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Background & Aims: Transient elastography (TE) is validated in chronic hepatitis C (CHC) to evaluate hepatic fibrosis; however, limited data are available in chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD). This prospective study is aimed to assess the accuracy and the efficacy of TE for the detection of fibrosis in patients with chronic liver disease of different etiology and to evaluate the effect of steatosis on the liver stiffness measurement (LSM)., Methods: TE was performed in 219 consecutive patients with chronic liver disease (35% CHC, 32% CHB, and 33% NAFLD) within 6 months of the liver biopsy., Results: LSM was related to the fibrosis stage in each group (CHC: p = 0.596, p < 0.001; CHB: p = 0.418, p < 0.001; NAFLD: p = 0.573, p < 0.001), but the correlation was less strong in CHB and NAFLD than in CHC patients. In CHB patients with histological cirrhosis (F4), the median stiffness value was almost two times lower than in patients with severe fibrosis (F3). In NAFLD patients with advanced fibrosis (F3) and severe steatosis (> 33%), the LSM values were lower than expected and were similar to those of patients with initial fibrosis (F1) and fat < 33%. TE underestimated the stage of fibrosis in 75% of patients with F3 and steatosis > 33%. At multiple logistic regression analysis, in CHC and CHB patients, LSM was the only predictive variable of severe fibrosis/cirrhosis (OR = 1.42, p = 0.003 and OR = 1.354, p = 0.003, respectively), while in NAFLD subjects BMI and AST (OR = 1.433, p = 0.002 and OR = 1.053, p = 0.020, respectively) but not LSM were independently related with advanced fibrosis and cirrhosis., Conclusions: This study confirms that TE can be considered a valid support to detect fibrosis in chronic liver disease related to HCV but it should be interpreted cautiously in CHB and NAFLD patients, where host or disease-related factors may modify its accuracy., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Serum albumin is commonly measured in hospitalized patients. It has habitually been included among the parameters used for nutritional assessment, and recently its use has become even more widespread. Yet, no data are available in the literature about the prevalence and clinical significance of hypoalbuminemia in patients hospitalized in an internal medicine ward. The aim of this study was to investigate the prevalence and clinical significance of hypoalbuminemia in in-hospital internal medicine patients., Methods: We retrospectively evaluated the albumin level of patients admitted to the Department of Internal Medicine and Biomedical Sciences of the University of Parma during the year 2000. We then evaluated sex, age, nutritional status, some laboratory parameters, associated diseases, and length of hospitalization in hypoalbuminemic patients in comparison with a group of patients without hypoalbuminemia., Results: Hypoalbuminemics (46.5% of patients) were older, more frequently anemic, and had a higher erythrocyte sedimentation rate (ESR) and longer hospitalization; they were mostly normal weight or overweight. These patients also had chronic liver (18.6% vs. 4.5%), onco-hematological (33.8% vs. 12%), and infectious diseases (13.4% vs. 2.3%) and nephropathies (6.3% vs. 2%) more often than patients without hypoalbuminemia. The presence of onco-hematological diseases was related to anemia (O.R.=5.73; 95% CI: 3.184-10.310), lymphopenia (O.R.=2.76; 95% CI: 1.584-4.801), and hypoalbuminemia (O.R.=2.5; 95% CI: 1.178-5.307)., Conclusions: Hypoalbuminemia is very frequent in an internal medicine ward. In this setting, serum albumin is related to the length of hospitalization and to other parameters with a well-known prognostic value (age, hemoglobin) and clinical usefulness (ESR). It may also play a role in the evaluation of the possible association of onco-hematological diseases.

Objective: Our aim was to identify early predictors of poor neurodevelopmental outcome and of subsequent epilepsy in very early preterm and late preterm newborns with neonatal seizures., Study Design: Fifty-one preterm infants with gestational age (GA)

Objective: To investigate whether changes in tubuloglomerular feedback (TGF) dependent upon the tubular effects of buffering anions affect the renal haemodynamic response to L-arginine in healthy (control) individuals and patients with essential hypertension., Methods: Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF) and fractional excretion of sodium (FENa), chloride (FECl) and lithium (FELi) were measured in 10 control individuals and 10 hypertensive patients during two 3-h infusions of 0.012 mmol/kg per min L-arginine buffered with either HCl or citric acid., Results: FELi, FECl and FENa increased (P < 0.001) comparably in controls and hypertensive individuals with arginine-HCl and decreased with arginine-citrate (P < 0.001). MAP was unchanged in controls with arginine-HCl and decreased by 3% with arginine-citrate (P < 0.001), and decreased in hypertensive individuals with both arginine-HCl and arginine-citrate (by 3 and 7%, respectively; P < 0.001). GFR increased with arginine-citrate in controls and hypertensive individuals (by 6.1 and 5.4%, respectively; P < 0.001), but did not change with arginine-HCl in controls and declined by 4.6% in hypertensive individuals (P < 0.05). RBF increased equally after arginine-citrate in controls and hypertensive individuals (by 34 and 33%, respectively; P < 0.001); it also increased after arginine-HCl (22 and 13%, respectively; P < 0.001), but less than after arginine-citrate (P < 0.001), and 41% less in hypertensive individuals than in controls (P < 0.001)., Discussion: Because arginine-HCl, unlike arginine-citrate, inhibits tubular reabsorption and elicits much less renal vasodilatation than does arginine-citrate, renal haemodynamics in response to L-arginine are modulated by changes in reabsorption and TGF according to the tubular effects of the attendant anion. As renal vasodilatation in hypertensive individuals was reduced only with arginine-HCl, which activates TGF, the blunted vasodilatation of the hypertensive kidney in response to arginine-HCl reflects an exaggerated response to an activated TGF.

Background: Rates of cardiovascular morbidity and mortality are greater in heavy alcoholics than in either teetotallers or light-to-moderate drinkers., Objective: On the assumption that factors leading to atherosclerotic damage remain operative even after long-term alcohol withdrawal, we studied the possible mechanisms of raised cardiovascular risk in former heavy alcoholics., Methods: Forty-two apparently disease-free, normotensive alcoholics detoxified for 37.1 +/- 31.9 (SD) months, median 24, participated in the study. They were compared with 39 lifetime alcohol-abstaining control subjects, carefully matched for age, sex, body mass index, smoking and dietary habits, physical activity, lipids and fasting glucose. Endothelial function (flow-mediated dilation of brachial artery, high-resolution ultrasound technique), blood pressure, and some parameters of endothelial activation, oxidative stress, vascular inflammation and insulin sensitivity were measured., Results: The maximal percentage of flow-mediated dilatation was reduced in detoxified alcoholics (10.1 +/- 4.6 versus 14.9 +/- 7.4, P < 0.001) who also showed significantly higher blood pressure (systolic 127.5 +/- 12.9 versus 118.2 +/- 10.7 mmHg, P < 0.001; diastolic 79.4 +/- 7.1 versus 74.6 +/- 6.4 mmHg, P < 0.01; mean 95.4 +/- 8.2 versus 89.1 +/- 7.3 mmHg, P < 0.001), uric acid (5.0 +/- 1.1 versus 4.4 +/- 0.8 mg/dl, P < 0.05), high-sensitivity C-reactive protein (2.1 +/- 2.0 versus 1.0 +/- 0.9 mg/l, P < 0.01), endothelin-1 (0.38 +/- 0.11 versus 0.17 +/- 0.10 pg/ml, P < 0.001) and fasting insulin (10.4 +/- 4.5 versus 5.6 +/- 1.6 muU/ml, P < 0.001) with abnormal homeostasis model assessment index of insulin resistance (2.3 +/- 1.1 versus 1.2 +/- 0.4, P < 0.001)., Conclusion: Previous heavy alcoholism, in spite of long-term withdrawal, is associated with endothelial dysfunction and a wide cluster of haemodynamic, vascular and metabolic abnormalities that indicate an unfavourable cardiovascular and metabolic risk profile even in apparently disease-free former alcoholics.

Objective: To verify the prevalence of periodontal disease (PD) in patients with ischemic heart disease. PD is a serious public dental health care problem with a differentiated distribution in regards to severity, age group, type of infection, co-morbidities and risk factors., Methods: Four hundred and eighty patients were examined at the Ischemic Cardiopathy Outpatient Clinic of the Hospital das Clínicas of the Ribeirão Preto Medical School, São Paulo University, as well as 154 patients without heart disease from the same institution. Fifty-eight patients with heart disease and 62 patients without heart disease between the ages of 30 and 79 met the criteria to be included in the investigation. In accordance with recommendations of WHO (1999) the Community Periodontal Index (CPI) and the Periodontal Attachment Loss Index (PALI) were used., Results: Patients with heart disease had a prevalence of sextants with moderate to advanced PD (76.3% versus 20.2%; p < 0.00001). In these patients, 1.1% of the sextants were found to be healthy versus 32.0% of those without heart disease (p < 0.00001). In regards to the progression of PD, 6.0% of the sextants of the patients with heart disease did not exhibit attachment loss versus 68.0% of those without heart disease (p < 0.00001). Dental biofilm was observed in 100.0% of the patients with heart disease and in 82.3% of those without heart disease (p < 0.001). Treatment of periodontal pockets > 6 mm was required in 79.3% of the patients with heart disease versus 9.7% of those without heart disease (p < 0.0001)., Conclusion: PD was very prevalent in the groups studied with a higher degree of severity in those with ischemic heart diseases. The elevated prevalence of risk factors found, indicates that intervention strategies are required.

Background: The role of the loss of p27 protein expression in the oncogenesis of colorectal cancer is still in debate. In this study, we prospectively examined the immunohistochemical expression of p27 in 108 consecutive colorectal cancers, and we analysed the relationship with the results, the clinicopathological data, microsatellite instability (MSI) and other genetic alterations of tumours., Methods: Unselected patients (108) who underwent curative colorectal resection for sporadic colorectal cancer in a three-year period were evaluated for MSI using 6 microsatellite markers, and for the presence of p27, p53, Fhit, Mlh1 and Msh2 proteins by means of immunostaining. The relationships between these markers were analysed. p27 protein expression was examined for association with disease recurrences and survival., Results: Lack of p27 expression was noted in 33 out of 108 (30.5%) colorectal cancer cases (P<0.05). This altered expression was significantly higher in proximal cancers (P<0.05), mucinous tumours (P<0.001), poorly differentiated histology (P<0.01), cancers with MSI (P<0.05), tumours with altered expression of Mlh1 (P<0.01), of Msh2 (P<0.05), and of Fhit (P<0.01). Overall survival was better in the patient group with altered level of phenotypic p27 expression, although the difference does not reach statistical significance (P=0.069). The analysis performed only for patients with tumour at stage II showed significantly better survival when the tumour exhibited altered p27 expression (P<0.02)., Conclusions: The results of the present study support the hypothesis that altered expression of p27 may be part of the genetic pathway involving MSI, which is responsible for the development of some colorectal cancers.

Introduction: Simultaneous dual atrioventricular nodal conduction (SDNC) through slow (SP) and fast pathway (FP) is a rare phenomenon observed upon the induction of atrioventricular nodal reciprocating tachycardia (AVNRT). The aim of this study is to report the electrophysiological features of patients showing typical AVNRT induced through SDNC., Methods and Results: Among 461 consecutive patients with typical AVNRT submitted to radiofrequency catheter ablation (RFCA), seven patients (1.5%) with SDNC at tachycardia onset (group I: 6 female; age 60-72 years, mean 65.2 +/- 3.8 years) and 118 age-matched controls (group II: 60 female; age 60-88 years, mean 68.4 +/- 6.8 years) were considered. Controls were further subdivided into two subgroups according to age: subgroup A (94 patients, age 60-75 years) and subgroup B (24 patients, age >75 years). The value of the following parameters was significantly higher in group I than in group II and in subgroup A: A-H interval [113 +/- 26 vs. 89 +/- 27 (P < 0.01) vs. 84 +/- 19 (P < 0.001)], ventriculoatrial conduction effective refractory period [355 +/- 85 vs. 293 +/- 87 (P < 0.05) vs. 281 +/- 82 (P < 0.05)], SP conduction time upon AVNRT induction [444 +/- 104 vs. 350 +/- 72 (P < 0.01); vs. 345 +/- 67 (P < 0.001)], AVNRT cycle length [484 +/- 103 vs. 396 +/- 71 ms (P < 0.05); vs. 384 +/- 69 (P < 0.05)], and rate of AVNRT induction from ventricle [71% vs. 10% (P = 0.001); vs. 6% (P = 0.001)]. Differences were mostly not significant between group I and subgroup B. SP location and RFCA success rate were similar in all groups., Conclusion: In a population of AVNRT patients, SDNC at AVNRT induction is infrequent and it prevails beyond the fifth decade of life and in females. SDNC is associated with peculiar AVN conduction features, which resemble the age-related modifications of AVN conduction.

An association between Graves' disease (GD) and chronic hepatitis C (C-HC) has been observed both in the presence and the absence of recombinant interferon-alpha (rIFN-alpha) treatment. rIFN-alpha-induced GD is characterized by suppressed thyroid-stimulating hormone levels; normal or elevated free triiodothyronine (FT3) and free thyroxine (FT4) values; the presence of thyroid peroxidase antibodies, antithyroglobulin antibodies, and thyroid receptor antibodies; and high iodine thyroid uptake. In contrast, GD developed during C-HC without rIFN-alpha is less clearly defined. In this study, we examined two groups of patients: group A, 28 patients with C-HC treated with rIFN-alpha who developed GD after 1 to 9 months, and group B, 10 patients with C-HC who developed GD without a previous rIFN-alpha treatment. At the time of GD, both groups started methimazole therapy; thyroid function was reevaluated after 3, 6, 9, and 12 months. Group A patients continued IFN. After 12 months, all patients of group A were euthyroid, and 21 of them (75%) had already stopped methimazole treatment, whereas all patients of group B were euthyroid and only 2 (20%) had stopped methimazole. In conclusion, the data show a better course of GD, with a more precocious and significantly higher number of recoveries in patients with rIFN-alpha-induced GD than in rIFN-alpha-unrelated disease. Further studies are needed to establish whether the two types of GD differ not only from a clinical point of view but also because of different underlying pathogenetic mechanisms.

Objective: Treatment with interferon (IFN) of patients affected by chronic hepatitis C (CH-C) may produce alterations in thyroid function, such as hypothyroidism, Graves'-like hyperthyroidism and destructive thyrotoxicosis (DT). IFN-induced DT is characterized by suppressed serum TSH levels, normal or elevated FT4 and FT3 concentrations, with the presence or absence of thyroid peroxidase antibodies and antithyroglobulin antibodies, the absence of thyroid receptor antibodies and radioactive iodine uptake suppressed or <5%., Design: IFN-induced DT is a mild clinical disease, because thyroid-destructive processes last for a short time and involve a small portion of the gland. At present, the therapeutic approach in DT suggests IFN withdrawal and 1-2 months of methylprednisolone treatment., Methods: In consideration of possible untoward side effects of steroid treatment in patients with CH-C, we studied two groups of patients with CH-C who developed DT after treatments with various preparations of recombinant IFN (with or without ribavirin). Patients sequentially entered the study during a 4-year period, at the time of DT diagnosis, when IFN therapy was discontinued. The first 12 subjects (group A) were treated with 8-16 mg/day methylprednisolone for 30-40 days after IFN withdrawal; in the following 15 patients (group B), IFN withdrawal was not followed by any additional treatment. All patients underwent clinical and laboratory controls of thyroid function at 1, 2, 3 and 6 months after DT diagnosis., Results: The results showed restoration of euthyroidism in both group A and group B patients at 6 months after DT diagnosis, regardless of steroid treatment., Conclusions: The simple withdrawal of IFN therapy in patients with CH-C, who had developed DT, appears to be effective in the treatment of the thyroid disease. This therapeutic approach should be preferred in order to avoid possible undesired side effects of steroid therapy in patients with CH-C., (2005 S. Karger AG, Basel)

Background: It has been reported that, in the initial phase of ischemic cardiomyopathy, the earliest alterations of left ventricular function are detected during the relaxation phase. The aim of this study was to look for precocious abnormalities in the early stage of ischemic cardiomyopathy in both left ventricular systolic and diastolic phases., Methods and Results: Using simultaneous left ventricular catheterization and echo-Doppler techniques, we studied both systolic and diastolic function in 44 (37 males and 7 females, mean age 55.7+/-8) normotensive, clinically stable, coronary artery disease patients with normal left ventricular ejection fraction in comparison to 9 age- and sex-matched normal control subjects (7 males and 2 females, mean age 54.7+/-9). Mean values of E deceleration time, tau, left ventricular end-diastolic volume and pressure, and end-systolic volume and lowest diastolic pressure were significantly higher (from P<.05 to P<.01), whereas mean dP/dt/P values significantly lower (P<.05) in coronary artery disease patients than in controls. A strict relationship (P<.001) between dP/dt/P and tau, left ventricular lowest and end-diastolic pressure was found in all subjects studied., Conclusion: Early and subtle abnormalities in parameters of both systolic and diastolic function can be found in the majority of coronary artery disease patients with normal ejection fraction.

Background: The physiological inhibitory control of glucagon-like Peptide 1 (GLP-1) on gastric emptying and the contribution of this peptide in the regulation of food intake as a satiety factor suggest that impaired secretion and/or activity of GLP-1 may be involved in the pathogenesis of obesity. We investigated food-mediated GLP-1 secretion as well as plasma activity of dipeptidyl-peptidase IV (DPP-IV), the enzyme responsible for rapid inactivation of the circulating peptide, in morbidly obese patients, before and after weight loss resulting from biliopancreatic diversion., Methods: Twenty-two morbidly obese non-diabetic patients (BMI = 47.5 +/- 1.8) and 9 age-matched healthy volunteers were studied. A mixed meal (700 kcal) was administered to all subjects and blood samples were collected at 0, 15, 30, 60, 120 min for the determination of circulating glucose, insulin, GLP-1 (7 - 36 amide) concentrations and plasma DPP-IV activity. The patients repeated the test meal after 50 % overweight reduction resulting from surgical treatment (BMI = 33.8 +/- 1.1)., Results: While nutrient ingestion significantly increased plasma GLP-1 levels in the control group (30', 60': p < 0.01), the test-meal failed to modify basal peptide values in the obese patients, and an overall reduction in circulating GLP-1 occurred during the observation period (p < 0.001). Plasma DPP-IV activity in the same patients resulted as being significantly higher than controls, both at fasting and in response to the meal (p < 0.05). With respect to preoperative values, an overall increase in circulating GLP-1 levels occurred in all patients following biliopancreatic diversion (p < 0.001). Plasma DPP-IV activity, on the other hand, continued to be abnormally increased, even after considerable weight loss (p < 0.05 vs. controls)., Conclusions: First: In morbid obesity, the accelerated inactivation of circulating GLP-1 could at least partially account for plasma peptide levels lower than normal, the defective availability of such a satiety factor possibly contributing to eating behaviour abnormalities; Second: plasma DPP-IV hyperactivity in the obese did not seem to be affected by the overweight degree, the increase in postoperative GLP-1 levels mainly resulting from hyperstimulation of GLP-1 secretory cells due to surgical manipulation of gastrointestinal tract. If the abnormally accelerated degradation of GLP-1 in obesity is confirmed, selective DPP-IV inhibitors could actually represent an ideal approach to obesity management.

Background: Stimulated sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, and cortisol are thought to affect blood pressure in early withdrawal of alcoholics. Hyperactivity of sodium-retaining systems with consequent volume expansion also could interact with sodium sensitivity as previously found in long-term withdrawing alcoholics., Methods: To investigate this hypothesis, blood pressure and sodium balance were measured during the first 8 days of withdrawal in 18 chronic alcoholics on a 150 mM Na diet. Results were related to the Salt Sensitivity Index of blood pressure as measured in the same alcoholics after 1 year of abstinence., Results: Early withdrawal study: there was a positive sodium balance (+288.6 +/- 45.6 mM; p < 0.0001) and rise in mean arterial pressure (+11.8 +/- 2.9 mm Hg; p = 0.001) during early withdrawal on 150 mM Na diet. Salt Sensitivity Study after long-term detoxification: the shift from low (55 mM) to high sodium (260 mM) intake produced a larger (p = 0.04) increase in mean arterial pressure in alcoholics (+9.3 +/- 2.0 mm Hg) than in 30 teetotal controls (+5.1 +/- 1.1) (Salt Sensitivity Index, 0.047 +/- 0.008 vs. 0.023 +/- 0.0053; p < 0.05). Changes in mean blood pressure during withdrawal were highly related to sodium sensitivity index (r = 0.8; p < 0.001)., Conclusions: Early withdrawing alcoholics exposed to a normal sodium intake experience positive Na balance and increase in blood pressure that is related to sodium sensitivity measured after long-term detoxification. This suggests that salt sensitivity plays a key role in blood pressure regulation in early withdrawing alcoholics.

The stability over a 12-year period of several coronary heart disease (CHD) risk factors was evaluated in 348 individuals who had remained healthy following baseline measurements made of the same variables in 1981. CHD risk factors evaluated were fasting and post-glucose challenge (120-minute) plasma glucose and insulin concentrations, plasma triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) concentrations, and the ratio of LDL/HDL cholesterol concentrations. Approximately 40% to 60% of individuals in the highest CHD risk quartile (or lowest in the case of HDL cholesterol concentrations) in 1981 were still at highest risk in 1993. A similar proportion of individuals at lowest risk in 1981 were still in that category in 1993. At least 50% of the participants in this prospective analysis experienced a change by 1 quartile or more in each of the metabolic CHD risk factors measured, and these differences were highly statistically significant for all variables measured with the exception of the TG and HDL cholesterol concentrations. These results demonstrate that the implicit assumption in epidemiological studies that CHD risk factors at baseline remain stable may require examination., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Unlabelled: To investigate a possible role of an enteroinsular axis involvement in the pathogenesis of type 2 diabetes, plasma glucagon-like peptide 1 (GLP-1) 7-36 amide response to nutrient ingestion was evaluated in type 2 diabetics affected by different degrees of beta-cell dysfunction., Methods: 14 patients on oral hypoglycaemic treatment (group A: HbA1C = 8.1 +/- 1.8 %) and 11 age-matched diabetic patients on diet only (group B: HbA1C = 6.4 +/- 0.9) participated in the study. 10 healthy volunteers were studied as controls. In the postabsorptive state, a mixed meal (700 kCal) was administered to all subjects, and blood samples were regularly collected up to 180' for plasma glucose, insulin, glucagon, and GLP-1 determination., Results: In the control group, the test meal induced a significant increase in plasma GLP-1 at 30' and 60' (p < 0.01); the peptide concentrations then returning toward basal levels. beta-cell function estimation by HOMA score confirmed a more advanced involvement in group A than in group B (p < 0.01). In contrast, the insulin resistance degree showed a similar result in the two groups (HOMA-R). In group A, first-phase postprandial insulin secretion (0 - 60') resulted, as expected, in being significantly reduced compared to healthy subjects (p < 0.001). In the same patients the mean fasting GLP-1 value was similar to controls, but the meal failed to increase plasma peptide levels, which even tended to decrease during the test (p < 0.01). In group B, food-mediated early insulin secretion was higher than in group A (p < 0.001), although significantly reduced when compared to controls (p < 0.01). Like group A, no GLP-1 response to food ingestion occurred in group B patients in spite of maintained basal peptide secretion. Whereas the test-meal did not significantly modify plasma glucagon levels in the control group, glucagon concentrations increased at 30' and 60' in both diabetic groups (p < 0.01)., Conclusions: 1) The functional integrity of GLP-1 cells results as being seriously impaired even in the condition of mild diabetes; 2) the early peptide failure could contribute to the development of beta-cell deterioration which characterizes overt type 2 diabetes.

The urinary excretion of insulinotropic glucagon-like peptide 1 (GLP-1) was investigated as an indicator of renal tubular integrity in 10 healthy subjects and in 3 groups of type 2 diabetic patients with different degrees of urinary albumin excretion rate. No significant difference emerged between the groups with respect to age of the patients, known duration of diabetes, metabolic control, BMI, or residual beta-cell pancreatic function. Endogenous creatinine clearance was significantly reduced under conditions of overt diabetic nephropathy, compared with normo and microalbuminuric patients (p < 0.01). Urinary excretion of GLP-1 was significantly higher in normoalbuminuric patients compared to controls (490.4 +/- 211.5 vs. 275.5 +/- 132.1 pg/min; p < 0.05), with further increase under incipient diabetic nephropathy conditions (648.6 +/- 305 pg/min; p < 0.01). No significant difference resulted, in contrast, between macroproteinuric patients and non-diabetic subjects. Taking all patients examined into account, a significant positive relationship emerged between urinary GLP-1 and creatinine clearance (p = 0.004). In conclusion, an early tubular impairment in type 2 diabetes would occur before the onset of glomerular permeability alterations. The tubular dysfunction seems to evolve with the development of persistent microalbuminuria. Finally, the advanced tubular involvement, in terms of urinary GLP1 excretion, under overt diabetic nephropathy conditions would be masked by severe concomitant glomerular damage with the coexistence of both alterations resulting in a peptide excretion similar to control subjects.

We have investigated the possibility of detecting early abnormalities of left ventricular function at the initial phase of ischemic cardiomyopathy. Sixteen normotensive patients with coronary artery disease and normal left ventricular ejection fraction and 6 control patients were studied by invasive hemodynamic techniques in combination with transmitral Doppler flow or with echo-tissue Doppler imaging. The extent of the percentage of left ventricular longitudinal shortening and the systolic peak velocity at echo-tissue Doppler were significantly higher in the control patients than in patients with ischemic cardiomyopathy (P <.01). Left ventricular end-diastolic pressure was higher (P <.05), whereas mean values of isovolumic contraction and relaxation indexes (dP/dt/P: P <.05; +dP/dt: P <.05; -dP/dt: P <.01) were lower in patients with ischemic cardiomyopathy. Tau was significantly longer in ischemic patients (42.7 +/- 8.8 versus 34.5 +/- 3.7 ms, P <.05). In the control patients, the aortic valve closure to peak E interval by transmitral Doppler flow was significantly longer than that measured by echo-tissue Doppler (P <.001), whereas in patients with ischemic cardiomyopathy, this interval difference was still present and significantly shorter (P <.05). In patients with coronary artery disease and normal ejection fraction, minor and early abnormalities of left ventricular function related to isovolumic contraction and relaxation as well as to longitudinal shortening could be detected. In addition, a suction-like effect, detected during early filling evaluation with echo-tissue Doppler, is significantly decreased but not abolished during the early stages of coronary artery disease.

Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.

The study was initiated to evaluate the ability of hyperinsulinemia (as a surrogate measure of insulin resistance) to predict the development in a previously healthy population of three putative outcomes of this abnormality--glucose intolerance, hypertension, and coronary heart disease (CHD). The study involved defining the incidence at which these changes occurred between 1981 and 1993 to 1996 in 647 individuals who were free of any disease when initially studied. The study population consisted of approximately 90% of the subjects evaluated in 1981, divided into quartiles on the basis of the plasma insulin response to a glucose challenge as determined in 1981. The results indicated that the 25% of the population with the highest insulin response in 1981 had significant (P < .001) increases in the incidence of impaired glucose tolerance (IGT) or type 2 diabetes (eightfold), hypertension (twofold), or CHD (threefold). Furthermore, the ability of hyperinsulinemia to predict the three clinical endpoints was independent of differences in age, gender, or body mass index (BMI). Finally, if CHD is considered the clinical endpoint, multiple logistic regression analysis indicates that the values for plasma triglyceride (TG) and mean arterial blood pressure ([MAP] as measured in 1981) also predict the development of CHD. These results indicate that the untoward clinical effects of insulin resistance and/or compensatory hyperinsulinemia, glucose intolerance, hypertension, and CHD clearly can develop in less than 15 years.

The aim of this study was to evaluate the influence of age and other clinical and echocardiographic parameters on left ventricular filling in a group of 174 untreated patients with mild to moderate hypertension (aged 20-82 years; mean 51.2 years) and in 189 age-matched normotensive subjects. All subjects underwent an echocardiographic study with pulsed Doppler evaluation of left ventricular filling. Left ventricular dimensions and indexes of systolic function were similar and within normal limits in both groups. Left ventricular filling was altered in hypertensive subjects < 65 years with a decrease of peak early velocity (peak E), an increase of peak atrial velocity (peak A) and a reduced E/A ratio. However in subjects > or = 65 years, we did not observe any differences in transmitral flow velocity pattern between hypertensive and normotensive subjects. The stepwise regression analysis showed that age alone explains up to 8% of peak E variance, 14% of peak A and 26% of E/A ratio in hypertensives, while in normotensives it explains up to 18% of peak E variance, 50% of peak A and 61% of E/A ratio. The other variables entered into the regression slightly improved the predictive power. In conclusion, age is the major independent factor affecting left ventricular filling in both groups, even if its predictive power was smaller in the hypertensive group. The similarity of diastolic filling pattern in elderly hypertensive and normotensive subjects suggests that the 'aging factor' plays an important role in influencing left ventricular filling pattern so as to mask the effect of hypertension in the elderly patients.

Pulsed Doppler measurements of left ventricular filling (LVF), two-dimensional and M-mode echocardiograms were performed in 189 healthy subjects, in order to evaluate factors influencing LVF Doppler indexes in normal subjects. LVF Doppler indexes (peak E, peak A, peak E/peak A, deceleration rate of peak E (ED) were related by univariate and multivariate analyses with the following parameters: age, sex, heart rate, systolic and diastolic blood pressure, aortic root and left atrial dimensions, left ventricular mass index, left ventricular shortening fraction. The stepwise analysis showed that age by itself explained up to 18% of peak E variance, 50% of peak A variance, 61% of peak E/peak A variance and 25% of ED variance. The other variables entered into the regression, slightly improved the predictive power (less than 10%). In conclusion, age is the major independent factor affecting LVF in normal subjects, although other variables show significant correlation also after age adjustment.

This study aimed determining the chronic effects of nifedipine (N) on left ventricular filling in 25 patients (mean age 55) with mild to moderate arterial hypertension. M-mode, B-mode and pulsed Doppler measurements were performed at baseline, after 30 min from administration of sublingual N (10 mg) and after 6 months of therapy with slow release N (max dose: 60 mg die). Acute and chronic N reduced significantly both systolic (p less than 0.001) and diastolic pressure (p less than 0.001). At the end of the treatment with slow release N, and septal wall thicknesses had a slight but significant decrease (p less than 0.01). Diastolic and systolic dimension were not modified. Left ventricular mass index decreased significantly from 141 +/- 34 to 130 +/- 31 g/m2 (p less than 0.05). The Doppler-derived diastolic filling indexes (peak E, ratio peak E/A,E deceleration) were abnormal at baseline, and had a significant increase after sublingual and chronic therapy. Changes in left ventricular mass index and diastolic filling indexes were not correlated. A significant correlation was found between peak E changes after acute and chronic N administration (r = 0.732 and p less than 0.001). The results of this study demonstrate that both acute and chronic administration of N modify transmitral flow velocity pattern, suggesting that, in hypertensive patients, left ventricular filling abnormalities are partly dynamic and reversible. Our findings also demonstrate that acute N effects may predict the chronic results.

Instantaneous measurements of ejection phase indices throughout the whole systole have been performed in 10 normal subjects (normal group), and in 8 coronary artery disease (CAD) patients (CAD group). All the patients of the CAD group were selected from 230 CAD patients because of their normal values in standard ejection phase indices (i.e. ejection fraction, EF; mean velocity of circumferential fiber shortening, VcfM; mean normalized systolic ejection rate, MNSER). An 'instantaneous' evaluation of the ventricular function, by means of a frame-by-frame analysis throughout the ejection period, allowed us to detect abnormalities of ventricular ejection in the early phase of systole in these CAD patients. In comparison with the control group, the CAD group presented similar peak values of dV/dt, dV/dt/EDV and Vcf, and a significantly longer time to peak values of these indices; EF curve analysis showed similar values at the end of systole in the two groups, but the mean curve of the CAD group was significantly lower in the first third of ejection when compared with that of control group. A segmental wall motion analysis in the early phase of systole showed a diffuse delayed ventricular wall motion (tardokinesis) related to abnormalities demonstrated by frame-by-frame analysis of ejection phase indices. Our results confirm that the CAD patients may have abnormalities of ventricular performance in the early phase of systole even when standard ejection phase indices are still within the normal range. In addition, the chronological appearance of these abnormalities during the whole systole has been clearly assessed; finally, these data confirm the importance of acceleration in blood ejection from the left ventricle as an index of ventricular function.

The authors studied the modification of systolic time intervals (STI), pre-ejection period (PEP) and left ventricular ejection time (LVETc), before and after isometric exercise, in 294 diabetic patients without clinical evidence of cardiomyopathy and in good metabolic control compared to 132 normal subjects. The study was aimed at detecting preclinical alterations of left ventricular function. Diabetic patients considered together did not show any difference in STI in basal conditions or after isometric exercise compared to normal subjects. When diabetic patients were divided into sub-groups according to their treatment, the insulin-treated diabetics showed modification of STI after isometric exercise, which indicated an alteration of left ventricular function. Also subjects treated with oral hypoglycemic agents showed similar but less evident changes. In diabetic patients on diet only and in those with duration of diabetes of 6 months or less, STI was identical to that of normal subjects. These data do not explain the pathogenesis of myocardial involvement, although they are in accordance with studies which have laid emphasis on the alteration of compliance of the diabetic heart.

The reliability of a new noninvasive method for evaluating ejection fraction and the mean velocity of circumferential fiber shortening by apexcardiography and carotid pulse tracing has been evaluated. Three groups of subjects were considered. Group 1: 30 normal subjects (mean age 43 years); Group 2: 34 patients with aortic valve disease (mean age 51 years); Group 3: 76 patients with coronary artery disease (mean age 50 years). The mechano-cardiographic tracing points were acquired by an ultrasonic digitizing system and compared with the same indexes measured from the ventriculogram. In 53 patients M-mode echocardiographic evaluations also were performed. The correlations between the apexcardiographic derived ejection phase indexes and the angiographic measurements were highly significant in all subjects and in each group of patients. The correlations between the ejection phase indexes determined by echocardiography and the same angiographic data were also significant, but the r-values were somewhat lower than those found between the apexcardiographic and angiographic parameters in the same patients. Our results have assessed the reliability of this new method and demonstrated that this noninvasive technique can be applied not only in coronary disease but also in aortic valve disease and in normal subjects. It can be concluded that the apexcardiographic evaluation of cardiac performance appears applicable to patients in whom a means of assessing and sequentially following ventricular function is indicated.

The effects of digitalis on the left ventricular diastolic phase are very scant. In order to gain a better insight into this problem, we measured the hemodynamic effects of an intravenous injection of K-strophantidin (0.005 mg/kg in a bolus given within 5-10 min) during the diastolic phase in 9 normal male subjects and in 9 male patients with coronary artery disease (CAD), maintaining a normal overall ejection fraction despite of the presence of some hypokinetic segments. Administration of K-strophantidin decreased significantly in normal controls the left ventricular volumes at 1/3, 1/2, 2/3 of the diastolic phase, whereas it did not produce significant change in CAD patients. Digitalis decreased the first and increased the second filling peak of the volumetric variable dV/dt in the normal controls, but not in the CAD patients. In the latter group the 2 peaks before digitalis administration were similar. The effects of digitalis on the dV/dt measured during the second filling peak were significantly different in the 2 groups. The increments of pressure in middle and end diastole in CAD patients were significantly greater than those observed in normal controls. Results of the present study suggest that digitalis has a negative influence on the left ventricular filling phase both in normal and CAD subjects. In fact digitalis modifies in normals the pattern of the left ventricular filling phase whereas it induces an untoward increase in the middle and end diastolic pressure in CAD patients.

Changes in R-wave amplitude (delta R) during treadmill test were studied in 84 coronary artery disease (CAD) patients and in 150 normal subjects. The evaluation of ECG recordings (CB5 lead) was carried out by a computer program. At maximal exercise, R-wave decreased by 2.1 +/- 2.8 mm in normal subjects, while in CAD patients mean delta R was significantly lower (0.4 +/- 1.7 mm). When the evaluation of delta R was performed at comparable heart rate and work load values, no significant differences were observed between normals and CAD patients. Using as criterion for a positive test an ischemic ST segment depression greater than or equal to 1.0 mm, the diagnostic sensitivity was 66.7%, while the specificity was 94.0%. When an increase or no change in R-wave was taken as evidence of an abnormal response, sensitivity and specificity values were 57.1% and 65.3% respectively. After a critical review of different parameters able to affect delta R, the difficult physiopathological evaluation and the poor diagnostic reliability of delta R were emphasized. The different heart rate and work load values attained by normals and CAD patients proved to be a further confounding factor in delta R comparison between the two groups.

Distribution of arterial blood pressure and prevalence of hypertension have been reported in 172 subjects (568 males and 144 females), derived from screening of a bank clerks population. 99 subjects were found to be hypertensive: 46 (46.4 p. 100) were aware of being hypertensive, 24 (24.3 p. 100) resulted to be under treatment and only in 5 subjects blood pressure values were effectively controlled. The relationships between arterial blood pressure and some recognized or suspected coronary risk factors were also determined by multiple regression analysis. Age, heart rate, body mass index, glycemia after loading, turned out the variables most correlated with blood pressure. The multiple regression analysis showed that overall evaluation of coronary risk factors explained up to 21 p. 100 of the systolic blood pressure variation and to 17 p. 100 of diastolic pressure in male subjects, while for women the obtained values were 34 p. 100 and 24 p. 100 respectively. After a critical evaluation of different parameters able to affect arterial blood pressure, the difficult approach to hypertension preventive and therapeutic problems was emphasized.

In order to evaluate both quantitatively and qualitatively exercise ST response in females, we have studied 232 healthy subjects (age range 35-59 years): 82 women (mean age 45.8 years) and 150 men (mean age 46.1 years). All subjects had performed a maximal treadmill exercise in 1976 and were followed up for 6 years in order to exclude the presence of subclinical coronary artery disease. Exercise ST segment responses were evaluated in a single bipolar lead (CB5) and were classified as 'positive' by visual interpretation when a 1.0-mm or greater 'ischemic' ST depression occurred. A computer system was employed to evaluate exercise ST changes quantitatively. The following ST parameters were evaluated: ST depression at R + 80 ms point (ST2); mean ST depression (STmean), and ST time-voltage integral (STarea). Computer analysis of resting ECG has shown lower ST voltages in females than in males. ST2, STarea, and STmean changes from basal to maximal exercise values were not significantly different in men and women. A similar prevalence of 'positive' responses in males and females was also found by ECG visual interpretation. In conclusion, our data show that in healthy subjects exercise ST segment response is comparable in males and females and indirectly suggest that the lower predictive value of exercise ECG in women is likely to be related to different coronary artery disease prevalence.