[Role of sympathetic nerve fibers in hemodynamic responses to stress in rats]. Hemodynamic responses to acute stress exposure were studied in normotensive control (C) and chronically sympathectomized (S) rats. Male Sprague-Dawley rats received daily sc injections of either saline (C) or guanethidine (S) from 1 to 13 weeks of age. Doppler flow probes were then implanted for the measurement of blood velocity in the sub-diaphragmatic aorta, superior mesenteric artery and distal aorta (hindquarters). After 10 days of recovery and 24 hours before the study, the caudal artery was cannulated. In the conscious freely moving rats, mean arterial pressure (MAP), heart rate (HR) and indices of regional blood flows and vascular conductances (G as blood flow/MAP ratio) were recorded beat to beat, before and during emotional stress (jet of air for 2 min). In basal conditions, mean values of MAP and HR were similar in C (107 +/- 2 mmHg; 399 +/- 8 bpm, n = 9) and S (106 +/- 3 mmHg; 384 +/- 12 bpm, n = 7) rats. The effects of stress on MAP, HR, aortic (AoG), mesenteric (MeG) and hindquarters (HqG) vascular conductances are expressed as percentage changes from baseline (delta): [table: see text] These results highlight the role of vascular sympathetic nerves in pressor responses and systemic and mesenteric vasoconstrictions induced by stress in the rat. They also indicate that vasodilatation in the hindquarters vascular bed is not secondary to withdrawal of sympathetic vasoconstrictor tone but rather to active phenomena which do not involve the stimulation of vascular beta 2-adrenoceptors by neuronal catecholamines nor the release of vasodilator cotransmitters from the sympathetic nerve endings.


[Methods of computerized approach of dysautonomia from a non-invasive pressure signal]. examination of an automated exploration of autonomic neuropathy using the Ewing score and evaluation of sympatho-vagal tone. continuous non-invasive collection of blood pressure (BP) data by means of Finapress fingerprobe. The signal was analysed after digitization at 500Hz, sampled and computerised. Values of systolic BP (SBP), diastolic BP (DBP) and heart rate (HR) are analysed by Anapres (Notochord). the pressure monitor is placed on the finger and the reading calibrated to the BP value recorded by auscultatory method on the contralateral arm to give a gap of less than 10 mmHg. BP and HR response to five different manoeuvres are recorded, namely: at rest over 7 minutes, after lying decubitus for 15 minutes; on rising suddenly over 3 seconds, and then over 9 minutes standing still; during 2 respiratory manoeuvres (a) deep breathing over 6 cycles per minute, (b) Valsalva pressure at 40 mmHg sustained over 20 seconds; isometric exercise with sustained handgrip at 30% maximal force sustained over 3 minutes. a dedicated computer programme displays in graphic form BP and HR over each manoeuvre and allows the operator to locate the exact cut-off of normality for each test of the Ewing score and also measure the balance of sympatho-vagal tone by Fourier transformation of the interval data of HR or BP peaks. this approach allows evaluation of autonomic function and sympatho-vagal tone by means of 40 minutes of clinical testing and two minutes of automated analysis. This approach seems useful in the assessment of the autonomic nervous system in diabetes.


[Pheochromocytoma, first manifestation of Von Hippel-Lindau disease: a possibility to be considered]. Von Hippel-Lindau (VHL) disorder is an autosomal dominant disease characterized by the almost constant development of hemangioblastomas in the central nervous system (cerebellum, spinal cord and retina). In addition, various types of tumors including renal cell carcinomas, pancreatic cysts and pheochromocytomas are frequently observed in VHL gene carriers. Linkage of the VHL locus to the RAF-1 oncogene on the short arm of chromosome 3 (3p25-26) has been recently reported. Pheochromocytoma is of particular interest because of the risk of inaugural malignant hypertensive crisis but especially because of a great degree of interfamily variability (from 0 to 92% of affected members in previously reported large kindreds). We have studied a French series of 25 pheochromocytoma (11 males, 14 females) in VHL affected patients. Twenty pheochromocytoma (80%) occurred in a familial context, whereas 5 (20%) were consistent with "apparent sporadic cases". The mean age at pheochromocytoma diagnosis was 27 years (5-55 years). Bilateral tumours have been documented in 13 cases (52%). The prevalence of pheochromocytoma revealing VHL was 14 out 25 (56%). In these cases, VHL diagnosis was considered up to 25 years later. In 6 cases (2 deceased) pheochromocytoma was the only manifestation of VHL. Thus, search for VHL must be systematic in the presence of pheochromocytoma, in the interest of the patients themselves and of potential at-risk family members (prevention of hypertensive crisis linked to latent tumours). Basic check-up (neurological and somatic examination, ophthalmoscopy, familial inquiry) may be completed with cerebral CT scan or MRI and abdominal ultrasonography followed, if positive or doubtful, by abdominal MRI or selective angiography.


[Comparison of 3 methods of measurement of blood pressure in insulin-dependent diabetic patients with or without incipient diabetic nephropathy]. Incipient diabetic nephropathy is characterized by a urinary albumin excretion (UAE) between 30-300 mg/24 h and a slightly elevated blood pressure. We measured blood pressure in 14 insulin-dependent diabetic subjects (IDDs) with persistent microalbuminuria (group A) and 50 IDDs with persistent normoalbuminuria (group B) using 3 different methods: 1) Sphygmomanometer, by a nurse, on supine position since 10 min, on the third day of hospitalization; 2) automatic device (Dinamap), on supine position, every 5 min, during 30 min; 3) ambulatory blood pressure (Spacelab 90202 every 15 min between 8 a.m. and 8 p.m.; values obtained with this last method were compared to the mean values of healthy subjects of same age. Recorded UAE was the median value of 3 twenty-four-hours urines. Blood pressure was not different among the two groups with any of the three methods: 1) SBP/DBP A: 136 +/- 14/81 +/- 9 vs B: 131 +/- 13/78 +/- 8 mmHg; ns; 2) SBP/MBP/DBP A: 134 +/- 17/96 +/- 12/79 +/- 10 vs B: 127 +/- 13/90 +/- 10/74 +/- 10 mmHg; ns; 3) A: 132 +/- 12/97 +/- 11/84 +/- 9 vs B: 127 +/- 11/91 +/- 9/82 +/- 12 mmHg; ns. There were no concordance between microalbuminuria/normoalbuminuria and systolic or diastolic blood pressure higher/lower than the mean of the healthy subjects (X2 = 1.6; ns). However, UAE was significantly related to MBP measured with 1): r = 0.29; p = 0.027, but not with 2): r = 0.24; ns, nor with 3): r = 0.26; ns. These results suggest that: 1-blood pressure of IDDs should be measured in standardized conditions; 2-diurnal ambulatory blood pressure recording does not predict incipient nephropathy in these subjects.


[Value of nocturnal blood pressure in treated non-insulin-dependent hypertensive patients]. The purpose of the study was to evaluate the loss of nocturnal (N) decline in blood pressure (BP) in type II treated hypertensive diabetics. The study concerned 36 hypertensive diabetics 59 +/- 10 years old, 20 men and 16 women, with poor metabolic control (HbA1C: 9.6 +/- 3%), without dysautonomia; 14 had macroproteinuria and/or microalbuminuria (mu alb) (< 30 micrograms/min). An ambulatory BP monitoring (Spacelabs 90207) was performed in all patients. Left ventricular mass index (LVMI) and E/A were determined by Doppler-echocardiography. Two groups (G) were individualized: G1 (n = 17), with a normal circadian rhythm (diurnal and N.BP significantly different); G2 (n = 19) with a loss of N decline in systolic (S) and diastolic (D) BP or both; and compared to non diabetic treated hypertensive controls (G3). There was no difference neither in LVMI (125 +/- 43 g/m2), E/A (0.7), 24 h-mean (M) BP in the three groups, nor in HbA1C levels and mu alb occurrence in G1 and G2. Mean N.SBP and mean N.DBP were more closely related to LVMI in G2 than in G1 and G3. [table: see text] Half of these hypertensive diabetics, with bad metabolic control, have an altered circadian BP pattern; the prognostic value of nocturnal BP, related to LVMI despite the antihypertensive treatment, is suggested.


[Measurement of blood pressure in obese patients: reliability and value of finger measurement (Finapres)]. Indirect measurement of the blood pressure in obese persons is still inaccurate, especially if the arm circumference deeply differs from one measure point to the other, so that the use of a wide bladder is inappropriate. Some alternative solutions have been described: oscillometric device on the arm or on the forearm, different shapes of the cuff-bladder, auscultation on the radial artery with the cuff on the forearm. We tested the capability of the Finapres device which measures the finger arterial blood pressure, beat to beat, using the volume clamp method of Penâz. In six obese patients (BMI > 30, arm circumference > 35 cm) treated for hypertension were undergoing functional respiratory tests. The finger pressure was measured simultaneously with intrabrachial on homolateral arm. Blood pressure was measured at rest and after a cold pressor test. [table: see text] The use of the Finapres seems to be possible. The correlation with the systolic is excellent, where as the correlation with the diastolic is weaker; which however is usual in any diastolic correlation between non invasive and invasive device. The CPT does not modify the correlations. Moreover the Finapres allows dynamic exploration which is of particular interest in obese persons because their blood pressure is particularly variable.


[Does ambulatory determination of blood pressure allow the measurement of white coat effect?]. The aim was to find an objective indicator in order to evaluate white coat effect (WE). The first hour average values after placing an ambulatory blood pressure recorder (15 mn intervals) were compared to those of the 4 following hours of diurnal activity. A first hour systolic arterial blood pressure (SBP 1H) increase of 10 mmHg or more was considered as an ambulatory WE positive (AWE+) and was compared to clinical WE (CWE). CWE+ was observed in 78 pts and AWE+ in 72 among a group of 172 unselected pts referred for hypertension. the correlation between AWE and CWE is weak (r = 0.49) but significant (p < 0.001). There was no difference between the two groups in age, sex, clinical blood pressure, heart rate or ambulatory BP after the first hour (table). There was a significant difference in SBP between the 2 groups (p < 0.001) during the first hour only. [table: see text] Ambulatory blood pressure recording is able to recognize and evaluate the white coat effect. We suggest to consider independently the first hour of each recording and to compare it with the mean pressure measured during the period of diurnal activity.


[Ambulatory blood pressure monitoring and left ventricular hypertrophy: correlations and trial of predictive value]. The purpose of the study is to make a selection of patients with left ventricular hypertrophy from Ambulatory Blood Pressure Monitoring (ABPM) values. We studied 39 patients, 23 men and 16 women, without treatment. These patients had systolic pressure > 140 mmHg and/or diastolic pressure > 90. With ABPM we measured mean systolic (MS) and diastolic (MD) pressure during the day (D) and the night (N), the percentages of systolic values (%S) > 160 mmHg and of diastolic values (%D) > 95 mmHg. With echocardiography we measured left ventricular mass index (LVMI: Devereux) and with pulsed Doppler peak of early (E) and late (A) ventricular filling and the ration A/E. We found the same amount of correlations between ABPM and echocardiographic parameters as other authors. [table: see text] The study of LVMI found a difference between groups when MD were > 140/90 (*) and A was significantly greater in patients with MSD > 140 (*). LVMI was greater in patients with MDD > 80 (*) and A was greater in patients with MSN > 120 (*). Predictive value of MSD > 140: 53% specificity: 79%. Predictive value of MSN > 120: 80% specificity: 45.8%. We concluded that the correlations between ABPM and echocardiographic disturbances are not very strong, but significant. If the predictive value of MSF is low, his specificity is rather high and conversely MSN has a good predictive value for selection of hypertrophic patients.


[Chaotic aspect of heart rate and blood pressure in diabetic patients]. We applied a simplified version of the method suggested by Sugihara-May (Nature 1990: 344: 734-41) to study the control of heart rate (HR) in subjects with diabetes mellitus. The method aims to predict the future of an observation, if a series of observations on the same phenomenon is available. The method quantifies the fact that the series is predictable more or less longtime in the future. A random series is only shortly predictable in the future. HR and blood pressure were measured from beat to beat (by the Finapres system) for about 0.5 hours in 11 subjects with diabetes mellitus and normal blood pressure (group D) and in 10 controls subjects (group N). The subjects were sitting in a temperature-controlled quiet room, isolated from all external stimuli. The 2 groups were matched for age, and had the same weight and height. No difference was observed in mean-value and standard deviation (SD) of BP and HR between the 2 groups. Groups N/D: SBP = 112 +/- 11/123 +/- 11 mmHg, NS; DBP = 64 +/- 9/67 +/- 12 mmHg, NS; HR = 70 +/- 10/69 +/- 7 b/min, NS. Standard deviation of PAS = 5.5 +/- 1.6/5.7 +/- 1.9 mmHg, NS and SD of DBP = 3.5 +/- 0.9/3.4 +/- 1.2 mmHg, NS. The SD of HR (3.0 +/- 0.5/2.3 +/- 1.0 b/min in groups N/D) was somewhat lower in diabetics than in control subjects but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)


Abnormalities of renal function in essential hypertension with increased circulating levels of insulin-like growth factor I. An increase in glomerular filtration rate and in tubular Na+ reabsorption from the parenteral administration of insulin-like growth factor I (IGF-I) have been reported in human subjects. To evaluate whether glomerular hyperfiltration and Na+ hyper-reabsorption present in some essential hypertensives are associated to an excess of IGF-I, the plasma levels of this factor and several parameters of renal function were studied in 30 non-treated essential hypertensives and in 30 normotensive controls. IGF-I levels were higher in hypertensive as compared to controls. With the 95% (upper) limit of the normotensive population as a cut-off point, a subgroup of six hypertensives had an abnormally high IGF-I level. Mean blood pressure was slightly lower in these six patients (112 +/- 7 mmHg) than in the remaining patients (120 +/- 2 mmHg). As compared to normotensives and hypertensives with normal IGF-I levels, patients with increased IGF-I levels were characterized by lower (P < 0.01) fractional Na+ excretion and higher (P < 0.05) creatinine clearance. The analysis of the relation of plasma renin activity and the concurrent daily rate of Na+ excretion showed that patients with increased IGF-I were low-renin hypertensives and patients with normal IGF-I were normal-renin hypertensives. These results indicate that an association exists between exaggerated circulating levels of IGF-I and abnormalities of renal function present in some patients with essential hypertension. It is suggested that IGF-I can play a role in low-renin essential hypertension.


[Microalbuminuria and hypertension in obese patients]. The present study was designed to evaluate the frequency of an increase in the urinary albumin excretion rate (UAER) and the factors involved in this parameter in non-diabetic obese patients; 122 non-diabetic obese patients were investigated. None had proteinuria or history of nephropathy or uropathy. Fourty of them had moderate hypertension. Compared with a group of 22 lean controls, UAER was significantly higher in the obese patients (19.0 +/- 2.0 (SEM) mg/24 h vs 3.2 +/- 0.6 mg/24 h, p < 0.001). UAER was elevated (> 20 mg/24 h) in 29 patients (23.7%). Prevalence of microalbuminuria was not significantly different in hypertensive than in normotensive patients. However UAER was significantly higher in the 32 patients with a family history of hypertension (29.6 +/- 6.3 mg/24 h vs 15.3 +/- 1.5 mg/24 h, p < 0.002). In patients with microalbuminuria, body weight was significantly higher (100.3 +/- 3.9 kg vs 91.8 +/- 1.9 kg, p < 0.05), plasma albumin was significantly lower (38.3 +/- 0.6 g/l vs 40.3 +/- 0.3 g/l, p < 0.005) and the estimated value of fractional albumin clearance was significantly higher. These results show the high frequency of microalbuminuria in non-diabetic obese patients. They suggest that UAER level may be an index of family hypertension in obese patients and that microalbuminuria is part of a widespread abnormality of the capillary permeability.


[Increase of erythrocyte aggregation in hypertensive men with dyslipidemia]. We have already reported that erythrocyte aggregation (EA) is increased in hypertensive subjects. To study the influence of other risk factors in EA, we have measured aggregation index IA and disaggregation shear rate threshold (gamma c) by a laser technique and the biochemical parameters in 16 normotensive normocholesterolemic subjects (NT/NCT) and 45 hypertensive subjects where 17 were normocholesterolemic (HT/NCT), 18 were pure hypercholesterolemic (HT/HCTIIa) and 10 were hypercholesterolemic hypertriglyceridemic (HT/HCTIIb). The results show that IA and gamma c are more important in HT/NCT than NT/NCT patients and much more in patients with hypercholesterolemia and hypertriglyceridemia. The cumulative effects of hypertension and hyperlipidemia merit take into consideration in pathophysiology of cardiovascular complications and could help to new strategy therapeutic developments for treatment of these complications.


[Erythrocyte sodium-lithium countertransport in diabetic children: 12 months development and relationship with familial hypertension]. It has been suggested that an increased erythrocyte Na-Li countertransport (Na-Li CNT) rate in patients with IDDM is associated to the risk of developing diabetic nephropathy. Little is known, however, about the possible influence of metabolic control on Na-Li activity. Aims of the study were to evaluate Na-Li CNT at the onset of IDDM and during the remission phase and its relationship with some clinical and metabolic parameters. Twelve insulin-dependent diabetic children (6 males, 6 females; mean age 10 +/- 0.6 years) were studied at the onset and 1, 4, 12 months after the diagnosis; 6 of them had a family history of hypertension. Twelve healthy children (6 males, 6 females; mean age 12 +/- 0.3 years) served as controls. As compared to control subjects (212 +/- 24 mumol/l RBC/h), red cell Na-Li countertransport activity of diabetic children was significantly higher at the onset (354 +/- 31 mumol/l RBC/h) of IDDM and at the first month (348 +/- 36 mumol/l RBC/h). Red cell Na-Li countertransport activity returned toward normal range at the fourth (239 +/- 33 mumol/l RBC/h) and twelfth month (162 +/- 34 mumol/l RBC/h). No correlation was found between the values of red cell Na-Li countertransport activity and those of clinical and biochemical parameters at any time. Patients with hypertensive relatives showed at baseline evaluation a significantly higher red cell Na-Li countertransport activity than those without (436 +/- 28 vs 273 +/- 34 mumol/l RBC/h; p < 0.002). This difference, although not statistically significant, was still evident at the late follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


[Atherosclerosis of an arterialized venous graft. Reduction by rigid external support]. Vein grafts undergo early intimal thickening and accelerated atherosclerosis. To assess the role of increased wall stress and distension in the pathogenic responses, 11 New Zealand white rabbits underwent interposition of an autologous jugular vein graft in the left common carotid artery. To relieve wall stress and reduce distension, the half proximal part of the vein was wrapped with a polytetrafluoroethylene graft (i.d. 4 mm). Animals were fed 1% cholesterol for 8 weeks. Vein graft and carotid artery were perfusion fixed with Karnovsky solution at 100 mmHg. They were stained with Sudan IV, and 5-microns cross sections were stained with hematoxylin-eosin and orcein. The internal diameter was reduced by 46 +/- 10% in wrapped vein graft segments as compared with unwrapped ones. The percentage of luminal surface covered by sudanophilic lesions (%AS) was assessed by automatic planimetry. Results (mean +/- SD) were as follows. [table: see text]. Abundant foam cells were found in the intima of unwrapped veins, whereas they were absent or rare in wrapped segments. We concluded that atherosclerotic lesions could be prevented in vein grafts by reducing wall stress and distension.


[In vitro study of the role of endothelium on the vasorelaxant effect of magnesium on the aorta from DOCA-salt hypertensive rats]. Vasorelaxant effects of magnesium (Mg) have been described in man and in animal with arterial hypertension. Some studies have shown relationships between extracellular Mg (magnesium e.c.) and endothelial function. So, our study is designed to determine whether elevated extracellular Mg leads to an endothelium-dependent vasorelaxant effect on contractile tension developed by noradrenaline in isolated aorta from DOCA-salt hypertensive rats. Elevated extracellular Mg (4.8 mM) in the bath significantly depressed the dose-response curve to noradrenaline in aorta with endothelium. Following disruption of endothelium, the vasorelaxant effect of elevated extracellular Mg on contractile response to noradrenaline was greatly inhibited. Furthermore, in presence of L. NG nitroarginine (L-NAME) (10(-4) M), inhibitor of endothelial nitric oxide (NO) biosynthesis, the vasorelaxant effect of extracellular Mg on contractility to noradrenaline was partially inhibited. The addition of sodium nitroprussiate (5 10(-9) M), known to spontaneously release NO, caused the reappearance of Mg vasorelaxation which had disappeared in aorta without endothelium. In conclusion, vascular endothelium seems to play an important role in the Mg-induced depressed contractile response to noradrenaline in isolated aorta from DOCA-salt hypertensive rat. Endothelial NO seems to be implicated in the endothelium-dependent action of extracellular Mg.


[Systemic and coronary hemodynamic effects of inhibition of nitrogen monoxide synthesis in conscious dogs]. Fourteen mongrel dogs were chronically instrumented on the circumflex coronary artery for measurement of coronary diameter (CD; Piezoelectric crystals) and coronary blood flow (CBF: Doppler flow probe). Coronary resistance (CR) was calculated as mean arterial blood pressure (MAP)/CBF. Systemic and coronary effects of three intravenous doses of NG-nitro-L-arginine (L-NAME: 0.1; 0.3; 1 mg/kg) were recorded (n = 5). Systemic and coronary effects of two vasodilators, acetylcholine (ACH) (endothelium-dependent: 0.3 micrograms/kg) and nitroglycerin (NTG) (endothelium-independent: 1 microgram/kg) were compared before and after L-NAME (1 mg/kg) (n = 6). Finally, the effects of L-NAME (1 mg/kg) were compared one week before and three days after denudation (balloon catheter) of the circumflex coronary artery (2 cm up and downstream from the crystals attachment site). All experiments were performed in conscious dogs. L-NAME induced a dose-dependent constriction of large epicardial coronary arteries [-1.5 +/- 0.5% from 3.1 +/- 0.3 mm, p < 0.05; -4.0 +/- 0.7% from 3.2 mm, p < 0.001; -5.3 +/- 1.2% from 3.0 mm, p < 0.01; respectively]. L-NAME 0.3 and 1 mg/kg induced a significant increase in MAP [+12.5 +/- 3.0% from 90 +/- 4 mmHg, p < 0.01; +11.3 +/- 3.5% from 96 +/- 7 mmHg, p < 0.05; respectively] and CR [+18.0 +/- 8.3% from 9.8 +/- 3.0 mmHg/cm.s, p < 0.01; +18.7 +/- 8.2% from 10.4 +/- 3.0 mmHg/cm.s, p < 0.01; respectively] with a significant bradycardia, but CBF was not modified. Effects of ACH were unchanged after L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)


[Absence of labetalol interference on urine metanephrine determination in hypertensive patients]. The dosage of urinary catecholamines and their metabolites is a main element of diagnosis in the research of a pheochromocytoma in patients with high blood pressure. The literature reports high values of these compounds in patients treated with labetalol (an alpha/beta-blocker). An analytical interference has been evoked to explain these misleading results, which have not been observed with other beta-blockers. The goal of this work was to look for this eventual analytical interference in the dosage of urinary metanephrine by reversed phase liquid chromatography coupled with electrochemical detection, in patients with high blood pressure. Eighteen hypertensive patients, 52 +/- 14 years old, were included in the study. In 8 patients, a dosage of metanephrine, normetanephrine and creatinine on a 24 hours urine sample was performed before (D1) and 24 hours after (D3) the prescription of labetalol (200 mg twice a day). In the other group, labetalol was not prescribed but dosage was made in the same conditions. Urinary excretion of these compounds (metanephrine+normetanephrine) divided by urinary creatinine was not modified in the treated group (0.16 +/- 0.08 vs 0.14 +/- 0.04), nor in the reference group (0.17 +/- 0.08 vs 0.17 +/- 0.08). This study shows that administration of labetalol in patients with essential hypertension does not interfere with urinary metanephrine and normetanephrine determination after 48 hours of treatment. This implies that research for a pheochromocytoma is possible in patients with hypertension and receiving labetalol, by using reversed phase liquid chromatography coupled with an electrochemical detector for the dosage of urinary metanephrine and normetanephrine.


[Comparative effects of angiotensin converting enzyme inhibitors and calcium inhibitors related to baseline ambulatory blood pressure. A French multicenter study]. This multicenter study was aimed at determining whether the baseline ambulatory blood pressure (BP) level does influence the efficacy of angiotensin-converting enzyme inhibitors (CEI) and that of calcium antagonists (CA) to the same degree. The BP recordings of 236 patients with mild to moderate hypertension were reviewed: these subjects previously entered clinical trials comprising a mean 2-week placebo period and a mean 6-week active treatment phase (CEI = 115, CA = 121). The 24-hour baseline ambulatory BP was considered as high when greater than 139/87 mmHg, according to Staessen's meta-analysis. In the patients with an high baseline ambulatory BP, CEI and CA have had roughly a similar effect (reduction in systolic = 9.5 +/- 7.8% vs 7.7 +/- 6.3%, NS; reduction in diastolic = 9.8 +/- 8.6% vs 8.3 +/- 5.8%, NS). Conversely, the patients with a baseline ambulatory BP level lower than or equal to 139/87 mmHg experienced a greater reduction in ambulatory BP with CEI than with CA (systolic = 7.9 +/- 7.0% vs 0.6 +/- 6.7%, p = 0.0001; diastolic: 5.0 +/- 7.4% vs 1.9 +/- 7.6%, p = 0.040). Finally, further analysis found the threshold of drug efficacy to be 120/80 and 135/85 mmHg in CEI and CA patients respectively. 1) CEI are more effective than CA in patients with a low ambulatory BP only. 2) The risk of a visceral hypoperfusion seems however to be limited, since CEI do not reduce diastolic ambulatory BP further, when its baseline level is lower than 80 mmHg.


[Efficacy of antihypertensive treatment in the French population. A multicenter survey]. In order to assess the efficacy of antihypertensive treatment in the population, a study was undertaken in 5 French cities during the commercial fairs of Grenoble, Marseilles, Nice, Toulouse and Lille. The blood pressure was measured according to the WHO recommendations in volunteers. The study included a total of 7107 subjects of both sexes, with 4064 subjects in the 35-64 year age group. The therapeutic efficacy was evaluated in the 791 hypertensive patients who knew their antihypertensive therapy. Taking < 160/95 mmHg as the criterion of efficacy, 52 to 73% of the hypertensive patients were well controlled. However, if the therapeutic objective of normalisation of the blood pressure (BP < 140/90 mmHg) is taken as the criterion of efficacy, only 23 to 29% of the hypertensive patients were controlled whilst their BP remained significantly higher than that of normotensive controls of the same age. The difference in efficacy of antihypertensive therapy between the cities may be explained by the heterogenicity of the populations whereas the treatment did not differ significantly. After adjustment analysis with respect to sex showed that women were better controlled than men whatever the criterion chosen. The group controlled at BP < 160/95 mmHg only differed from the group < 140/90 with respect to the average BP value which was higher before treatment and decreased less with treatment; though this did not achieve statistical significance. In matters of public health, if the ideal blood pressure is taken as < 140/90 mmHg, this study shows that the objective is only attained in one out of four patients in the population studied.


[SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report]. Syst-Eur is a multicentre placebo-controlled outcome trial, designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic blood pressure less than 95 mmHg. The present paper in an interim report on the first 316 patients randomized into this trial. The placebo (N = 170) and active treatment (N = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- standard deviation), sitting blood pressure (178 +/- 12/85 +/- 7 mmHg), percentage men (34%) and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p < 0.001) on active treatment than in the placebo group (19 +/- 20/6 +/- 10 mmHg versus 7 +/- 19/1 +/- 10 mmHg for the sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained. New centres are being recruited in order to randomize a total of 3,000 patients.


[Effects of verapamil and nifedipine on blood pressure during rest and exertion and on left ventricular hypertrophy]. The effects of 6 months treatment with nifedipine 20 mg SR (N) or verapamil 240 mg SR (V) on rest and exercise BP and left ventricular mass (LVM) and function were evaluated in 31 essential hypertensive patients (mean age: 54, 19 males, 12 females), never treated with calcium antagonist. After a 15 days placebo run in, BP was measured at rest and during a maximal bicycle exercise test (stages: 30 watts, 3 min). 2D guided M mode echocardiography and pulsed Doppler allowed assessment of left ventricular mass (Devereux's formula) and function (fractional shortening FS, peak early (E) and late (A) velocities of LV filling). Patients were randomised to N (n = 18) or V (n = 13) and reassessed 6 months later. All echo-Doppler recordings were read blindly by 2 observers. rest BP was similarly reduced in both groups (V: 148 +/- 12/88 +/- 5 vs 162 +/- 10/101 +/- 7; N: 148 +/- 15/90 +/- 7 vs 170 +/- 14/101 +/- 8), as well as exercise maximal BP (V: 224 +/- 32/93 +/- 11 vs 243 +/- 21/104 +/- 11; N: 206 +/- 27/90 +/- 10 vs 231 +/- 17/97 +/- 8). The duration of exercise was significantly increased with V (15 +/- 5 min vs 12 +/- 4, p < 0.05) and insignificantly decreased with N (11 +/- 2 vs 12 +/- 3). Left ventricular mass was higher in V group at entry and was significantly more reduced with V (250 g +/- 74 vs 302 g +/- 92, p < 0.01) than with N (225 g +/- 54 vs 234 g +/- 69).(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of sulphate-reducing ectosymbiotic bacteria from anaerobic ciliates using 16S rRNA binding oligonucleotide probes. The identity of ectosymbiotic bacteria of some marine, free-living anaerobic ciliates (Metopus contortus, Caenomorpha levanderi and Parablepharisma sp.) was studied using fluorescent-dye-conjugated oligonucleotides complementary to short sequence elements of 16S ribosomal RNA. The ectosymbiotic bacteria of all species hybridized with a eubacterial probe and those of the two former mentioned species hybridized with a general probe for sulphate-reducing bacteria, but not to a probe specific for Desulfobacter. The results support indirect evidence suggesting that ectosymbiotic bacteria of anaerobic ciliates are sulphate-reducers which depend on host metabolites for substrates.


Maleylacetate reductase of Pseudomonas sp. strain B13: dechlorination of chloromaleylacetates, metabolites in the degradation of chloroaromatic compounds. The maleylacetate reductase of 3-chlorobenzoate-grown cells of Pseudomonas sp. strain B13 has been purified 50-fold. The enzyme converted 2-chloromaleylacetate to 3-oxoadipate with temporary occurrence of maleylacetate; 1 mol of chloride was eliminated during the conversion of 1 mol of 2-chloro- and 2,3-dichloromaleylacetate; 2 mol of NADH were consumed per mol of 2-chloro- and 2,3-dichloromaleylacetate while only 1 mol was necessary to catalyze the conversion of maleylacetate or 2-methylmaleylacetate. The maleylacetate reductase failed to use fumarylacetate as a substrate. The role of the enzyme in the chloroaromatics degradation is discussed.


The hyp operon gene products are required for the maturation of catalytically active hydrogenase isoenzymes in Escherichia coli. The hyp operon of Escherichia coli comprises several genes which are required for the synthesis of all three hydrogenase isoenzymes. Deletions were introduced into each of the hypA-E genes, transferred to the chromosome and the resulting mutants were analysed for hydrogenase 1, 2 and 3 activity. The products of three of the genes, hypB, hypD and hypE were found to be essential for the synthesis of all three hydrogenase isoenzymes. A defect in hypB, as previously observed, could be complemented by high nickel concentrations in the medium, whereas the effects of mutants in the other genes could not. Lesions in hypA prevented development of hydrogenase 3 activity, did not influence the level of hydrogenase 1 but led to a considerable increase in hydrogenase 2 activity although the amount of hydrogenase 2 protein was not drastically altered. Lesions in hypC, on the other hand, led to a reduction of hydrogenase 1 activity and abolished hydrogenase 3 activity. HYPA and HYPC, besides being required for hydrogenase 3 formation, therefore may have a function in modulating the activities of the three isoenzymes with respect to each other and adjusting their levels to the requirement imposed by the physiological situation. Mutations in all five hyp genes prevented the apparent processing of the large subunits of all three hydrogenase isoenzymes. It is concluded that the products of the hypA-E genes play a role in nickel incorporation into hydrogenase apoprotein and/or processing of the constituent subunits of this enzyme. The importance of their roles is also reflected in their phylogenetic conservation in distantly related organisms.


[Symptomatic profile of depression].

[Symptomatic profile of depression]. There is no precise documentation about an universal nuclear composition of the depressive syndrome. Moreover, secondary manifestations of depression are even more controversial. In this paper the symptomatic profile of a sample of depressive patients attended in the Hospital Universitario de Canarias is analyzed. The characteristics, profiles and frequencies of the symptomatic pattern are discussed and commented.


[Effect of family environment on adaptation to the hemodialysis program in patients with chronic renal insufficiency]. In our study we have analyzed the influence of family environment on adjustment of renal patients to the HD as well as on the attitude towards kidney transplantation. The study included 57 patients (34 M, 23 F), mean age 52.3 years, and they had been on dialysis for an average of 34.5 months. We obtained information about adaptation and behavior in the care unit, and attitude and motivation towards renal transplantation. Biochemical variables were used to register disruption of medical compliance or dietetic transgression (K, PRC, BUN, weight gain, etc.). The patient's family climate was assessed through use of the Family Environment Scale (FES, Moos and Moos, 1981). The results showed that patients with aggressiveness and noncompliance during HD sessions tended to have high family conflict in family members. The most positive attitudes towards renal transplantation were found in the patients that came from families with the greatest degree of cohesion and expressiveness. In summary, family social climate is a variable influencing outcome of these patients. Its routine assessment would permit the prediction of adaptation to the therapeutic program as much as better efficacy of HD treatment.


A study on the mechanical reliability of the Dacomed snap gauge: implications for the differentiation between organic and psychogenic impotence. Two experiments were conducted testing reliability of expansion chamber determined gauge element breakage ranges; 20 trials with sexually functional males provided comparative data on the gauge in actual application. Circumference of the expansion chamber and increases in penile circumference were simultaneously monitored via a mercury strain gauge. Results for both experiments indicated considerable overlap at gauge element breakpoints, and yielded an overall misdiagnosis rate of 15.5% in a young, healthy population.


[Follow-up study at 6 months of a sample of drug addicts]. Global outcome of 94 drug abusers who began treatment in a Mental Health Center is studied in a six month follow-up. Drug use, medical, familial, occupational, legal and psychological status related with drug addiction are also analyzed. In the follow-up 90.4% patients were located, and the outcome was good in drug abuse, medical and familial areas. According to Global Outcome Scale, 36% scored high (optimal or good outcome) and 33% scored low (poor or very poor outcome).


Measurement of sexual aggression in college men: a methodological analysis. Researchers have devoted increased attention in recent years to the measurement of sexual aggression in college populations. This review describes and critically examines current methods of measuring sexual aggression which rely on a self-reported history of such behavior. We suggest that the construct validity of these approaches can be enhanced through a systematic consideration of instrumentation and methodological issues. Twenty-six empirical studies were evaluated with regard to sample characteristics such as size, type, representativeness, and subject exclusion criteria, as well as study design, measurement method, statistics reported, use of debriefing, and control for socially desirable response bias. Specific instrumentation methodology to measure a self-reported history of sexual aggression was examined in detail.


[Treatment with naltrexone in opiate dependents: 2 years' follow-up]. Outcome of a maintenance treatment with naltrexone (350 mg/week) are examined in a sample of 365 patients with opiate dependence disorder. Treatment was followed in an outpatient facility, in a setting similar to patient's own environment. The average attendance rate was of 198 days. Six months after the onset of the treatment, 52% of the patients still remained drug-free. Results of treatment was correlated with family support, HIV, work adjustment, use of other drugs and partner using drugs.


Adult sexual orientation in relation to memories of childhood gender conforming and gender nonconforming behaviors. Heterosexual, bisexual, and homosexual men recalled the extent to which they had engaged in gender conforming (masculine) and gender nonconforming (feminine) behaviors as a child. Adult sexual orientation was predicted as accurately by memories of childhood gender conforming behaviors as by memories of childhood gender nonconforming behaviors. However, childhood scripts as recalled by homosexual men were considerably more diverse. Twenty-two of 61 homosexual men reported having experienced few, if any, of the gender conforming behaviors and most, if not all, of the gender nonconforming behaviors. Another 18 homosexual men had the same profile of recalled childhood experiences as heterosexual men (high probability of masculine behaviors and low probability of feminine behaviors). Such diversity has implications not only for commentaries on the basis for homosexuality but for issues to be addressed in future research.


Effects of recalled childhood gender nonconformity on adult genitoerotic role and AIDS exposure. HNRC Group. The connections between childhood gender nonconformity (assessed by the Freund Feminine Gender Identity Scale, or FGI) and adult genitoerotic role (assessed by a sex history) were examined. The core sample was a group of 106 men who had sex with other men before 1980 and who are currently enrolled in two longitudinal studies of AIDS. Although other workers have cautioned against assuming a priori that childhood gender role is inherently related to adult preferences for particular sexual acts, our data suggest that there is at least a statistical association between these two concepts. In particular, the FGI (and many of its factors and items) are significantly associated with preferences for receptive anal intercourse and, less clearly, with oral-anal contact--but not with oral-genital intercourse or insertive and intercourse. Suggestions for AIDS prevention and safe-sex awareness are made on the basis of these findings. The data also suggest that in sex research involving homosexual men, the correct genitoerotic role distinction is not insertive vs. receptive behaviors, or even insertive vs. receptive and intercourse, but receptive anal intercourse vs. all other behaviors.


[Neuropsychological changes in drug addicts infected with human immunodeficiency virus]. The early organic mental disorder, caused by the human immunodeficiency virus type 1 (HIV) in the drug dependents (DD), if it is not taken into account, can disturb the diagnosis of the neuropsychiatric and the toxic disorders. The authors attempt to outline, with several neuropsychological tests (visuo-perceptual, memory, attention) and with the physical and neurologic exploration, if cognitive abnormalities are present in two groups of DD after detoxification period. The first group is infected by the HIV (n: 48), and the second one is not (n: 33). Differences can be found only in the Bender visuo-perceptual test, which are not justified by the divergences found between the groups about the drug dependence history and the present drug of abuse intake. The importance of the early diagnosis of these abnormalities is argued in order to get a suitable treatment of the possible neuropsychiatric complications in the DD development, and restrain the extent of the cognitive damage by HIV infection.


Paraphilias: a double-blind crossover comparison of clomipramine versus desipramine. A relationship has been suggested between clinical presentation of paraphilias and obsessive-compulsive disorder (OCD) with respect to the unwanted repetitive nature and insight into the irrationality of the paraphiliac behavior. This has led to speculation that paraphiliac disorders might belong to an "obsessive compulsive spectrum." To address this issue, and because of the striking selective benefit of serotonin reuptake blocking antidepressants (such as clomipramine) in the treatment of OCD, 15 paraphiliacs entered a double-blind crossover comparison of clomipramine vs. desipramine preceded by a 2-week single-blind placebo period. Four subjects responded to placebo and were dropped from the study. Three others failed to complete the study. Although the study is limited by the small number of patients and the heterogeneity of the paraphilias, the observed benefit from both tricyclics (over the initial placebo) encourages further study. For the 8 subjects completing the protocol, there was no preferential response to the more specific serotonin reuptake inhibitor suggesting a difference in underlying pathophysiology between paraphilia and OCD.


Evaluation of the toxicity, pathology, and treatment of cyclohexylmethylphosphonofluoridate (CMPF) poisoning in rhesus monkeys. Cyclohexylmethylphosphonofluoridate (CMPF) is an organophosphate cholinesterase inhibitor with military significance. The purpose of these studies was 1) to determine the acute toxicity of CMPF in the male rhesus monkey, 2) to evaluate the efficacy of pyridostigmine (PYR) pretreatment plus atropine and oxime (2-PAM or H16) treatment, and 3) to evaluate the pathological consequences of acute poisoning. An i.m. LD50 of CMPF was estimated using an up-and-down dose selection procedure and 12 animals. The 48-h and 7-day LD50 was 46.6 micrograms/kg, i.m. In the protection experiments, pyridostigmine (0.3-0.7 mg/kg/24 h) was administered by surgically implanted osmotic minipumps for 3-12 days resulting in 21-65% inhibition of erythrocyte acetylcholinesterase activity. Animals were challenged with 5 x L50 CMPF (233 micrograms/kg) and treated with atropine (0.4 mg/kg) and either 2-PAM (25.7 mg/kg) or HI6 (37.8 mg/kg) at the onset of signs or 1 min after challenge. Osmotic pumps were removed within 30 min after agent challenge. Pyridostigmine, atropine, and either 2-PAM or H16 were completely effective against CMPF, saving ten of ten animals in each group. In comparison, three of five animals challenged with 5 x LD50 of soman and treated with atropine and 2-PAM survived 7 days. The primary histologic lesions in the acute toxicity group were neuronal degeneration/necrosis and spinal cord hemorrhage. The CMPF treated groups (total of 20 animals) had minimal nervous system changes with no significant lesion difference resulting from the different oxime therapies. The primary non-neural lesions were degenerative cardiomyopathy and skeletal muscle degeneration which occasionally progressed to necrosis and mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)


HLö 7 dimethanesulfonate, a potent bispyridinium-dioxime against anticholinesterases. HLö 7 dimethanesulfonate (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2,4-bis [(hydroxyimino)methyl]pyridinium dimethanesulfonate) is a broad-spectrum reactivator against highly toxic organophosphorus compounds. The compound was synthesized by a new route with the carcinogenic bis(chloromethyl)ether being substituted by the non-mutagenic bis(methylsulfonoxymethyl)ether. The very soluble dimethanesulfonate of obidoxime was also prepared by this way. HLö 7 dimethanesulfonate is the first water-soluble salt of HLö 7 that should be suitable for the wet/dry autoinjector technology, because aqueous solutions of HLö 7 are not very stable (calculated shelf-life 0.2 years when stored at 8 degrees C, 1 M solution, pH 2.5). The crystalline preparation contains 96% of the syn/syn-isomer, less than 2% of the syn/anti-isomer and some minor identified by-products. HLö 7 was very efficient in reactivating acetylcholinesterase (AChE) blocked by organophosphates as long as ageing did not prevent dephosphylation. HLö 7 was superior to HI 6 (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2- [(hydroxyimino)methyl]pyridinium dichloride) in reactivating soman and sarin-inhibited AChE from erythrocytes, and literature data indicate that HLö 7 exceeds HI 6 by far in reactivating tabun-inhibited AChE. In atropine-protected, soman-poisoned mice HLö 7 was three times more potent than HI 6 (protective ratio 5 versus 2.5), and in sarin-poisoned mice HLö 7 was 10 times more potent than HI 6 (protective ratio 8 for both oximes). In atropine-protected guinea-pigs HLö 7 was less effective than HI 6 (protective ratio: 2.3 versus 5.2 for soman; 5.2 versus 6.8 for sarin; 4.3 versus 3.8 for tabun). The mean survival time of anaesthetized guinea-pigs exposed to 5 LD50 soman (6.3 min) was increased by atropine (27 min) and atropine + HLö (57 min). HLö 7 alone did not prolong the survival. The most impressive effect of HLö 7 was on respiration: 3 min after i.v. injection of HLö 7 and atropine, the depressed respiration increased rapidly to 60% of control and remained at that level during the observation period (60 min). With atropine alone, respiration recovered only slowly. Behavioural and physiologic parameters were determined in atropine-protected mice exposed to a sublethal soman dose. The running performance was significantly improved by HLö 7. Even central symptoms, e.g. hypothermia and convulsions, were decreased markedly by HLö 7 (evaluation 60 min after poisoning). The pharmacokinetic data for HLö 7 in male beagle dogs are similar to those of HI 6.(ABSTRACT TRUNCATED AT 400 WORDS)


Protection of guinea pigs against soman poisoning with ferrocene carbamate. The protective effect of ferrocene carbamate pretreatment against soman poisoning was studied in guinea pigs. At doses corresponding to 1/20 x and 1/10 x LD50 of this carbamate a 20% and 45% decrease of the acetylcholinesterase in blood and brain, respectively, was obtained. In combination with additional pretreatment, diazepam, and therapy, HI-6 and atropine, the protective ratios (LD50 of soman in treated animals/LD50 of soman in untreated animals) were around 20 and 40, respectively. Animals pretreated with the high dose of the ferrocene carbamate that survived 10 x and 15 x LD50s of soman showed no remaining signs of poisoning after 24 h. Thus, the ferrocene carbamate afforded a better protection against soman than physostigmine. The explanation for this could be due to the properties of the ferrocene carbamate, not correlated to its cholinesterase inhibiting activity. This hypothesis is discussed.


Comparison of DNA adduct formation between 2,4 and 2,6-dinitrotoluene by 32P-postlabelling analysis. Using 32P-postlabelling, we examined DNA binding by 2,4 and 2,6-dinitrotoluene (DNT) in Fischer-344 rats. DNA binding between the two compounds was compared to determine if differences in adduct formation and persistence could partly explain the known isomer-specific hepatocarcinogenicity of DNTs. The differences in cytotoxicity between the two isomers were also assessed. Both 2,4 and 2,6-DNT induced adduct formation in hepatic DNA. Three distinct adducts were detected following single i.p. administration of 2,4-DNT, while the 2,6-isomer produced four different adducts. Depending on the concentration administered, the two compounds differed in their relative yields. 2,6-DNT produced a greater total adduct yield relative to the 2,4-isomer at low concentrations. Following administration of high concentrations, however, 2,4-DNT predominated. The maximum adduct levels measured were 3.0 and 1.8 adducted nucleotides per 10(6) nucleotides for 2,4 and 2,6-DNT, respectively. Substantial amounts of adducts from both compounds were found to persist over time. After 2 weeks, the mean persistence for 2,4 and 2,6-DNT induced adducts were 42% and 46%, respectively. Qualitative examination for liver toxicity showed 2,6-DNT to be more cytotoxic, inducing extensive hemorrhagic centrilobular necrosis. Rats treated with 2,4-DNT did not show any observable signs of hepatocellular necrosis. Under the conditions of this study, the differences between 2,4 and 2,6-DNT in adduct formation and persistence do not appear to be sufficient to account for their differences in carcinogenicity. The toxicity of 2,6-DNT may be a determining factor in the potent carcinogenicity observed with this compound.


Sex- and age-related nephrotoxicity due to 1,2-dichloropropane in vitro. Sex- and age-related nephrotoxicity due to 1,2-dichloropropane was studied in vitro by means of renal cortical slices obtained from Wistar rats. Reduced glutathione content, organic anion accumulation (p-aminohippurate), and release of malondialdehyde (to measure the extent of lipid peroxidation), aspartate aminotransferase, gamma-glutamyltransferase and lactate dehydrogenase into the incubation medium were determined. Sex differences in naive rats parameters were slight, but male were more susceptible to toxic effects of 1,2-dichloropropane than female rats; glutathione depletion, lipid peroxidation, and loss of organic anion accumulation were higher in male than in female slices. During senescence, naive male rats showed a progressive decrease of glutathione content (statistically significant from 7-9 months of age), increase of spontaneous lipid peroxidation from the same age, and increase of signs of cytotoxicity (release of aspartate aminotransferase and lactate dehydrogenase into the incubation medium) from 3-4 months of age. A loss of organic anion accumulation started from 7-9 months of age. Slices from rats of 3-4 months old showed the apparently highest susceptibility to 1,2-dichloropropane but depletion of glutathione content and loss of organic anion accumulation were at the same level in the oldest rats. The age decrease of control values caused the differences in the percentage ratio and then, apparently, a lower DCP effect. On the contrary, the increase of aspartate aminotransferase released in the incubation medium by DCP-treated slices corresponded to the age-related increase in cytotoxicity.


The role of glutathione in the acute nephrotoxicity of sodium dichromate. Ascorbate treatment 30 min prior to sodium dichromate (20 or 30 mg/kg, s.c.) shows higher potency than that of glutathione (GSH) in protecting against both the metabolic disturbance and nephrotoxicity induced by dichromate. However, ascorbate treatment after 2 h of dichromate intoxication had no effect on dichromate-induced blood urea nitrogen (BUN) elevation 3 days after intoxication. In contrast, dichromate-induced glucosuria, which reached maximum levels at 3 days after treatment, was significantly decreased by GSH or N-acetyl cysteine (NAC) treatment, even if its administration was after 24 h of dichromate intoxication. Pretreatment with GSH depletors such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) had no effect on dichromate-induced nephrotoxicity. GSH levels in the liver and kidney were not affected at 3 h after dichromate treatment. However, dichromate significantly increased tissue GSH levels with a marked increase in liver per kidney GSH ratio at 24 h after treatment, if food was withheld subsequent to dichromate treatment, indicating that GSH biosynthesis resulted from the accelerated protein breakdown. These results suggest that GSH-mediated dichromate reduction is not a kinetically favorable pathway in vivo; however, GSH plays an important role in protection against dichromate-induced nephrotoxicity. In addition, the cellular metabolism of dichromate in the early period after treatment is important in the pathogenesis of its nephrotoxicity.


4-Methylpyrazole partially ameliorated the teratogenicity of retinol and reduced the metabolic formation of all-trans-retinoic acid in the mouse. Oral administration of retinol (50 mg/kg) to NMRI mice on day 11 of gestation (vaginal plug = day 0) led to the metabolic formation of high quantities of all-trans retinoic acid and all-trans-4-oxoretinoic acid, both known as potent teratogenic agents in the mouse. A 96% reduction of the area under the concentration-versus-time-curve (AUC) of metabolically generated all-trans retinoic acid in maternal plasma, and an 84% decrease in the embryonic AUC were observed when mice had been pretreated with the alcohol dehydrogenase inhibitor 4-methylpyrazole. A similar reduction was observed for the major metabolite of all-trans retinoic acid in the mouse, all-trans-4-oxoretinoic acid. However, 4-methylpyrazole pretreatment decreased the AUC of retinol by 10% in maternal plasma and 15% in embryo. Treatment with retinol alone resulted in 55.6%, 43.9% and 56.0% skeletal anomalies of the forelimbs, hindlimbs and craniofacial structures, respectively. Pretreatment with 4-methylpyrazole lowered the retinol induced skeletal defects to 31.3%, 24.0% and 31.3%, respectively, in the forelimb, hindlimb and craniofacial region. Typical retinoid-induced malformations for gestational day 11, e.g. bent or reduced zeugopod or stylopod elements, or cleft palate, were significantly reduced by 4-methylpyrazole pretreatment but were still detected in significantly higher prevalence than in control mice. These data suggest that the teratogenic activity of a single high dose of vitamin A in mouse is partially but not exclusively dependent on the metabolic activation of retinol to all-trans retinoic acid. Thus it could be hypothesized that retinol is either a proximate teratogen or a coteratogen with all-trans retinoic acid.


Hair analysis for drugs of abuse. IV. Determination of total morphine and confirmation of 6-acetylmorphine in monkey and human hair by GC/MS. The reliable analytical method for total morphine in hair was established by GC/MS-SIM. The calibration curve for morphine in hair showed linear over 0.5-100 ng/mg hair. Though the limit of detection was 0.1 ng/mg hair with an S/N > 3 of the base ion(m/z 429) for morphine, the limit of confirmation by detection of three major ions was 0.5 ng/mg. The hydrolytic extraction of the morphine analogs in hair with 10% HCl for 1 h at 100 degrees C gave quantitative recovery of morphine. The reproducibility of recovery of morphine spiked to the control hair was 2.9-7.3% in a concentration range between 2 and 50 ng/mg hair. The three monkeys were administered once a day with morphine at 10 mg/kg and heroin at 2.5 mg/kg, respectively, for 10 days and their back hair newly grown for 10 weeks was cut for analysis. The levels of total morphine in monkey hair intoxicated with morphine and heroin were 3.4 and 5.2 ng/mg, respectively. Taking their doses into account, it is concluded that the morphine level in hair from monkeys administered with heroin was 6 times higher than that with morphine. In hair from monkeys and humans intoxicated with heroin, 6-acetylmorphine was detected at the level of 0.7-7.2 ng/mg as a major component in hair together with morphine and no heroin. Drug concentrations of sectional hair shaft cut 2 cm each from the root side were compared with the self-reported drug histories of three cases. The results of sectional analysis of heroin abuser's hair suggested that the relationship between the distribution of morphine along hair shaft and the drug use history showed a good correlation, though the accumulation of heroin metabolites in body could result from chronic use of heroin.


Toxicological detection of selegiline and its metabolites in urine using fluorescence polarization immunoassay (FPIA) and gas chromatography-mass spectrometry (GC-MS) and differentiation by enantioselective GC-MS of the intake of selegiline from abuse of methamphetamine or amphetamine. Selegiline (R(-)-N-methyl-N-(1-phenyl-2-propyl)-2-propinylamine), a selective MAO-B inhibitor used as an antiparkinsonian, is excreted in urine as N-desmethyl selegiline (norselegiline), R(-)-methamphetamine (R(-)-MA), R(-)-amphetamine (R(-)-AM) and their conjugated p-hydroxy derivatives. We found that the fluorescence polarization immunoassays (FPIA) TDx amphetamine/methamphetamine II (AM/MA II) and TDx amphetamine class (AM class) lead to positive results for up to 2 days after a single oral dose of 10 mg selegiline (detection limit: 0.1 mg/l, each). Every urine specimen from long term selegiline patients (10 mg/day) showed positive TDx results during the selegiline regimen. Positive TDx results were confirmed using gas chromatography-mass spectrometry (GC-MS). Selegiline metabolites, particularly MA, could be detected in urine for up to 7 days after intake of a single oral dose of 10 mg selegiline (detection limit: 0.01 mg/l for MA and AM). Norselegiline, the only specific selegiline metabolite, was only detectable for about 12 h. Moreover, norselegiline was not detected in all urine samples from long term selegiline patients (10 mg/day). Since differentiation of selegiline intake from MA/AM abuse by detecting norselegiline was not possible in most cases, an enantioselective GC-MS procedure was developed. It allowed differentiation of the enantiomers of the selegiline metabolites and thereby separation of selegiline intake (only R(-)-enantiomers) from methamphetamine and/or amphetamine abuse (racemates or S(+)-enantiomers). After derivatization with S(-)-N-trifluoroacetyl-prolyl chloride (TPC), the two enantiomers of MA and AM were each separated as diastereomers employing the routinely used achiral GC capillary.(ABSTRACT TRUNCATED AT 250 WORDS)


Potential neurotoxin formation in thermally degraded synthetic ester turbine lubricants. Under extreme conditions of thermal degradation, a potent neurotoxin, trimethylolpropane phosphate (TMPP), may be formed by reaction of tricresyl phosphate (TCP, an anti-wear additive) and trimethylolpropane esters (TMPE) of carboxylic acids that may be contained in turbine engine lubricant formulations. The neurotoxin is only formed at extreme temperatures (350-700 degrees C), which has minimized concern for use of the synthetic lubricants under intended applications; however, since researchers are often not privy to the proprietary composition of such lubricants, extreme caution should be exercised in studies of or applications of synthetic lubricants degraded under extreme conditions.


[Classification of allergens by positive percentage agreement and cluster analysis based on specific IgE antibodies in asthmatic children]. Classification and characterization of allergens is important because allergic patients are sensitized by a variety of allergens. One hundred and sixty-one sera from asthmatic children were investigated for specific IgE antibodies against 35 allergens including 20 inhalants and 15 foods by means of the MAST method. We assessed the allergenic properties of the allergens based on positive percentage agreement and cluster analysis. There was a high positive percentage agreement of specific IgE antibodies between house dust and Dermatophagoides spp., a relatively high agreement between 5 molds, cat and dog epithelium, mugwort and wormwood and 5 grasses. Among the food allergens, the positive percentage agreements were relatively high, especially between cow's milk, casein, cheese, and between 3 cereal grains. In the cluster analysis, house dust and Dermatophagoides spp. made a big cluster; therefore 32 allergens except house dust and mites were analyzed. From the results of the cluster analysis, the major cluster consisted of (1) ragweed, (2) mugwort and wormwood, (3) timothy, sweet vernal, velvet and cultivated rye, (4) wheat, barley and rice, (5) molds, (6) cow's milk, casein, soybean and cheese, (7) shrimp and crab, (8) egg white, (9) Japanese cedar, (10) dog epithelium, (11) cat epithelium. The cluster of grass pollens and cereal grains made one cluster. These results tend to confirm the presence of species cross-reactivities within the major classes of allergens.


[Evaluation of allergenicity of the extract of Japanese juniper pollen reacting to sera from asthmatic children--by the methods of enzyme-linked immunosorbent assay and immunoblotting]. We investigated the allergenicity of pollen extract of Japanese juniper (Juniperus rigida, Cupressaceae family) to sera of 49 asthmatic children by the methods of enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Three bands stained with Coomassie Brilliant Blue R were detected on SDS-PAGE. Sera from 27 (55.1%) out of the 49 children showed positive reaction to the pollen extract in ELISA. The same sera from the 27 children were used as the first antibody in immunoblotting, which confirmed the presence of a band of protein with 70 K dalton molecular weight (M.W) common to the all sera. This band was bound with concanavalin A in lectins. We successfully purified the antigenic substance of Japanese juniper pollen from this band by the electroelution method. The major allergen of Japanese juniper pollen is glycoprotein with 70 KM.W. On sandwich-ELISA, there was no reaction of Sugi Basic Protein (SBP) and anti-SBP to Japanese juniper is an allergen that has no cross-reactivity with SBP.


[Sugi (Cryptomeria japonica D. Don) pollen scattering out of season]. We investigated the preseasonal blooming conditions of the male flowers of Sugi (Cryptomeria japonica D. Don) which flowers commonly in spring. We also investigated atmospheric Sugi pollen during all seasons for three years from 1988 through 1991 to determine pollen scattering in autumn. Our results showed that a discernible amount of pollen is scattered from the middle of October into December; this scattering would be expected in the following spring. Almost none of the buds of the flowers collected in October and in November bloomed when incubated at temperatures ranging from 6 degrees C to 20 degrees C after low-temperature treatment to arise the blooms from dormancy. However, small numbers of the male flowers from various Sugi trees bloomed and scattered pollen under these conditions. We found that the ratio of the blooming male flowers was one-third or less per blossom. The ratio changed depending on the growth stage and incubation conditions. In conclusion, the density of airborne Sugi pollen scattering is not high in autumn in general. However, the density would be expected to be high enough to induce allergic reactions and clinical symptoms in some areas of Sugi growth, especially in a good harvest year.


[The inhibitory effects of platelet activating factor (PAF) on ciliary activity of human paranasal sinus mucosa]. The effect of platelet activating factor (PAF) on human paranasal ciliated cells was investigated in vitro. Normal human paranasal sinus mucosa was obtained by surgical procedure and incubated with Eagle's MEM containing 10% FCS in the form of tissue culture. Ciliary activity was viewed at 37 degrees C under an inverted microscope equipped with a thermoregulator and a humidified CO2 chamber, recorded on video tapes and photoelectrically measured. Ciliary inhibition was observed by the treatment with PAF, in a dose dependent manner, at concentrations from 10(-10) M to 10(-6) M. The inhibitory effect of 10(-8) M PAF on ciliary activity was completely blocked when the mucosa was treated with 10(-6) M CV-3988 or 10(-6) M CV-6209 (specific PAF receptor antagonists). By the radioimmunoassay, the concentration of PAF in tissue culture was reduced by half within 12.5 min, and within 60 min it was only 5% of the initial concentration. There was no significant difference in ciliary inhibition between irrigation after a 60 min incubation with 10(-8) M PAF and non-irrigation. These results indicate that PAF inhibited ciliary activity directly and specifically, and induced irreversible damage primarily within the first 60 min after the challenge.


[Involvement of allergic mechanism in minimal change nephrotic syndrome (MCNS)]. In this study we evaluated the involvement of allergic mechanisms in patients with adult onset MCNS (17 cases) by measuring serum IgE levels and RAST scores to house dust 1 (H.D.1), house dust 2 (H.D.2), Dermatophagoides farinae (D.f.), Dermatophagoides ptenonyssinus (D.p.). Out of the 17 cases, three cases showed high levels of IgE (more than 1000 IU/ml) and the mean level of serum IgE was 877 IU/ml before treatment. All cases were treated with steroid and/or cyclophosphamide. After the treatment, all cases returned to remission. The level of IgE decreased to the normal range in four out of seven cases which had shown high levels of IgE before treatment. RAST was carried out on seven of the 17 cases. RAST scores for D.f. and D.f. were found to be positive in three cases, but these became negative in two cases after treatment. In five cases relapsed, the all cases showed to have the increased level of serum IgE and two of four cases which were examined RAST score showed to have the increased RAST score for D.f. and D.p. Thus, the data indicated that allergic mechanism, especially against D.f. and D.p. antigen, seemed to play one of the factors in the pathogenesis of MCNS.


[A case of sarcoidosis associated with Sjögren's syndrome]. A 49-year-old woman, who has had a past history of Raynaud's phenomenon since 1981, dry mouth since 1987 and dry eyes since 1990, was admitted to our hospital complaining of general fatigue, bilateral gonalgia, and shortness of breath in April 1991. Physical examinations revealed bilateral parotid gland enlargement and bilateral uveitis. Her family history included mixed connective tissue disease in her eldest daughter. Laboratory findings indicated an elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and elevation of serum lysozyme and angiotensin converting enzyme levels. Antinuclear antibodies, anti-SSA antibodies, anti-SSB antibodies were positive, while tuberculin test was negative. Chest X-rays showed bilateral hilar lymphadenopathy and small nodular shadows in both lung fields. Increases in lymphocytes and the CD4/CD8 ratio of T cells were noted in alveolar lavage fluid. Renal biopsy revealed non-caseous granulomas. Other remarkable findings included positive Schirmer's test, apple tree lesions by sialography and chronic sialoadenitis by biopsy of the labial minor salivary gland. On the basis of all these findings, we diagnosed her as suffering from sarcoidosis with Sjögren's syndrome. After oral administration of prednisolone, her shortness of breath, hilar lymphadenopathy and small nodular shadows in the lung field disappeared, but the patient was transferred to the department of urology due to the onset of hydronephrosis. This case is noteworthy because sarcoidosis associated with Sjögren's syndrome has been reported in only 11 cases in the literature.


[Sodium cromoglycate nebulized solution has an acute bronchodilative effect in patients with aspirin-intolerant asthma (AIA)]. Sodium cromoglycate (SCG) (Intal) is a well-known anti-allergic agent which protects against allergen- and exercise-induced bronchospasms. The effect has been recognized non-acute, unlike that of bronchodilators. However, we have found that some patients with aspirin-intolerant asthma (AIA) show significant improvement soon after a single inhalation of SCG nebulized solution. In this study, we investigated the acute bronchodilator effect of SCG given by nebulizer in adult asthmatics, especially compairing AIA with non-AIA (aspirin-tolerant asthma) patients. Twenty patients with AIA and 11 with non-AIA participated in the study. After performing spirometry on remission, they inhaled either SCG via a nebulizer or 4 ml of placebo in a randomized double-blind fashion. After inhalation, spirometry was performed every ten minutes for one hour. The placebo used was a saline solution of the same osmolarity as that of the SCG nebulized solution. Placebo inhalation provoked asthmatic attacks in five of the patients with AIA and one with non-AIA, but SCG did not. In the AIA group, twelve out of the twenty patients also had improved nasal symptoms soon after inhalation of SCG. Forced expiratory volume in one second (FEV1) was significantly improved 10 minutes after inhalation of SCG. Fifty minutes after SCG inhalation, the percent degree of FEV1 improvement was approximately 17%. However, FEV1 was significantly decreased by approximately 14% after inhalation of placebo. In the non-AIA group, FEV1 was not increased after inhalation of SCG. V25 was not changed after inhalation of SCG in AIA and non-AIA groups.(ABSTRACT TRUNCATED AT 250 WORDS)


[Morphology of the compensatory-adaptive responses in the placenta of multiparous women in uncomplicated pregnancy]. 125 placentas of women with many (5-17) deliveries and 100 control placentas (with 1-2 deliveries) were studied morphologically. It is shown that placentas of women with 1-2 deliveries retain their structure, compensatory reactions are most active in the central part of the placenta. After 5-9 deliveries hemodynamic disturbances are observed, disorganization processes are less pronounced, the level of compensatory-adaptive processes increases. Hemodynamic disturbances and structural disorganization are observed after 10-17 deliveries with pronounced compensatory processes in the peripheral parts of the placenta. Dissociated disturbance of the villi maturation are revealed after numerous deliveries.


[Characteristics of bone marrow stromal cell-precursor cells in children with congenital hip dislocation]. Basing on cloning in vitro, colony-forming stromal cells (CFSC) of the bone marrow were studied in 66 children with a congenital dislocation of the hip. Degenerative processes in the bones of the hip joint were followed by a significant decrease of CFSC cloning. A direct correlation between the results of surgical treatment and cloning efficiency is established. Thus, the cloning efficiency may be used as a criterion for determining feasibility, time of surgery and its prognosis.


[Morphofunctional interrelationships between the placenta and the fetal kidneys in uncomplicated pregnancy and gestoses]. A histostereometric study of the placenta and kidneys was performed in non-complicated pregnancy (37 cases) and gestoses (31 cases) during the second part of the pregnancy. Two big groups of alterations are distinguished characterizing functional morphology of placenta in gestoses: increased specific volume of the involutive-degenerative changes and decreased specific volume of the terminal villi this being the substrate of chronic placenta failure. Correlation analysis revealed an increase of positive and negative links between placental structures in gestoses. Hypoxic alterations with an increase in stromal component develop in combined and "pure" gestoses and this was confirmed by quantitative and correlation analysis.


[Functional morphology of parathyroid cells in disorders of calcium metabolism]. Cell composition of the parathyroid gland was studied under normal conditions, after the hypo- or hyperloading with calcium gluconate and at hyperfunction. Three types of parathyrocytes were established that probably reflect different stages of their life cycle: the first--poorly differentiated cell, the second--mature differentiated cell and the third--degenerated cell. The majority of cells were represented by the parathyrocytes of the 2nd type the varieties of which reflect a non-active (A-subtype) and active (B-subtype) phases of secretion. The number of A-cells is increased under the condition of the hyposecretion and the relative number of B-cells under the condition of experimental hypersecretion.


[Role of glomus shunts of the anorectal cavernous bodies in the mechanism of hemorrhoid development]. Histological examination of the hemorrhoids in 67 preparations of the rectum of adult persons showed the significance, in their development, of glomus and glomus blocking arteriovenous anorectal cavernous bodies, the two-three-fold increase of their volume was established. The dilatation of the glomus body lumen (from 20-30 to 270-480 microns) in the cavernous body wall is due to the epithelioid cell atrophy and sclerosis. When persistent dilatation and shortening of the distance between glomus mouths occurs, arterial blood passes from the peripheral branches of the superior rectal artery directly to the vena lumen, resulting, first, in the development of a simple compensatory and then varicose angioma-like flebectasia.


[Intraoperative finding of complicated congenital heart defects in dogs]. Vitium cordis found in a dog comprised a defect of the interatrial septum, pulmonary artery trunk aneurysm and right pulmonary artery atresia. The heart chambers were filled with polymer protacryl mass for obtaining the cast. No such anomalies have been described in the literature so far. The probability of observing such type of vitium cordis in the human clinics is not excluded.


[A hypothesis about resorptive cellular resistance as a special form of antimicrobial host protection]. The ability of macrophages to phagocyte granulocyte debris ("cleaning" reaction) is evolutionary developed and represents the mechanism of cellular resistance preceding immunity. Activation of the mononuclear phagocyte system and acquisition by the macrophages of the capacity to the intracellular chlamydia destruction as well as other infectious agents parasitizing in the intact cells occurs in the process of the granulocyte debris phagocytosis. This phenomenon termed by the author as a resorptive cellular resistance is one of host barrier mechanisms.


[Changes in myocardial enzyme activity of patients with dilated cardiomyopathy and the relationship of these parameters to disturbed myocardial contractility and coronary atherosclerosis]. Endomyocardial biopsies from 20 patients with dilated cardiomyopathy (DCMP) were studied histochemically. The decrease of the mitochondrial enzyme activity and increase of the activity of lysosomal and hydrolytic enzymes were found. These alterations reflect degenerative processes in cardiomyocytes followed by activation of their degradation and utilization. This results in the decrease of the myocardium contractile volume and its contractile function damage. There was no correlation between the level of the enzyme activity in the myocardium and the degree of the contractile function activity. There was a tendency to the increase of the above changes in patients with early signs of coronary atherosclerosis.


[DNA synthesis in myocytes of the heart conduction system in myocardial infarction induced in young rats]. The myocardial infarction was induced in 13- and 21-day-old rats. The extent of the DNA synthesis activation in myocytes of conduction system compartments compared with atrial and ventricular myocytes was evaluated by cumulative indices of labeled nuclei after 30-times-repeated 2H-thymidine injections at 12h intervals. Labeling indices in atrial myocytes are two to six times higher (0.01 < P < 0.001) in rats with infarction than in control. On the contrary, in conduction system compartments there are no statistically significant differences between control and experimental groups (P > 0.05). An activation of DNA synthesis can occur in myocytes of His bundle in some animals.


[Functional morphology of the myocardium in acute experimental peritonitis]. Structural disorganization of the myocardium starts at the very early stages of acute experimental peritonitis, the maximum surface of the contractural lesions is registered one day and the maximum decrease of the adrenergic nervous fiber density 6 hrs after the start of the experiment. The change of the mitochondria surface and the biochemical process intensity in the cardiomyocytes depend on the disease stage. In the process of recovery the cardiomyocyte and microcirculatory bed repair starts to dominate.


[Primary glomerulonephritis: incidence, dynamics, clinical manifestations of morphologic types (on the basis of kidney biopsies at the Department of Pathology, I. M. Sechenov Moscow Medical Academy, from 1970 to 1989)]. Incidence and clinical manifestations of main morphological variants of primary glomerulonephritis (2142 biopsies) were studied retrospectively. Correlative changes in the clinical and morphological structure of primary glomerulonephritis with the increase in the incidence of nephrotic forms (minimal alterations, focal segmental glomerulohyalinosis, membranous nephropathy) and a trend to reduce the mesangiocapillary glomerulonephritis in patients with nephrotic and nephrotic-hypertensive syndrome were noted. A bimodal distribution of patients with membranous nephropathy with increasing age probably indicate the change of etiologic factors in the age groups.


[Differentiation, electrically stimulated nuclear motility and ultrastructure of buccal epithelial cells from normal people and psoriatic patients]. The comparative analysis of cell differentiation, ultrastructure and volt-stimulated cell nuclear motility was made on buccal epithelium scraped from normal persons and psoriatic patients. About 70% of cells in normal epithelium were classified as cells of the 5th differentiation stage. The same percent of cells exhibited the stimulated nuclear motility. In buccal epithelium of psoriatic patients 54% of cells belonged to the 4th differentiation stage, but ultrastructurally they were of the 3-5th differentiation stages. In epithelial cells of psoriatic patients only 25% of cells were classified as the 5th differentiation stage and 34% of cells had nuclear motility. Their percent increased by 60 when 10(-7) M adrenaline was added in vitro. The results allow conclusion that the nuclear motility is characteristic of degraded epithelial cells with defective tonofilamentous cytoskeleton but with retained electrochemical K(+)-potential.


[Thymus mass in infants in the first year of life, who died as a result of sudden death syndrome]. Thymus weight was studied in 117 infants of the first year of life who died a sudden death, in 195 breast-fed infants who died of various diseases and in 27 infants aged up to one year who died a violent death without disease symptoms. There was a great variability of the thymus weight in all the groups, although its values were statistically lower in the syndrome of sudden death whatever the method of comparison. No proof of the children thymomegaly in the syndrome of sudden death is found.


[Lobular breast cancer in males].

[Lobular breast cancer in males]. Mammary carcinoma occurs in males about 100 times more seldom than in females. 1/30 of all mammary carcinoma in males is lobular cancer. One such observation of lobular carcinoma in a male of 58 developing against the background of fibroadenomatosis is described.


[Cecum gangrene as a complication of amyloidosis in myeloma]. It is a report of a rare case of amyloidosis in myeloma with a predominant localization in the caecum wall with the narrowing of blood vessels and a caecum gangrene and peritonitis as complications. Rarity of the case resulted in an erroneous clinical diagnosis and unjustified appendectomy.


[Methods for the rapid preparation of paraffin blocks]. Two accelerated chloroform-paraffin processings of materials with the use of ultrasound (US) and microwave (MW) irradiation in the stove "Electronica" as well as a combined method with US- and MW-irradiation are proposed to shorten drastically the duration of the prehistologic processing.


[Local defense mechanisms in chronic nonspecific pulmonary inflammation]. The mechanisms of non-immune and immune injuries in chronic nonspecific lung inflammation are analysed on the basis of authors' research and literature. The data given concern the changes of the bronchial mucociliary transport system, incomplete functions of alveolar macrophages and polymorphonuclear neutrophils in chronic inflammatory foci, increase in the number of intra- and extracellular bacteria, metabolism of lung phagocytes in different chronic inflammatory lung diseases. The urgency of lung phagocyte and lymphocyte investigation both in specific cellular and humoral immune reactions, as well as in realization of immunopathologic mechanisms developing in chronic inflammation is emphasized.


Short time treatment with high-efficiency paired filtration dialysis for chronic renal failure. With the aim of treating with short sessions even chronic uremic patients with cardiovascular instability, we have developed our previous findings about paired filtration dialysis (hemofiltration-hemodialysis in series) by a method we call high-efficiency paired filtration dialysis (HEPFD). We have treated with this method for 6 months 6 chronic anuric uremic patients previously treated for 6 months with hemofiltration (HF) because of their cardiovascular instability. By comparison with HF, HEPFD shows much higher clearances of small molecules with consequent significant decrease of their predialytic values, improvement of Kt/V value, lower beta 2-microglobulin clearance (its predialytic value remains unchanged), and the same tolerability. HEPFD allows short, efficient, and well-tolerated treatments even in patients with cardiovascular instability.


Adsorption of nafamostat mesilate by hemodialysis membranes. The adsorption of the anticoagulant nafamostat mesilate (FUT-175) by five different hemodialysis membranes was studied in vivo and in vitro. In vivo, FUT-175 was adsorbed strongly by a polyacrylonitrile (AN69) membrane and slightly by another polyacrylonitrile (J-PAN) membrane but not by Cuprophan (CU), hemophan (HE), or polymethylmethacrylate (PMMA) membranes during hemodialysis performed in 4 patients in whom FUT-175 was used as an anticoagulant. Only during hemodialysis using the AN69 membrane did FUT-175 not induce a significant prolongation of celite-activated coagulation time. In vitro studies showed that FUT-175 was adsorbed by the AN69, J-PAN, and PMMA membranes but not by the CU and HE membranes. Methylene blue, a dye that possesses a cationic portion in its chemical structure, stained AN69, J-PAN, and PMMA membranes. Since FUT-175 also possesses a cationic portion, we conclude that FUT-175 is adsorbed by negatively charged membranes via an ionic bond and is unsuited for use as an anticoagulant in hemodialysis using an AN69 membrane because of that membrane's marked capacity to adsorb FUT-175.


Systemic levels of tumor necrosis factor alpha during hemodialysis with cellulosic membranes: no effect of the sterilization procedure. Extractable constituents of dialyzer membranes (e.g., monomers and beta-glucans) may induce the production of cytokines in vitro. We therefore studied circulating tumor necrosis factor alpha (TNF alpha) levels in 23 stable hemodialysis patients during treatment with dry Cuprophan membranes (ETO-sterilized n = 10, steam-sterilized n = 13) longitudinally over a period of 4 weeks. After 4 weeks, those 5 patients of each group showing the highest TNF alpha levels were switched to steam-sterilized, wet Cuprophan membranes. No significant increase in plasma TNF alpha was observed during hemodialysis with either ETO- or steam-sterilized dry Cuprophan membranes. A substantial TNF alpha increase (> or = 100% compared to pre-HD values), however, was observed during 14 of 84 treatment sessions. In 5 selected patients with ETO-sterilized, dry Cuprophan dialyzers, TNF alpha rose from (mean +/- SEM) 17.2 +/- 3.0 (pre-HD) to 20.9 +/- 6.2 (120 min) and 21.9 +/- 4.5 pg/ml (240 min). Corresponding levels in patients with steam-sterilized, dry Cuprophan were 16.2 +/- 5.4 (pre-HD), 21.9 +/- 6.8 (120 min), and 16.0 +/- 3.7 pg/ml (240 min), respectively. There was no difference between ETO- and steam-sterilized dialyzers. No significant reduction in mean TNF alpha plasma levels or in frequency of elevated peak levels was achieved when these patients were switched to wet Cuprophan dialyzers for another 4 weeks. It is suggested that an induction of elevated TNF alpha levels during hemodialysis is possible but is not observed regularly during treatment with Cuprophan membranes.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulation of differentiation and proliferation of rat hepatocytes by lactose-carrying polystyrene. We noticed that hepatocytes recognize the structure of oligosaccharides via asialoglycoprotein receptors and synthesized lactose-carrying styrene polymer (PVLA) as an asialoglycoprotein model. We found that the regulation of differentiated function and proliferation of hepatocytes that were cultured on polystyrene dishes can be achieved by varying the amount of PVLA coated on the dishes. The 3H-thymidine uptake of cultured hepatocytes is low for cells cultured on dishes coated with high amounts of PVLA in which the hepatocytes are round and is highest for those cultured on dishes with a low PVLA coating level in which the hepatocytes are spread in shape. Moreover, bile acid release as a typical differentiated function of hepatocytes was maintained at higher levels in hepatocytes attached on dishes coated with a high level of PVLA. Our results indicated that regulation of differentiated function and proliferation in hepatocytes could be achieved by specific ligand-mediated recognition of microscopic surface structure. Thus, it may be possible to regulate proliferation and differentiation of hepatocytes by design of the culturing substrata.


Polylysine-immobilized chitosan beads as adsorbents for bilirubin. Hyperbilirubinemia generally relates to an elevated bilirubin level in the blood and is usually an indication of a disease of the blood, liver, or biliary tract. Hemoperfusion using synthetic resins as sorbents has been one of the ways to reduce bilirubin. In this study, chitosan, a natural polysaccharide having structural characteristics similar to glycosaminoglycans and which is nontoxic and biocompatible, has been used for bilirubin binding. Several layers of poly-L-lysine have been coated covalently onto chitosan beads, using N2 plasma and carbodiimide treatments. Such surface-modified chitosan beads exhibited high binding affinities for bilirubin (1.13 +/- 0.18 mg/g beads) in aqueous phosphate buffer solutions at 4 degrees C in relation to activated charcoal (0.74 +/- 0.2 mg/g). The polylysine-coated resins have been reported to have an improved binding affinity for bilirubin over cholestyramine. It seems that the surface-immobilized polylysine has an increased bilirubin binding affinity and is highly stable. The binding capacity is proportional to the amount of polylysine bonded to the chitosan beads. The hemolytic potential of all modified beads is compatible with polystyrene control tubes. Studies were also performed against albumin as proof of specificity toward bilirubin binding. The albumin-coated beads have shown the highest blood compatibility and selectivity over the other modified beads. However, it appears that polylysine-modified chitosan may be an excellent sorbent system for hemoperfusion due to its high binding affinity, capacity, and blood compatibility. Further studies are needed to determine its behavior under clinical conditions.


Complement activation during low-density lipoprotein apheresis. Complement system activation was investigated in two girls with familial homozygous hypercholesterolemia undergoing two monthly sessions on LA15 or LA40 (Kaneka liposorber). We determined blood levels of C3c and C3a, leukocyte counts, and plasma levels of C3c and C3a in the extracorporeal circulation device at the start of the sessions and 15 and either 60 or 120 min into them. Sequential eluates were collected from LA40 at the end of the sessions (0.5M NaCl, 1M hydroxylamine). Anaphylatoxin C3a increased throughout, especially with LA40. As previously reported, C3a was trapped in the dextran column but was noticeably present in efferent plasma. Besides many proteins, nonnative complement fragments bearing C3a and C3d antigens were detected in almost all the eluates, suggesting possible in situ complement activation. Practically, complement activation induced by the first filter is a risk; long-term side effects may arise from this extracorporeal circulation device.


Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and stroma free hemoglobin on pulmonary vascular responsiveness to vasoactive substances in isolated perfused rat lungs. We examined the effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances in isolated perfused rat lungs. The lungs isolated from rats were perfused with 6% PHP, 6% SFH, or 6% hydroxyethylstarch (HES) solution, and the effects of intrapulmonary arterial injection of norepinephrine (NE), angiotensin II (ANG-II), acetylcholine (ACh), and nitroglycerin (NG) were examined by measuring perfusion pressure. NE and ANG-II produced a dose-dependent increase in perfusion pressure in all groups. The NE response in the PHP- or SFH-perfused group was significantly larger than that in the HES-perfused one. ACh decreased perfusion pressure in both PHP- and HES-perfused groups but increased perfusion pressure in the SFH-perfused group. NG decreased perfusion pressure in all groups. Present results indicate that pulmonary arterial responses to endothelium-derived relaxing factor (EDRF) induced by ACh would not be affected in the presence of PHP.


A compact centrifugal pump for cardiopulmonary bypass. A majority of the cardiopulmonary bypass (CPB) systems still utilize bulky roller pumps. A direct-drive small centrifugal pump intended for second-generation CPB pump has been developed. The pump has a 50 mm diameter impeller and provides a 6 L/min flow at 3,000 rpm against 300 mm Hg. A flexible drive shaft allows us to separate the pump head from the console resulting in easier manipulation. An in vitro study showed that the pump generated less hemolysis (index of hemolysis = 0.0011, comparable to the value for Bio-medicus BP-80). To improve blood flow around the shaft-seal region and to reduce thrombus formation around the shaft, six holes were drilled through the impeller. In biventricular bypass experiments using calves, our pump demonstrated excellent antithrombogenicity and durability for 48 h. And the compact and atraumatic centrifugal pump system showed excellent performance and easy manipulation under actual CPB conditions in animal.


Development of an atraumatic small centrifugal pump for second-generation cardiopulmonary bypass. A small and light direct-drive centrifugal pump has been developed for cardiopulmonary bypass. In the development process, blood compatibility studies including a hemolysis study, an in vitro fluid dynamic performance study, and in vivo durability and feasibility studies were performed. The centrifugal pump with a 50 mm diameter impeller resulted in almost the same index of hemolysis value as did a Bio-Medicus centrifugal pump. Heat dissipation from the motor was prevented by using a flexible drive cable. Forty-eight-hour sealing durability around the driving axis was accomplished by using a fluoro-rubber V-ring that connected to the hard chrome-plated stainless steel. In vitro and in vivo performances of the pump were satisfactory. Thrombus formation behind the impeller was prevented by using a holed impeller that generated blood flow from the back to the surface of the impeller. Elimination of air during priming procedures was also easier with this modification. This centrifugal pump has one-quarter of the priming volume, size, and weight of magnetically coupled centrifugal pump systems.


Versatile one-piece total artificial heart for bridge to transplantation or permanent heart replacement. A versatile, one-piece total artificial heart (TAH) system that can be driven by either an electromechanical acutator (EM-TAH) or a pneumatic source (P-TAH) has been developed. The common units for both TAHs are the conically shaped left and right pusher-plate-type pumps (63 ml SV) that sandwich a thin centerpiece (18 mm) having a respective actuator. The EM actuator, mounted in the middle of the centerpiece, consists of a direct-current brushless motor and a roller screw while the pneumatic actuator consists of a low-pressure air source. The outer diameter of the pumping unit is 97 mm with its central thickness being 82 mm; overall volume is 510 cc. The TAH is operated in the left master alternative ejection mode with the left pump fill signal. High-flex-life Hexsyn rubber is used as the diaphragm, and the blood-contacting surface is coated with dry gelatin. The TAH can provide 3-8 L/min flow with a preload of 1-10 mm Hg against 100 mm Hg afterload. Anatomical fit of the pumping unit has been demonstrated in the pericardial space of 26 heart transplant recipients with average body weight of 78 kg. To date, 2 P-TAH and 4 EM-TAH (1 week) implantations were performed in 80-100 kg calves demonstrating excellent anatomical fit, controllability, and biocompatibility. This versatile TAH is suitable for a bridge to transplantation or permanent heart replacement.


Effect of synchronous and asynchronous pulsatile flow during left, right, and biventricular bypass. Ventricular assist devices augment flow from the left atrium to the aorta and/or from the right atrium to the pulmonary artery. Most devices are used in the asynchronous full-to-empty mode (asynchronous) but may also be used in a synchronous counterpulsation mode (synchronous). This study determines the optimal assist modes to reduce myocardial oxygen consumption (MVO2) and metabolism. Twelve pigs were instrumented with carotid artery and Baim coronary sinus catheters for determination of MVO2 and myocardial lactate production (LACT). Six were implanted with a Pierce-Donachy left ventricular assist device (LVAD) and 6 with both right and left ventricular assist devices (BIVAD). Two periods each of control, synchronous, and asynchronous bypass were instituted, the midanterior descending coronary artery (LAD) was ligated, and the sequence was repeated. After each period, MVO2 and LACT were determined and myocardial biopsy specimens were obtained for tissue, lactate, and ATP assay. Following LAD ligation, biopsy specimens were obtained from both the infarct and noninfarct zones of the heart. MVO2 decreased (p < 0.05) in the asynchronous BIVAD mode compared with control. MVO2 was unchanged in synchronous BIVAD or either LVAD mode. Tissue ATP and tissue lactate were unaffected by any mode of bypass. Only BIVAD in the asynchronous mode reduced MVO2. When ventricular assist devices are utilized to aid recovery of the natural heart, two devices should always be inserted to allow biventricular assist. Synchronous counterpulsation offers no advantage.