Metformin-induced lactic acidosis in a type 2 diabetic patient with acute renal failure.

Metformin is a biguanide commonly used in type 2 diabetes mellitus (DM). Lactic acidosis, a potentially life-threatening metabolic disorder, may be due to a number of different causes, including metformin therapy. We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM, admitted to the emergency department with a history of dehydration due to diarrhoea and complicated by acute renal failure. Patient complained malaise and severe weakness and was tachypneic (Kussmaul's respiration), agitated and confused, with a Glasgow Coma Scale score of 13/15. Heart rate was 75 b/min and blood pressure 110/80 mmHg. The pH was 6.87, HCO3- 3 mmol/l, lactate 15 mmol/l, potassium 6.9 mEq/l. The renal function was markedly impaired with a creatinine of 9.75 mg/dl, and pancreatic enzymes, amylase and lipase, were also increased in absence of abdominal pain. Patient was treated with intravenous fluids, bicarbonate infusion and haemodialysis with bicarbonate buffered replacement fluid. Clinical conditions improved rapidly, with a progressive normalization of the acid-base balance and the other laboratory data. Authors discuss the pathophysiologic mechanisms of these alterations with particular regard to the role played by metformin as potential cause of lactic acidosis.

The Italian register of cardiovascular diseases: attack rates and case fatality for cerebrovascular events.

BACKGROUND: The Italian register of cardiovascular diseases is a surveillance system of fatal and nonfatal cardiovascular events in the general population aged 35-74 years. It was launched in Italy at the end of the 1990 s with the aim of estimating periodically the occurrence and case fatality rate of coronary and cerebrovascular events in the different geographical areas of the country. This paper presents data for cerebrovascular events. METHODS: Current events were assessed through record linkage between two sources of information: death certificates and hospital discharge diagnosis records. Events were identified through the ICD codes and duration. To calculate the number of estimated events, current events were multiplied by the positive predictive value of each specific mortality or discharge code derived from the validation of a sample of suspected events. Attack rates were calculated by dividing estimated events by resident population, and case fatality rate at 28 days was determined from the ratio of estimated fatal to total events. RESULTS: Attack rates were found to be higher in men than in women: mean age-standardized attack rate was 21.9/10,000 in men and 12.5/10,000 in women; age-standardized 28-day case fatality rate was higher in women (17.1%) than in men (14.5%). Significant geographical differences were found in attack rates of both men and women. Case fatality was significantly heterogeneous in both men and women. CONCLUSIONS: Differences still exist in the geographical distribution of attack and case fatality rates of cerebrovascular events, regardless of the north-south gradient. These data show the feasibility of implementing a population-based register using a validated routine database, necessary for monitoring cardiovascular diseases.

Hepatic artery aneurysm rupture in a woman with primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis. However, a small number of patients present with visceral aneurysms. Although such aneurysms are rare, their presence in patients who are usually treated with lifelong anticoagulation raises important therapeutic problems, in view of the risk of aneurysm rupture and acute abdominal hemorrhage. We report the case of a young woman with APS who presented with abdominal bleeding due to ruptured common hepatic artery aneurysm. She was successfully treated by proximal ligation. The features of such aneurysms are discussed.

Impaired glucose metabolism in patients with acute stroke and no previous diagnosis of diabetes mellitus.

BACKGROUND: About a third of patients with acute stroke and no prior diagnosis of diabetes have hyperglycaemia during the acute phase of stroke. Whether this is an acute stress response or a reflection of underlying diabetes is controversial. AIM: To assess whether impaired glucose metabolism in patients with acute ischaemic stroke and no previous diagnosis of diabetes persists after 3 months, and whether such persistence can be predicted. DESIGN: Prospective observational study. METHODS: We enrolled 106 patients with acute ischaemic stroke and no history of diabetes. Fasting blood glucose, serum insulin and the insulin resistance index HOMA were recorded during hospital stay. A standard oral glucose tolerance test was performed at discharge and 3 months later. RESULTS: Ten patients did not complete the study. Eighty-one patients (84.4%) had abnormal glucose metabolism at discharge and 62 (64.6%) after 3 months. Thirty-seven (38.5%) had impaired glucose tolerance at discharge and 26 (27.1%) after 3 months. Forty-four (45.8%) had diabetes at discharge, and 36 (37.5%) at 3 months. Post-load hyperglycaemia at discharge was a predictor of diabetes after 3 months. A plasma glucose cut-off of 11.7 mmol/l (210 mg/dl) had a specificity of 90.0% and a positive predictive value of 81.3%. HOMA increased progressively from patients with normal glucose metabolism to those with newly diagnosed diabetes. DISCUSSION: Impaired glucose tolerance and previously unrecognized diabetes could be detected early in the stroke course, and persisted after 3 months in more than two-thirds of our patients. Post-load hyperglycaemia during the acute phase of stroke may be useful in identifying patients with abnormal glucose metabolism, which places them at risk for adverse outcomes, including cardiovascular disease.

[Hemoptysis from dorsal tongue base varices secondary to portal hypertension]. / Presentazione atipica di ipertensione portale: sanguinamento da varici della base della lingua.

Portal hypertension secondary to cirrhosis of the liver is the main factor leading to the formation of portosystemic collaterals. The sites of such collateral circulation are well known. We describe a case of haemoptysis from dorsal tongue base varices, which are not recognised as portosystemic anastomosis, in a cirrhotic patient with portal hypertension.

Hyperlipidaemia: differences in management practices and attitudes in two regions in Europe--Sicily and the Stockholm area.

In order to compare attitudes and management concerning hyperlipidaemia and risk factors for coronary heart disease among doctors in northern and in southern Europe, a questionnaire study was undertaken among doctors in primary health care and departments of internal medicine in Sicily and Stockholm. The regions differed in culture and health-care structure. Guidelines were similar, but screening of healthy individuals was recommended in Sicily, and not in Sweden. One hundred and fifty-three general practitioners in Sicily and 120 in Stockholm, 211 internists in Sicily and 83 in Stockholm participated. Main outcome measures were management policies for investigation and treatment and also attitudes. Routine lipid checks at first visits were done by few doctors in Stockholm but by a majority in Sicily (p < 0.001); in the presence of general cardiovascular risk factors (other than heredity, diabetes, cardiovascular disease and hypertension), routine checks were carried out more often by both general practitioners (p < 0.001) and internists (p < 0.005) in Stockholm. Drug treatment was initiated at lower cholesterol levels for secondary and primary intervention, cardiovascular disease, cardiovascular risk factors and hereditary hyperlipidaemia by both groups in Sicily (p < 0.001), as was dietary treatment. Secondary prevention was considered important by all groups, but primary prevention only by Sicilian doctors. We concluded that there were differences in views and management practice between doctors in Sicily and in Stockholm on the investigation and treatment of patients with hyperlipidaemia. Doctors tested lipids at first visits in Sicily but not in Stockholm. Treatment was initiated at lower levels of cholesterol in Sicily.

A marked increase of ischemic stroke incidence between 1980 and 1994 in S. Caterina, Sicily.

Stroke death rates have been declining for some decades in most of the industrialized countries. It is not clear, whether this has been associated with a decrease in stroke incidence. We studied temporal trends in stroke incidence in a rural community in Sicily, during two periods 1980-84 and 1990-94. There was a total of 231 patients (120 of them women). The diagnosis of stroke was based on the clinical evaluation and CT scan since 1982 and onward. There were 109 ischemic strokes (51 women) mean age 72.7 years, in 1980-84 period; 122 ischemic strokes (69 women) mean age 75.1, in 1990-94 period. Cardiovascular risk factor rates did not change in the two periods considered. The relative annual stroke incidence rate increased 37.0%; (2.7 in 1980-84 to 3.7/1000 inhabitants in 1990-94, p = 0.0161. In the population older than 65 years, the same parameter increased by 21.1% between the two periods; (16.1 in 1980-84 to 19.5/1000 inhabitants in 1990-94, not significant). This increase was due mainly to a 45.3% significant relative increase in women, from 7.5 to 11.0/1000 inhabitants (p = 0.039). These findings suggest a need of the reconsideration of effective strategies for the prevention of stroke.

[Inverse relationship between fetal growth and arterial pressure in children and adults]. / Relazione inversa tra crescita fetale e pressione arteriosa in età infantile e adulta.

BACKGROUND: Increased prevalence of hypertension, ischaemic heart disease and stroke has been reported in subjects with impaired growth during fetal life and infancy. Blood pressure could mediate this relation. Indeed, reduced growth in fetal life and infancy has been associated with a raised blood pressure in children and adults. However, there is controversy about the relative importance of intrauterine environment and extrauterine adverse environment which can act throughout the life course. We therefore studied the relation between birth weight, which is known to be an indicator of fetal growth, and blood pressure in children and their parents. This association could thus be assessed in childhood before the external environmental influences became important, and in adulthood. METHODS: Seven hundred and fifteen healthy schoolchildren (379 boys) aged 3-12 years from primary schools, and 448 parents (252 women) aged 20-44 years, born at term, without hypertension or diabetes, were studied. Blood pressure and birth weight were measured. Birth weight was taken from the hospital records. Data were analysed by tabulation of means and linear regression and correlation techniques. Mean systolic and diastolic blood pressure were calculated according to birth weight and current weight as fourths of their distributions. RESULTS: There was a significant inverse relation between birth weight and systolic blood pressure both in children and adults. Current weight standardised regression coefficient showed a change of -2.68 mm Hg (95% Cl - 2.0 to 3.26, p = 0.027) for each Kg increase in birth weight in children, and -3.82 mmHg (95% Cl -3.21 to -4.39, p = 0.011) in adults. Within each current body weight group the reduction in mean systolic blood pressure from the lowest to the highest birth weight group was larger in adults (10.4 mmHg) than in children (4.1 mmHg). Adults but not children showed also an inverse relation between birth weight and diastolic blood pressure. Weight standardised regression coefficient was -3.0 mm Hg (95% Cl -2.45 to -3.62, p = 0.036). CONCLUSIONS: Blood pressure in inversely related to birth weight in childhood. This relation becomes stronger in adulthood. Therefore, reduced growth during fetal life may be linked with an increased risk of developing hypertension and cardiovascular disease.

[Sublingual captopril in hypertensive crises]. / Captopril sublinguale nelle crisi ipertensive.

Captopril is widely used in severe hypertension. Oral administration takes one-two hours to achieve a maximum effect and is not useful in hypertensive crisis. Few reports describe a more rapid effect on blood pressure following sublingual administration. We evaluated the effect of sublingual captopril 50 mg, in 26 patients with hypertensive crisis. Blood pressure levels started to decrease within 10 minutes and the maximum effect was observed 30 minutes after administration of the tablet. In all patients mean (CI 95%) systolic blood pressure dropped from 202.5 (199-206) mmHg to 160.6 (156-165) mmHg and diastolic blood pressure from 105.6 (102-109) mmHg to 86.9 (83-7-90.1) mmHg. This effect was maintained over two hours. There were no side effects. Sublingual captopril is highly effective in hypertensive crisis and its gradual hypotensive action avoid dangerous abrupt fall in blood pressure.

Discrepancies in the measurement of isovolumic relaxation time: a study comparing M mode and Doppler echocardiography.

Mitral valve cusp separation on M mode echogram, the mitral valve opening artefact, and the onset of forward transmitral flow recorded by Doppler echocardiography have all been taken to mark the end of isovolumic relaxation, while its onset has been taken either as the aortic closure sound (A2) recorded phonocardiographically or the aortic closure artefact determined by Doppler technique. Possible differences in the measurement of the isovolumic relaxation time were studied when these landmarks were used in 44 healthy people, 14 patients with mitral stenosis, 21 patients with left ventricular hypertrophy, and 24 patients with dilated cardiomyopathy by recording M mode echograms of the mitral valve, and pulsed and continuous wave Doppler spectra of transmitral flow, with simultaneous electrocardiograms and phonocardiograms. A2 was effectively synchronous with the aortic artefact. However, when the onset of Doppler flow was regarded as the end of isovolumic relaxation, the interval was significantly longer than when mitral cusp separation on M mode echograms was used: by 25 (10) ms in healthy individuals, by 25 (15) ms in patients with left ventricular hypertrophy, and by 50 (35) ms in patients with dilated cardiomyopathy. In patients with mitral stenosis the interval was only 5 (5) ms longer. The mitral valve opening artefact consistently followed the onset of flow and corresponded much more closely to the E point on the M mode echogram. This shows that it occurred during the rapid filling period and well beyond isovolumic relaxation by any definition. Thus isovolumic relaxation time measured from A2 to the onset of transmitral flow or the mitral valve opening artefact differs from that derived from A2 to mitral valve cusp separation. These intervals cannot be used interchangeably to measure "isovolumic relaxation time".

Relationship of QRS amplitude to left ventricular dimensions after acute blood volume reduction in normal subjects.

The relationship between the acute reduction in left ventricular dimensions induced by intravenous frusemide and scalar electrocardiographic QRS amplitude was studied in 14 normal subjects. The major electrocardiographic change was a significant increase in QRS voltages inversely proportional to the changes in left ventricular dimensions. This effect was opposite to the change predicted by the Brody effect. Surface electrocardiographic voltages are greatly influenced by myocardial cell orientation and the effective dipoles of the wave of activation are parallel to the long axes of cardiac fibres. As in the normal ventricle the arrangement of fibres is mainly circumferential, the body surface potentials are strongly affected by longitudinal wave front voltages. We suggest that during acute reduction of blood volume the inverse relationship of left ventricular volume and QRS amplitude can be explained by a reduced short-circuiting effect of blood mass on a longitudinally directed wave of activation.

Relation of third and fourth heart sounds to blood velocity during left ventricular filling.

To investigate the relation between changes in left ventricular inflow velocity and the timing of third and fourth heart sounds, simultaneous phonocardiograms and continuous wave Doppler traces were recorded in 48 patients (aged 17-78) with heart disease and in 21 normal children. The onset of the first vibration of the third heart sound coincided with peak left ventricular inflow blood velocity to within 5 ms in all but two of the patients. The mean (SD) difference between the two events was 5 (5) ms, which did not differ significantly from zero. The relation was similar in patients with primary myocardial disease (11), and in those with valve disease (26), hypertension (five), and coronary artery disease (four). In the normal children, the mean interval was 2.5 (5) ms--not significantly different from zero. By contrast, the first deflection of the fourth heart sound consistently preceded the timing of peak atrial inflow velocity by 55 (10) ms. Agreement was much closer between the onset of atrial flow and the onset of the atrial sound (mean difference 1 (5) ms, not significantly different from zero). Gallop sounds seem to be closely related to changes in ventricular inflow velocity, and thus to the effects of forces acting on blood flow. The forces underlying the third sound seem to arise within the ventricle and are responsible for sudden deceleration of flow during rapid ventricular filling. The fourth sound, occurring at the onset of the "a" wave, is more likely to arise from dissipation of forces causing acceleration of blood flow--that is, atrial systole itself.

Isolated congenital left ventricular diverticulum.

We describe a patient with congenital left ventricular diverticulum as an isolated lesion. The patient was asymptomatic until adult life and the diagnosis was apparent on cross-sectional echocardiography. The finding was confirmed by cardiac catheterisation.

Non-invasive assessment of changes in left ventricular diastolic time intervals after acute blood volume reduction in haemodialysis.

The effects of acute blood volume reduction induced by haemodialysis on diastolic time intervals were studied in 19 patients by echo- and phonocardiography. Haemodialysis significantly decreased left ventricular diameters. The isovolumic relaxation time was prolonged and negatively correlated with left ventricular end diastolic dimensions. To study the effect of load reduction on left ventricular filling time, cardiac cycles with the same R-R interval, before and after haemodialysis, were compared. At any given R-R interval dialysis resulted in a significant prolongation of the filling time. This study shows that diastolic time intervals are dependent on left ventricular loading conditions, and this effect should be considered when these time intervals are evaluated in the clinical setting.

[Echopolycardiographic evaluation of left ventricular function after hemodialysis]. / Valutazione eco-policardiografica della funzionalità ventricolare sinistra dopo emodialisi.

The acute effects of haemodialysis on left ventricular (LV) function were studied by echocardiography and systolic time intervals in 19 patients maintained on long-term haemodialysis. Dialysis resulted in a significant reduction in body weight, an increase in heart rate and a small reduction in systolic blood pressure. A significant decrease was observed in LV diastolic and systolic dimensions, with an increase in the mean rate of circumferential shortening (mean VCF). The LV ejection time (LVET) decreased significantly, while changes in the pre-ejection period (PEP) were insignificant. The PEP/LVET ratio increased in all patients. Haemodialysis reduced the serum potassium levels; an increase was noted in the serum calcium concentrations, with a significant, although small, correction of blood pH. The major haemodynamic change induced by dialysis was a decrease in blood volume with a reduction in LV pre-load. These changes are suggested by the reduction in body weight and by the shortening in LV end-diastolic dimension and LVET. There was also a reduction in after-load, as expressed by the shortening in LV systolic diameter and by the decrease in systolic blood pressure. It should be emphasized that the study of LV function in patients on chronic dialysis is greatly influenced by the loading conditions. In such patients the assessment of LV function by echocardiography and systolic time intervals provides information regarding the haemodynamic changes induced by dialysis; however, no direct evidence can be derived about the functional state of the left ventricle.