Comparison of antihypertensive effects of nicardipine with nitroglycerin for perioperative hypertension

BACKGROUND: To compare the efficacy of intravenous (iv) nicardipine with nitroglycerin for the treatment for patients with perioperative hypertension. METHODS: Forty patients with perioperative hypertension randomly divided into two groups were treated with intravenous calcium entry blocker, nicardipine, or vasodilator, nitroglycerin. Haemodynamic measurements including mean arterial and pulmonary arterial pressure, central venous and pulmonary capillary wedge pressure, and cardiac output were recorded; peripheral and pulmonary vascular resistance were calculated. RESULTS: Both medications were effective in reducing blood pressure and controlling haemodynamics. During the maintenance by continuous iv infusion, nicardipine controlled hypertension more rapidly than nitroglycerin (nicardipine 10.5 +/- 2.5 min and nitroglycerin 18.7 +/- 2.8 min, p < 0.05) without significant alteration in heart rate. The total frequency of dose adjustments required to achieve therapeutic response was significantly less in the nicardipine-treated group (2.5 +/- 0.3 for nicardipine and 6.2 +/- 1.4 for nitroglycerin, p < 0.05). Incidence of hypotensive episodes during the infusion were observed in both groups [nicardipine 5% (1/20) and nitroglycerin 30% (6/20), p < 0.05]. CONCLUSIONS: Intravenous nicardipine is as effective as nitroglycerin in the treatment of perioperative hypertension. Specific advantages have been identified such as stable dose-response effect, less hypotensive and tachycardial effects during the use of iv nicardipine in treatment of hypertensive patients.     

Thromboembolism in chronic atrial flutter: is the risk underestimated?

OBJECTIVES: We sought to evaluate the risk of thromboembolic events in the presence of chronic atrial flutter and to determine the impact of anticoagulation therapy, if any, on this risk. BACKGROUND: Thromboembolic events are thought to be rare after cardioversion of atrial flutter. METHODS: This study was a retrospective analysis of 110 consecutive patients referred to the electrophysiology laboratory for cardioversion of chronic atrial flutter from 1986 to 1996. Atrial flutter was present for at least 6 months. Of the 110 patients reviewed, 100 had adequate information available regarding the effectiveness of anticoagulation (mean age 64 years, range 27 to 86; 75 men, 25 women; mean left ventricular ejection fraction 42%). RESULTS: Thirteen patients (13%) had a thromboembolic event. Of these, seven were attributable to causes other than atrial flutter. In the remaining six patients (6%), thromboembolic events occurred during a rhythm of atrial flutter or after cardioversion to sinus rhythm. Other causes of thromboembolism were excluded. Effective anticoagulation was associated with a decreased risk of thromboembolism (p = 0.026). CONCLUSIONS: Patients with chronic atrial flutter are at an increased risk of thromboembolic events. Effective anticoagulation may decrease this risk.     

Acute aortic dissection complicating pregnancy

BACKGROUND: Acute aortic dissection occurring during pregnancy represents a lethal risk to both the mother and fetus. Our purpose was to study the prevalence, treatments, and outcome of this rare problem and to suggest therapeutic guidelines. METHODS: During the past 12 years, 6 pregnant women were admitted with an acute aortic dissection. Four had a type A and 2 had a type B dissection (Stanford classification). RESULTS: Two of the 4 patients with a type A dissection underwent a combined emergency operation consisting of first cesarean section and then ascending aortic repair. Cesarean section was carried out 5 days after the emergency procedure on the aorta in the third patient, and 16 weeks later in the fourth patient. All 4 fetuses were delivered alive. One fetus died 6 days later, but the other 3 are alive and well at long-term follow-up. Of the 2 patients with a type B dissection, 1 was operated on for celiac ischemia; the other was treated medically. In both cases the fetus died in utero. There were no maternal deaths in either group. CONCLUSIONS: Cesarean section with concomitant aortic repair is recommended for pregnant women with a type A dissection, depending on the gestational age. The maternal hemodynamic status will determine the sequence of the two procedures. Medical treatment is advised for patients with a type B dissection, but surgical repair is indicated if complications such as bleeding or malperfusion of major side branches occur.     

Costs and effects of microsurgery versus radiosurgery in treating acoustic neuroma

This study analyses costs and effects of treating acoustic neuroma patients by using microsurgery compared to radiosurgery. Radiosurgery is the stereotactic application of radiotherapy and an innovative medical technology. Cost and effect estimates of conventional treatment were based on a retrospective study in the Netherlands. Similar data for a comparable group of patients in Sweden were collected for radiosurgery, as this treatment option is currently not available in the Netherlands. Fifty-three acoustic neuroma patients who had been operated on the University Hospital Rotterdam between November 1990 and February 1995 were included. This group was compared with 92 acoustic neuroma patients treated with radiosurgery (Gamma Knife. Stockholm, Sweden) in the same period. Data on health care use were collected from patient files. To obtain data on production losses and quality of life, a questionnaire was sent by mail in February 1995. This booklet consisted of the Health and Labour-questionnaire (HLQ), the Short Form-36 (SF36) and the EuroQol. The response rate was 92%. Direct costs for microsurgery amounted to Dfl. 20.072,- and for radiosurgery to Dfl. 14.272,-. Indirect costs were respectively Dfl. 16.400,- and Dfl. 1.020,-. General health rating was better for radiosurgery than for microsurgery. On the whole, differences in clinical outcomes between the two patient groups were small. Assuming a reasonable occupancy rate of the expensive radiosurgery equipment, we demonstrated that for the short term treating patients with acoustic neuroma with an extra-meatal tumour diameter of less than 3 centimeters, radiosurgery is more cost-effective than microsurgery.     

Phosphorylation by protein kinase C is required for acute activation of cystic fibrosis transmembrane conductance regulator by protein kinase A

Protein kinase A (PKA) stimulates Cl secretion by activating the cystic fibrosis transmembrane conductance regulator (CFTR), a tightly regulated Cl- channel in the apical membrane of many secretory epithelia. The CFTR channel is also modulated by protein kinase C (PKC), but the regulatory mechanisms are poorly understood. Here we present evidence that PKA-mediated phosphorylation alone is not a sufficient stimulus to open the CFTR chloride channel in the presence of MgATP; constitutive PKC phosphorylation is essential for acute activation of CFTR by PKA. When patches were excised from transfected Chinese hamster ovary cells, CFTR responses to PKA became progressively smaller with time and eventually disappeared. This decline in PKA responsiveness did not occur in the presence of exogenous PKC and was reversed by the addition of PKC to channels that had become refractory to PKA. PKC enhanced PKA stimulation of open probability without increasing the number of functional channels. Short-term pretreatment of cells with the PKC inhibitor chelerythrine (1 microM) reduced the channel activity that could be elicited by forskolin in cell-attached patches. Moreover, in whole cell patches, acute stimulation of CFTR currents by chlorophenylthio-cAMP was abolished by two chemically unrelated PKC inhibitors, although an abrupt, partial activation was observed after a delay of >15 min. Modulation by PKC was most pronounced when basal PKC phosphorylation was reduced by briefly preincubating cells with chelerythrine. Constitutive PKC phosphorylation in unstimulated cells permits the maximum elevation of open probability by PKA to reach a level that is approximately 60% of that attained during in vitro exposure to both kinases. Differences in basal PKC activity may contribute to the variable cAMP responsiveness of CFTR channels in different cell types.     

Immunoglobulin G responses against human papillomavirus type 16 virus-like particles in a prospective nonintervention cohort study of women with cervical intraepithelial neoplasia

BACKGROUND: Infection with cancer-linked human papillomavirus (HPV) types such as HPV type 16 (HPV16) is the most important risk factor in the development of cervical cancer. It has been shown that immunoglobulin G (IgG) antibody responses against HPV16 virus-like particles (VLPs) are specifically associated with genital HPV16 infection. PURPOSE: The aim of this study was to determine the temporal relationships between the presence of HPV16 VLP-specific IgGs, HPV16 infection patterns, and the course of premalignant cervical disease. METHODS: Plasma samples from 133 women who had been diagnosed originally with mild to moderate cervical dyskaryosis and enrolled in a prospective non-intervention cohort study conducted in Amsterdam, The Netherlands, from 1991 through 1996 were analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked immunosorbent assay. A detailed analysis was performed on 43 women with different HPV16 infection patterns during a follow-up period of 10-34 months. Progression or regression of cervical intraepithelial neoplasia (CIN) lesions was monitored by cytologic and colposcopic testing at intervals of 3-4 months. HPV typing in cervical smears was performed by use of a polymerase chain reaction-based assay. Statistical analysis of the serologic data was performed by use of the Mann-Whitney U test or 2 x 2 table analyses. RESULTS: The presence of HPV16 VLP-specific IgGs in the plasma of the patients was found to be associated with the presence of HPV16 DNA in the cervical smear. Significantly higher proportions of patients with persistent HPV16 infections (i.e., who were polymerase chain reaction positive in three to 11 consecutive tests) than of patients with cleared HPV16 infections were found to be positive for the presence of HPV16 VLP-specific IgGs (18 [69.2%] of 26 versus nine [28.1%] of 32, respectively; P = .003). HPV16 VLP-specific IgGs were consistently detected in all women (n = 11) who were persistently HPV16 DNA positive during follow-up and whose disease ultimately progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in situ). CONCLUSION: HPV16 VLP-specific IgG responses are present in the plasma of a majority of patients with persistent HPV16 infections and histologically confirmed high-grade lesions but only in a smaller subset of patients with cleared HPV16 infections and either normal cervical histology or low-grade CIN lesions. IMPLICATIONS: These results suggest that HPV16 VLP-specific antibodies are not responsible for the clearance of virally induced CIN lesions but that they might, in patients with persistent HPV16 infections, be indicative of an increased cervical cancer risk.     

Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations

Oxidized low density lipoprotein (LDL) and acetyl LDL are recognized by the scavenger receptor class A type I/II (SR-AI/II) on macrophages and liver endothelial cells. Several investigators have suggested that there are additional receptors specific for oxidized LDL, but characterization of these alternate receptors for oxidized LDL and evaluation of their quantitative importance in uptake of oxidized LDL has been difficult because of overlapping ligand specificity with SR-AI/II. The purpose of this study was to determine the importance of SR-AI/II in the removal of modified LDL from the bloodstream in vivo. The clearance rate of oxidized LDL from plasma in normal mice was very rapid, and > 90% of injected dose was removed from the blood within 5 min. Clearance rates of oxidized LDL were equally high in SR-AI/II knockout mice, indicating that this receptor is not required for removal of oxidized LDL from plasma. Surprisingly, there was no difference in the clearance rate of acetyl LDL in wild-type and SR-AI/II knockout animals. The plasma clearance of radioiodinated acetyl LDL was almost fully blocked by a 50-fold excess of unlabeled acetyl LDL, but the latter only inhibited oxidized LDL clearance by approximately 5%. Both modified LDLs were cleared mostly by the liver, and there was no difference in the tissue distribution of modified LDL in control and knockout mice. Studies in isolated nonparenchymal liver cells showed that Kupffer cells accounted for most of the uptake of oxidized LDL. Extensively oxidized LDL and LDL modified by exposure to fatty acid peroxidation products were efficient competitors for the uptake of labeled oxidized LDL by SR-AI/II-deficient Kupffer cells, while acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors.