Endothelial Vascular Function in Hypertensive Patients After Renin—Angiotensin System Blockad

It is unclear whether single and combined pharmacologic inhibition of the renin-angiotensin-aldosterone system have similar effects on endothelial function and blood pressure (BP). The authors evaluated 63 hypertensive patients divided into 4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%±2.4% vs 13.5%±2.0%; hydrochlorothiazide, 7.3%±2.0% vs 12.8%±3.1%; QUIN, 7.2%±2.8% vs 13.2%±2.1%; IRBE, 7.1%±2.8% vs 13.0%±2.9%; and IRBE + QUIN, 7.5%±1.9% vs 12.8%±3.0%. Nitroglycerin-mediated responses were: normal, 26.0%±1.9% vs 24.0%±2.5%; hydrochlorothiazide, 17.0%±2.2% vs 18.3%±2.6%; QUIN, 17.8%±3.2% vs 23.4%±3.0%; IRBE, 16.8%±3.6% vs 24.7%±2.0%; and IRBE + QUIN, 17.3%±3.0% vs 25.1%±2.5%. Antihypertensive therapy restored BP to normal and improved the endothelium-dependent and -independent dysfunction after renin-angiotensin-aldosterone system blockade. In a further finding, the combined effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade was not superior to the action of either of these treatments separately.     

Design-based stereological estimation of hepatocyte number, by combining the smooth optical fractionator and immunocytochemistry with anti-carcinoembryonic antigen polyclonal antibodies.

BACKGROUND/AIMS: Hepatocytes (HEP) have been the major target for structural quantification in the liver, but an estimation of their total number (N), their percentage in relation to the global number of liver cells and the evaluation of the percentage of binucleated hepatocytes (BnHEPs) have never been performed with modern design-based stereological techniques. The establishment of sound technical guidelines and baseline quantitative data in non-pathological conditions are relevant to properly evaluate HEP hyperplasia and BnHEP responses. METHODS: In this study, we combined immunocytochemistry with sound design-based stereology for estimating the N of HEP and the N of non-hepatocytic cells (NHCs). For obtaining systematic uniform random sections (30 microm thick), a smooth fractionator sampling scheme was applied to the liver of five male Wistar rats (3 month old). Those sections were immunostained with polyclonal antibodies against carcinoembryonic antigen. Because biliary canaliculi were then marked, an unequivocal counting of mononucleated hepatocytes (MnHEP) and BnHEP was allowed. RESULTS: The N of HEP was estimated to be 1.93 x 10(9), with a coefficient of error (CE) of 0.02, corresponding to 129 x 10(6) HEP/g of liver. BnHEP represented 26% of total HEP number. The N of NHC was estimated as 1.31 x 10(9) (CE=0.02). CONCLUSION: The strategy here presented provides a reliable method for accessing the N of HEP (distinguishing MnHEP from BnHEP) in situations in which these parameters are relevant, namely for evaluating the magnitude of an hyperplastic liver response from its very early onset.     

Fixation of cementless acetabular cups: A radiographic 4-8-year study of 102 porous-coated components

We studied fixation changes over time in 113 porous-coated Howmedica (PCA) cementless acetabular cups inserted in 90 patients 1984-1988. The mean follow-up was 5 years. Radiographic fixation was classified as stable, fibrous-stable, or unstable. 9 cups, 3 in neutral position and 6 vertical, were revised. At follow-up, 40/75 neutral cups were stable versus 7/27 vertical cups. Most stable cups and two thirds of the unstable cups were clinically good. After the first 2 years, 28/75 neutral cups and 10/27 vertical cups changed their fixation: 12 had improved fixation and 26 had a worse one.     

Rare associations of dens invaginatus and mesiodens.

Dens invaginatus is a developmental variation resulting from an alteration in the normal growth pattern of the dental papilla. Synonyms of this disturbance include dens in dente, invaginated odontome, tooth inclusion, and dentoid in dente. Radiographically, it is observed as infolding of a radiopaque ribbon-like structure, with equal density as enamel, extending from the cingulum into the root canal and sometimes reaching the root apex, assigning the appearance of a small tooth within the coronal pulp cavity. This article presents 2 case reports. The first describes an 8-year-old girl with dens invaginatus in a mesiodens; the second report describes a 16-year-old boy presenting with 2 mesiodens, both associated with dens invaginatus.     

An External Aortic Root Device for Decreasing Aortic Regurgitation: In Vitro and In Vivo Animal Studies

Objectives: The purpose of this study was to determine if a device placed externally around the aortic root decreases regurgitant flow in acute aortic regurgitation. Background: Aortic regurgitant flow is dependent on central aortic pressure and the aortic root and leaflet geometry. It may be possible to decrease aortic regurgitant severity by reducing aortic root size or dimension changes. Methods: Aortic regurgitation was created in eight calf heart specimens suspended in a continuous flow system. Retrograde and antegrade aortic flow and distending aortic pressure were measured at baseline and after placement of an external aortic device at the level of the aortic annulus. In two additional specimens, the incompetent aortic valve was visualized fiberoptically before and after placement of the external device. Acute aortic regurgitation was created surgically in four live calves by excising a portion of the aortic leaflets. Antegrade and retrograde flow, left ventricular pressure, and central aortic pressure were measured at baseline, after creation of aortic regurgitation, and after placement of the external device. Results: In the in vitro calf specimens, regurgitant flow decreased from 46.9 cc/sec to 15.1 cc/sec (66.0%± 21.8% decrease) after placement of the external device (p < 0.001). The regurgitant orifice area decreased from 0.13 ± 0.04 cm² to 0.04 ± 0.02 cm² after device placement (p < 0.001). Antegrade flow was reduced to a smaller extent (20.0%± 19.2% decrease) by the device (p < 0.05). Placement of the device around the aorta resulted in improved coaptation of the leaflets with a marked reduction in defect size by endoscopic visualization. Use of the external aortic device was associated with improvement in aortic regurgitant severity in three of four calves with surgically created aortic regurgitation. Concluslons: In these preliminary studies, acute experimental aortic regurgitant severity is decreased by the use of an external aortic device, probably due to reduction in aortic annular dimension changes and improved aortic leaflet apposition. Further studies are needed to determine the effectiveness of this device in chronic aortic regurgitation. (J Card Surg 1994;9:304–313)     

Association of myopathy with large-scale mitochondrial dna duplications and deletions: Which is pathogenic?

We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50–year-old woman with an adult-onset progressive myopathy. The predominant mtDNA abnormality was a 21.2–kb duplicated molecule. In addition, a small population of the corresponding partially deleted 4.6–kb molecule was detected. Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase chain reaction analysis, COX-negative fibers contained a low number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.     

Effects of a toxin from the mucus of the caribbean sea anemone (Bunodosoma granulifera) on the ionic currents of single ventricular mammalian cardiomyocytes

The effects were studied of a toxin (Bainh) isolated from the secretion of the Caribbean sea anemone Bunodosoma granulifera on electrical and mechanical activities of rat ventricular muscle. The effects on the ionic currents of single rat and dog ventricular cardiomyocytes were studied using the whole-cell recording patch-clamp technique. In the concentration range from 1 to 10 mg/ml, Bainh increased the force of contraction and induced an increase in action potential duration of ventricular multicellular preparations. In single cardiomyocytes, at concentrations up to 10 mg/ml Bainh showed no significant effects on the sodium current. However, at 0.5–1 mg/ml it increased the L-type Ca current (I_CaL) by 25–50%. This increase in I_CaL was not voltage dependent and was reversible after washout. The transient outward current was not significantly affected by Bainh (1–10 mg/ml). In this concentration range, Bainh markedly (≈75%) increased the inward-going rectifier current, I_K1. This effect that was not voltage dependent and was fully reversible upon returning to control solution. It is suggested that these effects on ionic currents could explain the positive inotropic action of Bainh on cardiac multicellular preparations.     

Cyclic guanosine 3'3' monophosphate concentrations in pre-eclampsia: effects of hydralazine

Objective To elucidate the role of the L-arginine: nitric oxide pathway in pregnancy and pre-eclampsia.
Participants Pregnant women (nulliparous, age < 25 years). Normotensive pregnancy (   n = 22  ) was defined when blood pressure remained at levels of < 120/80 mmHg and there was no proteinuria. Women with pre-eclampsia (   n = 22  ) had blood pressure measurements of > 140/90 mmHg and proteinuria of > 300 mg/l. Nonpregnant normotensive women (   n = 22  ) were studied as controls.
Study Design Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5'monophophate (GMP), arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine.
Results L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD15.7)μM] were increased significantly (   P < 0.05  ) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) μM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) μM]. Concentrations of cyclic GMP in plasma and urine increased significantly (   P < 0.05  ) in women treated with hydralazine.
Conclusions The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine.