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Biomedical subjects

A Gasbarrini

Publications and source records attributed to A Gasbarrini.

At least 163 records · Page 9Linked to original sources

Ageing affects anoxia/reoxygenation injury in rat hepatocytes.

BACKGROUND: The reoxygenation phase after a period of anoxia leads to oxyradical formation, responsible for damage to cell membranes. Ageing is associated with functional and structural changes in liver cells, which modify their sensitivity to reoxygenation injury. The aim of this study was to determine the effects of ageing on the sensitivity of hepatocytes to anoxia/reoxygenation. METHODS: Oxyradical formation and cell injury were evaluated in hepatocytes isolated from rats of different ages exposed to 2 h of anoxia and 1 h of reoxygenation. Anion superoxide was measured by lucigenin-enhanced chemiluminescence, hydrogen peroxide by luminol-enhanced chemiluminescence, and cell damage by lactate dehydrogenase (LDH) release. RESULTS: During anoxia, oxyradical production dropped to background levels in both groups. LDH release was significantly greater in ageing hepatocytes. During reoxygenation, a massive generation of anion superoxide and hydrogen peroxide, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradicals and cell injury were significantly greater in liver cells obtained from ageing rats. CONCLUSIONS: The data confirm that hepatocytes produce high levels of free radicals during post-ischemic reoxygenation and suggest that ageing cells are more sensitive to reperfusion injury.

Aging↗

Helicobacter pylori infection in patients affected by insulin-dependent diabetes mellitus.

BACKGROUND/AIM: Insulin-dependent diabetes mellitus (IDDM) is the result of an autoimmune destruction of pancreatic Langerhans beta cells. Helicobacter pylori infection, the most common cause of gastritis and peptic ulcer, has been associated with some autoimmune diseases. The aim of this study was to evaluate the prevalence of H. pylori infection and gastrointestinal (GI) symptoms in patients with IDDM. METHODS: 116 patients (50 males and 66 females, mean age: 35 +/- 11 years) affected by IDDM were evaluated; 50 healthy subjects matched for age and sex were utilized as a control group. H. pylori infection was determined by a [13C]urea breath test. IDDM duration, daily dosage of insulin and prevalence of GI symptoms (bloating, pyrosis, epigastric pain, belching, halitosis, nausea) were assessed. RESULTS: The prevalence of H. pylori infection was similar in IDDM patients and in controls (37 vs 34%, respectively). In both groups, the mean age was higher in infected subjects. The mean IDDM duration was significantly greater in infected patients (19 +/- 12 vs 13 +/- 10 years, P < 0.006). Prevalence of infection was directly related to the duration of IDDM (<1 year, 23%; 1-3 years, 32%; >3 years, 40%). The daily dosage of insulin did not differ between infected and non-infected subjects. H. pylori contaminated patients showed a significantly higher prevalence of bloating, pyrosis and epigastric pain when compared with non-infected subjects; conversely, prevalence of belching, halitosis and nausea did not differ between groups. CONCLUSION: The prevalence of H. pylori infection is high in patients affected by IDDM; however, it does not differ from the infection rate observed in a control group. The rate of infection increases with IDDM duration. Bloating, pyrosis and epigastric pain appear to define infection status better.

Adult↗

Importance of changes in epithelial cell turnover during Helicobacter pylori infection in gastric carcinogenesis.

The role of Helicobacter pylori in gastric carcinogenesis is supported almost exclusively by epidemiological data and prospective histopathological studies. From biological and molecular points of view, there is no evidence that H pylori or its cytotoxic products have any mutagenic effects. Nevertheless, this infection is associated with profound changes in the pattern of epithelial cell turnover in gastric glands, though the importance of these changes in gastric carcinogenesis is still controversial. H pylori infection increases cell proliferation and alters the distribution of cycling cells within these glands, but these changes can be reversed by successful eradication of the infection. Apoptosis seems to be increased in gastric epithelial cells during H pylori infection, as shown by in vitro studies. There is some, though no conclusive, evidence that this finding also occurs in H pylori positive subjects. It seems that cagA status influences the effect of H pylori on epithelial apoptosis in infected patients. An association of in vitro H pylori induced apoptosis with changes in the expression of pro- and anti-apoptotic genes is reported in the literature, but further study is necessary to clarify the effect of H pylori infection on the molecular events of the apoptotic pathway.

Apoptosis↗

Osteosarcoma of the extremities with synchronous lung metastases: long-term results in 44 patients treated with neoadjuvant chemotherapy.

Between September 1986 and September 1991, 44 patients with lung metastases originating from an osteosarcoma of an extremity were treated with: primary chemotherapy, simultaneous resection of primary and metastatic lesions (when feasible), and then further chemotherapy. After primary chemotherapy, lung metastases disappeared in 5 patients, whereas in 11 patients they remained surgically unresectable. All 16 patients received local treatment of the primary tumor only. In the remaining 28 patients simultaneous surgical treatment of the primary and the metastatic tumor was performed. The removal of metastatic lesions was complete in 25 and incomplete in 3 patients. With a median follow-up of 8 years (5.5-10.8) all 14 patients who never achieved a tumor-free status died. Of the 30 patients who achieved remission 5 (17%) remained continuously free of disease and 25 developed new metastases, associated with local recurrence in 4 cases. The 5-year overall survival for all 44 patients of the study was 14%, and the 5-year disease-free survival for the 30 patients who reached remission was 17%. These results are significantly worse than those achieved with the same chemotherapy protocol in 144 contemporary patients with localized disease at presentation (73% disease-free and 79% overall survival). We conclude that, despite aggressive chemotherapy which is successful in patients with localized disease, the prognosis remains very poor for patients with osteosarcoma of the extremities with lung metastases at presentation, and justifies the use of novel therapies.

Adolescent↗

Predictive factors for local recurrence in osteosarcoma: 540 patients with extremity tumors followed for minimum 2.5 years after neoadjuvant chemotherapy.

We investigated predictive factors for local recurrence in 540 patients with non-metastatic osteosarcoma of the extremity treated with surgery and neoadjuvant chemotherapy, between March 1983 and October 1994. The median follow-up was 7.5 (2.5-15) years. Local recurrences developed in 31 (6%) patients after a median time of 2 (0.5-7) years. Local recurrence did not correlate with patients' age and sex, histologic subtype, site and tumor volume, presence of pathologic fracture, chemotherapy regimen and type of surgery. Local recurrence-free survival (LRFS) correlated with the quality of surgical margins and response to chemotherapy: the 7-year LRFS was 97% after adequate surgical margins and 71% after inadequate surgical margins (p < 0.0001), and was 95% in good responders and 90% in poor responders (p = 0.001). Only 1 of 31 patients with local recurrence was free of disease 15 months after the last treatment, 3 were alive with uncontrolled disease and 27 died. This post-relapse outcome is significantly worse than in patients who relapsed with metastases only (25% free of disease, 0.5-9 years after the last treatment). We conclude that, in osteosarcoma of the extremity, limb-salvage procedures should be planned only when the preoperative staging indicates that it is possible to achieve adequate surgical margins. If the pathologic examination of the surgical specimen shows inadequate surgical margins, an immediate amputation should be considered, especially if the histologic response to preoperative chemotherapy was poor.

Adolescent↗

Osteosarcoma of the bones of the foot--an easily misdiagnosed malignant tumor.

OBJECTIVE: To evaluate the frequency of osteosarcoma involving the foot and determine the clinical outcome of affected patients. MATERIAL AND METHODS: We retrospectively reviewed the cases of osteosarcoma encountered between 1911 and 1992 at the Rizzoli Orthopedic Institute. In particular, we analyzed whether common clinical, radiographic, or histologic features could lead to a correct diagnosis of osteosarcoma of the foot. RESULTS: The bones of the foot were the primary site of osteosarcomas in 12 cases--0.6% of the entire series of such tumors at our institution during the study period. The mean age of the patients was 33 years. Initial symptoms were usually pain and swelling. Late diagnosis was common; the mean time interval between the first symptoms and diagnosis was 28 months. Misdiagnoses occurred in 6 of the 12 cases (50%): osteoblastoma, chondroblastoma, chondrosarcoma, osteoid osteoma, desmoid fibroma, and osteomyelitis were, respectively, the initial diagnoses. Histologically, 5 of the 12 tumors (42%) were low-grade lesions. Four of the seven patients with a high-grade tumor died of metastatic disease after a mean survival of 50 months. Eight patients are alive with no evidence of disease after a mean follow-up of 162 months. CONCLUSION: When a painful swelling in a bone of the foot is observed, even if numerous benign conditions (such as fractures, infections, or benign bone tumors) are far more likely to occur, osteosarcoma must be ruled out to avoid delays in the treatment. Osteosarcomas of the foot may easily be misdiagnosed, especially because they almost always occur in adults, in contrast to osteosarcomas in general. High-grade tumors of the foot are as aggressive as other osteosarcomas and should be managed accordingly--with use of a safe-margins surgical procedure and chemotherapy.

Adolescent↗

Helicobacter pylori infection and ischaemic heart disease.

Helicobacter pylori infection is probably one of the most widely spread infectious diseases in man and a growing body of knowledge provides evidence in favour of a causal link between this infection and the majority of upper gastrointestinal conditions. For example, we now know that peptic ulcer disease is an infectious disease; if the infection is diagnosed and treated, ulcer can be cured. On the other hand, in recent years, a number of epidemiological studies have focused on the possible relation between ischaemic heart disease and several infectious disorders, such as chronic dental infections, Cytomegalovirus, Coxsackie viruses, Chlamydia and, finally Helicobacter pylori. The results of studies on the association between ischaemic heart disease and Helicobacter pylori have, in particular, often been contradictory, and only some studies adjusted the results for confounding factors, and the adjustment of the results in some cases modified the association. In conclusion, even if coronary atherosclerosis may now be considered as an inflammatory process, according to several histologic and pathophysiologic studies, we cannot, for the moment, be sure that it is an infectious disease.

Antigens, Bacterial↗

Helicobacter pylori infection and vascular diseases.

Helicobacter pylori infection has recently been associated to some organic functional vascular disorders and, both observational and interventional studies have been carried out. A correlation between Helicobacter pylori infection and ischaemic heart disease was first described in 1994. Recent data, moreover, indicate a role of the bacterium in some functional vascular disorders such as primary headache and primary Raynaud phenomenon; indeed, some patients following eradication of Helicobacter pylori showed a significant improvement in the manifestations of these diseases. The host immune response against the bacterium may play an important role in the pathogenesis of vascular disorders, probably through a chronic stimulation of the release of vasoactive substances, such as cytokines, prostaglandins and others. However, various confounding factors such as co-infections, genetic and immunological host-factors, different strains of Helicobacter pylori or other may influence the data. Well designed case/control and randomized interventional studies are still needed to assess the real role of Helicobacter pylori in vascular disorders.

Antibodies, Bacterial↗

Vascular and immunological disorders associated with Helicobacter pylori infection.

Helicobacter pylori, the main aetiological factor for gastritis and peptic ulcer has been associated with some extradigestive diseases. In particular, vascular disorders, such as ischaemic heart disease, primary Raynaud phenomenon and headache appear to be related to the presence of the bacterium. Moreover, some autoimmune diseases, such as Henoch-Schonlein purpura, Sjögren syndrome and others have been shown to have a link with Helicobacter pylori infection Probably, in subjects with a particular predisposition, the release of substances with a vasoactive and proinflammatory activity, which is determined by Helicobacter pylori infection, may influence some extradigestive districts.

Antibodies, Bacterial↗

Acute liver injury related to the use of niperotidine.

BACKGROUND/AIMS: H2-receptor antagonists are widely used for the therapy of peptic disease, since they ensure a protracted and intense inhibition of gastric acidity. Niperotidine (piperonyl-ranitidine) is a new H2 blocking agent recently proposed for clinical use. METHODS: Twenty-five cases of acute hepatitis associated with the use of niperotidine were reported in Italy between March and August 1995. Intercurrent viral infections, recent drug and alcohol consumption and blood transfusions were excluded as causes. RESULTS: All patients showed an increase in the parameters of liver cell injury and the clinical symptoms of acute hepatitis. After withdrawal of the drug, all patients showed a good outcome, except one who developed a fulminant hepatitis and died from digestive tract bleeding. CONCLUSIONS: The absence of other causes of acute liver injury suggests that the observed liver injury may be a niperotidine-adverse reaction. Moreover, the lack of a relationship between the dose of the drug and the degree of liver damage, the variable latent period and the rarity and unpredictability of the injury are suggestive of an idiosyncratic reaction.

Acute Disease↗

Intermittent anoxia reduces oxygen free radicals formation during reoxygenation in rat hepatocytes.

The sensitivity of liver cells to anoxia is a major problem afflicting liver preservation and transplantation. Intermittent ischemia has been proposed to reduce reperfusion injury. The aim of the study was to assess oxygen free radical formation and cell injury during continuous or intermittent anoxia/reoxygenation in rat hepatocytes. Anion superoxide was measured by lucigenin-enhanced chemiluminescence and cell damage by LDH release and trypan blue uptake. During anoxia, superoxide generation dropped to background level in both groups; trypan blue uptake and LDH release, which increased progressively, were significantly greater in hepatocytes exposed to continuous compared to intermittent anoxia. During reoxygenation, a massive generation of superoxide anion formation, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradical generation and cell injury were significantly greater in cells exposed to continuous compared to intermittent anoxia. The data, showing that intermittent oxygen deprivation reduce liver cell injury and oxygen free radical formation determined by anoxia/reoxygenation, suggest a novel possible approach to the reduction of reperfusion injury.

Animals↗

Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy.

BACKGROUND: Most of the studies of the treatment of non-metastatic osteosarcoma of the extremity have reported results in terms of probability of survival up to five years with a minimum follow-up of less than two to three years. Definition of reliable indicators of prognosis and predictive factors for survival require mature data derived from a long-term survival analysis. PATIENTS AND METHODS: A review of 127 patients with non-metastatic osteosarcoma of the extremity, treated between March 1983 and June 1986, was performed. The treatment protocol consisted of primary chemotherapy with MTX (randomization to high vs. moderate dosages) and CDP followed by surgery. Postoperatively, patients with < 60% tumor necrosis received ADM and BCD; those with tumor necrosis > or = 60% < 90% (Fair Responders FR) were given MTX, CDP and ADM. Up to January 1984, patients with tumor necrosis > 90% received MTX and CDP only, and after then they were given the same treatment as for FR. A multivariate analysis to test predictive factors for survival was performed. RESULTS: With a median follow-up of 134 months (range 114-153), the 12-year DFS was 46%. A good histologic response, an LDH baseline value within the normal range, and the use of high-dose MTX were positive predictive factors for DFS. With a median time of observation for survivors of 130 months, the 12-year overall survival was 53%. None of the patients who relapsed with local or distant recurrences other than lung metastasis are now alive. Patients with a relapse-free interval longer than 24 months had a significantly better post-relapse survival than those with a shorter relapse-free interval (40% vs. 7%; P = 0.0159). All of the patients who were not surgically treated had disease progression and died within 40 months after the first recurrence. The surgically-treated patients had a 30% post-relapse survival probability. CONCLUSIONS: In non-metastatic osteosarcoma of the extremity, chemotherapy-induced tumor necrosis, the baseline LDH serum value and the use of HDMTX are significant predictive factors for DFS. The relapse-free interval and the possibility of metastasectomy are significant factors conditioning the post-relapse survival.

Adolescent↗

Generation of free radicals during anoxia and reoxygenation in perfused osteoblastlike cells.

Sensitivity to ischemia and reperfusion injury is a main problem afflicting tissues exposed to a prolonged period of oxygen deprivation. The generation of oxygen free radicals, in particular, is considered a major cause of postischemic reperfusion injury. However, studies on the mechanisms of production of free radicals are limited by the difficulty to measure in real time their formation and to discriminate between the different oxyradical species. The aim of this study was to determine whether the formation of oxygen free radicals occurs in murine osteoblastlike cells (MC3T3-E1) exposed to anoxia and reoxygenation and to explore its relation to the reoxygenation injury. Cells were cast in agarose and perfused with oxygenated Krebs-Henseleit bicarbonate buffer. Anoxia was obtained by shifting the gas phase of the media to 95% N2-5% CO2. Oxygen free radicals were detected by enhanced chemiluminescence: anion superoxide or hydrogen peroxide was measured by adding lucigenin or luminol plus horseradish peroxidase to the media, respectively. Cell injury was assessed by the rate of lactate dehydrogenase release. During the control period, lucigenin and luminol plus horseradish chemiluminescences were 15 +/- 1 nA per chamber and 20 +/- 2 nA per chamber, respectively. and lactate dehydrogenase release was 10 +/- 1 mU per minute. During anoxia, both chemiluminescences dropped to background levels, although lactate dehydrogenase release increased progressively to 38 +/- 7 mU per minute. During reoxygenation, O2 formation increased sharply to 45 +/- 6 nA and decreased to control levels; H2O2 production increased slowly, reaching 42 +/- 7 nA at the end of the reoxygenation period; lactate dehydrogenase declined progressively to control values. These results show that osteoblastlike cells produce measurable amounts of superoxide and hydrogen peroxide radicals during reoxygenation. Because lactate dehydrogenase release did not appear to relate to chemiluminescence, oxyradical flux may serve as a signal for other events that eventually lead to cell injury.

Animals↗

Extraintestinal pathology associated with Helicobacter infection.

Helicobacter pylori appears to be the most important cause of gastritis and gastric and duodenal ulcer. Its eradication, in fact, promotes healing of these diseases and significantly reduces ulcer recurrence. In the last few years, moreover, besides a local tissue damage, an association between H. pylori infection and various extraintestinal pathologies has also been described. The presence of more toxic strains of H. pylori and the multiplicity of the substances produced, directly or indirectly, in response to the bacterium, besides a genetic predisposition of the individual, are all factors which may enhance the ability of Helicobacter to generate both local and systemic damage.

Bacterial Toxins↗