Immune checkpoint inhibitors for POLE or POLD1 proofreading-deficient metastatic colorectal cancer.

BACKGROUND: POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity and efficacy of immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking and it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs. PATIENTS AND METHODS: In this global study, we collected 27 patients with mCRC harboring POLE/D1 mutations leading to proofreading deficiency and treated with anti-programmed cell death-ligand 1 alone +/- anti-cytotoxic T-lymphocyte antigen-4 agents. We collected clinicopathological and genomic characteristics, response, and survival outcomes after ICIs of POLE/D1pd mCRC and compared them with a cohort of 610 dMMR/MSI-H mCRC patients treated with ICIs. Further genomic analyses were carried out in an independent cohort of 7241 CRCs to define POLE and POLD1pd molecular profiles and mutational signatures. RESULTS: POLE/D1pd was associated with younger age, male sex, fewer RAS/BRAF driver mutations, and predominance of right-sided colon cancers. Patients with POLE/D1pd mCRC showed a significantly higher overall response rate (ORR) compared to dMMR/MSI-H mCRC (89% versus 54%; P = 0.01). After a median follow-up of 24.9 months (interquartile range: 11.3-43.0 months), patients with POLE/D1pd showed a significantly superior progression-free survival (PFS) compared to dMMR/MSI-H mCRC [hazard ratio (HR) = 0.24, 95% confidence interval (CI) 0.08-0.74, P = 0.01] and superior overall survival (OS) (HR = 0.38, 95% CI 0.12-1.18, P = 0.09). In multivariable analyses including the type of DNA repair defect, POLE/D1pd was associated with significantly improved PFS (HR = 0.17, 95% CI 0.04-0.69, P = 0.013) and OS (HR = 0.24, 95% CI 0.06-0.98, P = 0.047). Molecular profiling showed that POLE/D1pd tumors have higher tumor mutational burden (TMB). Responses were observed in both subtypes and were associated with the intensity of POLE/D1pd signature. CONCLUSIONS: Patients with POLE/D1pd mCRC showed more favorable outcomes compared to dMMR/MSI-H mCRC to treatment with ICIs in terms of tumor response and survival.

Spontaneous cervical extradural hematoma in a cutaneo-meningospinal angiomatosis (Cobb syndrome): case report.

Spontaneous spinal extradural hematoma is a rare clinical entity, commonly associated with coagulopathies, tumours or vascular malformations. They are often a neurosurgical emergency, therefore prompt diagnosis and early treatment are necessary. The Cobb syndrome is a neurocutaneous syndrome in which there are metameric vascular skin nevus and spinal arteriovenous malformation. The authors report the case of a 52-year-old woman with acute cervical myelopathy and a cervical cutaneous hemangioma on clinical examination. It is stressed the importance of clinical suspicion of cutaneo-meningospinal angiomatosis based on a spinal cord syndrome in the presence of a vascular skin nevus of the same metameric level.

Unilateral supraorbital keyhole approach in patients with middle cerebral artery (M1-M2 segment) symmetrical aneurysms.

A left middle cerebral artery aneurysm at the bifurcation (M1-M2 segment) and a right smaller aneurysm, symmetrical to the previous one were diagnosed in a 69-year-old female after angiographic examination for subarachnoid hemorrhage. The preoperative radiological study did not enable us to identify the bleeding aneurysm so a left supraorbital keyhole approach was performed to operate on the bigger aneurysm. In the same surgical session, using the same way of approach, we decided to attack also the right aneurysm which then revealed itself as being responsible for bleeding. The postoperative angiograms confirmed the complete exclusion of both aneurysms and the patient was discharged after good recovery. Although there are remarkable controversies about the surgical strategies for multiple aneurysms, our experience gives us the opportunity to emphasize the supraorbital keyhole approach and to reconsider the "timing" of multiple/bilateral aneurysms.

Hemodynamic effects of creatine phosphate in patients with congestive heart failure: a double-blind comparison trial versus placebo.

BACKGROUND: The use of metabolic drugs effective in addition to conventional therapy represents a significant challenge in patients with left ventricular dysfunction. HYPOTHESIS: The aim of this double-blind, placebo-controlled study was to investigate the hemodynamic effects of acute intravenous (i.v.) administration of creatine phosphate (CP) and of short-term treatment in patients with congestive heart failure (CHF) from ischemic heart disease (IHD) or dilated cardiomyopathy in addition to conventional therapy. METHODS: We compared the hemodynamic effects of exogenous creatine phosphate (CP) and placebo in a double-blind, crossover design study in 13 hospitalized patients (12 men, 1 woman, mean age 52 +/- 8 years) with CHF. All patients were in New York Heart Association (NYHA) class II-III and received conventional pharmacologic therapy for CHF; this was not changed during the study period. The study design consisted of two treatment periods (CP or placebo and placebo or CP, respectively) of 4 days each, separated by a 2-day washout interval. The intravenous infusion consisted of 6 g CP or placebo (acute treatment) or 6 g CP or placebo daily for 4 days (short-term treatment) diluted in 50 ml of NaCl 0.9%; infusion duration was about 10 min. Mono-bidimensional echocardiographic examination (Hewlett Packard Sonos 1000, with a 2.5 MHz transducer) was performed at baseline, after acute infusion, and 12 h after the end of short-term treatment. Data were analyzed by ANOVA and Student's t-test for paired data; the results obtained after acute and short-term therapy were compared with the baseline values. RESULTS: After placebo therapy, no significant change was observed. The results after treatment with CP showed a significant reduction of end-systolic diameter [baseline: 4.5 +/- 0.6; acute: 4.2 +/- 0.5, (p < 0.001); short-term 4.3 +/- 0.6 cm, (p < 0.05)] and systemic vascular resistance (baseline: 1064.9 +/- 483.7; acute: 947.5 +/- 390.2 (p < 0.05); short-term: 950.7 +/- 394.3 dyne-s-cm-5 (p < 0.05); moreover, a significant increase of percent ejection fraction [baseline: 48 +/- 12%; acute 53 +/- 12% (p < 0.01); short-term 52 +/- 11% (p < 0.01)], and of percent fractional shortening [baseline: 25 +/- 7; acute 28 +/- 8 (p < 0.05); short-term 28 +/- 7% (p < 0.05)] was observed. CONCLUSION: CP was shown to improve cardiac function, even in the presence of a conventional CHF pharmacologic therapy.

Neurocysticercosis treated with albendazole long term follow-up of a case.

The authors report a case of neurocysticercosis treated with Albendazole (methyl-5-propyl-thio-2-benzimidazilcarbamate). Computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain presented various small bilateral parenchymal calcifications in the white matter and two inflammatory granulomatous formations localized respectively in the left and right posterior parietal lobe. After the serological diagnosis (Elisa-test) of cysticercosis, the patient was treated with albendazole (Zentel) with oral doses of 15 mg/kg/die for 20 days, and successively with a lower dose for another 40 days. Repeated CT and MRI showed a gradual reduction in the granulomas in comparison with the ones previously found, until the complete disappearance of the neuroradiological evidence of them. No side-effects were recorded during the treatment nor symptoms or neurological consequences in the period up until two years after the initial observation.

[ECG-dipyridamole and ECG-exercise test in the assessment of ischemic cardiopathy: effects of the acute administration of nitroglycerin]. / ECG-dipiridamolo ed ECG da sforzo nella valutazione della cardiopatia ischemica: effetti della somministrazione acuta di nitroglicerina.

It is known that intravenous administration of dipyridamole can induce chest pain and ECG signs of ischemia in patients with coronary artery disease. In the present study we evaluated ECG and hemodynamic changes in response to dipyridamole (0.56 mg/kg in 10 min) under basal conditions and 3 hours after administration of nitroglycerin (10 mg/24 h patch) in 14 patients with coronary artery disease. The effects of nitroglycerin were also compared to those induced by the same drug on a bicycle stress test in the same patients. Exercise stress test induced specific ST changes in all patients when performed off-drug. Nitroglycerin administration completely prevented exercise-induced ischemia in 2 patients, and significantly prolonged exercise time in the remaining patients (p < 0.01). This effect was accompanied by a significant increase in heart rate (HR) and rate-pressure product at the threshold of ischemia (HRBP, p < 0.01); furthermore we observed a significant increase in HR at the maximal work load (p < 0.05). In the absence of treatment, dipyridamole infusion induced ST segment changes and/or typical chest pain in 12/14 patients. Moreover we observed a significant increase (p < 0.05) in HR, BP and HRBP during the test with respect to basal conditions. Following nitroglycerin administration, dipyridamole infusion failed to induce ischemia in 4 patients, and the time to ST depression in the remaining 8 patients (459 +/- 69 vs 610 +/- 127 s; p < 0.05) was significantly prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ambulatory monitoring of left ventricular function in patients with ischemic heart disease: effects of coronary revascularization]. / Monitoraggio ambulatoriale della funzione ventricolare sinistra (VEST) in pazienti con cardiopatia ischemica: effetti della rivascolarizzazione coronarica.

The aim of this study was to assess the efficacy of coronary artery bypass using an ambulatory radionuclide monitoring system of left ventricular function (VEST) during daily activities in patients with previous myocardial infarction and coronary artery disease. Ten patients with previous myocardial infarction, clinical evidence of residual angina and angiocardiographically proven coronary artery disease of at least two epicardial vessels were studied by VEST 8 +/- 2 days before and 15 +/- 3 days after surgical myocardial revascularization. VEST allows to monitor both left ventricular function and 2 ECG leads. During the radionuclide monitoring (at least 60 min) all patients underwent handgrip test (compression of a dynamometer for 2 min at the 75% of maximal capacity), a mental stress (arithmetic operation consisting in subtracting 17 from 17,000 for 4 min), walking (140 yards) and climbing stairs (8 flights). No significant changes in left ventricular function during mental stress and handgrip both before and after the surgical procedure were observed. In the preoperative evaluation, walking induced a significantly increase in heart rate from rest to peak exercise (73 +/- 13 versus 79 +/- 11 b/min, respectively; p < 0.01). After coronary artery bypass, heart rate (rest: 92 +/- 18 b/min, effort: 98 +/- 19 b/min; p < 0.01), ejection fraction (rest: 47 +/- 8%, effort: 53 +/- 10%; p < 0.01), cardiac output (rest: 43 +/- 8 edv/min, effort: 51 +/- 11 edv/min, p < 0.01), and stroke volume (rest: 47 +/- 9%, effort: 53 +/- 9%; p < 0.01) increased at maximal effort compared to the control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[The usefulness of bioimpedance in patient monitoring in an intensive-therapy heart-surgery unit: a comparison with thermodilution]. / Utilità della bioimpedenza nel monitoraggio del paziente in unità di terapia intensiva di cardiochirurgia: comparazione con la termodiluizione.

Haemodynamic monitoring of intensive care unit (ICU) patients can be carried out by thermodilution system. This method is invasive, does not give a continuous monitoring and complications can occur. Thoracic electrical bioimpedance (TB), a non invasive, fast, easily repeatable method, is able to measure some important haemodynamic parameters: end diastolic volume (EDV), stroke volume, cardiac output (CO), ejection fraction (EF), some contractility indexes, systemic vascular resistances (SVR) and cardiac work. The aim of the present study is to compare CO and SVR obtained by thermodilution with the same indexes obtained by TB. Therefore, 20 ICU patients (12 males and 8 females, mean age 54 +/- 11 years) were studied. Out of them, 16 had been submitted to cardiac surgery in the previous 7 days and 4 were waiting for cardiac surgery. The patients were divided in 2 groups: Group A (N 4) included patients with valvular malfunction and/or cardiac arrhythmias and Group B (N 16) included patients with normal valvular function and sinus rhythm. CO obtained by TB was well related with the one obtained by invasive (INV; r = 0.878; p < 0.001). The mean value of difference of the 2 methods was 12.29 +/- 11.83 for the whole group of 20 patients but it was 26.07 +/- 14.16 in the Group A and 8.84 +/- 8.09 in the Group B confirming the less reliability of the method in patients with abnormal valvular function or in the presence of cardiac arrhythmias. As a consequence, SVR obtained by TB and INV resulted well related (r = 0.752; p < 0.001). The mean value of differences was 11.14 +/- 9.01 in the group of 20 patients and particularly 19.55 +/- 10.87 in the Group A and 9.04 +/- 7.07 in the Group B. In a subgroup of 9 patients, CO was measured at successive times (0, 30, 60, 90 min) by both TB and INV; when comparing the 2 CO values a significant correlation was observed. In conclusion, TB represents a valid method in haemodynamic monitoring of the ICU patients.

Comparison of left ventricular function in insulin- and non-insulin-dependent diabetes mellitus.

Diabetes mellitus has been reported to have controversial effects on left ventricular (LV) function in patients with no evidence of coronary artery disease. In this study, LV function at rest was evaluated in 2 groups of diabetic patients, with insulin-dependent (IDD; n = 16) and non-insulin-dependent (NIDD; n = 23) diabetes mellitus, with no evidence of coronary artery disease. All patients underwent an electrocardiographic stress test, and first-pass and equilibrium radionuclide angiography at rest and during supine exercise. Data in each group of diabetic patients were compared with those obtained from age- and sex-matched normal subjects. In both groups of diabetic patients plasma catecholamine levels were significantly greater than in control subjects. Ejection fraction at rest and during exercise did not differ between each group of diabetic patients and their respective control group. In patients with IDD, peak ejection rate (4 +/- 1 end-diastolic count/s) was significantly greater than in control subjects (2.6 +/- 0.1 end-diastolic count/s; p < 0.001); similarly, peak filling rate (4.3 +/- 1.0 end-diastolic count/s) was significantly greater than in controls (3.0 +/- 0.2 end-diastolic count/s; p < 0.001). Cardiac output and systemic vascular resistances did not differ between patients with IDD and control subjects. In contrast, patients with NIDD had significantly reduced cardiac output compared with that of control subjects (5.7 +/- 0.2 vs 5.9 +/- 0.2 liter/min; p < 0.01), and increased systemic vascular resistances (1,422 +/- 137 vs 1,314 +/- 68 dynes.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of atenolol on the relationship between heart rate and QT interval in patients with exercise-induced myocardial ischemia.

The aim of this study was to analyze the relationship between heart rate and QT interval (HR-QT) during exercise in control subjects (Group A) and in patients with coronary artery disease (CAD) with effort angina and without previous myocardial infarction (MI) (Group B). The diagnosis of CAD was confirmed by coronarographic examination. The correlation HR-QT was significant (p < 0.001) in both groups on effort and at recovery. The analysis of the regression HR-QT was carried out separately, both on effort in upright position and at rest in supine position, to avoid the influence of posture on QT length. During effort, the regression line showed lower slope and intercept values in Group B (p < 0.001) than those for Group A. A similar behavior was also observed at rest. Thus, at the highest heart rate, where ECG signs of ischemia (ST depression > 1 mm) frequently occurred, a longer QT interval was present in Group B. Moreover, in Group B, the QT interval in the presence of ECG signs of ischemia was significantly longer (p < 0.01) than in Group A at comparable heart rates both on effort and at rest, thereby confirming the result obtained by comparing both regression lines. The same effort protocol was repeated in Group B patients after acute administration of atenolol 100 mg per os. After atenolol administration, the analysis of the regression HR-QT in Group B clearly showed a shorter QT interval than that obtained in washout period during the baseline test at the highest heart rates where the ECG frequently showed signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of coronary artery disease with Tc 99m-methoxy isobutyl isonitrile and transesophageal pacing.

Recently the use of a new radioactive agent with physical and biological properties more favorable than those of thallium 201, methoxy-isobutyl-isonitrile (MIBI) labeled with technetium 99m (Tc 99m), has permitted simultaneous performance of perfusion and function studies in ischemic cardiopathy. Transesophageal atrial pacing (TAP) technique has evolved as an alternative provocative test of ischemia. The authors compared the capability of Tc 99m-MIBI myocardial scintigraphy, combined with TAP, with that of Tc 99m-MIBI, combined with maximal stress test, in the diagnosis of ischemic cardiopathy. They studied 11 patients with a clinical history of angina pectoris. Myocardial scintigraphy was performed at rest, after stress test, and after TAP. Finally, all the patients underwent coronary angiography. The analysis of myocardial perfusion images on both Tc 99m-MIBI associated with TAP and with stress demonstrated, in 165 myocardial segments examined: 143 normal, 20 reversible defects, 2 irreversible defects. The concordance of localization between coronarographic data and scintigraphic reversible and irreversible defects was 85%. In conclusion TAP proves to be a valid and sensitive provocative test of ischemia when combined with myocardial scintigraphy and with Tc 99m-MIBI.

Pacemaker malfunction due to subcutaneous emphysema--a case report.

The authors describe a cas of pacemaker malfunction due to a critical increase of impedance resulting from air entrapment in the pacemaker pocket.

Follow-up of a respiratory rate modulated pacemaker.

The efficacy of 27 respiration sensitive rate modulated pacemakers (Biorate RDP-3 Biotec) implanted in the left pectoral area was evaluated every 3 months during a mean follow-up period of 29 months (range 10-50 months). Rate modulation function was unchanged other than for three patients in whom the auxiliary leads became displaced. Two implants lost ventricular sensing in this nonprogrammable model. In all but the three patients, Holter monitoring demonstrated pacing rate variation corresponding to daily activity. Stress test duration increased from 8.2 +/- 1.5 minutes (in fixed rate VVI rate) to 12.83 +/- 2.0 minutes (in the VVIR mode) (P less than 0.05). Right arm movement increased the pacing rate by 5 +/- 3 beats/min (NS), while the left arm movement increase was 30 +/- 5 beats/min (P less than 0.05). Mental, arithmetic, and nifedipine tests did not change the rate modulated pacing rate. The system responded to a change in respiratory rate by an increase in stimulation rate. A satisfactory response in sensitivity and velocity was present only with medium-high workloads. Interference with rate modulation occurred with movement of the arm ipsilateral to the implanted pulse generator.

[Cardiac function (angiocardioscintigraphic evaluation) and plasma catecholamine levels in non-insulin-dependent diabetics]. / Funzione cardiaca (valutazione angiocardioscintigrafica) e livelli plasmatici di catecolamine nei diabetici non insulino-dipendenti.

Cardiac mortality is more frequent in diabetic patients than in normal subjects and particularly heart failure occurs 4-6 times more frequently in these patients than in normals also excluding diabetics with coronary artery disease (CAD). To study cardiac function, 20 patients with type II diabetes mellitus (11 M and 9 F, mean age 48 +/- 9 years), and 13 normal subjects (6 M and 7 F, mean age 48 +/- 13 years), were submitted to radionuclide ventriculography with technetium 99m to evaluate some indices of cardiac function at rest and during effort. The diabetic patients were on good metabolic control testified by a satisfactory fasting and post prandial glycaemia, absence of glycosuria in the last 3 monthly controls and a normal value of glycosylate haemoglobin; they had no vascular or neurological complications; CAD was excluded submitting these patients to a maximal effort ECG on an ergometer. The normal subjects were comparable to diabetic patients for age, sex, mean arterial pressure, body mass index and body surface area. At rest, stroke volume, peak filling rate, cardiac output, ejection fraction (EF), were significantly lower in diabetic patients than in normal subjects. Systemic vascular resistances (SVR) were higher in diabetics than in normal subjects (p less than 0.01). Mean EF during effort increased in both normals and diabetics but 30% of diabetic patients showed no increase in EF during effort (less than 5%). Preload, represented by end-diastolic volume or blood volume, did not differ in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Fourier analysis in patients with different pacing modes.

The purpose of this study was to evaluate the usefulness of phase analysis in detecting the altered activation sequence induced by different pacing modes. Radionuclide ventriculography and planar gated blood pool scintigraphy were performed at rest in 56 patients with different pacemakers. This method permitted us to localize the pacemaker impulse site in the right ventricle and its diffusion in the heart. In patients with VVI pacemaker, this technique showed an evident asynchronism of contraction and relaxation of each ventricle and the standard deviation of phase angle (sigma), calculated by computer, is greater during pacing than sinus rhythm for left (LV) and right (RV) ventricles (LV sigma: 17 degrees +/- 4 vs 11 degrees +/- 3, less than 0.001; RV sigma: 31 degrees +/- 7 vs 14 degrees +/- 4, P less than 0.001). In the patients with VVI rate responsive pacemakers, the LV sigma changed from 18.5 +/- 3 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.001, while the RV sigma changed from 30 degrees +/- 8 to 14 degrees +/- 4, P less than 0.001. Instead in the patients with DDD pacemakers, the LV sigma changed from 15.5 degrees +/- 2 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.05, while the RV sigma changed from 29.1 degrees +/- 6 to 14 degrees +/- 4, P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anaerobic threshold in the evaluation of heart function in patients with rate-responsive pacemaker]. / La soglia anaerobica nella valutazione della funzione cardiaca in pazienti con pacemaker rate-responsive.

It is very difficult to evaluate the ability of carrying out physical exercise in patients with rate responsive (RR) pacemaker (PM). However, the anaerobic threshold (AT) proved to be a useful parameter in the evaluation of cardiac function. The AT can be easily reproduced and not influenced from emotional aspects of both the patient and the physician, moreover being under maximum and then easy to achieve. Aims of our study were: to evaluate if the cardiopulmonary stress test can represent a method to be used for a more correct rate responsive pacemaker programming; to compare the data obtained of 3 rate responsive pacemakers steered by different sensors. We have studied 24 patients, of whom 10 with Activitrax (A), 8 with Meta (M), and 6 with Phymos MPT (P) pacemakers. Patients were submitted to symptoms limited cycloergometer stress test at 2 different settings: fixed rate at 70 b/min; increasing rate at until 85% of maximum heart rate for each patient, with range 0 + 10 W/min. Gas exchange data were continuously collected using an automated system (Medical Graphic System 2001) based on Whipp and Wasserman's method.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of ticlopidine in the prevention of thromboembolic events in patients with VVI pacemakers.

This study was designed to evaluate whether long-term treatment with ticlopidine reduces the incidence of thromboembolic episodes in patients with a VVI pacemaker. One hundred eleven patients with a VVI pacemaker were randomly assigned to two groups: group A (52 patients) was treated with ticlopidine at the dose of 250 mg a day; and group B (59 patients) was not treated and served as a control group. The primary analysis of efficacy of ticlopidine was based on the occurrence of thromboembolic episodes and of cardiovascular and cerebrovascular deaths. The mean follow-up period was 66 months. In group A, there was a significant reduction in the incidence of thromboembolic episodes (P less than 0.05) with a smaller incidence of total cardiovascular and cerebrovascular deaths (8 in group A and 18 in group B; P = 0.05) as compared with group B. Twelve percent of patients had moderate side effects with 1 dropout (epistaxis). Our data confirm the high incidence of thromboembolic events in patients with a VVI pacemaker and demonstrate the efficacy of ticlopidine in preventing them.

[Heart function (angioscintigraphic evaluation) and sympathetic tone in insulin-dependent diabetes mellitus]. / Funzione cardiaca (valutazione angioscintigrafica) e tono simpatico nel diabete mellito insulino-dipendente.

Cardiac failure is a frequent feature in diabetic patients and it often causes their death. But how and when cardiac disease begins in this kind of patient is still debatable. For example, cardiac failure can be present even in the absence of atherosclerotic involvement of coronary arteries in young diabetics. The aims of our study were to evaluate the cardiac function and sympathetic tone of 16 young type 1 diabetic patients (8 M and 8 F, mean age: 27 years, SD +/- 5) in comparison with 10 normal subjects (4 M and 6 F, mean age: 30 years, SD +/- 7). Diabetic patients were choose from a large population because of the following features young age, absence of clinical and instrumental evidence of micro- or macroangiopathy, clinical evidence of diabetic autonomic neuropathy, proteinuria or arterial hypertension. They were in good metabolic control on daily insulin therapy of two or three administrations. Cardiac function was evaluated at rest and during submaximal exercise on a cycloergometer in supine position using radionuclide ventriculography with technetium 99m. Sympathetic tone was checked using the five clinical tests according to Ewing and the plasmatic level of catecholamines at rest was evaluated using high pressure chromatography. The ejection fraction, cardiac output, stroke volume of diabetics were comparable with those of normal subjects even in the presence of comparable systemic vascular resistance. The increase in ejection fraction during effort was normal. Only in one diabetic patient (incidentally the oldest one) did ejection fraction decrease (7%) during effort. The peak ejection and filling rates were significantly higher (p less than 0.001) in diabetic patients compared to those of normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

[HR/QT ratio during ergometric test: influence of ischemia and beta blocking therapy]. / Relazione FC/QT durante test ergometrico: influenza dell'ischemia e della terapia betabloccante.

The aim of this study was to analyze the HR/QT relation during exercise in a group of patients with effort angina (Group B) in comparison with the same relation obtained in a group of normal subjects (Group A) comparable for age and sex. The regression analysis was carried out separately during effort in upright position and during rest in clinostatic position to avoid influences on QT by the patient's posture. During effort in patients of the Group B the regression shows a lower value of the slope and of the intercept (p less than 0.001) than those obtained in the subjects of the Group A. A similar behaviour is shown also from the regressions obtained during rest in the same groups. Thus at the highest HRs we observed a longer QT in the Group B. Moreover QT of ischemic patients in the presence of ECG signs of ischemia (ST less than or equal to 1 mm) resulted significantly longer (p less than 0.01) either during effort and at rest, respect to that obtained in Group A at comparable HRs. The analysis of the regression HR/QT after administration of atenolol 100 mg per os in a subgroup of patients of Group B clearly shows a less prolonged QT at the highest HRs where ECG ischemia frequently appears. This fact is demonstrated by the presence of a higher slope (p less than 0.05) respect to that obtained in the same group without therapy. In conclusion, myocardial transient ischemia provokes a longer QT in patients with ischemic heart disease in comparison with normal subjects. Acute therapy with atenolol per os is able to condition the regression HR/QT showing a relative shortening of QT at the highest HRs respect to that carried out in the same patients in absence of therapy.