Analysis of 160 consecutive living unrelated kidney transplants: 1983-1997.
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Actuarial Analysis↗
Biomedical subjects
M Rossi
Publications and source records attributed to M Rossi.
Sperm-mediated gene transfer: production of pigs transgenic for a human regulator of complement activation.
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Animals↗
Altered collagen of human pathological fibroblasts impairs the synthesis of fibronectin.
Human fibroblasts with mutated type I collagen have marked defective adhesive capacities on exogenous type I collagen and exogenous fibronectin in comparison to normal fibroblasts. This defective cell adhesion could be partly explained by the decreased level of cell surface receptors of the beta 1-integrin family, i.e., the alpha 2 integrin subunit for type I collagen and the alpha 5 integrin subunit for fibronectin, observed in pathological fibroblasts. However, it appeared that the presence of altered collagen interfered both with fibronectin biosynthesis and with its surface expression. Using a binding assay on immobilized fibronectin, we demonstrated that the mutated collagen had a weaker binding to fibronectin. In addition, the pathological fibroblasts plated on a mixture of normal exogenous type I collagen and fibronectin exhibited the same maximal level of adhesion as control fibroblasts. These results indicate that fibroblasts with the mutated collagen exhibit a decreased binding to normal fibronectin, a modification of synthesis and surface expression of fibronectin, and, finally, altered adhesive capacities.
Cell Adhesion↗
Aetiology of pneumonia following isolated closed head injury.
Patients undergoing mechanical ventilation (MV) after an isolated closed head injury (ICHI) have often been found to develop hospital-acquired pneumonia (HAP) well before subjects who require MV for different reasons. In a prospective study of patients receiving MV after an ICHI. 38 subjects (out of 65 with clinically suspected HAP) had a bacteriological diagnosis established on the basis of correspondence between cultures made from bronchoalveolar lavage and protected specimen brush (with quantitative thresholds of 10(4) and 10(3) cfu ml-1, respectively). Patients were separated according to the time of onset of HAP, with 20 subjects who developed HAP within 4 days of the start of MV (early onset pneumonia, EOP) and 18 subjects who developed HAP after the fourth day (late onset pneumonia, LOP). In those who had LOP, an expected spectrum of organisms was found, with Gram-negatives (especially Pseudomonas sp.) accounting for the majority of isolates. However, in EOP cases, Gram-positive bacteria (especially Staphylococcus sp. and Streptococcus pneumoniae) were found to largely predominate (P = 0.0000026). This confirms the high incidence of staphylococcal pneumonia in neurosurgery patients, and also provides evidence that the vast majority of such staphylococcal pneumonia are EOP. Unlike most previous reports, the microbiological findings from the present study suggest that a cut-off point of 4 days successfully distinguishes between EOP and LOP. Since these two clinical entities differ significantly in terms of pathogenesis and aetiology, preventive measures and therapeutical protocols have to be tailored accordingly.
Adolescent↗
A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system.
OBJECTIVES: To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. DESIGN: A prospective randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. INTERVENTIONS: Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated. MEASUREMENTS AND MAIN RESULTS: Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. CONCLUSION: Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.
Adult↗
Type I hereditary angio-oedema. Variability of clinical presentation and course within two large kindreds.
OBJECTIVES: Hereditary angio-oedema (C1-inhibitor deficiency) is a disease with protean manifestations which is often misdiagnosed initially. The purpose of this study was to delineate the clinical spectrum and course of this potentially life-threatening disease. SETTING: Ten members of two unrelated affected kindreds were repeatedly hospitalized in our service with attacks of angio-oedema. Among the 271 members of the two kindreds 69 were identified who reported typical attacks. DESIGN AND SUBJECTS: Detailed information on the clinical course and laboratory data (C1-inhibitor concentration and activity, C4 concentration) were obtained from 59 of the 69 affected subjects. RESULTS: C1-inhibitor concentration and activity were low in all affected patients. The disease had become manifest by age 30 years in 98%. Most patients suffered from attacks of subcutaneous swellings and abdominal pain, and half of the patients have had attacks affecting the airways. The frequency of attacks ranged from less than one to over 26 per year. Forty-two per cent had to be hospitalized at least once. Four have died of acute airway obstruction. Thirty-eight attacks in 10 patients hospitalized in our service were all treated successfully with fresh frozen plasma or with C1-inhibitor concentrate. Trauma, stress, insect stings and foodstuff were triggering factors, but the majority of attacks occurred without an identifiable trigger. Oral contraceptives and pregnancy led to worsening of symptoms. Nonetheless, all 36 pregnancies reported were carried to term. Twenty-five patients were on continuous treatment with attenuated androgens or tranexamic acid, but only seven were free of attacks in the year preceding the survey. CONCLUSION: Hereditary angio-oedema is an autosomal dominant disease with great variability of clinical expression and severity, even within a single kindred. It often goes unrecognized over years, and it may lead to death if, in case of impending airway obstruction, specific therapy is not instituted.
Acute Disease↗
Cutaneous vasodilation to acetylcholine in patients with essential hypertension.
Endothelium-dependent vasodilation is reduced in the forearm of patients with essential hypertension. To evaluate whether endothelium-dependent vasodilation is also reduced in the skin microcirculation of patients with essential hypertension, we evaluated the effect of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, an endothelium-independent vasodilator, on cutaneous and total forearm blood flow in normotensive subjects (n = 8) and matched patients with essential hypertension (n = 9). We infused acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml forearm tissue/min) and sodium nitroprusside (1, 2, and 4 microg/100 ml forearm tissue/min) into the brachial artery, and we measured cutaneous blood flow (laser Doppler flowmeter) and muscle blood flow (strain-gauge venous plethysmography) modifications. Both the cutaneous and muscle blood flow increases induced by acetylcholine were reduced in patients with essential hypertension as compared with normotensive controls, whereas the skin and muscle vasodilation induced by sodium nitroprusside was similar in the two groups of patients. These data confirm the impairment of endothelium-dependent vasodilation in the muscle vascular bed of patients with essential hypertension and demonstrate the presence of endothelial dysfunction in skin microcirculation.
Acetylcholine↗
Stabilization of Enzymes against Thermal Stress and Freeze-Drying by Mannosylglycerate.
2-O-(beta)-Mannosylglycerate, a solute that accumulates in some (hyper)thermophilic organisms, was purified from Pyrococcus furiosus cells, and its effect on enzyme stabilization in vitro was assessed. Enzymes from hyperthermophilic, thermophilic, and mesophilic sources were examined. The thermostabilities of alcohol dehydrogenases from P. furiosus and Bacillus stearothermophilus and of glutamate dehydrogenases from Thermotoga maritima and Clostridium difficile were improved to a significant extent when enzyme solutions were incubated at supraoptimal temperatures in the presence of 2-O-(beta)-mannosylglycerate, but no effect on the thermostability of glutamate dehydrogenase from P. furiosus was detected. On the other hand, there was a remarkable effect on the thermal stabilities of rabbit muscle lactate dehydrogenase, baker's yeast alcohol dehydrogenase, and bovine liver glutamate dehydrogenase, which were used as model systems to evaluate stabilization of enzymes of mesophilic origin. For all of the enzymes examined and at the highest temperatures tested, 2-O-(beta)-mannosylglycerate was a better thermoprotectant than trehalose. The stabilizing effect exerted by 2-O-(beta)-mannosylglycerate on enzymes suggests a role for this compound as a protein thermostabilizer under physiological conditions. 2-O-(beta)-Mannosylglycerate was also effective in the protection of enzymes against stress imposed by freeze-drying, with its protecting effect being similar to or better than that exerted by trehalose. The data show 2-O-(beta)-mannosylglycerate to be a potential enzyme stabilizer in biotechnological applications.
Journal Article↗
Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection.
Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade gastric B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile enterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.
Animals↗
Atherosclerosis vascular damage in elderly athletes and sedentary people.
The objective of this study was to determine the degree of vascular atherosclerotic damage at the carotid and femoral levels in a group of subjects over sixty years old practicing endurance sports. Using high-resolution Doppler-color flow ultrasonography the authors carried out a vascular screening, comparing two distinct groups of subjects, the first consisting of 20 elderly male subjects (age 65.6 +/- 5.6 years) practicing endurance sports (runners) and the second of 20 subjects of the same gender and age (63.5 +/- 4.5 years), clinically healthy, but leading a sedentary life. All subjects were nonsmokers, nondiabetics, with normal lipid values and normal blood pressure. The authors examined the internal, external, and common carotid arteries, bilaterally, as well as the common femoral, deep femoral, and superficial femoral arteries of both legs. For each vessel they documented: (1) presence of plaques, (2) position and quantity of the plaques, (3) stenosis percentage produced by the plaques, (4) echographic structure of the plaques. In the group of sportsmen they calculated a global score of atherosclerotic damage of 5.58 +/- 2.21. This is statistically significant (P < 0.001) as compared with the global score observed in the sedentary group (9.24 +/- 3.9, range 6-14). The sportsmen exhibited small atherosclerotic plaques that were not hemodynamically significant; these plaques were present in 7 subjects (35%). In 4 of them (20%) the lesions were located in one carotid artery system. In the other 3 subjects (15%) the lesions were identified in one femoral artery system. In none of the sportsmen were they able to demonstrate simultaneous atherosclerosis of carotid and femoral arteries. In the sedentary subjects, atherosclerotic lesions were identified in 15 of them (75%). In 2 subjects hemodynamically significant plaques were located in one carotid artery system. In the other 13 subjects the plaques found were not hemodynamically significant; in 6 subjects this type of lesion was present in both femoral and carotid arteries; in 5 the lesions were located in one carotid artery system, and in 2 in one femoral artery system. In conclusion, endurance exercise appears to protect the elderly against atherosclerotic vascular damage.
Aged↗
Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight.
Melanin-concentrating hormone (MCH) has recently been proposed as both a central stimulator and an inhibitor of food intake. To clarify its role, we investigated the effects of MCH and the prepro-MCH-derived peptide neuropeptide E-I injected intracerebroventricularly (icv) in rats. MCH (0.15-15 micrograms) was injected icv at the beginning of the light phase. Food intake at 2 h showed a dose-dependent increase from 325 +/- 7% of the control value (1.5-microgram dose; P < 0.05) to 462 +/- 30% of the control value (15-microgram dose; P < 0.005). When 10 ng, 100 ng, and 5 micrograms MCH were injected icv at the beginning of the dark phase, only 5 micrograms stimulated feeding (166 +/- 16% of the control value; P < 0.05). At no dose did MCH inhibit feeding. Twice daily icv injections of MCH (5 micrograms) caused an average 197 +/- 9% increase in 2-h food intake for the first 5 days. Injections from days 6-8 did not stimulate feeding. Food intake and body weight at 24 h remained unchanged. Intracerebroventricular neuropeptide E-I had no effect on food intake alone and did not alter MCH-induced feeding. These studies show a dose-dependent stimulation of feeding by acute central administration of MCH. Tolerance is seen with chronic administration. These findings support a role for MCH in the immediate regulation of food intake, but not in body weight control.
Animals↗
Perturbation of conformational dynamics, enzymatic activity, and thermostability of beta-glycosidase from archaeon Sulfolobus solfataricus by pH and sodium dodecyl sulfate detergent.
The conformational dynamics of beta-glycosidase from Sulfolobus solfataricus was investigated by following the emission decay arising from the large number of tryptophanyl residues that are homogeneously dispersed in the primary structure. The fluorescence emission is characterized by a bimodal lifetime distribution, suggesting that the enzyme structure contains rigid and flexible regions, properly located in the macromolecule. The enzyme activity and thermostability appear to be related to the dynamic properties of these regions as evidenced by perturbation studies of the enzyme structure at alkaline pH and by addition of detergents such as SDS. The pH increase affects the protein dynamics with a remarkable loss of thermal stability and activity; these changes occur without any significant variation in the secondary structure as revealed by far-UV dichroic measurements. In the presence of 0.02% (w/v) SDS at alkaline pH, the enzymatic activity and thermostability are recovered. Under these conditions, the conformational dynamics appear to be similar to that evidenced at neutral pH. Further increases in SDS concentration, at alkaline pH, render the activity and thermostability of beta-glycosidase similar to those observed in the absence of detergent.
Circular Dichroism↗
[Prosthetic bilateral laparoscopic hernioplasty. Extra-peritoneal approach].
The use of prosthetic mesh in inguinal hernia repairs is becoming increasingly popular. In recent years different laparoscopic procedures for prosthetic repair of inguinal hernias have been developed. The authors describe their initial experience with a totally extra-peritoneal prosthetic approach in laparoscopic repair of bilateral inguinal hernias. From November 1993 to May 1994, ten consecutive patients with bilateral primary inguinal hernias underwent laparoscopic repair under general anesthesia. A totally extra-peritoneal approach has been performed beginning through a 2 centimeter vertical midline sub-umbilical incision. Two additional trocars have been inserted on the midline: a 10/12 mm one halfway between the umbilicus and the pubis and 5 mm one 2 cm above the pubis. Average operative time was 141 minutes. Two cases were converted to traditional open Stoppa procedure because of holes made in the peritoneum during blunt dissection of the hernia sac. In the remaining 8 cases a polypropylene mesh of about 8 cm in height and 13 cm in length have been placed on each hernia site. No major complications have been observed and recovery was quick in all cases. In conclusion we think that laparoscopic hernia repair through a totally extra-peritoneal approach is technically feasible for general surgeons trained in laparoscopic surgery. Nevertheless the operation in costly and the patient's benefit in terms of rapid recovery, complications and recurrences has not yet been demonstrated in controlled prospective trials.
Adult↗
[Instrumental diagnosis of obstructive jaundice: brushing versus biopsy].
We report on a series of 60 patients (31 men and 29 women; mean age: 63 years, range: 37-87 years) submitted to brushing and/or biopsy of the biliary tree through a percutaneous biliary drainage. The tumor involved the biliary bifurcation in 13 cases (21.7%), the biliary duct in 32 cases (53.4%), the right hepatic duct in 1 case (1.6%) and the left hepatic duct in 1 case (1.6%). The metal endoprosthesis was obstructed in 6 cases (10%), while a stenosis of the biliodigestive anastomosis was shown in 7 cases. We used a particular bristle brush and a flexible forceps of the alligator type for cholangioscopic biopsy. Forty-three patients had a malignant stenosis; the diagnosis was confirmed histologically and with clinical follow-up. The comparative adequacy of brushing versus biopsy resulted as follows: 33.3% versus 89.6% sensitivity, 100% specificity for both methods and 59.3% versus 89.6% accuracy. We had 14 versus 3 false negatives and no false positives. Neither brushing nor biopsy brought about any complications. To conclude, biopsy is more accurate and sensitive than brush cytology (91.6% vs 59.3% and 89.6% vs 33.3%, respectively) and therefore it is a safer and faster method to diagnose obstructive jaundice.
Adult↗
[The antagonistic effect of aspirin on the expression of prostaglandin participation in the antihypertensive activity of ACE inhibitors].
ACE-inhibitors antagonize both angiotensin production and bradykinin breakdown, resulting in enhancement of vasodilating prostaglandin release. This provides an explanation for the experimental observation that cycloxygenase blockers (such as aspirin or indomethacin) may counteract the antihypertensive efficacy of the ACE-inhibitors; it may be also possible that hypertensive patients taking aspirin as an antiplatelet agent may fail to benefit from ACE-inhibition. This study was aimed at: evaluating the magnitude and incidence of the inhibitory phenomenon; defining the minimal aspirin dosage that produces an antagonistic effect, as well as the possible reasons for a different individual susceptibility. We have studied untreated patients with mild (10 cases, Group 1), moderate (16 cases, Group 2) or severe (26 cases, Group 3) hypertension. The ACE-inhibitor enalapril was used at doses of 10 mg bid (groups 1 and 2) or 20 mg bid (Group 3). Active drug treatment periods had a 5-day duration. A daily dose of aspirin of 100 mg had no effect on the antihypertensive efficacy of enalapril. On the contrary, when a dose of 300 mg was used, 60, 57 and 50% of patients in Group 1, 2 and 3, respectively, showed a > 20% restraint of the mean arterial pressure fall with enalapril (20% was the lower arbitrary limit for defining antagonism). Inhibition was independent of the sequence of drug administration. In these patients counteraction averaged 60, 70 and 90%, respectively. In them, and not in the remaining patients in each group, aspirin substantially attenuated the renin rise elicited by ACE-inhibition. These data suggest that: a dosage of 100 mg aspirin is devoid of any inhibitory effect; more that 50% of ACE inhibited patients are, at least in the short term, susceptible to the action of 300 mg aspirin, regardless of the severity of hypertension; counteraction is seemingly mediated through a prostaglandin inhibition and depends on the individual predominance of prostaglandin activation (also as a renin secretory stimulus) or angiotensin inhibition by the ACE-inhibitor.
Angiotensin-Converting Enzyme Inhibitors↗
Synthesis and antimicrobial activity of N, N-dialkyl-2-substituted-5-diazo-imidazole-4-carboxamides.
A series of 2-substituted-5-diazoimidazole-4-carboxamides has been synthesized, and their antimicrobial activity has been tested in vitro. Some of the compounds show antifungal activity related to the presence of small groups on the 4-carbox-amido moiety, while the presence of substituents in position 2 was detrimental.
Anti-Bacterial Agents↗
[The diagnostic accuracy and reproducibility of computed tomography with water distention and induced hypotonia in the preoperative staging of gastric tumors].
Thirty-five patients with gastric cancer were preoperatively examined with CT performed in the prone position. Patient preparation consisted in filling the stomach with tap water and i.v. glucagon administration. The CT images were independently reviewed by two radiologists, who staged each tumor according to the TNM classification. The results were compared with surgical and histological findings. The overall accuracy for T staging ranged 74-77%, overstaging 17-23%; understaging was 3%. Diagnostic sensitivity, specificity and accuracy for serosal invasion were 100%, 80%, 85% and 100%, 84% e 88%, respectively, for the two radiologists. The overall accuracy for N staging was 48% and 51% for the two observers, respectively. Considering N1 and N2 as a single group, accuracy ranged 68-77%. The interobserver agreement analyzed by the "K tests" was 80%, with a K index of 60%. CT performed with the patient in the prone position, after preparation with gastric wall hypotony and distension with water, is a valid technique permitting excellent depiction of the gastric wall and providing useful preoperative information to the surgeon.
Adult↗
Asr genes belong to a gene family comprising at least three closely linked loci on chromosome 4 in tomato.
Asr1, Asr2 and Asr3 are three homologous clones isolated from tomato whose expression is believed to be regulated by abscisic acid (ABA); the corresponding genes thus participate in physiological and developmental processes such as responses of leaf and root to water stress, and fruit ripening. In this report, results obtained with Near Isogenic Lines reveal that Asr1, Asr2 and Asr3 represent three different loci. In addition, we map these genes on the restriction fragment length polymorphism (RFLP) map of the tomato genome by using an F2 population derived from an interspecific hybrid cross L. esculentum x L. penelli. RFLP data allow us to map these genes on chromosome 4, suggesting that they belong to a gene family. The elucidation of the genomic organization of the Asr gene family may help in understanding the role of its members in the response to osmotic stress, as well as in fruit ripening, at the molecular level.
Chromosome Mapping↗