Effects of chronic elevation of atrial natriuretic peptide and free fatty acid levels in the induction of type 2 diabetes mellitus and insulin resistance in patients with mitral valve disease.

BACKGROUND AND AIMS: The relationship between atrial natriuretic peptide (ANP), increased free fatty acid (FFA) and insulin resistance in patients with mitral valve disease (MVD), a group characterised by elevated atrial pressure and increased ANP levels, is not defined. The present study was performed to evaluate, in MVD patients, the relationship between increased ANP and FFA levels and insulin resistance and the role of mitral valve replacement/repair in ameliorating these metabolic alterations. Conversely, coronary heart disease (CHD) patients were evaluated before and after coronary artery bypass grafting (CABG), since they are known to be insulin resistant in the presence of chronic FFA increase. METHODS AND RESULTS: Fifty MVD patients and 55 CHD patients were studied before and 2 months after surgery and compared with 166 normal subjects. Before surgery, 56% of MVD patients had impaired glucose tolerance or newly diagnosed type 2 diabetes after a standard oral glucose load and this percentage decreased to 46% after surgery. In CHD, impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetic patients were 67% of patients before and after CABG. In MVD, left atrial (LA) volume, ANP, FFA incremental area and insulin levels were higher and Insulin Sensitivity (IS) index significantly reduced while after surgery, LA volume, ANP and FFA significantly decreased and IS index significantly improved. In CHD, insulin resistance and hyperinsulinaemia were present both before and after surgery with increased tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels. CONCLUSION: In MVD, a higher degree of abnormal glucose tolerance and insulin resistance are associated to increased levels of ANP and FFA, while these metabolic alterations are improved by mitral valve replacement/repair surgery. Clinical Trial.gov registration number NCT 00520962.

Intra-procedural monitoring protocol using routine transthoracic echocardiography with backup trans-oesophageal probe in transcatheter aortic valve replacement: a single centre experience.

AIM: The aim of this study is to describe our 9-year experience in transcatheter aortic valve replacement (TAVR) using transthoracic echocardiography (TTE) as a routine intra-procedural imaging modality with trans-oesophageal echocardiography (TEE) as a backup. METHODS AND RESULTS: From January 2008 to December 2017, 1218 patients underwent transfemoral TAVR at our Institution. Except the first 20 cases, all procedures have been performed under conscious sedation, with fluoroscopic guidance and TTE imaging monitoring. Once the TTE resulted suboptimal for final result assessment or a complication was either suspected or identified on TTE, TEE evaluation was promptly performed under general anaesthesia. Only 24 (1.9%) cases required a switch to TEE: 6 cases for suboptimal TTE prosthetic valve leak (PVL) quantification; 12 cases for haemodynamic instability; 2 cases for pericardial effusion without haemodynamic instability; 4 cases for urgent TAVR. The 30-days and 1-year all-cause mortality were 2.1% and 10.2%, respectively. Cardiac mortality at 30-days and 1-year follow-up were 0.6% and 4.1%, respectively. Intra-procedural and pre-discharge TT evaluation showed good agreement for PVL quantification (k agreement: 0.827, P = 0.005). CONCLUSION: TTE monitoring seems a reasonable imaging tool for TAVR intra-procedural monitoring without delay in diagnosis of complications and a reliable paravalvular leak assessment. However, TEE is undoubtedly essential in identifying the exact mechanism in most of the complications.

[Acute renal failure after videolaparoscopic surgery: an avoidable complication?]. / L'insufficianza renale acuta postchirurgia laparoscopica: evitabile complicanza?

Videolaparoscopic surgery exposes the abdominal organs to the mechanical effect of pneumoperitoneum at pressure values between 12 and 15 mm Hg, which are considered safe. Nevertheless, experimental data have shown that this pressure range can represent a hemodynamic risk factor as it may induce a decrease in the venous return to the right ventricle, a decrease in cardiac output, and activation of the sympathetic nervous system and renin angiotensin system. We report two cases of acute renal failure that occurred soon after videolaparoscopy in young female patients without any evidence of ongoing renal disease. Patient A was 29 years old and was submitted to videolaparoscopic surgery in a follow-up program after surgical treatment of ovarian cancer; patient B was 15 years old and was submitted to the surgical removal of a monolateral ovarian cyst. In neither of the cases was it necessary to perform hemodialysis. Patient A underwent a renal biopsy under ultrasound guidance; optic microscopy showed only in ra- and extraglomerular capillary congestion. In both cases the acute renal failure resolved completely and the patients where discharged with normal renal function. Taking in to account that normal renal venous pressure levels are around 4 mmHg we think that a) a 15 mmHg pneumoperitoneum may represent a risk factor during videolaparoscopic surgery mainly if the patient's extracellular volume is not properly expanded; b) administration of nonsteroidal anti-inflammatory drugs in order to prevent surgical pain may inhibit vasodilatory prostaglandin availability; c) onset of oliguria during the surgical procedure suggests that extracellular volume expansion is required.

A program for computing power spectra on a microcomputer.

A computer program is presented that will calculate Fourier transforms and power spectra. The program is written in assembly language for the Z-80 microprocessor and has been used on a Radio Shack TRS-80 microcomputer to analyze time-dependent data from laboratory experiments.

Excitation of dorsal column nucleus neurons by air-jet moving across the skin.

Single unit recordings from dorsal column neurons were made during application of mechanical somatic stimuli moving at controlled velocities across the neuron's receptive field. The neurons responded in stereotypic patterns which changed with altered stimulus parameters of velocity, direction and intensity. Spatial analysis of the response patterns indicates that the neurons generate action potentials when the stimulus probe activated particular discrete locations within the receptive field.

Morphological alterations of neurons and astrocytes in guinea pigs exposed to low levels of inorganic lead.

Both astrocytes and neurons potentially undergo structural and functional alterations in the brains of animals exposed to low levels of lead (Pb). No morphometric studies of astrocytes have been reported to date in animals in low Pb exposure. In the present study, morphometric measurements of astrocytes and pyramidal neurons in the frontoparietal cortex were made in guinea pigs exposed postnatally (5 or 10 days) or prenatally (gestational day 22 to birth) to low Pb levels. Although few significant effects of Pb treatment were detected by the rigorous statistical model applied, a recurring trend was noted for postnatal Pb treatment to increase astrocyte maximum diameter (dmax). In addition, prenatal Pb treatment was associated with increased apical and basal dendritic length, increased total apical dendrites per cell and an increased basal branching complexity in neurons.

Minimal change nephrotic syndrome with cecum adenocarcinoma.

Membranous glomerulonephritis is the most common glomerular disease associated with malignancy, the association of minimal change glomerulopathy with solid tumor is still uncommon. We report a 72-year-old man with nephrotic syndrome due to minimal change glomerular disease; an accurate seek of underlying malignancy revealed a cecum adenocarcinoma. We had a complete remission of nephrotic syndrome after surgery of carcinoma.

Myocardial revascularization with bilateral internal thoracic artery in patients with left main disease: an incremental risk?

Although the long-term patency of the internal thoracic artery (ITA) has been well proved, there is still some concern about its preoperative performance. We considered 80 patients with left main disease (mean age 60.2 years) who underwent coronary artery bypass grafting in our institute from March 1988 to September 1992. Patients with left main disease were divided into 2 groups: group I-38 patients receiving only ITA grafts on the left coronary system and group II-42 patients having a single ITA graft together with saphenous vein grafts on the left coronary system. No patients in group I received a saphenous graft on the left coronary system and three patients with right coronary artery involvement received total arterial myocardial revascularization with the use of the inferior epigastric artery. Perioperative complications in group I and group II patients were, respectively: myocardial necrosis in 2 (6.9%) and 3 (8.8%), use of intraaortic balloon pump in 2 (6.9%) and 2 (5.9%). No death occurred in either group. In our experience, the use of bilateral ITA grafts in patients with left main stenosis was not related to an incremental risk. We conclude that left main disease should not be considered as counterindication to the extensive use of arterial conduits.

Bone mineral and aluminum concentrations in patients undergoing CAPD.

CAPD results in continuous peritoneal transfer of hormones and minerals involved in the pathogenesis of renal osteodystrophy (RO). Moreover, although CAPD patients seem to have better control of serum phosphate concentration than hemodialysis patients, the need for aluminum-containing phosphate binders (ACPB) may still be present. In a prospective study meant to investigate the evolution of RO, we obtained 79 bone biopsies in 29 uremic patients (20 male, 9 female; age 25-59, mean 46). Of these, 22 were obtained at the beginning of treatment, 24 after 24 months, 23 after 36 months and 10 after 60 months. All patients were treated with CAPD (Viaflex, Baxter 2-2.5 L x 4-5 bags/day; Ca(++) + 3.5, Mg(++) 1.5 mEq/L) as the first modality of therapy and received oral calcitriol, aluminum hydroxyde and/or calcium carbonate and magnesium hydroxyde in order to maintain serum calcium (Ca) and phosphorus within the normal range. Qualitative bone histology, bone Ca and magnesium (Mg) (Flame atomic absorption spectroscopy) and aluminum (Al) concentration (Graphite furnace atomic absorption spectrometry) were determined. CAPD achieves a good control of RO as indicated by the tendency toward a decreased incidence of mixed osteodystrophy and predominant hyperparathyroid bone disease and improvement of osteoid lesions. A defective Ca content of bone is persistent in the observed period and positively correlated to bone Mg concentration. An increased level of Al was shown in the serum and bone. The highest bone Al content was found among patients with predominant osteoid bone disease. Also in CAPD, patients consuming ACPB are at risk of bone Al accumulation despite the low Al levels in the dialysate.

[Diabetic nephropathy and arterial hypertension: the physiopathological aspects and antihypertensive treatment]. / Nefropatia diabetica ed ipertensione arteriosa: aspetti fisiopatologici e trattamento antiipertensivo.

The purpose of our review is to delineate the pathogenic steps linking arterial hypertension in diabetes to diabetic nephropathy. The results of recent studies suggest that arterial hypertension in diabetes might lay a decisive pathogenetic role in the evolution of diabetic nephropathy: the existence of a higher ratio of erythrocytic Na/Li counter-transport in nephropathic diabetics as well as higher pressure values in the parents of diabetics who develop nephropathy indicates that hypertension may be casually related to renal complications. Diabetes-associated hypertension involves the modification of two important pressure- regulation factors: 1. an alteration in extracellular volume and increased renal absorption of sodium which leads to an expanded pool; 2. increased cardiovascular reactivity to norepinephrine and angiotensin II, an effect which might be related to increased intracellular calcium. Hyperfiltration seems to be present at the onset of diabetes, and arterial hypertension increases the transglomerular pressure gradient which is thought to play an important role in the pathogenesis of kidney damage. Antihypertensive drugs such as ACE-inhibitors and calcium channel blockers tend to protect the regulation of renal function. This could be explained by the fact that ACE-inhibitors suppress the trophic effects of angiotensin II on the nephron, while calcium channel blockers might interfere with intracellular processes involved in cell hypertrophy that require the interaction of calcium ions. In the management of diabetes prevention of diabetic nephropathy requires early and careful correction of diabetes-associated hypertension. We discuss the major groups of antihypertensive drugs, their metabolic side-effects and intrarenal induced hemodynamic changes.

[Treatment of arterial hypertension in diabetic nephropathy. Certainties and hypotheses]. / Le traitement de l'hypertension artérielle dans la néphropathie diabétique. Certitudes et hypothèses.

Clinical observation has long emphasized the importance of arterial hypertension in the course of diabetic nephropathy and recent studies suggest that hypertension might play a decisive pathogenetic role in the course of the disease, hence the necessity of correcting the hypertension of diabetic patients has by now been universally accepted. There is, however, still some uncertainty concerning the usefulness of acting preventively on so-called microhypertension; in other words, whether early antihypertensive drug treatment can prevent diabetic nephropathy. This paper discusses the criteria to be followed in the choice of antihypertensive medication during diabetic nephropathy giving special attention to pathophysiological considerations. Moreover, it also discusses the effects of antihypertensive drugs currently regarded as first-choice agents, i.e. calcium antagonists and the angiotensin converting enzyme inhibitors, on intrarenal hemodynamics.

[The pathogenesis of arterial hypertension in diabetes mellitus and its role in nephropathy]. / Patogenesi dell'ipertensione arteriosa nel diabete mellito e suo ruolo nella nefropatia.

This paper synthesizes the pathogenic steps of arterial hypertension in diabetes mellitus: hyperosmolarity due to the hyperglycemia and increased sodic tubular reabsorption accounting for the expansion of the extracellular volume with hypervolemia; abnormalities of the ionic membrane pumps leading to abnormal intracellular calcium distribution, thereby inducing an increased vascular tone; atypical vasomotor reactivity to cathecolamines; modifications of the renin-angiotension-aldosterone system. The pathophysiological derangements by which hypertension could induce nephropathy are examined: the vasodilatation which can be detected from the onset of diabetes, may be a determinant in the transmission of systemic hypertension to the glomerular microcirculation with resulting enhancement of the hydrostatic transglomerular pressure gradient (i.c. the major factor producing glomerular injury), glomerular plasmatic flow and filtration rate. The nephron hyperfiltration increases the movement of plasmatic proteins across the glomerular capillary wall with subsequent mesangial hyperactivity and sclerosis. Antihypertensive treatment in diabetes follows general guidelines and it should be instituted even in the case of microhypertension being facilitated in this setting the appearance of microalbuminuria i.e. the starting point of nephropathy. Even if experimental studies are to favor ACE inhibitors as the first-line drugs for abating glomerular hypertension by mitigation of the direct effect of angiotensin II on the efferent arteriolar tone, clinical observations suggest that, regardless of type of treatment, the normalization of systemic arterial pressure, by reversing glomerular hypertension may be effective in preventing diabetic nephropathy.

[Current approach in the prevention and treatment of diabetic nephropathy]. / Attuali orientamenti di prevenzione e trattamento della nefropatia diabetica.

Diabetic renal microangiopathy accounts for enormous morbidity and mortality, particularly in patients who develop diabetes in childhood or early youth; in the last few years its pathogenesis has been therefore extensively studied, aiming to prevent renal complications or at least of slowing down its progression toward uremia. Though not always in accordance with theoretical expectations, the results of clinical trials have nevertheless widened our therapeutic possibilities; in fact, besides the attainment of an optimal metabolic control, other possible interventions include a careful correction of albeit minimal elevations in arterial pressure; the interference with intrarenal hemodynamic parameters; the correction of insulin-independent metabolic pathways, abnormally activated in the diabetic, such as non enzymatic glycation and polyol pathway; the treatment of endothelial and platelet alterations; the improvement of the rheologic properties of blood.

[The treatment of arterial hypertension in diabetes mellitus. Choices and problems]. / Trattamento dell'ipertensione arteriosa in corso di diabete mellito. Scelte e problemi.

Recent studies indicate that arterial hypertension in diabetes mellitus is a paramount pathogenetic step in the evolution and acceleration of diabetic macro- and microangiopathy and in particular in the development of nephropathy and uremia. This paper deals with the clinical problems of antihypertensive treatment in diabetic patients and discusses the antihypertensive repertory with the aim at determining the best drug choice in the individual case. In the light of our present pathophysiologic knowledges of the intrarenal effects of the various classes of antihypertensive drugs the possibility of preventing diabetic nephropathy is discussed.