Activity of renin-angiotensin-aldosterone system (RAAS) and vasopressin level in patients with primary pulmonary hypertension

AIM: Assessment of RAAS and vasopressin in patients with primary pulmonary hypertension (PPH). MATERIALS AND METHODS: Activity of plasma renin (APR), angiotensin-converting enzyme (ACE), plasma levels of angiotensin II (AII) and vasopressin (VP), serum concentration of aldosteron (AS) were measured by radioimmunoassay and enzyme immunoassay in 21 PPH patients with circulatory failure (age 34.7 +/- 2.1 years), 11 patients with NYHA functional class II-III, 10 with class IV, and 10 control subjects (age 29.8 +/- 1.5 years). RESULTS: Compared to controls, 21 PPH patients had elevated RAAS parameters: APR up to 3.52 ng/ml/h (p < 0.05), activity of ACE up to 43.13 units, AII level up to 33.93 ng/ml (p < 0.01), AS up to 468.86 ng/ml (p < 0.01), VP up to 5.26 ng/ml (p < 0.001). Circulatory failure progression resulted in activation of all the RAAS components. This and VP activation was the greatest in PPH patients with ACE > 5 ng/ml/h. PPH patients with mean pressure in the pulmonary artery higher than 60 mm Hg demonstrated higher ARP, AS, VP, AII, ACE than those who had this pressure under 60 mm Hg. CONCLUSION: PPH patients display a noticeable activation of RAAS and VP. This activation seems to be secondary as the changes increase with elevation of the pressure in the pulmonary artery and aggravation of circulatory insufficiency. Plasma renin activity determines the degree of RAAS activation as a whole. The discovered activation of RAAS in PPH gives grounds for doubts in the validity of using ACE inhibitors in the treatment of PPH.     

The effect of a two-week anti-orthostatic hypokinesia on the cardiac function and on the latter''s regulation in monkeys

Medical practice guidelines are being developed rapidly and advocated as a crucial component in transforming and improving the delivery of health care services. However, little is known about the ability of hospitals to institute guidelines outside of experimental settings. This article approaches guideline implementation from the viewpoint of process innovation assimilation and presents specific recommendations for organizational tactics leading to successful implementation of practice guidelines.     

Hypermutability of mouse chromosome 2 during the development of x-ray-induced murine myeloid leukemia

In an effort to identify the precise role of a deletion at regions D-E of mouse chromosome 2 [del2(D-E)] during the development of radiation-induced myeloid leukemia, we conducted a serial sacrifice study in which metaphase chromosomes were examined by the G-banding technique. Such metaphase cells were collected from x-irradiated mice during the period of transformation of some of the normal hematopoietic cells to the fully developed leukemic phenotype. A group of 250 CBA/Ca male mice (10-12 weeks old) were exposed to a single dose of 2 Gy of 250-kilovolt-peak x-rays; 42 age-matched male mice served as controls. Groups of randomly selected mice were sacrificed at 20 hr, 1 week, and then at intervals of 3 months up to 24 months after x-irradiation. Slides for cytogenetic, hematological, and histological examination were prepared for each animal at each sacrifice time. An expansion of cells with lesions on one copy of chromosome 2 was evident in 20-25% of treated mice at each sacrifice time. The majority of such lesions were translocations at 2F or 2H, strongly suggesting hypermutability of these sites on mouse chromosome 2. No lesions were found in control mice. The finding leads to the possibility that genomic lesions close to 2D and 2E are aberrants associated with radiation leukemogenesis, whereas a single clone of cells with a del2(D-E) may lead directly to overt leukemia. The data also indicate that leukemic transformation arises from the cumulative effects of multiple genetic events on chromosome 2, reinforcing the thesis that multiple steps of mutation occur in the pathogenesis of cancer.     

Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals

To compare multiple and singleton pregnancies in the treatment of threatened preterm delivery with prolonged intravenous ritodrine, 32 women with multiple pregnancy (26 twins, 6 triplets, 70 fetuses, 30.3 +/- 3.5 weeks) and 51 women with singleton pregnancy (31.3 +/- 2.6 weeks) admitted for threatened preterm delivery without rupture of the membranes were the subjects of a retrospective study of obstetric data, perinatal outcome and maternal adverse effects. Significance was assessed by chi 2 test and Student's t test. Multiple pregnancies were associated with a marked increase in the duration of tocolysis (17.2 +/- 17.3 vs. 7.6 +/- 8.1 days, P < 0.01), incidence of delivery before 37 weeks (87.5 vs. 35.3%, P < 0.01) and incidence of maternal cardiovascular complications (34.4 vs. 4.0%, P < 0.01), including three cases of pulmonary edema. The incidences of delivery before 32 weeks (12.5 vs. 7.8%) and of neonatal death (2.9 vs. 0%) were not significantly different in the two groups. Multiple pregnancies dramatically increased the incidence of maternal adverse effects of prolonged intravenous ritodrine therapy. Neonatal benefit is questionable and was difficult to establish since it was not a randomized study.     

The effect of an original analog of the C-terminal fragment of vasopressin on the behavior of white rats

Ethinylestradiol (EE) has evident paradoxical effects on cancer risk for human breast and hepatic cancer which parallel in some respects its effects on estrogen-induced neoplasms in the hamster kidney and liver. EE has been shown to be only weakly carcinogenic in the hamster kidney, but the most potent carcinogenic estrogen in the hamster liver following prolonged treatment. Unexpectedly, when EE and potent carcinogenic estrogens, such as diethylstilbestrol (DES), 17beta-estradiol (E2) and Moxestrol (MOX), are administered concomitantly, estrogen-induced carcinogenesis in the kidney is completely prevented. In studying this novel finding, we found that, compared with E2 exposure alone, EE at 0.05 and 1.0 nM significantly (P < 0.001) inhibited the rise in proliferation of cultured primary hamster proximal renal tubular (PRT) cells in the presence of E2 (1.0 nM). Consistent with these findings, combined EE + DES treatment for 5.0 months reduced hamster kidney c-myc, c-fos and c-jun RNA expression to 43, 37 and 52%, respectively, compared with levels observed after DES treatment alone. Interestingly, TAM + DES treatment for the same period also resulted in the same low level of RNA expression of these proto-oncogenes. c-MYC, c-FOS and c-JUN protein products were comparably reduced after either EE + DES or TAM + DES treatment. It appears that c-fos expression and c-FOS protein levels in the hamster kidney were more responsive to TAM inhibition. These data demonstrate that EE possesses unique anti-tumorigenic properties in vivo in the hamster kidney. Additionally, the observed anti-estrogen-like effect of EE on cell proliferation of cultured PRT cells suggests that EE may interfere critically with estrogen receptor (ER)-mediated mitogenic pathway(s) affected by potent carcinogenic estrogens, thus preventing subsequent gene dysregulation and, hence, tumor development. Based on competition studies, the differential binding of EE to hamster kidney ER relative to that of the other estrogens (E2, DES, MOX) appears not to contribute to the prevention of estrogen carcinogenesis at this organ site by EE.     

Comparative study of permeability of derivatives of gamma-aminobutyric and gamma-hydroxybutyric acids through hemato-encephalic barrier]

The authors studied the permeability of the blood-brain barrier (CEB) to two nootropics: calcium ketogomopantothenate (KRA-Ca), a GABA derivative, and and calcium salt of oxybutyrate (OB-Ca), a derivative of GOBA. It was established that both preparations penetrate the CEB easily and are found in the brain at different intervals after their administration. However, essential differences in the distribution constant of these drugs were disclosed: KPA-Ca permeated the CEB more intensively and was accumulated in larger amounts in the late-term intervals.     

The effect of the special instruction of bronchial asthma patients on the efficacy of their treatment

As the data collected in a survey we conducted show, a major part of the modern general practitioner's work continues to be in the field of family medicine. This fact is also confirmed by the results of other surveys of general practice today. Patients still appreciate their GPs as a source of good medical care and counseling for the whole family. Our own study has shown that most patients would even like to see an expansion of the GP's counseling activities. The duration of the doctor-family relationship extends over many years, and is frequently longer than a decade.     

Expression of matrix metalloproteinases and their inhibitors in aneurysms and normal aorta

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by degradation of collagen and elastin resulting from increases in matrix metalloproteinase (MMP) activity. Previous authors have identified isolated increases in expression of specific MMPs in AAAs, but none have compared relative levels of expression of particular MMPs to one another or to those of their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). This study proposes to quantify relative mRNA levels for interstitial collagenase (MMP-1), 72 kd type IV collagenase (MMP-2), 92 kd type IV collagenase (MMP-9), TIMP-1, and TIMP-2 in normal aorta (NA) and AAA to provide insight as to the relative importance of each in aneurysm formation. METHODS: Competitive polymerase chain reactions (PCRs) with gene-specific external standards and cDNA derived from AAAs (n = 8; mean age, 67.4 years) and NA (n = 5; mean age, 40.6 years) were used to quantify mRNA levels. Results were normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels, determined by means of competitive PCR, and compared by means of Mann-Whitney statistics. RESULTS: Significant increases in MMP mRNA expression in AAA over NA were observed for MMP-1 (3.64 versus 0.3, p = 0.007), MMP-9 (78.03 versus 3.35, p = 0.003), TIMP-1 (835.32 versus 477.2, p = 0.027), and TIMP-2 (18.09 versus 4.14, p = 0.003). The ratio of MMP to TIMP mRNA levels was higher in AAA than NA (0.135 versus 0.045, p = 0.018). CONCLUSIONS: Increases in expression of MMP-1, MMP-9, and MMP/TIMP ratios may result in increased proteolysis and matrix degradation, which characterize AAAs. MMP-9 appears to be the predominant metalloproteinase expressed in AAA, because its mRNA levels were more than 20 times and 2 times higher than those of MMP-1 and MMP-2, respectively. TIMP-1 mRNA levels were in molar excess to those of any of the metalloproteinases studied.     

Collateral blood supply through the ophthalmic artery: a steal phenomenon analyzed by color Doppler imaging

OBJECTIVE: This study aimed to evaluate the retrobulbar circulatory effects of reversed ophthalmic artery flow (ROAF) on the ophthalmic artery branches by means of color Doppler imaging. DESIGN: The design was a case-controlled study. PARTICIPANTS: Among 56 consecutive patients with severe (>70% stenosis) occlusive carotid artery disease, 15 patients (26.8%) with ROAF were identified. The control group consisted of 15 patients with similar degrees of carotid artery stenosis and forward ophthalmic artery flow. INTERVENTION: Arteriography and measurement of the retrobulbar hemodynamic parameters with color Doppler imaging were performed. MAIN OUTCOME MEASURES: Blood flow velocities and resistive index in the ophthalmic, central retinal, and temporal short posterior ciliary arteries were measured. RESULTS: Arteriography confirmed the diagnosis of ROAF in all 15 patients. There was no patient with ROAF diagnosed by arteriography and not diagnosed by color Doppler imaging. The frequency of bilateral severe occlusive carotid artery disease was significantly higher in the ROAF group (40%) compared to the control group (6.6%) (P = 0.04). Patients with ROAF showed significantly reduced vascular resistance in the ophthalmic artery (P = 0.03), higher vascular resistance, and lower blood flow velocities in the central retinal and temporal short posterior ciliary arteries (P < 0.05). CONCLUSION: This study suggests that patients with ROAF show a steal phenomenon, characterized by a shunt to the low-resistance intracranial circuit and reduction of retrobulbar blood flow.     

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.