Haemostatic disorders in dogs naturally infected by Leishmania infantum.
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Biomedical subjects
Publications and source records attributed to D Santoro.
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Nuclear magnetic resonance (NMR) microscopy is a completely noninvasive technique that can be used to acquire images with high spatial resolution through opaque objects such as plant organs and tissue parts. The image contrast can be chosen to represent the anatomical details or to visualize the spatial distribution of a range of physico-chemical parameters such as the apparent diffusion constant of water or the velocity of water flow within plants in vivo. In addition, images can be generated which show the spatial distribution of metabolites. Furthermore, it is possible to detect chemical compounds labelled with the stable isotope (13)C and to generate images showing the spatial distribution of the (13)C label in the intact plant. The ability to monitor water flow and transport of (13)C-labelled tracer in intact plants with NMR microscopy favours the use of this technique in the investigation of long-distance transport processes in plants. A short introduction into the technical principles of NMR microscopy is provided and the problems associated with applications to plants are summarized. The potential of the technique is explained with applications to Zinnia elegans plants, wheat grains and Brassica napus siliques.
Delivery of therapeutic genes represents an appealing possibility to accelerate healing of wounds that are otherwise difficult to treat, such as those in patients with metabolic disorders or infections. Experimental evidence indicates that in such conditions potentiation of neo-angiogenesis at the wound site might represent an important therapeutic target. Here we explore the efficacy of gene therapy of wound healing with an adeno-associated virus (AAV) vector expressing the 165 amino acid isoform of vascular endothelial growth factor-A (VEGF-A). By gene marker studies, we found that AAV vectors are highly efficient for gene transfer to the rat skin, displaying an exquisite tropism for the panniculus carnosus. Gene expression from these vectors is sustained and persistent over time. Delivery of VEGF165 to full thickness excisional wounds in rats resulted in remarkable induction of new vessel formation, with consequent reduction of the healing time. Histological examination of treated wounds revealed accelerated remodeling of epidermis and dermis, with formation of a thick granular layer, containing numerous newly formed capillaries, as well as vessels of larger size. These data underline the importance of neo-angiogenesis in the healing process and indicate that VEGF gene transfer might represent a novel approach to treat wound healing disorders.
In 1938 Procaccini showed scientific interest in a new kind of ameba, and called it "nephrouroameba" from which the disease "nephrouroamebiasis" is derived. He wrote a paper titled "La Nefrouroamoebiasi" thus describing its history, the biopathogenetic evolutionary cycle of the protozoon, its therapeutic, epidemiological, anatomo-biological, diagnostic, cultural, biological and morphological features. Between 1934 and 1939, Procaccini had the opportunity to follow many patients belonging to a group of Italian soldiers serving in the Eastern Italian Army in Ethiopia. At that time he was responsible for the biopathological laboratory. After a short preclinical stage of fatigue, patients suffering from nephrouroamebiasis showed a nephrotic syndrome with gross hematuria. The symptoms ceased within a few days but residual microhematuria, albuminuria and urine casts persisted for many months. After microscopic observation, he reproduced some protozoons and classified them as a kind of ameba. Critical analysis of his report leads to the morphological identification of Trichomonas, thus excluding his classification as nephrouroamebas.
In the presence of hydrogen donor solvents and at elevated temperatures, aromatic ketones can be selectively deoxygenated to the corresponding hydroaromatic compounds. The kinetics for reduction of 7H-benz[d,e]anthracen-7-one (benzanthrone, 6) into 7H-benz[d,e]anthracene (benzanthrene, 1) in 9,10-dihydroanthracene (3) solvent has been investigated in detail. The relatively slow hydrogenation of 6 is due to reversibility of the initial hydrogen-transfer step according to a reverse radical disproportionation (RRD). The dynamics could well be rationalized using the energetics of species computed by density functional theory (DFT). The application of hydrogen donors such as 1 as a hydrogen-transfer agent, although favorable in terms of a low benzylic carbon-hydrogen bond dissociation enthalpy, is limited due to the slow self-hydrogenation, which in case of 1 gives 5,6-dihydro-4H-benz[d,e]anthracene (7).
Keliximab, a Primatized IgG1 CD4 mAb, was reconfigured to an IgG4 antibody. The gamma4 constant region was further modified by substituting glutamic acid for serine at position 235 in the CH2 domain (IgG4-E), to remove residual binding to Fcgamma receptors, and substitution of serine with proline at position 228 in the hinge region (IgG4-PE) for greater stability. Pharmacokinetic analysis in rats gave a t(1/2) of approximately 4 days for IgG4-E and 9 days for IgG4-PE, consistent with a greater stability of the IgG4-PE molecule. The effects on T cell subsets were assessed in chimpanzees given escalating doses of IgG4-PE: 0.05 mg/kg on Day 16, 1.5 mg/kg dose on Day 43, and 15 mg/kg on Day 85. Receptor modulation was observed at the two highest doses, but no depletion of T cells at any dose. The in vitro and in vivo results demonstrate the potential of this IgG4-PE mAb for use in human trials.
The two words that mean sexual dysfunction, impotence and erectile dysfunction (ED), express two different concepts. Impotence is a general male sexual dysfunction that includes libidinal, orgasmic, and ejaculatory dysfunction. ED is the inability to achieve or maintain an erection sufficient to allow satisfactory sexual intercourse and is part of the general male sexual dysfunction termed impotence that includes libidinal, orgasmic, and ejaculatory dysfunction. Uremic men of different ages report a variety of sexual problems, including sexual hormonal pattern alterations, reduction in or loss of libido, infertility, and impotence, conditioning their well-being status. In evaluating and treating sexual dysfunction, a nephrologist must consider factors involved in its pathogenesis, such as hypothalamic-pituitary-gonadal axis alterations, psychological problems related to chronic disease, secondary hyperparathyroidism, anemia, autonomic neuropathy, derangements in arterial supply or venous outflow, and the normal structure of cavernous body smooth muscle cells. The introduction of sildenafil to treat impotent patients has completely changed the approach to evaluating these subjects because this drug is considered an effective well-tolerated treatment for men with ED. In the past, we proposed an algorithm that gave the opportunity to explore the previously mentioned factors using such instrumental interventions as the nocturnal penile tumescence test, penile echo color Doppler, nervous conduction velocity, and cavernous body biopsy, addressed to prescribe needed surgical or medical interventions. The complexity of the proposed algorithm requires many diagnostic procedures and much time and economic resources to localize the pathological lesions responsible for ED. Because of the new oral drug sildenafil, we propose a new algorithm to test the possibility of obtaining an erection and classify patients as responders or nonresponders to the sildenafil test.
Autonomic nervous system dysfunction is a common feature in uremia and may have a number of clinical sequelae. Simple cardiovascular reflex screening can be performed in patients during conservative treatment, on periodic dialysis therapy, or after kidney transplantation to diagnose and follow up autonomic function impairment. Other approaches, such as heart-rate variability studies in the frequency domain by power spectral analysis, can provide a more accurate investigation of the disease.
Insulin lispro is absorbed more rapidly and has a shorter duration of action than regular human insulin. It improves glycaemic control but large-scale studies are required to identify regimens that optimise efficacy and safety with local dietary habits. This study involved 1184 Italian patients with Type 1 diabetes, randomised to insulin lispro (n=586) or regular human insulin (n=598) as pre-meal bolus for 3 months. Optimisation of basal NPH insulin was carried out in both groups. The number of administrations of NPH insulin was increased when using insulin lispro but, because basal and bolus insulins were mixed before meals, the total number of injections per day was unchanged. Compliance to administration time was significantly (p<0.001) greater with insulin lispro than with regular human insulin. Post-prandial blood glucose levels were lower with insulin lispro after breakfast (p<0.001), lunch (p<0.005) and dinner (p<0.001). The HbA1c level was decreased from baseline by both insulins, but the percent increase in patients with acceptable (<8%) HbA1c was greater with insulin lispro. While frequency of hypoglycaemia was decreased from baseline by both insulins, the proportion of episodes classified as severe was significantly increased from baseline with regular human insulin, but not with insulin lispro. Thus, compared with regular human insulin, improved glycaemic control was achieved with insulin lispro without an increase in severe hypoglyeaemia.
BACKGROUND AND AIM: While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients. METHODS AND RESULTS: Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001). CONCLUSIONS: Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.
BACKGROUND: There is good evidence that power spectral analysis (PSA) of heart rate variability may provide an insight into the understanding of autonomic disorders. METHODS: We investigated 30 chronic uremic patients who were on periodic bicarbonate hemodialysis by a battery of six cardiovascular autonomic tests (beat-to-beat variations during quiet breathing and deep breathing, heart rate responses to the Valsalva maneuver and standing, blood pressure responses to standing and sustained handgrip) and PSA of heart rate variations. RESULTS: Eleven patients (37%) had an abnormal response to only one parasympathetic test. Twelve patients (40%) had a definite parasympathetic damage, as indicated by at least two abnormal heart rate tests, whereas four (13%) had combined parasympathetic and sympathetic damage. Multivariate analysis of the cardiovascular tests revealed that 19 patients (63%) had moderate-to-severe autonomic neuropathy (AN), and 11 patients exhibited normal autonomic function. Among the symptoms suggestive of autonomic dysfunction, only impotence in males was significantly associated with test-proven AN. The PSA of the heart rate variability demonstrated a good discrimination of low-frequency (LF) and high-frequency (HF) bands (LF, 0.03 to 0.15 Hz; HF, 0.15 to 0.33 Hz) among controls, uremic patients without test-proven AN, and uremic patients with test-proven AN. A significant reduction of the LF value on supine uremic patients without AN suggests that an early sympathetic involvement exists that traditional autonomic tests were unable to detect. CONCLUSIONS: Our study indicates that the current opinion of a major parasympathetic damage in chronic uremic patients on hemodialysis has to be modified in favor of a more widespread autonomic dysfunction involving both the sympathetic and parasympathetic pathways.
The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min x 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min x 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.
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Protein ingestion increases renal blood flow and glomerular filtration rate (GFR). This study investigated in healthy adults if the renal response to protein ingestion includes changes in urinary sodium (Na) excretion rate and Na balance. Renal clearance of Na and inulin (used as index of GFR) were measured in 25 healthy adults before (90 min) and after (180 min) a standard meal and, as control, before and after administration of water and Na-chloride (saline). The meal consisted of red lean meat (2 g protein/kg body weight); in control experiments, water and Na were given to match water and Na content of the meal. ANOVA for repeated measures, Student's t-test, and linear regression were used for statistical analysis. GFR and urinary Na excretion increased over baseline after the meal (p < 0.001), not after saline. The post-meal natriuretic response was accounted for an early (0-90 min) increase in glomerular filtered load of Na (p < 0.001) and a late (90-180 min) reduction in tubular Na reabsorption (p < 0.02). Urine flow rate and plasma Na did not significantly change after the meal and in control experiments. Analysis of Na balance showed that post-meal Na excretion was significantly higher than baseline also after Na balance returned to pre-meal values. In healthy individuals, a meat meal stimulates natriuresis and causes a net decrease in Na balance. The renal natriuretic response to the meal appears secondary to the meal-induced changes in renal hemodynamics. The data are in keeping with the hypothesis that dietary protein intake affects also renal Na handling.
The subcutaneous reservoir is a new vascular access for patients on regular hemodialysis (HD). A double chamber in Titanium- Pirolytic Carbon with siliconic boreable superior caps is inserted in to a subcutaneous subclavian side, and always in subcutis connected to two siliconic catheters located in the right jugular resulting in the right atrium. The puncture of each chamber is performed with a special hemodialysis-cannula telescopically assembled on a "dilatation tube", in which a stylet is inserted. In correct sequence, the cutaneous planes and the caps are bored, dilated, and finally the HD cannula after sliding over the previous structures is positioned in the inner chamber, closing the HD circuit. In our study two patients were implanted, with a survival of 24 months, good compliance, no cardiovascular impairments and lack of catheteral pathology.
Increased anticardiolipin antibodies (aCL) serum levels have been recently described in haemodialysis patients and in renal transplant recipients, with a prevalence ranging from 4.8 to 46.4%. The causes and the clinical significance of aCL positivity in these patients are uncertain. We measured IgG- and IgM-aCL serum levels in 61 haemodialysis patients, in 14 renal transplant recipients and in 38 healthy controls. Increased levels of IgG-aCL were found in 4 haemodialysis patients (6.55%), in 2 transplant patients (14%) and in 2 of the healthy controls (5.26%). IgM-aCL serum levels were normal in all the patients. After one year of follow-up, no vascular events have been observed in aCL positive patients. It is probable that the presence of aCL in the serum of patients with end-stage renal disease is only an epiphenomenon and does not play a pathogenetic role.
BACKGROUND: Recent Italian legislative directives have focused on lowering health-service costs and improving the quality of health care. The AI-CARE study on unstable angina represents the initial observational step in a survey on health-care quality in the Italian region Emilia-Romagna. AIM OF THE STUDY: This study was performed to identify the processes usually involved in the management of patients with unstable angina admitted to a regional cardiology department. The consumption of health service resources and the clinical events related to angina were evaluated. METHODS: AI-CARE is an observational, descriptive and prospective study. Between 15/3/95 and 15/6/95, the patients admitted consecutively to 25 cardiology units for unstable angina, as diagnosed on a clinical basis, were enrolled in the study. A six-week follow-up was provided. The data regarding demographics, history, entry electrocardiogram, symptoms, examinations, treatment and outcome were recorded on a detailed personal questionnaire. The participating centers have been divided according to complexity of organization: 18 with intensive care unit as level I, five with hemodynamic laboratory as level II and two with cardiosurgery as level III. Mortality, myocardial infarction, revascularization procedures and readmissions for angina were considered clinical events. RESULTS: We recruited 463 patients. At discharge, 411 patients were affected with unstable angina while other 40 developed non-Q wave infarctions. The final study population comprised 451 patients. The mean age was 68 years (range 61-76). There were 316 men (69%, mean age 68) and 135 women (mean age 72). All 451 patients were stratified according to the Braunwald classification: IIIB in 66.9%, IIIC in 9.9%, IB in 9.9%. Mean hospital stay was 10 +/- 6 days, while mean stay in intensive care units was 4.3 +/- 2.9 days. Medical treatment included antiplatelet agents (89%), nitrates i.v. (81%), nitrates per os (86%), heparin (55%) and beta-blockers (47%). The most common non-invasive test performed was echocardiogram (70% of patients), Holter ECG and exercise stress testing (19%). Selective coronary arteriography was performed in 50% of patients (23% during the first 10 days). Additionally, 32% of patients underwent revascularization. During follow-up, ten patients (2.21%) had a myocardial infarction, nine patients (1.99%) died and 49 patients (10.8%) were readmitted for angina. CONCLUSIONS: This study indicates that in spite of the poor use of diagnostic procedures (especially coronary arteriography) and myocardial revascularization, mortality and morbidity were relatively low. Our data are similar to the results of the recent Italian EARISA study but differ greatly from the results of foreign studies. Consequently, further observation of our study population is needed.
DESIGN OF STUDY: Two groups of patients undergoing long-term dialysis were studied in order to evaluate the importance of ethylene oxide (EtO) in causing allergic reactions during dialysis. The first group of 50 subjects had never shown any hypersensitivity reactions related to dialysis, whereas the second group of 20 subjects had previously complained of reactions. All the patients underwent a prick test with a standard kit of aeroallergens in order to assess the presence of atopy (in doubtful cases a RAST test was carried out with the same aeroallergens). A blood sample for the investigation of EtO specific IgE antibodies was taken from all the patients; the immunoenzymatic method was used. RESULTS: Sensitivity to EtO is significantly higher in the group of patients with previous allergic reactions during dialysis (55 vs 6% in the control group).