronary bed out of proportion to other vascular beds, is relatively more potent at lower doses than other vasodilators and exhibits a delayed and more prolonged action in all regional vascular beds.     

Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3

Supplementation with high doses of alpha-tocopherol has increased the oxidation resistance of LDL in many clinical trials. There have been only a few placebo-controlled trials in healthy persons of alpha-tocopherol doses usually contained in dietary supplements. We carried out a single-blind, placebo-controlled, randomized trial to examine the effect of 200 mg RRR-alpha-tocopheryl acetate/d on the oxidation resistance of atherogenic lipoproteins (VLDL+LDL including intermediate-density lipoproteins) in 40 smoking men. VLDL+LDL oxidation resistance was assessed as conjugated dienes after copper induction and hemin degradation after hydrogen peroxide induction. Also, the LDL total peroxyl-radical trapping antioxidant parameter (LDL TRAP) and plasma malondialdehyde were measured at baseline and after 2 mo of supplementation. Plasma RRR-alpha-tocopherol concentrations were measured at 2-h intervals for 12 h at baseline and after 2 mo of supplementation. Compared with placebo, 200-mg RRR-alpha-tocopheryl acetate supplementation elevated plasma and VLDL+LDL alpha-tocopherol concentrations, LDL TRAP, and oxidation resistance of VLDL+LDL. Plasma alpha-tocopherol increased by 88% (P < 0.0001), VLDL+LDL alpha-tocopherol increased by 90% (P < 0.0001), and LDL TRAP by 58% (P < 0.0001). The time to the start of oxidation (lag time) was prolonged by 34% when assessed with a copper-induced method and by 109% when assessed with a hemin + hydrogen peroxide-induced method; the time to maximal oxidation was prolonged by 21% (copper-induced method) in the vitamin E-supplemented group. Changes in plasma alpha-tocopherol, lipid-standardized alpha-tocopherol, and VLDL+LDL alpha-tocopherol correlated significantly with changes in LDL TRAP, lag time, and time to maximal oxidation. Differences in changes between groups in the area under the curve for plasma alpha-tocopherol were significant (P < 0.009). Our results suggest that 200 mg oral RRR-alpha-tocopheryl acetate/d had a clear effect on the in vitro oxidation of VLDL+LDL in smoking men.     

Do antral washouts have a place in the current management of chronic sinusitis?

Antral washouts have been widely used in the management of chronic sinusitis. With the advent of modern antibiotics and powerful topical nasal steroids, we sought to establish if a role remains for this procedure. One hundred and fourteen patients with chronic sinusitis were randomised into two groups. Patients in Group A received antral washouts followed by antibiotics and topical nasal steroids. Patients in the Group B received antibiotics and topical nasal steroids alone. In each group 51.6 per cent and 50 per cent of patients respectively improved with treatment. The outcome of treatment is also not influenced by endoscopic abnormality. The difference was not statistically significant (p = 0.86). The study indicates that half of patients with chronic sinusitis will improve with medical treatment but the addition of antral washout confers no additional benefits.     

Evaluation of the efficacy of sequential intravenous-oral administration of pefloxacin in community-acquired lower respiratory tract infections in patients with underlying conditions

We studied the efficacy of sequential intravenous-oral pefloxacin therapy in community-acquired lower respiratory tract infection in 24 patients with one or more underlying conditions. Twenty-eight patients were enrolled into the study but only 24 patients were evaluated. There were 16 males and 8 females with a mean age of 66.9 +/- 11.2 years (mean +/- SD, range 46 to 87 years). The underlying conditions present were bronchiectasis, chronic obstructive lung disease and diabetes mellitus. Patients who were older than 70 years but without any underlying condition were also enrolled. All received 4 days of intravenous pefloxacin 400 mg twice a day followed by oral pefloxacin 400 mg twice a day for another 10 days. Assessment of success was based on clinical, microbiological and radiological improvement. Pefloxacin produced 79.2% clinical cure rate. Another 8.3% showed improvement. Pefloxacin was well tolerated. There were few adverse effects and none of the patients required a change of antibiotic. Pefloxacin was an effective and well tolerated treatment for respiratory tract infection and had the advantage of broad in-vitro antibacterial activity, twice daily dosing and sequential availability in an intravenous and oral formulation.     

Endothelin-1 concentrations and optimisation of arterial oxygenation and venous admixture by selective pulmonary artery infusion of prostaglandin E1 during thoracotomy

PURPOSE: To demonstrate a superselective intraarterial chemotherapy as a therapeutic alternative in the treatment of previously treated recurrent lymph node metastases in breast cancer. METHODS: 14 patients with recurrent lymph node metastases in cases of breast cancer were presented to be treated by intraarterial chemotherapy of 25 mg mitoxantrone/m2 over a period of 24 hours. In two patients with superclavicular lymph node involvement an intraarterial therapy could not be carried out because of a vascular connection to the anterior spinal artery. Involved lymph stations could be reached in superselective technique by side branches of the subclavian artery. Heparin coverage was given intravenously. Every patient had had surgery, radiation, systemic chemo- and hormonal therapy before and was now graded as inoperable. Therapy indication was given by local tumour-induced symptoms. RESULTS: In the 12 treated cases complete remission was seen in three, partial remission in 4, a steady state in two and a progressive disease in three. There were no complications or severe side effects. CONCLUSION: Intraarterial chemotherapy is an effective and well tolerated treatment in recurrent lymph node metastases in cases of breast cancer even if conventional therapies can no longer be used.     

Hyperdynamic circulation of cirrhotic rats: role of substance P and its relationship to nitric oxide

BACKGROUND: It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO. METHODS: Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization. RESULTS: Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05). CONCLUSIONS: Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.     

Item assessment in the development of a diagnostic motor performance test for myopathy in children

The authors conducted an assessment study of newly developed motor performance items for the diagnosis of myopathy. 17 children who had had muscle biopsy for this diagnosis in the recent past were administered 14 items based on the measurement of static, dynamic and explosive muscle strength and muscle endurance. Individual items did not have perfect discriminative power, but the results were encouraging enough to warrant detailed study with combinations of the items, so that in future fewer children will have to undergo unnecessary muscle biopsies.     

Visual, cognitive, and neurodevelopmental outcome at 51/2 years in children with perinatal haemorrhagic-ischaemic brain lesions

To determine predictive values of early visual and neurocognitive assessment in children with perinatally acquired haemorrhagic or ischaemic brain lesions selected on the basis of ultrasound, 63 children (37 boys, 26 girls), who had been followed and examined until the age of 18 months, were reexamined at 5 1/2 years. Good correlations between visual and neurodevelopmental assessments at 18 months and at 5 1/2 years were found. When ultrasound abnormalities were combined with early visual and neurocognitive assessment data, good predictive values, especially for the group of children who had grade 2 to 4 leukomalacia, were found for visual acuity and neurodevelopment.