Why data on frailty and SARS-CoV-2 infection are basic to progress.

Several studies showed that frailty was a predictor of in-hospital death in older adults with COVID-19. The mechanisms through which frailty increases the severity of COVID-19 are several, including immunosenescense and dysregulated inflammation. Whether individuals affected by frailty exhibit a higher susceptibility to SARS-CoV-2 infection remains an open question. Here we report the case series of 40 older persons that in February 2020, before the first case of COVID-19 was detected in Italy, went together on a winter holiday. Back home, 7 of them developed influenza-like symptoms and one was hospitalized due to COVID-19 pneumonia. Between May and July, the seniors were offered the possibility to be tested for SARS-CoV-2 antibody positivity. Twenty-seven of them accepted: 13 had a positive serological test whereas no active infection was found. Comparing the characteristics of those who tested positive and the others, we found that the former group was frailer, exhibiting higher Clinical Frailty Scale scores.

Fractional-order nonlinear hereditariness of tendons and ligaments of the human knee.

In this paper the authors introduce a nonlinear model of fractional-order hereditariness used to capture experimental data obtained on human tendons of the knee. Creep and relaxation data on fibrous tissues have been obtained and fitted with logarithmic relations that correspond to power-laws with nonlinear dependence of the coefficients. The use of a proper nonlinear transform allows one to use Boltzmann superposition in the transformed variables yielding a fractional-order model for the nonlinear material hereditariness. The fundamental relations among the nonlinear creep and relaxation functions have been established, and the results from the equivalence relations have been contrasted with measures obtained from the experimental data. Numerical experiments introducing polynomial and harmonic stress and strain histories have been reported to assess the provided equivalence relations. This article is part of the theme issue 'Advanced materials modelling via fractional calculus: challenges and perspectives'.

[Cat scratch pneumonia: a case report]. / Un caso di polmonite secondaria a graffio di gatto.

Pasteurella multocida infections can be caused by scratches or bites of many animals including pets. An unrecognized infection can lead to severe complications such as arthritis, osteomyelitis, respiratory infections and even meningitis or endocarditis. We present the case of a woman affected by soft tissue infection caused by Pasteurella multocida complicated by bacteremia and pneumonia.

Decreased sympathetic inhibition in gastroesophageal reflux disease.

This study was undertaken to evaluate autonomic nervous system function in patients with gastroesophageal reflux disease. Based on clinical criteria, 28 consecutive patients with no history of heart, metabolic, or neurologic disease (mean age 41 y, range 20-62 y) reporting with upper gastrointestinal symptoms typical of gastroesophageal reflux underwent esophageal manometry, ambulatory 24-hour pH study with electrocardiographic monitoring, power spectral analysis of heart rate variability, and cardiovascular tests. Twelve healthy subjects served as controls. A positive result of prolonged esophageal pH study (pH in the distal esophagus less than 4, lasting more than 4.2% of recording time) was observed in 21 patients (reflux group); seven patients were categorized in the nonreflux group. No patient showed arrhythmias or any correlation between heart rate variability changes during electrocardiographic monitoring and episodes of reflux (pH less than 4, lasting more than 5 minutes). A decrease of sympathetic function occurred only in the reflux group (p <0.05) supported by the lower increase of systolic/diastolic blood pressure at sustained handgrip. No other cardiovascular tests showed statistically significant differences in the control or nonreflux groups. Total time reflux showed an inverse correlation with sympathetic function in the reflux group (r = -0.415, p <0.028). We concluded that there is some evidence for a slightly decreased sympathetic function in patients with gastroesophageal reflux disease that is inversely correlated with total time reflux. In these patients, decreased sympathetic function may cause dysfunction of intrinsic inhibitory control with increased transient spontaneous lower-esophageal sphincter relaxations, thus resulting in gastroesophageal reflux disease.

Identification of multiple somatostatin receptors in the rat somatosensory cortex during development.

The present study was aimed at identifying somatostatin receptor subtypes on the basis of their ligand-binding properties in the rat somatosensory cortex during fetal and postnatal development. Characterization of somatostatin-binding sites was performed in individual cortical layers by using three radioligands and eight competitors with known selectivities for the five somatostatin receptor subtypes. Binding sites sensitive to sst2-selective ligands were detected with high densities in the intermediate zone of the fetal cortex. From embryonic day 21 to 21 days postnatal (P21), mixed populations of receptors were detected in the cortical plate and emerging layers I-VI. Putative sst2 receptors were detected throughout the entire period but displayed different affinities for somatostatin and analogs, and a different sensitivity to GTP, depending on the developmental stage and the cortical layer considered. High densities of binding sites exhibiting characteristics of the sst1, sst3/5, and sst4 receptor subtypes were observed from P4 to P7, P7 to P14, and P7 to P21, respectively. In addition, each type of site exhibited a particular distribution pattern across the cortical layers that varied during the development. In the adult cortex, binding sites with sst1 and sst2 receptor characteristics were predominant. This study provides evidences of developmental expression windows of four sst receptor subtypes in selected areas of the rat cerebral cortex.

[Adult coeliac disease, epilepsy and cerebral calcifications. A case report]. / Malattia celiaca dell'adulto, epilessia e calcificazioni cerebrali. Descrizione di un caso clinico.

Coeliac disease has a prevalence of between 1/300 and 1/2000 in Europe. A net increase has been observed in the past few years and has been correlated with the greater attention focused on this pathology. The clinical signs may be heterogeneous and their onset may occur at any age. In addition to the classic presentation of the typical malabsorption syndrome, an ''atypical'' presentation has been described, especially in ''adults'', with more frequent involvement of extraintestinal sites and more often in a mono/paucisymptomatic form. The classic variety of coeliac disease is currently thought to be merely the tip of an iceberg whose submerged parts are represented by the subclinical variations, correlated clinical syndromes not yet fully identified and an asymptomatic variety (silent, latent or potential) characterised by various degrees of permanent or transient diet-related alterations to intestinal mucosa. Recently, the association between coeliac disease and epilepsy was described in patients with bilateral occipital calcifications. This study reports the case of a 36-year-old man with manifestations of late onset coeliac disease after a long history of epilepsy starting in infancy and associated with cerebral calcifications.

Esophageal dysmotility and gastroesophageal reflux in intrinsic asthma.

This study was undertaken to determine the prevalence of esophageal motor abnormalities, the incidence of gastroesophageal reflux, and the coexistence of gastroesophageal reflux with esophageal dysmotility in patients with intrinsic asthma. Based on clinical criteria, 34 consecutive asthmatics, 15 patients with gastroesophageal reflux, and 10 subjects with upper gastrointestinal symptoms with normal results of esophageal manometry and 24-hr esophageal pH test (controls) were studied. Esophageal motor disorders were noted in 23 of 34 asthmatics, and in 10 of 15 patients with acid reflux but in none of the subjects of the control group. A positive result of the prolonged esophageal pH study (pH in the distal esophagus less than 4 for more than 4.2% of the recording time) was obtained in 14 of 17 patients with asthma (only 17 of the original patients were tested because the others did not give informed consence for this test) and in all patients with gastroesophageal reflux. None of the members of the control group had positive test results. The findings of this study show that: (1) it is possible to identify a group of subjects with nonallergic asthma presenting with esophageal dysmotility, (2) the 24-hr esophageal pH study must be properly done in such patients; (3) esophageal motor abnormalities are often associated with positive pH results; and (4) more reflux was observed while in a supine position (especially during the night) than that observed either in control or reflux patients. Based on these results, patients with intrinsic asthma with reflux can benefit from both acid suppressive and prokinetic drugs with notable clinical implications regarding standard treatment for asthma, and those with prevalent supine compared to upright reflux could even benefit from surgery.

des-AA-1,2,5[D-Trp8, IAmp9]somatostatin-14 allows the identification of native rat somatostatin sst1 receptor subtype.

Somatostatin exerts multiple activities by interacting with at least five different receptor subtypes (sst[1-5]). The affinity of des-AA(1,2,5)-[D-Trp8, IAmp9]somatostatin-14 (CH-275) was studied by competition experiments using the non-selective radioligand [125I][Leu8, D-Trp22, Tyr25]somatostatin-28 in areas of the rat brain and pituitary known to express identified receptor subtypes. In the cerebellar nuclei and cerebral cortex, which possess the somatostatin sst1 receptor subtype, CH-275 exhibited a moderate affinity (IC50: 10-50 nM). Conversely, in the hippocampus, immature cerebellum and pituitary which contain different subsets of receptors mRNAs (sst[2-5]), the IC50 values were > 1 microM. These data indicate that CH-275 is an appropriate ligand for the identification of native rat somatostatin sst1 receptor subtype.

Comparison of postoperative complications after Küstner and Pfannenstiel transverse suprapubic incisions.

We compared postoperative morbidity with the Küstner (n = 53) and Pfannenstiel (n = 131) incisions in a consecutive series of women undergoing surgery for benign gynecological conditions. The incidence of febrile morbidity (15.1% vs 23.7%, chi 2(1) = 1.19, P = 0.28) and wound infection (5.7% vs 9.2%, P = 0.56, Fisher's exact test) were higher in the Pfannenstiel then in the Küstner group, but neither difference was statistically significant. One suprafascial hematoma was observed after a Küstner incison compared with eight subfascial hematomas after a Pfannenstiel incision (1.9% vs 6.1%, P = 0.45, Fisher's exact test). The postoperative hospital stay was statistically significantly lower in the Küstner than in the Pfannenstiel group (6.3 +/- 1.4 vs 7.1 +/- 1.2 days, P < 0.01, Student's t test). The Küstner incision warrants further evaluation and usage.

Transient expression of somatostatin receptors in the brain during development.

The study of somatostatin receptors by means of autoradiography in tissue sections revealed high densities of binding sites in the immature central nervous system. In rat cerebral cortex, the receptors are present in the intermediate zone and in association with cells migrating through the cortical plate. Somatostatin receptors in the intermediate zone of fetuses and in the cortical plate of postnatal rats exhibit high and low affinities respectively for the somatostatin analogue MK 678. In the rat cerebellum, the external granule cell layer, a germinal matrix containing interneuron precursors, contains a high density of receptors. These receptors exhibit high affinity for MK 678 throughout the period of cell multiplication. In granule cell cultures from eight-day-old rats, MK 678, octreotide and somatostatin are able to inhibit cAMP formation induced by forskolin or pituitary adenylyl cyclase-activating polypeptide. Somatostatin reduces the intracellular Ca2+ concentration in cultured granule cells; this response desensitizes rapidly. These results suggest that the somatostatin receptors in the external granule cell layer are type 2 receptors (sstr2). A low density of receptors with low affinity for MK 678 was also detected in the external granule cell layer and in the granule cell layer of neonatal rats. In adult rats the cerebellum is devoid of somatostatin receptors. These observations indicate that somatostatin probably exerts morphogenetic activities through different receptor types in several structures of the central nervous system.

Taurine-induced diuresis and natriuresis in cirrhotic patients with ascites.

Taurine is a non-protein sulfur amino acid widely distributed in mammalian tissues, with poorly understood functions. Taurine administration has a variety of hemodynamic effects, including improvement of cardiac function and suppression of sympathetic activity. Increased urinary volume and sodium excretion have been reported in taurine-fed hamsters. Since patients with ascitic liver cirrhosis have severe hemodynamic and renal abnormalities potentially sensitive to taurine feeding, we evaluated the effects of the i.v. infusion of taurine on urinary flow and sodium excretion and on the hormones involved in the control of hydrosaline homeostasis. Eight cirrhotic patients with tense ascites were given an i.v. bolus of taurine (16 mumoles in 40 ml of saline). The next day patients were given saline only, as a control. Diuresis, urinary sodium and plasma renin activity, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured for the following 6 hrs. Plasma taurine increased ten fold after infusion, then decreased exponentially. No side effects were recorded. After taurine, but not after saline, there was a prompt and significant increase in both urinary volume and sodium excretion. Diuresis increased from 340 +/- 43 to 817 +/- 116 microliters/min (p < 0.01); urinary sodium from 13.8 +/- 3 to 26.3 +/- 4 mumoles/min (p < 0.05). Both values returned to normal after 2-3 hrs. Taurine infusion caused a concomitant significant decrease in plasma renin activity (from 7.7 +/- 2.2 to 4.3 +/- 1.9 ng/ml/hr, p < 0.05) and aldosterone (from 588 +/- 47 to 348 +/- 89 pg/ml, p < 0.05), but no changes in atrial natriuretic peptide and arginine vasopressin. We conclude that i.v. taurine infusion in ascitic cirrhosis promotes a transient diuresis and natriuresis, apparently through the inhibition of the renin-aldosterone axis.

[Crohn's disease in prolonged remission: should one augment protein-calorie intake as compared to healthy subjects?]. / Maladie de Crohn en rémission prolongée: faut-il augmenter l'apport protéino-calorique comparativement à la population saine?

The aim of our two year prospective study was to evaluate whether adult Crohn's disease patients in prolonged remission (CDAI < 150), in order to maintain their body weight as close as possible to the ideal one, need a protein-calorie intake higher than the predicted one and that of healthy controls. Twenty-four out of 49 Crohn's disease patients in clinical remission completed the two year prospective study, during which they were free to eat "ad libitum", in quantity and in quality. Twenty-three of the 24 patients (96%) maintained their body weight > 95% of the ideal one. As compared to predicted intakes, mean calories were -12.23% (= 272 +/- 91 Kcal/day) lower (P < 0.01), and proteins +40.6% (20.16 +/- 13.6 g/day; = 0.32 g/kg b.w./day) higher (p < 0.001). Protein-calorie intake and glycolipid ratio were comparable to those of healthy controls (p = n.s.). In the group of patients who had a relapse during the follow-up, 9 out of 25 were found to be underweight at the onset of the survey. Their protein-calorie intake was equivalent to that of subjects who completed the study. We conclude that adult Crohn's disease patients in prolonged remission maintain their ideal body weight by a protein-calorie intake comparable to that of healthy population and do not need a tailored regimen.

Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis.

BACKGROUND: Hemodynamic studies have shown the efficacy of nitrates in reducing portal pressure in cirrhosis. We therefore studied the efficacy of isosorbide-5-mononitrate vs. propranolol in the prevention of first bleeding within a prospective controlled trial. METHODS: One hundred eighteen cirrhotics with esophageal varices were blindly randomized to receive 20 mg of isosorbide-5-mononitrate three times a day (n = 57) or propranolol (n = 61) up to the maximum tolerated dose. Both groups also received ranitidine (150 mg/day). RESULTS: The median follow-up was 29 months. Twenty-six patients dropped out (13 in the isosorbide group) because of poor compliance or complications unrelated to treatment. Eighteen patients died (9 in the isosorbide-treated group), 6 due to bleeding. The 1- and 2-year actuarial percentages of patients free of bleeding was 90.8% and 82.2% in the isosorbide-5-mononitrate--and 93.9% and 85.8% in the propranolol-treated groups, respectively (P = NS). These values are higher than those expected from the North Italian Endoscopic Club predicting scores. There were few major side effects in either group. The 2-year survival rate did not differ between the two groups (82.2% vs. 85.4%). CONCLUSIONS: Isosorbide-5-mononitrate administered orally is a safe and effective alternative to propranolol in the prophylaxis of bleeding in cirrhosis.

Tumor necrosis factor/cachectin in Crohn's disease. Relation of serum concentration to disease activity.

Inflammatory mediators seem to be involved in the pathogenesis of Crohn's disease. Tumor necrosis factor is a primary mediator of inflammatory responses which causes metabolic effects related to tissue wasting. The aims of this study were to establish the presence of tumor necrosis factor in Crohn's disease patients, to determine of its serum levels reflect disease activity and to examine the relationship if this cytokine with other assessments of the activity of the disease. Serum concentration of tumor necrosis factor, measured with a biological assay, was significantly raised in 56 Crohn's disease patients (201 determinations) as compared with 44 controls (P < 0.0001). Patients with inactive disease had significantly lower tumor necrosis factor levels (3.58 +/- 0.55 ng/mL) as compared to patients with active disease (8.17 +/- 1.01 ng/mL). There was a significant correlation between serum tumor necrosis factor concentration and disease activity (r = 0.237, P < 0.002). Higher tumor necrosis factor levels were detected in patients with colonic involvement (ileocolitis and colitis) as compared with ileal localizations, and the difference was significant (t = 2.16, P < 0.05). Besides, it correlated negatively with albumin, haemoglobin and cholesterol.

Helicobacter pylori infection: comparison among four different therapeutic regimens.

Helicobacter pylori is both virulent and pathogenic, yet it is not clear what is the best way to treat the infection. This study compares the ability of 4 regimens of colloidal bismuth subcitrate (CBS) 120 mg q.i.d. for 4 weeks, combined with one or two antibiotics, to eradicate helicobacter pylori and assesses the outcome of eradication on antral gastritis and on symptoms of non-ulcer dyspepsia in 140 consecutive subjects (44 duodenal ulcers and 96 non ulcer dyspepsia). Endoscopy with antral biopsies was repeated in all patients before (T0) and one month after stopping treatments (T2) while duodenal ulcers were endoscoped also at the completion of treatments (T1). The four regimens showed similar eradication and ulcer healing rates (p = ns). After treatments (T1), about 60% of dyspeptic patients achieved a subjective improvement, not significant despite therapeutic regimen, and persisting at T2. Antral gastritis significantly improved after treatments (p less than 0.0001), even with the persistence of the infection (p less than 0.001). The 4 regimens are relatively safe, as no abnormality in laboratory assessment was found, albeit the frequency of side effects (most of whom tinidazole related) and the difficulty of the schedules (6-10 tablets/day) may limit patient compliance.

Effect of sulodexide on blood viscosity in patients with peripheral vascular disease.

Thirty patients with Stage II peripheral vascular disease were treated with sulodexide, a new, medium molecular weight glycosaminoglycan, and placebo using a double-blind, crossover study design. After a 1-month wash-out period, patients were treated for 1 month with one or other trial medication and then crossed over to the alternative preparation for a further month. Measurements were made at baseline and at the end of each treatment period of serum, plasma and whole blood viscosities (at various shear rates), fibrinogen levels and red cell filterability. Tolerance parameters were also assessed at the same times. The results showed that there were statistically significant reductions in plasma and whole blood viscosity and in fibrinogen levels after sulodexide, but not after placebo. Neither treatment had any marked effect on red blood cell filterability. Local and systemic tolerance of the treatment was excellent, and some patients reported an improvement in symptoms whilst they were taking sulodexide; this, however, could not be quantified in this study. It is suggested that the viscosity and fibrinogen reducing effect of sulodexide make it a useful form of treatment in patients with atheromatous vascular diseases of the lower limbs.

Oral and intravenous pharmacokinetic profiles of doxofylline in patients with chronic bronchitis.

Serum doxofylline concentrations were evaluated after solid-phase extraction by high-performance liquid chromatography following administration of 100 mg doxofylline given as a single intravenous dose over 10 min or 400 mg doxofylline given orally twice daily for 5 days in six and eight non-smoking, fasting, chronic bronchitic patients, respectively. Doxofylline possessed a very short distribution phase following intravenous administration, with a sustained elimination phase (half-life 1.83 +/- 0.37 h). After oral administration, the peak serum doxofylline concentration was 15.21 +/- 1.73 micrograms/ml and the mean elimination half-life was 7.01 +/- 0.80 h; there was a large inter-subject variability. No side-effects were experienced by the patients during the study.

Circulating platelet activation in healthy subjects and in some pathological conditions. Method of study and results.

Current clinical methods for evaluating platelet function are artful tests which study the effects of various stimuli on platelets, whereas the clinician is much more interested in methods evaluating the activation of circulating platelets. The hallmark of activation of platelets is their shape change, i.e. the transformation of the platelets from smooth disks into spiny spheres; the aggregation begins when 30% of platelets are activated. In 1138 subjects (384 healthy individuals and 854 patients with various pathological conditions with high thrombotic risk) we have investigated circulating platelet activation and circulating platelet aggregates by fixation of blood cells in a glutaraldehyde mixture and by evaluation of platelet shape change and aggregates on a phase-contrast microscope. The method is precise, accurate and suitable for clinical purposes.

Effects of oral and intravenous defibrotide on blood viscosity in patients with peripheral obliterative arterial disease.

Patients with peripheral obliterative arterial disease received 400 mg of defibrotide intravenously (seven patients) or orally (nine patients). Blood and plasma viscosity were measured before therapy, at 30 minutes after and one hour after intravenous administration, and at 1, 2, 3, and 8 hours after oral administration. Thirty minutes after intravenous administration, blood viscosity at a shear rate of 30 sec-1 was reduced from 9.99 to 9.00 and at a shear rate of 180 sec-1 from 6.61 to 6.33 (P less than 0.05). Viscosity returned to baseline after 60 minutes. At 1, 2, and 3 hours after oral administration, blood viscosity at a shear rate of 30 sec-1 was reduced from 8.53 to 7.44, 6.88, and 7.19 (each P less than 0.01) and at a shear rate of 180 sec-1 from 5.88 to 5.51 (P less than 0.05), 5.14 (P less than 0.05), and 5.38 (P less than 0.01); the levels at eight hours were not significantly different from baseline values. Plasma viscosity was not affected by defibrotide. These data confirm previous evidence of a rheologic effect of defibrotide in patients with peripheral obliterative arterial disease and indicate that such an effect can be achieved with oral administration.