Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology).

BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Stereotactic Body Radiotherapy for Spine Oligometastases: A Multicentre Retrospective Study From the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

AIM: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) for spine oligometastases. MATERIALS AND METHODS: This was a multicentre retrospective study of a series of patients who received SBRT for spine oligometastases. The efficacy of SBRT was evaluated in terms of local control as the primary endpoint. Survival outcomes were also analysed to identify predictive factors for clinical outcomes. Toxicity was assessed according to CTCAE v4.0. RESULTS: Between March 2018 and July 2022, 183 lesions in 177 patients were analysed. In most patients, SBRT was delivered to a single spine metastasis (82%) for a median total dose of 21 Gy (14-35 Gy) in three fractions (one to five fractions) and a median BED10 = 119 Gy (57.7-152 Gy). Local control rates were 90.3% at 1 year, 84.3% at 2 years and 84.3% at 3 years. Distant progression-free survival rates were 33.1%, 18.5% and 12.4% at 1, 2 and 3 years, with prostate histology (P = 0.023), oligorecurrent disease (P = 0.04) and BED10 > 100 Gy (P = 0.04) found to be predictive on univariate analysis. A further oligometastatic progression was observed in 33 patients (18.6%) treated with a second course of SBRT, reporting at univariate analysis improved overall survival rates (P = 0.01). Polymetastases-free survival rates were 57.8%, 43.4% and 32.4%; concurrent therapy was related to improved outcomes at multivariate analysis (P = 0.009). Overall survival rates were 91.8%, 79.6% and 65.9%, with prostate histology and non-cervical metastases related to better overall survival at multivariate analysis. Pain-flare after SBRT was recorded in 3.3%; five patients underwent surgical decompression after SBRT; there were no grade ≥3 adverse events. CONCLUSIONS: In our experience of only oligometastatic patients, spine SBRT gave excellent results in terms of safety and efficacy. Prostate histology and oligorecurrent disease were predictive factors for improved clinical outcomes; also, patients who experienced a further oligoprogression after SBRT maintained a survival advantage compared with polymetastatic progression. No severe adverse events were reported.

A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

A case of psoriasis with secondary amyloidosis, associated symbrachydactyly of the hand and a transverse deficiency of the foot.

Secondary amyloidosis is associated with a variety of chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, familial Mediterranean fever, osteomyelitis, inflammatory bowel diseases and infective or neoplastic conditions. Few cases of secondary amyloidosis complicating psoriasis have been reported. We describe a 58-year-old patient with secondary amyloidosis, psoriasis, an associated symbrachydactyly of the hand and a transverse deficiency of the foot. To the best of our knowledge, no case of this association has been previously reported.

Catecholamine-induced regulation in vitro and ex vivo of intralymphocyte ionized magnesium.

Despite the importance of the adrenergic activity and of the metabolism of magnesium in some important cardiovascular pathologies, very little is known about how intracellular ionized magnesium (Mgi2+) is regulated by catecholamines. We made an in-vitro study of the variations in the concentration of ionized magnesium in human lymphocytes using the fluorescent probe furaptra in response to different catecholamines. We also made an ex-vivo study of the changes in intracellular ionized magnesium in lymphocytes in 20 subjects with essential arterial hypertension, 10 treated with 120 mg/d of propranolol and 10 with placebo. Norepinephrine and isoproterenol significantly decrease Mgi2+ and this effect is blocked by beta-blockers but not by alpha-blockers. The EC50 of the effect of norepinephrine is within the range of concentrations physiologically present in plasma. The substitution of extracellular sodium with choline blocks the decrease in intracellular ionized magnesium induced by norepinephrine, which leads us to suppose that the magnesium-reducing effect of catecholamines is a result of the activation of a Na+-Mg2+ exchanger. We were not able to demonstrate any change in intracellular ionized magnesium after 1 and 17 days of active treatment in essential hypertensives. The impossibility of demonstrating ex vivo the mechanism of catecholamine-mediated regulation that is evident in vitro is perhaps due to our experimental conditions or to substances which in vivo inhibit the action of the catecholamines on magnesium, such as insulin and/or glucose.

Intramural hematoma of the aorta: diagnosis and treatment.

OBJECTIVE: Increasing use of modern high-resolution imaging techniques yields to describe very early stages of aortic pathology which, if left untreated, may lead to overt aortic dissection. One typical example is aortic intramural hematoma (IMH) with a limited number of cases described in the literature and uncertainties still existing about the most appropriate treatment. Purpose of our study is to report our experience in the evaluation and treatment of IMHs. METHODS: From 1991 to 1999 175 patients were conveyed to our centre for aortic dissection; in nine of them diagnosis of acute IMH was performed. RESULTS: Diagnosis was obtained by means of conventional CT scan of the chest. All the patients underwent surgery, one patient died (11%). At the follow-up (mean 31 months) eight patients were alive and well and did not require any other cardiac surgery. CONCLUSIONS: The possibility to progress to overt aortic dissection may explain the need to an early diagnosis in the treatment of acute IMHs. Immediate surgical treatment is, in our experience, the preferred therapeutic option.

Intralymphocyte free magnesium in patients with primary aldosteronism: aldosterone and lymphocyte magnesium homeostasis.

It is known that hyperaldosteronism has been associated with magnesium deficiency, yet there are no data on the intracellular concentration of ionized magnesium ([Mg(2+)(i)]) in subjects with primary aldosteronism (PA). We measured intralymphocyte free magnesium ([Mg(2+)(i)]) and intralymphocyte free calcium ([Ca(2+)(i)]) in 16 patients with PA and 26 normotensive control subjects (NCs). [Mg(2+)(i)] and [Ca(2+)(i)] were also measured in blood lymphocytes incubated in vitro with aldosterone, according to a fluorimetric method. In subjects with PA, [Mg(2+)(i)] was significantly lower than that in NCs (mean+/-SD; PA 203+/-56 micromol/L, NCs 291+/-43 micromol/L, 95% confidence interval 57 to 119, P=0.001). In the patients, [Ca(2+)(i)] did not prove to be statistically different from that of NCs (mean+/-SD; PA 47.2+/-10.6 nmol/L, NCs 53.2+/-11 nmol/L). The lymphocytes exposed to the action of aldosterone showed a significant reduction in [Mg(2+)(i)] (n=15, NCs 271+/-28 micromol/L, aldosterone treatment 188+/-39 micromol/L, P=0.001, 95% confidence interval 57 to 108). The dose-effect curve of aldosterone on [Mg(2+)(i)] showed an EC(50) value of approximately 0.5 to 1 nmol/L aldosterone. The reduction in [Mg(2+)(i)] mediated by aldosterone is antagonized by the receptor inhibitor of aldosterone; it is inhibited by inhibitors of protein synthesis and is not measurable when the lymphocytes are incubated in an Na(+)-free medium. The data are consistent with the hypothesis that aldosterone affects the cellular homeostasis of magnesium, probably through modification of the activity of the Na(+)-Mg(2+) antiporter.

Continuous suture technique and impairment of the atrioventricular conduction after aortic valve replacement.

OBJECTIVE: Atrioventricular (AV) conduction impairment represents an infrequent complication following aortic valve replacement (AVR). Although several conditions have been considered as potential risk factors for such a postoperative event, the role of the surgical technique has not been evaluated. The aim of this study was to investigate if the suture technique for implantation of the prosthetic valve is a potential risk factor need of pacemaker (PM) implantation after AVR. METHODS: One hundred twenty-four patients undergoing AVR were enrolled in this study. A "continuous" suture technique was performed in 72 patients (58%; Group A), whereas an "interrupted" suture technique was used in 52 patients (42%; Group B). The incidence of "major," requiring PM implantation, as well as "minor," without PM implantation, impairment of the AV conduction was evaluated and compared in the two groups by means of univariate and multivariate analyses. RESULTS: The patients of the two groups were homogenous for all preoperative parameters except patient age. A longer clamp time was present in the patients of group B than those of group A (73 +/- 24 minutes and 60 +/- 24 minutes, respectively; p < 0.01). Postoperatively, hospital mortality consisted of four patients (3.2%) with no statistical importance between the two groups. Eleven patients of group A (17.5%) and one patient of group B1 (2.2%) required PM implantation (p < 0.05). Prolonged P-R interval was recorded in 15 patients of group A and in 5 patients of group B (p < 0.05). CONCLUSIONS: We showed that the continuous suture technique increases the need for postoperative PM implantation after AVR. No major differences have been observed, however, regarding in-hospital mortality and length of hospital stay, regardless of the type of prosthetic suture technique.

Intralymphocyte free magnesium and plasma triglycerides.

To evaluate the relative effect of hypertension and plasma triglycerides on intralymphocyte magnesium we measured ionized intralymphocyte magnesium (Mg(i)) concentration by means of a fluorimetric method based on the dye Furaptra in 4 groups of subjects: 18 normotensive normotriglyceridemic controls (NTNC), 9 hypertriglyceridemic normotensive patients (HTN), 8 hypertriglyceridemic essential hypertensive patients (HTEH), 17 normotriglyceridemic essential hypertensive patients (NTEH). Hypercholesterolemic, diabetic patients and alcoholics were excluded from the study. Mg(i) was found to be statistically reduced (ANOVA test F=10.41, P=0.0001) in both HTN and HTEH (M+/- SD, HTN: 0.235 +/- 0.01, HTEH: 0.236 +/- 0.01 mmol/l) as compared to both NTNC and NTEH (M +/- SD, NTNC: 0.294 +/- 0.008, NTEH: 0.297 +/- 0.009 mmol/l). A statistically significant negative correlation was found in the population as a whole between Mg(i) and plasma triglycerides (n=52, R= -541, P=0.00004). Our data suggest that hypertriglyceridemia per se and possibly the so-called plurimetabolic syndrome is characterized by low intralymphocyte free magnesium.

Effect of 5-HT4 receptor stimulation on the pacemaker current I(f) in human isolated atrial myocytes.

OBJECTIVE: 5-HT4 receptors are present in human atrial cells and their stimulation has been implicated in the genesis of atrial arrhythmias including atrial fibrillation. An I(f)-like current has been recorded in human atrial myocytes, where it is modulated by beta-adrenergic stimulation. In the present study, we investigated the effect of serotonin (5-hydroxytryptamine, 5-HT) on I(f) electrophysiological properties, in order to get an insight into the possible contribution of I(f) to the arrhythmogenic action of 5-HT in human atria. METHODS: Human atrial myocytes were isolated by enzymatic digestion from samples of atrial appendage of patients undergoing coeffective cardiac surgery. Patch-clamped cells were superfused with a modified Tyrode's solution in order to amplify I(f) and reduce overlapping currents. RESULTS AND CONCLUSIONS: A time-dependent, cesium-sensitive increasing inward current, that we had previously described having the electrophysiological properties of the pacemaker current I(f), was elicited by negative steps (-60 to -130 mV) from a holding potential of -40 mV. Boltzmann fit of control activation curves gave a midpoint (V1/2) of -88.9 +/- 2.6 mV (n = 14). 5-HT (1 microM) consistently caused a positive shift of V1/2 of 11.0 +/- 2.0 mV (n = 8, p < 0.001) of the activation curve toward less negative potentials, thus increasing the amount of current activated by clamp steps near the physiological maximum diastolic potential of these cells. The effect was dose-dependent, the EC50 being 0.14 microM. Maximum current amplitude was not changed by 5-HT. 5-HT did not increase I(f) amplitude when the current was maximally activated by cAMP perfused into the cell. The selective 5-HT4 antagonists, DAU 6285 (10 microM) and GR 125487 (1 microM), completely prevented the effect of 5-HT on I(f). The shift of V1/2 caused by 1 microM 5-HT in the presence of DAU 6285 or GR 125487 was 0.3 +/- 1 mV (n = 6) and 1.0 +/- 0.6 mV (n = 5), respectively (p < 0.01 versus 5-HT alone). The effect of 5-HT4 receptor blockade was specific, since neither DAU 6285 nor GR 125487 prevented the effect of 1 microM isoprenaline on I(f). Thus, 5-HT4 stimulation increases I(f) in human atrial myocytes; this effect may contribute to the arrhythmogenic action of 5-HT in human atrium.

Cardiac troponin I and Q-wave perioperative myocardial infarction after coronary artery bypass surgery.

OBJECTIVE: To monitor cardiac troponin I (cTnI), a newly developed biochemical index for cardiac damage, in patients during and after coronary artery bypass surgery (CABS) to determine whether the measurement of the serum levels of this marker could be of value in formulating an early diagnosis of Q-wave perioperative myocardial infarction (PMI). DESIGN: Prospective study with sequential measurements of biological markers in a selected surgical patient group. SETTING: University research laboratory and general university hospital (Cardiac Surgery Unit and Anesthesiology and Reanimation Unit). PATIENTS: Forty-two patients undergoing elective CABS without concomitant valvular replacement. INTERVENTIONS: There were no interventions required for this study. However, patients entered into the study had CABS, sequential arterial blood samples, ECG recordings, and echocardiograms performed. MEASUREMENTS AND MAIN RESULTS: Pre-, intra-, and postoperative (up to 48 hrs) measurements of cardiac troponin I, MB-CK, and total creatine kinase, as well as serial electrocardiograms and echocardiograms. Perioperative infarction was assessed as the development of new persistent regional wall motion abnormalities in echocardiography together with electrocardiographic alterations and MB-CK increases. Eight patients had Q-wave PMI. All PMI patients had elevated peak cTnI values (all >9.2 ng/mL), whereas the 34 nonPMI patients had peak values <9.0 ng/mL; therefore, sensitivity and specificity (with a 9.0 ng/mL cut-off value) are 100%. MB-CK measurement peak values did not demonstrate such a high specificity and sensitivity. CONCLUSIONS: Because of its high specificity and sensitivity, serial measurements of cTnI provide a rapid and accurate method for confirming or excluding the diagnosis of perioperative myocardial injury. cTnI evaluation can therefore be used both as an independent prognostic marker for patients undergoing cardiac surgery and as a powerful tool for detecting smaller PMIs often missed with standard PMI diagnostic criteria.

Intralymphocyte free magnesium and calcium and insulin tolerance test in a group of essential hypertensive patients.

In order to assess the links which are claimed to exist between peripheral insulin resistance and intracellular magnesium and calcium concentrations, we measured free intralymphocyte magnesium (Mg(i)) and calcium (Ca(i)) concentrations as well as the rate constant of plasma glucose disappearance (K(itt)) after insulin injection (insulin tolerance test: ITT) in a group of 16 normotensive control subjects (NC) and 34 essential hypertensive subjects (EH). Mg(i) and Ca(i) were measured in triplicate by means of a fluorimetric technique based on the dyes furaptra and fura-2 respectively. K(itt) values proved significantly reduced in EH as compared to NC (M +/- SD, EH: 4.49 +/- 1.31 vs 5.28 +/- 1.19, P <0.05; 95% confidence limits: 0.23-1.5). Mg(i) and Ca(i) were not statistically different in EH as compared to NC subjects (Mg(i), NC: 266 +/- 20 micromol/l; EH: 245 +/- 50 micromol/l; Ca(i), NC: 47 +/- 9 nmol/l EH: 46 +/- 13 nmol/l). We found a statistically significant inverse correlation in the whole study group between K(itt) and body mass index (R= -0.363, P<0.01) and a statistically significant positive correlation between K(itt) and Mg(i) (R=0.347, P=0.013) was found. In a step-up multivariate regression analysis including blood pressure, plasma lipids, BMI, plasma magnesium, fasting insulin, fasting glucose, Mg(i) and Ca(i), the dependent variable K(itt) is statistically significantly correlated with body mass index and Mg(i). In a first attempt to study the relationships between insulin resistance, Mg(i) and Ca(i) in nucleated cells, the chosen index of peripheral resistance seems to be linked to intracellular free magnesium.

[Peripheral insulin resistance and free intralymphocyte magnesium and calcium concentrations in patients with essential hypertension]. / Résistance périphérique à l'insuline et concentration intralymphocytaire de magnésium et de calcium ionisés chez des patients avec hypertension artérielle essentielle.

To ascertain the claimed links between peripheral insulin resistance and intracellular magnesium and calcium concentrations, we measured free intralymphocyte magnesium (Mg(i)) and calcium (Ca(i)) concentrations, as well as the rate constant of plasma glucose disappearance (K(itt)) after insulin injection (insulin tolerance test: ITT), in a group of 15 normotensive control subjects (NC) and 29 essential hypertensive subjects (EH). Mg(i) and Ca(i) were measured in triplicate by means of a fluorimetric technique based on the dyes furaptra and fura-2 respectively. K(itt) value were significantly reduced in hypertensive subjects as compared to control subjects (M +/- SD, EH: 4.54 +/- 1.31 vs 5.63 +/- 1.07; p < 0.02; 95% confidence limits: 0.22-1.96). Mg(i) and Ca(i) were not statistically different in hypertensive subjects as compared to control subjects (Mg(i), NC: 0.274 +/- 0.02 mmol/L; EH: 0.248 +/- 0.05 mmol/L; Ca(i), NC: 47.6 +/- 9 mmol/L, EH: 46.7 +/- 13.6 mmol/L). A statistically significant inverse correlation was found in the whole study group between K(itt) and body mass index (R = -0.394, p = 0.01) and a statistically significant positive correlation between K(itt) and Mg(i) (R = 0.386; p = 0.012). The latter correlation was no longer statistically significant if adjusted for body mass index. Our data are in favour of a link between index of peripheral insulin resistance and body mass index. A dependence from Mg(i) is possible but the study lack so far the statistical power to demonstrate it.

A major involvement of the cardiovascular system in patients affected by Marfan syndrome: novel mutations in fibrillin 1 gene.

The aim of our study was to characterize the molecular defect in Italian Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype. In particular, our ultimate goal was to identify the region(s) of the fibrillin 1 (FBN1) gene mainly involved in the health of the heart and of the aorta in terms of the cardiovascular system. We searched for a molecular defect in three patients with classic Marfan syndrome (MFS). The mutations were detected applying heteroduplex analysis to each of the 65 exons of the FBN1 gene amplified by polymerase chain reaction (PCR). Exons containing heteroduplex bands were sequenced directly from PCR products. This study reports the detection of three unique missense mutations in the FBN1 gene in three Italian patients: a 44-year-old adult male and 36-year-old female affected by classic MFS (with all the cardinal manifestations in the cardiovascular, ocular and skeletal systems), and an 11-year-old male affected by infantile (earlier onset) classic MFS. The first two are sporadic cases and present a Cys-->Arg amino acid substitution (T-->C substitution at nucleotide 7729) in exon 62 and a Cys-->Tyr amino acid substitution (G-->A substitution at nucleotide 6695) in exon 54. The third is a familial case which presents a Cys-->Trp aminoacidic substitution (C-->G substitution at nucleotide 3546) in exon 28. Our data confirm that cysteine substitutions in calcium binding epidermal growth factor (cbEGF)-like domains cause severe Marfan phenotype. Exon 24-32 cluster seems to produce an even more severe phenotype. The early characterization may be of clinical relevance for prevention and early surgical treatment of aortic aneurysm or dissection.

Intralymphocyte free magnesium in a group of subjects with essential hypertension.

Despite the importance of magnesium in essential hypertension, few data are available on the ionized intracellular concentration of this ion. We therefore studied intralymphocyte free intracellular magnesium (Mgi) in 32 untreated essential hypertensive subjects and 27 normotensive control subjects by means of a fluorimetric technique based on the use of the new magnesium-sensitive dye furaptra. We also measured intralymphocyte ionized calcium (Cai) with fura 2. No statistically significant differences were found in Mgi in hypertensive compared with normotensive subjects (essential hypertensive, 0.291 +/- 0.053 mmol/L; normotensive, 0.293 +/- 0.043 [mean +/- SD]). A statistically significant inverse correlation was established between Mgi and plasma triglycerides in essential hypertensive subjects (r = -.521, P = .002). The hypertensive group was arbitrarily divided into two subgroups according to plasma triglyceride levels (> 2 [n = 10] or < 2 mmol/L [n = 22]), and Mgi proved to be significantly lower in the subgroup with high plasma triglyceride levels compared with either the subgroup with normal triglycerides (P = .009; 95% confidence interval, 0.013-0.088) or the normotensive control group as a whole (P = .03; 95% confidence interval, 0.003-0.069) (high-triglyceride hypertensive subgroup, Mgi = 0.256 +/- 0.045 mmol/L; normal-triglyceride hypertensive subgroup, Mgi = 0.307 +/- 0.049). No statistically significant differences were found in Cai in hypertensive compared with normotensive subjects (hypertensive, 53 +/- 12 nmol/L; normotensive, 54 +/- 14). We did not find statistically significant correlations between Cai and plasma triglycerides, nor did we find any differences in Cai between the subgroup of hypertensive subjects with high plasma triglyceride levels and either the subgroup of hypertensive subjects with normal triglycerides or the normotensive control group as a whole. The discrepancies between our results in lymphocytes and data relating to either erythrocytes or platelets emphasize the need for caution before the results are extrapolated from one tissue to the other. The decreased Mgi levels in the subgroup of high-triglyceride hypertensive subjects may suggest a role for magnesium in plurimetabolic syndrome.

Erythrocyte Na(+)-H+ exchanger kinetics and Na(+)-Li+ countertransport activity in essential hypertensive patients.

The authors measured Na(+)-H+ exchanger kinetics together with Na(+)-Li+ countertransport V(max) in the erythrocytes of 21 subjects with essential hypertension and 16 normotensive control subjects. Na(+)-H+ exchange V(max) appeared to be increased in patients with essential hypertension, while the Na(+)-H+ exchanger affinity for intracellular proton sites (K50%) proved to be unchanged and the index of cooperativity among intracellular proton binding sites as measured by Hill's coefficient (Hill's n) decreased as compared with normotensive control subjects. Na(+)-Li+ countertransport V(max) appeared to be higher in patients with essential hypertension than in control subjects. The authors were unable to find any correlations between Na(+)-H+ exchanger kinetic parameters and metabolic variables such as parameters of insulin resistance and plasma lipids. On the basis of the data obtained, erythrocyte Na(+)-H+ exchanger activity was found to be abnormal in two kinetic variables in essential hypertensive patients and showed no simple linear correlations with the main variables of glucose metabolism, plasma lipids, renin or aldosterone.

Intraluminal gastric pH in chronic pancreatitis.

The aim of this study was to assess the circadian variations of intragastric pH in 28 inpatients with chronic pancreatitis (mean (SD) age 46.8 (12.4) years) and in 14 controls (45.4 (9.8)). pH Metry was performed using a monocrystalline antimony electrode placed in the body of the stomach under fluoroscopic control and connected up to a recorder (MKII Digitrapper, Synectics). The evaluation parameters, expressed as median and interquartile range, were: total period, postprandial periods (P1 and P2), interdigestive, and nocturnal phases. Patients with chronic pancreatitis were subdivided into three groups on the basis of severity of exocrine pancreatic insufficiency (secretin-caerulein test: lipase output at 60-90 min)--that is, those with severe insufficiency (chronic pancreatitis-SI: 13 patients, lipase output < 10% normal values and pancreolauryl test < 20%), those with only mild insufficiency (chronic pancreatitis-MI: seven patients), and those with normal secretion (chronic pancreatitis-NF: eight patients). The chronic pancreatitis-SI patients present significantly greater gastric acidification in the postprandial periods compared with controls (P1: p < 0.001; P2: p < 0.01), and with chronic pancreatitis-MI plus chronic pancreatitis-NF subjects (P1: p < 0.01; P2: p < 0.05), taken together. In conclusion, gastric acidity, exocrine pancreatic insufficiency, and impaired digestion are closely related during the course of chronic pancreatitis.

[Multicenter comparative study of meropenem, a new carbapenemic preparation, administered intramuscularly. Treatment of respiratory and urinary infections in hospitalized patients]l. / Studio multicentrico comparativo di un nuovo carbapenemico, meropenem, somministrato per via I.M. Trattamento delle infezioni respiratorie e delle infezioni urinarie in pazienti ospedalizzati.

263 hospitalized patients were enrolled in a multicentre study to assess efficacy and safety of i. m. meropenem, compared to ceftazidime, in the treatment of lower respiratory tract infections and urinary infections as well. Meropenem, administered at a dose of 500 mg tid, was therapeutically equivalent to the reference agent (1000 mg tid in RTI's and 500 mg tid in UTI's) in both indications. The two treatments were well tolerated, without any serious local or systemic side effect.

Erythrocyte Na(+)-H+ exchanger and Na(+)-Li+ countertransport activity in primary aldosteronism.

Several authors have described increased Na-H exchanger activity in essential hypertension but no data are available in secondary forms of hypertension such as primary aldosteronism. We measured Na-H exchanger kinetics together with Na-Li countertransport Vmax in the erythrocytes of eight patients with primary aldosteronism and in 15 normotensive control subjects. Plasma aldosterone, plasma renin and plasma potassium were also evaluated. Na-H exchanger Vmax appear to be increased in patients with primary aldosteronism and Hill's n, an index of co-operativity amongst intracellular proton binding sites, was significantly lower in patients than in controls. No statistically significant differences were found between affinity for intracellular protons (K50%) and for Na-Li countertransport Vmax between the two groups studied. We were unable to find any correlations between Na-H exchanger Vmax and Na-Li countertransport Vmax in the two groups considered as a whole. From the present data Na-H exchanger overactivity would not appear to be a specific feature of essential hypertension but seems to be characteristic in patients with primary aldosteronism.

Cardiac tamponade secondary to intrapericardial rupture of a hepatic amoebic abscess.

We report the case of a patient who underwent an emergency subxiphoid pericardiectomy with evacuation of 1700 cc of anchovy sauce-like fluid. On pericardial inspection a fistulous communication was seen with a cavity in the left hepatic lobe. No loculi or adhesions were found in the pericardial sac and no further surgical procedure was advised. The hepatic cavity and pericardium were drained: bacteriological investigation of the fluid yielded entamoeba histolytica and chloroquine was administered. Apart from the rarity of the observation in western countries, we discuss surgical approaches in cases of unknown purulent pericardial effusions, stressing the possibility of achieving a good surgical result even with a minor surgical procedure such as subxiphoid pericardiectomy and drainage.