Serum angiotensin converting enzyme activity in patients with untreated essential arterial hypertension

The serum angiotensin converting enzyme (ACE) in 30 patients with untreated essential arterial hypertension, 30 patients with chronic renal failure accompanied with arterial hypertension and 30 healthy individuals was measured. The subjects of both sexes have been old 35-60 years. The serum ACE activity was determined by the spectrophotometric method, using Hip-Gly-Gly as a substrate. The serum ACE activity significantly increased in patients with arterial hypertension (32.48 +/- 2.02; X +/- SEM) and patients with chronical renal failure accompanied with arterial hypertension (37.10 +/- 1.45) when compared to the healthy individuals (20.83 +/- 1.33). Possible mechanisms of increasing ACE activity with the patients suffering of arterial hypertension are discussed.     

Serum angiotensin-converting enzyme activity in patients with endemic nephropathy

Serum angiotensin-converting enzyme was measured in 60 patients with endemic nephropathy and in 30 healthy individuals. According to the arterial blood pressure, the patients with endemic nephropathy were further divided into groups with arterial hypertension (n = 30) and without arterial hypertension (n = 30). The activity of angiotensin-converting enzyme was determined by a spectrophotometric method using hippuryl-l-histidyl-l-leucine as a substrate. The serum activity of angiotensin-converting enzyme was significantly increased in the patients with endemic nephropathy (28.51 +/- 1.64 U/l) as compared with healthy individuals (20.83 +/- 1.33 U/l). The level of the enzyme was further increased if the endemic nephropathy was accompanied by arterial hypertension (37.09 +/- 1.45 U/l). The possible mechanisms of the increase in the angiotensin-converting enzyme activity are discussed.     

Ovarian angiotensin-converting enzyme activity in humans: relationship to estradiol, age, and uterine pathology

The present study was designed to measure angiotensin-converting enzyme (ACE) activity in the human ovary and in serum and to relate this activity to age, serum estradiol levels, and uterine and endometrial pathology. ACE activity was determined in 56 females by a radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. Ovarian ACE activity, but not serum ACE, was found to increase with age (P < 0.01) and was significantly greater in postmenopausal subjects (n = 31; 1.35 +/- 0.05 nmol/mg.min) than in subjects with active ovaries (n = 21; 0.65 +/- 0.2 nmol/mg.min; P = 0.0033). Ovarian ACE activities in fertile women in the preovulatory phase (n = 14) and the postovulatory phase (n = 7) were not statistically different (0.66 +/- 0.23 and 0.63 +/- 0.17 nmol/mg.min, respectively). Serum ACE activities were similar in females with active and nonactive ovaries (87.6 +/- 5.0 vs. 81.7 +/- 5.3 nmol/mL-min, respectively). Serum estradiol levels in fertile women were significantly higher than those in postmenopausal women (P = 0.0023). Serum estradiol levels were negatively correlated with age (r = -0.46; P = 0.0041) and were not correlated with either serum ACE activity (r = 0.080; P = NS) or ovarian ACE activity. In summary, human ovarian ACE activity, but not serum ACE, is positively correlated with age. Serum estradiol levels decrease with age, but are not correlated with either ovarian or serum ACE activity. Endogenous serum estradiol levels had no apparent effect on ovarian or serum ACE activity. The presence of uterine pathology affects ovarian ACE activity. The cause of the increased ovarian ACE activity is not clear, but may be related to the aging process.     

Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of severe disease with associated nephropathy

OBJECTIVE: To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy. METHODS: A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay. RESULTS: Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (+/- SD) pANCA log titers (103 +/- 5.6 versus 27 +/- 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA-associated nephropathy. CONCLUSION: Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.     

Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients

Genetic variability in the renin-angiotensin system may modify renal responses to injury and disease progression. We examined whether the M235T polymorphism of the angiotensinogen (AGT) gene, the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene, and the A1166--> C polymorphism of the angiotensin II type 1 receptor gene may be associated with disease progression in 168 Caucasian patients with IgA nephropathy. All patients had serial measurements of their creatinine clearance, proteinuria, and blood pressure (mean+/-SD) with a follow-up of 6.1+/-4.7 yr. The genotype frequencies for each gene were consistent with Hardy-Weinberg equilibrium, and were similar to those of 100 Caucasian control subjects. We examined two primary outcomes: (a) the rate of deterioration of Ccr, and (b) the maximal level of proteinuria. We found that patients with the AGT MT (n = 79) and TT (n = 29) genotypes had a faster rate of deterioration of Ccr than those with the MM (n = 60) genotype (i.e., median values, -6.6 and -6.2 vs. -3. 0 ml/min/yr, respectively; P = 0.01 by Kruskal-Wallis test). Similarly, patients with AGT MT and TT genotypes had higher maximal values of proteinuria than those with the MM genotype (i.e., median values, 2.5 and 3.5 vs. 2.0 g/d, respectively; P < 0.02 by Kruskal-Wallis test). Neither the ACE insertion/deletion nor angiotensin II type I A1166--> C gene polymorphism was associated with disease progression or proteinuria in univariate analysis. Multivariant analysis, however, detected an interaction between the AGT and ACE gene polymorphisms with the presence of ACE/DD polymorphism adversely affecting disease progression only in patients with the AGT/MM genotype (P = 0.008). Neither of these gene polymorphisms was associated with systemic hypertension. Our results suggest that polymorphisms at the AGT and ACE gene loci are important markers for predicting progression to chronic renal failure in Caucasian patients with IgA nephropathy.     

Association between myocardial infarction and angiotensin converting enzyme gene polymorphism in young patients

BACKGROUND: Different studies have shown a relationship between an insertion-deletion polymorphism of the angiotensin converting enzyme (ACE) gene and the risk of ischemic heart disease, although there are no data on this association in the Spanish population. MATERIALS AND METHOD: We have studied three groups of patients: I, healthy volunteers (n = 56, mean age 36.20 +/- 4.20 years); II, patients having presented an acute myocardial infarction (MI) < or = 50 years (n = 59, mean age 42.30 +/- 5.30 years), and III, patients with MI over the age of 50 years (n = 60, mean age 66.36 +/- 9.47 years). In all patients the genotype ACE gen was determined by an assay based on the polymerase chain reaction. RESULTS: The distribution of the ACE genotype between the three groups were not significative. Comparing the ratio of DD/II-DI in groups II and III there were 26/33 versus 15/45 (p = 0.02864). There was no difference in the smoking, hypercholesterolemia and hypertension between groups II and III; there were only differences in familial history of ischemic heart disease; diabetes mellitus was more prevalent in the III group. A multivariate analysis showed that smoking familial history of ichemic heart disease, hypercholesterolemia and DD genotype were more prevalent in young patients (OR 3.92, 2.85, 2.36 and 1.77), whereas diabetes mellitus was more prevalent in the group of older patients. There were no differences in the ACE genotype with respect to infarct location or gender. CONCLUSIONS: In our population DD ACE genotype is associated with MI in young patients, although smoking, family history and hypercholesterolemia show a more powerful association.     

Pathology of preinvasive and excellent prognosis breast cancer

BACKGROUND: Erythropoietin (EPO) therapy is a common and effective treatment for the correction of anemia in patients with end-stage renal disease. Simultaneous treatment with angiotensin-converting enzyme (ACE) inhibitors for the control of hypertension and/or heart failure is often necessary. Recent reports in the literature have raised concern about a potential interaction between these drugs, with a resultant decreased EPO efficacy. METHODS: To investigate whether this interaction occurs in chronic dialysis patients, we retrospectively reviewed the records of 175 patients receiving chronic dialysis. All study patients were treated with EPO for at least 3 months, and had normal iron indices. Patients were treated with ACE inhibitors for at least 3 months, at a constant daily dose for at least 1 month (group 1, n = 32), or did not receive ACE inhibitors (group 2, n = 143). Patients with infections or overt iron deficiency were excluded. Total weekly EPO doses and hematocrit (Hct)/hemoglobin (Hgb) values in the two groups were compared. Variables known to affect response to EPO were compared, including ferritin, transferrin saturation, dialysis dose and serum aluminum. RESULTS: Total weekly EPO dose was 17,358 +/- 6,871 units in group 1 and 17,612 +/- 7,744 units in group 2 (p = 0.854). The achieved Hct was 32.1 +/- 4.4% (group 1) and 30.5 +/- 4.0% (group 2) (p = 0.079). Similarly, Hgb, ferritin, transferrin saturation, Kt/V, and serum aluminum were not different. The dose or duration of ACE inhibitor therapy did not affect Hgb or Hct. Thus, ACE inhibitor therapy does not appear to affect response to EPO in chronic dialysis patients.     

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

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

In vitro activity of 9 antibiotics and 3 beta-lactamase inhibitors against 107 clinical isolates of Acinetobacter baumanii

Twenty eight of 227 patients undergoing restorative proctocolectomy for inflammatory bowel disease, familial adenomatous polyposis or functional disease were over the age of 50 years: ages 50 to 60 (n = 13), 60 to 70 (n = 10), and over 70 (n = 5). Major complications occurred in 5 patients over the age of 50 (18%) compared with 43 patients under the age of 50 (23%). Three patients above the age of 50 had their pouch excised (11%) compared with 23 under the age of 50 (12%). Functional outcome was assessed with a 12 point symptom score. This was similar in all age bands: under 50 years (mean = 2.2; sd +/- 2.2; n = 109), 50 to 60 years (mean = 2.5; sd +/- 2.5; n = 12), 60 to 70 years (mean = 2.8; sd +/- 2.3; n = 7) and over 70 years (mean = 4.0; sd +/- 3.7; n = 5): P > 0.05). When analysed for ulcerative colitis alone, no significant differences were seen between the two age groups. Restorative proctocolectomy in the elderly gives results which are comparable to the younger population.     

Angiotensin-converting enzyme activity in stools of healthy subjects and patients with celiac disease

Angiotensin-converting enzyme (ACE) is a dipeptidylcarboxypeptidase that occurs in three types of cells: endothelial, epithelial, and neuroepithelial. ACE activity is present in plasma, urine, and vascular endothelium. High levels of ACE are found in the brush border of human small bowel. The aim of this study was to evaluate ACE activity in human stools and to find a correlation with the intestinal loss of epithelial cells. Fifteen healthy subjects (HS) (8 males, 7 females; age range 6-56 years), 20 patients with celiac disease (CD) (11 males, 9 females; age range 15-53 years), and 18 patients with CD in remission after a gluten-free diet (CD-GFD) (8 males, 10 females; age range 14-54 years) were enrolled in the study. The fecal ACE activity was measured in all groups. Fecal samples were kept at -20 degrees C for a subsequent test. In HS, fecal ACE activity was 21.03 +/- 16.17 nmol/min/100 g (mean +/- SD). In patients with CD with subtotal mucosa atrophy, ACE activity was significantly higher (113 +/- 88.94) than in HS and CD on GFD (36.65 +/- 23.9). We have demonstrated ACE activity in human stools. ACE activity in stools seems to derive from the microvilli of the intestinal mucosa, thus suggesting the potential usefulness of ACE determination as an index of enterocyte damage.     

Electroneutral Na-coupled cotransporter expression in the kidney during variations of NaCl and water metabolism

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy varies considerably. Therefore, we tested the potential role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric responsiveness in an observational follow-up study. Sixty (II, N = 13; ID, N = 26 and DD, N = 21) young hypertensive IDDM patients suffering from diabetic nephropathy were investigated during three months before and for the initial six month period during ACE inhibition [captopril 44 (SD 22) mg/24 hr, no differences in drug dose between groups]. Blood pressure (MABP) and albuminuria (ELISA) were measured three (1 to 6) times before and three (1 to 13) times during ACE inhibition. At baseline the groups (II/ID/DD) had comparable (1) mean arterial blood pressure (MABP mm Hg) of 113 +/- 10/108 +/- 9/114 +/- 8, (2) albuminuria (geometric mean with 95% CI) 1394 (747 to 2608)/1176 (844 to 1797) and 1261 (827 to 2017) mg/24 hr, and (3) serum creatinine (geometric mean with 95% CI), 80 (68 to 93)/85 (76 to 97)/103 (85 to 119) mumol/liter, respectively. Angiotensin converting enzyme inhibition induced a significant reduction in MABP, albuminuria and kidney function in all three groups (II/ID/DD; P < 0.05): (1) MABP (mean +/- SD) 12 +/- 7/5 +/- 7/8 +/- 9 mm Hg (ANOVA, P = 0.02); (2) albuminuria [mean (95% CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, P < 0.01); and (3) increasing serum creatinine [mean (95% CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) % (ANOVA, NS), respectively. Adjusting for differences in reduction in MABP did not change the association between decrease in albuminuria and ACE/ID genotypes (P < 0.01). A multiple linear regression analysis revealed that the ACE/ID polymorphism, albuminuria and MABP at baseline independently influenced the decline in albuminuria after initiation of ACE inhibition (R2 = 0.21, P < 0.01). A significant association between changes in MABP and albuminuria was demonstrated (R2 = 0.16, P < 0.01). Our data show that hypertensive albuminuric IDDM patients with the II genotype are particularly susceptible to commonly advocated renoprotective treatment.     

Cervical reconstruction of the supra-aortic trunks: a 16-year experience

PURPOSE: The purpose of this study was to review 182 consecutive cervical reconstructions of supra-aortic trunks, which were performed over a 16-year period. METHODS: A total of 182 innominate, common carotid, or subclavian arteries were reconstructed with a cervical approach in 173 patients aged 23 days to 83 years. Indications included hemispheric (n = 79), vertebrobasilar (n = 56), upper extremity (24), and internal mammary/cardiac ischemia (n = 5), asymptomatic severe common carotid disease (n = 33), or other (n = 3). Primary atherosclerotic innominate (n = 6), common carotid (n = 84), and subclavian (n = 66) lesions underwent reconstruction. Thirty-one operations were performed for multiple trunk involvement, recurrent disease, arteritis, infection, dissection, coarctation, or aneurysm. There were 122 bypass grafting procedures (98 ipsilateral, 24 contralateral) and 60 arterial transpositions. RESULTS: One death (0.5%) and 7 nonfatal strokes (3.8%) occurred, none in patients who were asymptomatic. Perioperative morbidity included four asymptomatic occlusions (2%), 6 myocardial infarctions (3%), 10 pulmonary complications (5%), and 2 graft infections (1%). Follow-up periods ranged from 1 to 190 months (mean, 53 +/- 5 months). Nineteen patients (10%) were lost to follow-up. Fifty-seven late deaths occurred, most from cardiac causes. Seven reconstructions necessitated late revision. The cumulative primary patency rate at 5 and 10 years was 91% +/- 2% and 82% +/- 5%, respectively. The survival rate at 5 years was 72% +/- 4% and at 10 years was 41% +/- 6%. The stroke-free survival rate was 92% +/- 2% at 5 years and 84% +/- 2% at 10 years. CONCLUSION: Cervical reconstruction of symptomatic and asymptomatic supra-aortic trunk lesions carries acceptable death and stroke rates and provides a long-term patient benefit. This should be the preferred approach for asymptomatic lesions and for patients with significant comorbidity because it carries less morbidity than direct transmediastinal aortic-based reconstruction.     

DNA polymorphisms in the ACE gene, serum ACE activity and the risk of nephropathy in insulin-dependent diabetes mellitus

BACKGROUND: To determine the relationship between DNA polymorphisms in the angiotensin I converting enzyme (ACE) gene, serum ACE activity and the risk of diabetic nephropathy. METHODS: A case-control study was carried out in a population of Jewish insulin-dependent diabetes mellitus (IDDM) patients. Cases (77 IDDM patients with diabetic nephropathy) and controls (89 IDDM patients with normoalbuminuria) were genotyped with PCR protocols for detecting two DNA polymorphisms in the ACE gene: one in intron 7 detected with the restriction enzyme PstI and the other in intron 16 identified as an insertion/deletion (I/D). RESULTS: The risk of nephropathy was increased only in patients homozygous for the allele with the PstI site. These homozygotes had a nephropathy risk that was 2.3 times (95% C.I.: 1.2-4.5) that of the other genotypes. Furthermore, these individuals did not have elevated serum ACE activity. CONCLUSIONS: The results of this study are evidence that the risk of diabetic nephropathy in IDDM is influenced by genetic variability at the ACE locus, but the responsible variant is not the I/D polymorphism in intron 16. Our findings require further studies in other populations.     

Structural organization and chromosomal localization of the human ribosomal protein L9 gene

Monoclonal antibodies (MoAbs) raised against Trypanosoma cruzi microsomal fraction (Mc) and cross-reactive with mammalian tissues were used to evaluate the ability of cross-reactive T. cruzi antigens to induce an immune response in Chagas' disease. Thus, we studied the ability of sera from Chagas' disease patients (CDP) with different degrees of cardiac dysfunction to block the immune recognition of these MoAb to the target antigen determining for each serum an inhibition index (II). By means of this approach we inferred that blocking of monoclonal antibody binding to T. cruzi microsomes by subjects' serum represents antibodies with the same reactivity. After serological and medical examinations, individuals were separated into the following groups: Chagas' disease patients without manifest cardiac involvement (CDP-0), CDP with suspected or borderline cardiac disease (CDP-1), CDP with moderate myocardial dysfunction (CDP-2), CDP with overt cardiac dysfunction (CDP-3) and controls including healthy subjects (HS) and patients with idiopathic myocarditis (IMP). The reactivity between MoAb 5F2 and its target antigen was significantly (p < 0.05) inhibited by sera from CDP irrespective of the clinical stage [CDP: n = 46, 50 +/- 20, mean II +/- SD: control: n = 16, 18 +/- 8]. Moreover, 5F2 was able to distinguish (p < 0.05) sera from CDP with mild disease (CDP clinical grade 0/1: n = 26, 34 +/- 18) from that of CDP with severe disease (CDP clinical grade 2/3: n = 20, 67 +/- 7). Moreover, the inhibitory capacity of sera from asymptomatic CDP (CDP-0) correlated with patients age (r = 0.66, p < 0.05). CDP-0 below or equal 40 years of age had results (n = 15, 25 +/- 13) comparable (p > 0.05) to that of controls while mean inhibition of CDP-0 over 40 years of age (n = 5, 60 +/- 5) was indistinguishable (p > 0.05) from that of patients with severe disease. Competitive assay with MoAb 5A9B11 also showed significant differences (p < 0.05) between sera from CDP (n = 46, 46 +/- 24) and controls (n = 13, 5 +/- 5). On the contrary, the differences observed between CDP with different cardiac involvement was not significant (mild: n = 26, 31 +/- 22; severe: n = 20, 66 +/- 11). However a thorough study of data from asymptomatic sera revealed the existence of two levels of reactivity, with low and high capacity to inhibit the reaction of 5A9B11 against Mc. On the contrary, CDP sera showed a blocking activity for 1A10C11 comparable to that of controls (CDP: n = 25, 19 +/- 9; control: n = 12, 14 +/- 6). Some cross-reactive MoAbs recognized epitopes partially composed of carbohydrates. Interestingly, 5F2 and 5A9B11 epitopes did not appear to have carbohydrates moieties. In summary, immunoinhibition assays revealed differences in the immune response of chronic chagasic patients against parasite epitopes. These results have opened the possibility to identify a prognosis marker of the disease suggesting the clinical utility of monitoring levels of these anti-Mc antibodies in patients with chronic Chagas' disease.     

Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and diabetic retinopathy in subjects with IDDM and NIDDM

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p < 0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE I/D genotype was similar in subjects with IDDM, NIDDM, and controls (chi 2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (chi 2 = 3.42, df = 2, p = ns) or NIDDM (chi 2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (chi 2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.     

Coronary reoperations: indications and results

The aim of this study was to assess the results of coronary reoperations and to determine the indications. Between January 1972 and December 1990, 166 coronary reoperations were performed in 161 patients (5 patients were operated three times). The interval between the first and second operation was 93 +/- 46 months. The interval between recurrence of symptoms and reoperation was 27 +/- 40 months. Recurrence of symptoms was related to isolated problems with the bypass grafts in 23% of cases, to an aggravation of the coronary disease without problems with the bypass grafts in 17% of cases and to an association of the two conditions in 60% of cases. Mortality in the first 30 postoperative days was 7.8% (13/161). The predictive factors of mortality were age over 70 years and an interval between recurrence of symptoms and reoperation of over 12 months. The causes of death were myocardial infarction (n = 5), left ventricular failure (n = 4), sudden death (n = 3), and arrhythmias (n = 1). The average follow-up period of survivors (n = 134) was 40 +/- 32 months. Four patients have been transplanted. Seven patients died secondarily. The cause of death was cardiac in 4 cases and non-cardiac in 3 cases. The actuarial 5 year and 10 year survival rates were 85 +/- 3%. Actuarial absence of myocardial infarction, angina, Class III-IV cardiac failure and transplantation was 87 +/- 4% at 5 years and 69 +/- 10% at 10 years. These figures show that coronary reoperation gives good functional results and long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impairment of cerebrovascular reactivity in long-term type 1 diabetes

The early preclinical detection of cerebrovascular complications in individuals with diabetes is one of the goals of care described in the St. Vincent Declaration. In accordance with this goal, the aim of the present work was to investigate whether altered cerebral microvascular function in patients suffering from type 1 diabetes can be detected with a transcranial Doppler probe after the administration of acetazolamide. A total of 72 type 1 diabetic patients and 40 healthy control subjects entered the study. Patients were divided into two groups: those with long-term diabetes (disease duration of >10 years, n = 37) and those with short-term diabetes (disease duration of < or =10 years, n = 35). Mean blood-flow velocity in the middle cerebral artery (MCAV) was measured at rest and at 5, 10, 15, and 20 min after intravenous administration of 1 g acetazolamide with a transcranial Doppler probe and expressed as the percentage change from the pretest measurement. The percentage increase in MCAV (cerebrovascular reactivity) was calculated at each time point and compared between the groups. Cerebrovascular reserve capacity (CRC), expressed as the maximal percentage increase of the MCAV, was compared between the groups. Additionally, a reproducibility study of CRC was performed in 10 patients, using intraclass correlations. Cerebrovascular reactivity in the long-term diabetes group was lower (means +/- SD: 5 min, 23.4 +/- 15.4%; 10 min, 28.8 +/- 17.0%; 15 min, 30.0 +/- 15.6%; 20 min, 24.2 +/- 17.8%) than that of the control subjects (5 min, 43.5 +/- 23.9%; 10 min, 55.3 +/- 24.0%; 15 min, 56.7 +/- 23.8%; 20 min, 54.8 +/- 25.9%) and the short-term diabetic patients (5 min, 43.6 +/- 25.9%; 10 min, 52.2 +/- 27.7%; 15 min, 55.3 +/- 32.2%; 20 min, 45.8 +/- 35.8%). CRC was lower in the long-term diabetes group than in the control group or the short-term diabetes group. Impairment of cerebrovascular reactivity was associated with retino- and nephropathy and increased levels of fibrinogen. In contrast, CRC was independent from actual glucose, insulin, glycosylated hemoglobin, von Willebrand factor antigen, and alpha-2 macroglobulin levels. Transcranial Doppler measurements of the changes in MCAV after stimulation with acetazolamide can detect altered cerebral microvascular function in patients with diabetes. Cerebrovascular reactivity and reserve capacity are reduced in patients with long-term diabetes. Further prospective studies should delineate the clinical significance of our results.     

A study on angiotensin-I converting enzyme polymorphism in CAPD patients

To clarify the role of genes related to angiotensin-I converting enzyme (ACE), the author investigated polymorphism of the ACE gene in 60 patients undergoing chronic ambulatory peritoneal dialysis (CAPD) and 50 patients undergoing hemodialysis (HD). One hundred healthy subjects were used as controls. The polymorphism was classified into three genotypes, II, ID and DD, according to insertion (I) and deletion (D) using the polymerase chain reaction method. In dialysis patients (CAPD or HD, n = 110), 21.8% had the II genotype, 48.2% the ID genotype, and 30.0% the DD genotype. There was a significant difference in allele frequency between normal subjects (n = 100) (J = 0.63, D = 0.37) and dialysis patients (I = 0.46, D = 0.54) (chi 2 = 12.321, p < 0.001). The mean plasma ACE activity was 9.9 +/- 1.6 IU/l in CAPD patients with the II genotype, 11.6 +/- 4.7 IU/l in CAPD patients with the ID genotype, and 14.5 +/- 3.5 IU/l in CAPD patients with the DD genotype. The mean rate of decrease in residual urinary volume was 0.8 +/- 0.7% per month in CAPD patients with the II genotype 1.4 +/- 1.3% per month in CAPD patients with the ID genotype, and 2.5 +/- 2.0% per month in CAPD patients with the DD genotype. These data showed a significant decrease in urinary volume in CAPD patients with the DD genotype (p < 0.05). The mean rate of decrease in residual urinary volume was positively correlated with the plasma ACE activity (r = 0.13389, p < 0.02). In CAPD patients, the mean cardiothoracic ratio was 46.6 +/- 3.5% in cases with the II genotype, 47.6 +/- 5.5% in cases with the ID genotype, and 52.9 +/- 8.4% in cases with the DD genotype. These data indicated significant cardiac enlargement in DD genotype cases. It can be concluded that CAPD patients with the DD genotype lost their residual renal function more rapidly and had a larger heart, than patients with the other genotypes.     

The serum kinetics of bovine testicular hyaluronidase in dogs, rats and humans

There is experimental and clinical evidence that i.v. injection of bovine testicular hyaluronidase (BTH) reduces the extent of necrosis during myocardial infarction. The fate of i.v. administered BTH has not been described. In this study, serum kinetics of BTH enzyme activity in dogs, rats and humans were determined. Tissue distribution of BTH was determined with an 125I-labeled preparation of purified BTH. Serum BTH activity initially decreased exponentially with half-life 2.0 +/- 0.1 min in dogs with coronary artery occlusion (n = 8; 500 U of BTH/kg); 3.2 min in humans with acute myocardial infarction (n = 2; 500 U of BTH/kg); and 3.2 +/- 0.3 min in rats (n = 5; 5,000 U of BTH/kg). In dogs BTH disappearance showed two distinct phases. After injection of high dose BTH (5,000 U of BTH/kg), during the first 7 min serum half-life of BTH was 2.1 +/- 0.2 min (n = 8), but increased to 9.4 min in later serum samples. After the injection of 125I-labeled BTH into the rat, protein-bound 125I disappeared from serum with a half-life (3.4 min) that is similar to the serum half-life of BTH enzyme activity (3.2 min). Twenty minutes after injection of 125I-labeled BTH, 30% of the label was recovered in the liver. It is concluded that BTH activity has a short serum half-life of less than 10 min in dogs, rats and humans. In the rat model, the disappearance of serum BTH activity results from physical removal of circulating BTH molecules rather than serum inhibition or inactivation of BTH enzymatic activity.     

Is PstI polymorphism of the angiotensin I converting enzyme gene associated with nephropathy development in non-insulin-dependent diabetes mellitus (preliminary study)

Nephropathy is a frequent complication of long term diabetes. Diabetic nephropathy is the major determinant of premature morbidity and mortality both in insulin-dependent (IDDM) and in non-insulin dependent-diabetes mellitus (NIDDM). There is good evidence that genetic predisposition plays a major role in development of diabetic nephropathy. This hypothesis is based on the observation that diabetic nephropathy clusters within families, both in IDDM and NIDDM. Components of the renin-angiotensin system (RAS) are plausible candidate genes to examine for a association with microalbuminuria and diabetic nephropathy. In this study we compared the distribution of PstI melting polymorphism at the ACE locus among NIDDM patients with diabetic nephropathy and in patients who, despite long duration of NIDDM, remain without this complication. The 220 NIDDM patients for whom DNA was available were classified into two groups according to their renal status: normoalbuminuric control subjects (n = 80) who are NIDDM patients with an A/C ratio < 2.5 and nephropathy cases (n = 140) who are NIDDM patients with A/C ratio > 2.5. Albumin excretion rate was assayed by radioimmunoassay. HbA1c was assayed using HPLC methods, creatinine--using Jaffe methods and DNA analysis using PCR reaction, and then after the amplification product was digested with PstI enzyme. The study revealed that PstI sequence differences ("+/= and -") in the ACE gene do not contribute to genetic susceptibility to diabetic nephropathy in NIDDM.