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Biomedical subjects

B Conti

Publications and source records attributed to B Conti.

At least 37 records · Page 2Linked to original sources

Gastrobronchial fistula repair followed by esophageal leak--rescue by transesophageal drainage of the pleural cavity.

A gastrobronchial fistula (GBF) associated with bilateral aspiration pneumonia was diagnosed six years after an esophagectomy with gastric pull-up. After failed surgical repair, an uncontained esophagopleural leak developed. Fistula closure was attempted by implanting a Wilson-Cook endoprosthesis, which quickly became dislodged. Transesophageal drainage was positioned endoscopically through the suture-line defect and led to closure of the leak after 10 days.

Anastomosis, Surgical↗

A particular case with long-term follow-up of rare malignant hemangiopericytoma of the lung with metachronous diaphragmatic metastasis.

The authors report the case of a woman with a primary hemangiopericytoma of the lung and successive metachronous diaphragmatic metastasis treated with surgery only according to the patient's decision. The patient was first submitted to left lower lobectomy with resection of diaphragm and three ribs en-bloc for pulmonary sarcoma. One year later, a chest computed tomography (CT) scan showed a small lesion above the diaphragm on the left side. She refused the proposed operation and returned fifteen months later with a new thorax CT, and told us that she had in the meantime become pregnant and given birth. A rethoracotomy to remove the metastatic diaphragmatic tumor was performed. Chemotherapy with anthracycline and iphosphamide was proposed, but the patient again refused therapy for fear of side effects impairing another pregnancy. Currently, the patient is alive and disease-free, 68 months after the first treatment. The authors emphasize the long-term follow-up obtained with surgery alone in this kind of rare sarcoma.

Adult↗

Video-assisted thoracoscopic surgery for diagnosis, staging, and management of lung cancer with suspected mediastinal lymphadenopathy.

The aim of this report was to evaluate the effectiveness of video-assisted thoracoscopic surgery (VATS) in staging, diagnosis, and treatment of lung cancer. Fifty-two patients were scheduled for mediastinal lymph node VATS biopsy at the Oncologic Thoracic Surgery Department of the National Cancer Institute in Milan. Fifty patients underwent lymph nodal thoracoscopic biopsy (96%), whereas for the other 2 patients, histologic diagnosis was done by pleural metastatic nodule thoracoscopic biopsy (4%). We performed 17 lymph nodal biopsies in level 5 (33%), 14 in level 6 (27%), 12 in level 7 (23%), and 7 in level 8 (13%). No postoperative complications were observed, and 19 subjects (36%) underwent open lung resection. The histologic diagnosis was adenocarcinoma in 25 cases (48%), epidermoid carcinoma in 14 (27%), microcytoma in 9 (17%), and giant-cell lung carcinoma in 4 (8%); 10 patients were at stage I (19%), 9 at stage II (17%), 31 at stage III (60%), and 2 at stage IV (4%). The use of VATS allowed diagnosis of the suspected involved mediastinal lymph nodes in lung cancer patients and obviated the need for painful thoracotomy, enabling accurate staging and thus selection of the optimal treatment.

Adult↗

Clinical and pathologic predictors of survival in patients with thymic tumors.

BACKGROUND: The aim of this study is to evaluate the impact of thymectomy in patients with thymic neoplasms and to identify clinical and histopathological factors associated with improved long-term outcome of surgery. METHODS: We treated 74 patients between February 1987 and July 1993. There were 29 total and 36 simple thymectomies. These last cases, all non-myasthenic, had benign thymomas (n=30) but 6 had thymic carcinomas. Nine tumors were no-resected (5 thymomas and 4 thymic carcinomas). Minimum follow-up by Department of Thoracic Surgery Istituto Nazionale Tumori was 60 months after thymectomy. We divided the specimens according to Marino and Muller-Hermelink's classification: 54 thymomas, 18 thymic carcinomas and 2 no-diagnosis specify thymomas. There were 53 stage I, 1 stage II, 13 stage III, 5 stage IVa and 2 stage IVb according to Masaoka. RESULTS: Forty-six patients with treated thymoma were alive without disease at the end of follow-up, the remaining 8 died from recurrence in 6, a new tumor in 1 and a heart attack in the last. Of 18 thymic carcinomas 9 were alive at the end of follow-up (1 with recurrence), only 4 dead from recurrence. The actuarial survival of patients with thymomas was 88.5% at 5 years, (73.6% in cortical type, 85.7% in medullary type, 93.9% in mixed type, 100% in predominantly cortical type). Myasthenia gravis didn't influence the survival: 87.3 (no MG) vs 90%. Advanced stage thymomas significantly increased the risk of death from early stage I: 32.4 vs 100% at 5 years. In thymic carcinoma patients with well-differentiated thymic carcinoma (WDTC) died less than others: the actuarial probability of survival at 5 years was 90 vs 68%. CONCLUSIONS: Thymectomy was the best treatment to long term outcome. In our experience, survival was related to histotype and to local extension of tumor.

Adult↗

Major surgery in lung cancer in elderly patients? Risk factors analysis and long-term results.

BACKGROUND: In the Oncological Thoracic Surgery Department of the Istituto Nazionale Tumori of Milan a retrospective study was performed on lung cancer patients 70 years old or more with the aim of evaluate the role of surgical treatment and to analyse long-term results. METHODS: In our Institute from January 1988 to December 1993, 151 lung cancer patients 70 years old or more underwent surgery for lung cancer. One hundred and twenty-six of them (83%) were males and 25 were females (17%), the average age was 73.09+/-2.91 years (median: 77; range: 70-82). All the subjects were completely staged preoperatively. In order to establish operability criteria, we considered some selection parameters. Patients general conditions were evaluated using Karnofsky score accepting only the ones with 70% or more for surgery, all the cases performed cardio-respiratory functional evaluation. Patients with: a) FEV1 <60% of predicted value or FEV1 <1 l; b) PaO2 <60 mmHg e PaCO2 >40 mmHg were excluded from surgery. RESULTS: The operations performed were: 23 pneumonectomies, 6 bilobectomies, 93 lobectomies, 13 segmentectomies and 16 wedge resections. Eight cases were submitted to thoracectomy in association to pulmonary resection. Peroperative mortality was 3% and morbidity was 10%. Histological examination showed 69 adenocarcinomas, 65 squamous carcinomas, 4 large cells carcinomas, 4 typical carcinoids, 5 small cells carcinomas, 2 mucoepidermal carcinomas and 2 adenosquamous carcinomas. Eighty-six patients were classified at stage I, 38 at stage II, 24 at stage III and 3 at stage IV (multifocal disease). The actuarial 4-years global survival predicted with Kaplan Meier method was 40%, in particular it was 75% for stage I patients. CONCLUSIONS: In case of resectable primary pulmonary neoplasm, surgery represents the first choice therapy; patient's age doesn't seem to be an absolute contraindication, but it has to be evaluated with biological and not with age criteria. Using adequate selection criteria, it's possible to obtain, in patients older than 70 years, long-term survivals that don't seem to differ from global survivals.

Actuarial Analysis↗

Enzyme loaded biodegradable microspheres in vitro ex vivo evaluation.

Prolidase is a naturally occurring enzyme involved in the final stage of protein catabolism. Deficient enzyme activity causes prolidase deficiency (PD), a rare autosomal recessive inherited disorder whose main manifestations are chronic, intractable ulcerations of the skin, particularly of lower limbs. Although several attempts have been made towards the treatment of this pathology, a cure for this disease has yet to be found. The purpose of this work is to evaluate the possibility of enzyme replacement therapy through prolidase microencapsulation in biodegradable microspheres. The poly(D,L-lactide-co-glycolide) (PLGA) prolidase loaded microparticulate systems have been prepared utilizing the w-o-w double emulsion solvent evaporation method. They have been characterized "in vitro" by morphological analysis, total protein content and an in vitro dissolution test of active protein. "Ex vivo" evaluation of prolidase activity from the microspheres has been performed on cellular extracts of cultured skin fibroblasts from healthy subjects (controls) and from patients affected by PD. The results reported in this work on prolidase from pig kidney (available on the market) demonstrate the positive role of microencapsulation as a process of enzymatic activity stabilization inside PLGA microspheres achieving both in vitro and ex vivo active enzyme release. This formulation can be proposed as a parenteral depot drug delivery system.

Adult↗

Linkage disequilibrium pattern in the L-myc gene in Italian and Japanese non-small-cell lung-cancer patients.

Italian and Japanese non-small-cell lung-cancer patients were genotyped for an intragenic L-myc EcoRI restriction site polymorphism previously reported to be associated with lung-tumor prognosis in Asian populations but not in Caucasians. Screening of the L-myc sequence in Italian samples allowed identification of 2 additional 3'-UTR SNPs, located 2.3-3.0 kb from the EcoRI polymorphism, but no coding polymorphism was found. No significant association was found between any of the 3 SNPs and lung-tumor prognosis in Italian patients, consistent with the reported difference between Caucasian and Asian populations. Moreover, the newly discovered polymorphisms in the Italian group were not present in Japanese patients. Significant LD between EcoRI and the 2 other SNPs was detected in the Italian population, whereas no significant LD between the 2 3'-UTR markers was detected despite their close proximity (0.7 kb). Thus, the disparate conclusions about the role of L-myc polymorphism in tumor prognosis among different populations may rest in population-specific LD between the functional gene and the L-myc polymorphism.

Adenocarcinoma↗

Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam.

This work was aimed at evaluating the effects of gamma irradiation on the stability of microspheres made of a poly(lactide-co-glycolide) copolymer (PLGA) and loaded with 15% w/w of clonazepam (CLO). The influence of CLO on PLGA radiolysis mechanisms and the identification of possible irradiation markers were also investigated. Microspheres were prepared by means of a spray-drying method. gamma Irradiation was carried out either under vacuum or in air, at a dose of 25 kGy, by using a 60Co source. The stability of CLO loaded microspheres was evaluated over a 6-month period on the basis of drug content and dissolution profile. Radiolysis mechanisms were investigated by using electronic paramagnetic resonance (EPR) analysis. The microspheres irradiated under vacuum were stable over the considered period of time. After irradiation in air, CLO release rate increased by approximately 10%, and did not change further in the following period of storage. The EPR analysis showed some radicals arising from both the polymeric matrix and the active ingredient. Polymer/CLO spin transfer reactions suggest that CLO had a radio-stabilising effect on the polymeric matrix. In the loaded microspheres, the intensity in time of the CLO radical signal is sufficient for its possible use as irradiation marker.

Calorimetry, Differential Scanning↗

Long-term release of clodronate from biodegradable microspheres.

This paper describes the formulation of a biodegradable microparticulate drug delivery system containing clodronate, a bisphosphonate intended for the treatment of bone diseases. Microspheres were prepared with several poly(D,L-lactide-co-glycolide) (PLGA) copolymers of various molecular weights and molar compositions and 1 poly(D,L-lactide) (PDLLA) homopolymer by a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation procedure. Critical process parameters and formulation variables (ie, addition of stabilizing agents) were evaluated for their effect on drug encapsulation efficiency and clodronate release rate from microparticles. Well-formed clodronate-loaded microspheres were obtained for all polymers by selecting suitable process parameters (inner water/oil volume ratio 1:16, temperature-raising rate in the solvent evaporation step 1 degree C/min, 2% wt/vol NaCl in the external aqueous phase). Good yields were obtained in all batches of clodronate microspheres (above 60%); drug encapsulation efficiencies ranged between 49% and 75% depending on the polymer used. Clodronate release from all copolymer microspheres was completed in about 48 hours, while those from PDLLA microspheres required about 20 days. The change of microsphere composition by adding a surfactant such as Span 20 or a viscosing agent such as carboxymethylcellulose extended the long-term release up to 3 months. Clodronate was successfully entrapped in PLGA and PDLLA microspheres, and drug release could be modulated from 48 hours up to 3 months by suitable selection of polymer, composition, additives, and manufacturing conditions.

Biodegradation, Environmental↗

Emulsion spray-drying for the preparation of albumin-loaded PLGA microspheres.

The purpose of this work was to study the encapsulation of bovine serum albumin (BSA) in polylactide-co-glycolide (PLGA) microspheres using an emulsion/ spray-drying method. Albumin was dissolved in an aqueous phase (w) in the presence of surfactant and emulsified in an organic phase containing the polymer (o). To stabilize the emulsion, different types of surfactant (Pluronic F68, Pluronic F127, sodium oleate, dioctylsulfosuccinate) were added to the aqueous phase. The w/o emulsion was spray-dried to obtain BSA-loaded PLGA microspheres. The effect of type of surfactant on microsphere characteristics was evaluated. The microspheres were characterized for their morphology by scanning electron microscopy (SEM) and granulometric analysis; drug content determination and in vitro dissolution tests were performed. Results showed that the emulsion/spray-drying method is suitable for obtaining small microparticles (2-5 micron) characterized by high drug payloads (70%-80% encapsulation efficiency). The type of surfactant affects the microsphere shape and BSA release

Animals↗

Tissue-specific expression of rat IL-18 gene and response to adrenocorticotropic hormone treatment.

IL-18 is a pleiotropic cytokine also proposed to have a role in modulating immune function during stress. Initially found in immune cells, IL-18 mRNA is detectable in several tissues including the cells of the zona reticularis and the zona fasciculata of the adrenal cortex, where its levels are elevated by acute stress or adrenocorticotropic hormone treatment. In the present study, we compared the expression of IL-18 in the adrenal cortex with that of spleen and duodenum, two other IL-18-positive tissues. In situ hybridization showed that, in contrast to the adrenal cortex, in spleen and duodenum IL-18 is primarily localized to immune cells. In duodenum, IL-18 mRNA was also detectable in epithelial cells. Northern blot demonstrated that while the adrenal gland synthesized IL-18 mRNA of 1.1 kb, spleen and duodenum produced a 0.9-kb transcript. RT-PCR, sequencing, Western blot, primer extension, and rapid amplification of cDNA end analysis demonstrated that the three tissues synthesize IL-18 mRNAs containing the same coding region and produce the same IL-18 peptide, but differ in the length of their 5'-untranslated region, indicating tissue-specific usage of the promoter region. Finally, in contrast to the adrenal gland, adrenocorticotropic hormone treatment did not increase the levels of IL-18 mRNA in spleen and duodenum. These results demonstrate tissue-specific expression and promoter usage of IL-18 gene and suggest that the adrenal cortex and not immune cells may be the source of IL-18 during stress.

Adrenal Glands↗

Neurotoxic APP C-terminal and beta-amyloid domains colocalize in the nuclei of substantia nigra pars reticulata neurons undergoing delayed degeneration.

Increased amyloid precursor protein (APP) expression and intracellular accumulation of its toxic fragments have been associated with acute neuronal death processes. However, the role of APP fragments in delayed neurodegeneration remains poorly understood. We have characterized the appearance of APP domains in rat substantia nigra pars reticulata (SNpR) neurons targeted for delayed degeneration following neurotoxic striatal lesion. From 4 to 8 days postlesion (dpl) SNpR neurons ipsilateral to the lesion showed marked cytosolic accumulation of full length APP. Moreover, the nuclei of affected neurons also showed intense immunoreactivity (IR) for APP C-terminal and beta-amyloid domains but not for an N-terminal sequence. These data suggested the presence of APP C-terminal fragment. The absence of nuclear IR for a beta1-40 specific antibody supports this conclusion. Ultrastructural analysis of nigral sections from 6 dpl rats using a beta-amyloid domain antibody showed pronounced accumulation of immunogold-silver reaction product in the nuclei of affected SNpR neurons that was absent in control, contralateral SNpR neurons. These findings suggest that intranuclear APP C-terminal fragment may play a role in genomic events contributing to delayed neuron degeneration in the SNpR.

Amyloid beta-Peptides↗

Study on glycolic acid delivery by liposomes and microspheres.

Glycolic acid is used in many cosmetic products as exfoliant and moisturizer. Unfortunately, the greater glycolic acid cosmetic benefits the greater is the potential for skin irritation as far as burning. The aim of this work was to investigate the feasibility of topical controlled delivery systems loading glycolic acid in order to optimize the acid cosmetic properties lowering its side effects. For this purpose different types of microparticulate systems have been evaluated: liposomes, liposomes modified by chitosan addition and chitosan microspheres. Liposomes, composed of phosphatidylcholine and cholesterol (1:1 molar ratio) and with different glycolic acid/lipid molar ratio, were prepared by reverse phase evaporation method. Two types of interaction between liposomes and chitosan were investigated: chitosan addition into lipidic bilayer during liposome preparation and coating of already formed liposomes with chitosan. Glycolic acid loaded chitosan microspheres were prepared by the dry-in-oil emulsion method. The microparticulate systems were morphologically characterized by electron microscopy and particle size analysis. In vitro dissolution tests were performed to evaluate the feasibility of microparticulate systems in modulating glycolic acid release. The results obtained show that liposomes are always suitable to modulate glycolic acid release and that the best condition to achieve this control is obtained by the liposomal systems in which glycolic acid/lipid molar ratio is 5:1. Further significant release control is obtained by addition of chitosan into the liposomes, while chitosan microspheres are not able to control glycolic acid release even after crosslinking.

Administration, Topical↗

Ofuji papuloerythroderma.

Ofuji papuloerythrodema is a rare type of dermatosis marked by an erythrodermic manifestation which is intensely pruritic and results from the coalescing of brownish papules which in the main do not involve the great folds. The authors present the case history of a 72-year-old female, whose dermatosis appeared 8 years after the diagnosis of malignant lymphocytic lymphoma. The Authors describe the clinical and histopathological picture, illustrating the laboratory results and stressing the importance of the association of the two pathologies in a possible nosological overview.

Aged↗

Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment.

Interleukin (IL)-18 is a proinflammatory cytokine and a stimulator of cell-mediated immune responses. We have previously reported that acute stress stimulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governing the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or chronic corticosterone treatment on the levels of IL-18 mRNA and protein were examined by in situ hybridization and Northern and Western blot assays. Adult male Sprague-Dawley rats received a subcutaneous injection of ACTH or subcutaneous implantation of slow-release corticosterone pellets followed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold increase in IL-18 mRNA levels and elevated the content of pro-IL-18 peptide. Six days of chronic corticosterone treatment did not alter the basal levels of IL-18 mRNA and reduced those of pro-IL-18. Finally, ACTH treatment of animals under the corticosterone regimen induced a 2-fold increase in IL-18 mRNA and elevated the levels of the pro-IL-18 protein. The levels of the precursor, p45, and the active subunit p10 peptides of the IL-18-processing enzyme, IL-1beta-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1beta was not detected under these experimental conditions. These data demonstrate that the production of IL-18 in the adrenal cortex is stimulated by ACTH treatment and is not inhibited by the direct action of corticosterone. In contrast to the anti-inflammatory action of GCs, IL-18 may have an immunostimulatory role during acute stress.

Adrenal Cortex↗

Identificaiton of chlamydia penumoniae DNA in caroitd plaques.

Chlamydia pneumoniae (CP) is a bacterium that in recent years has been investigated as an etiologic agent for atherosclerosis. It is a ubiquitous microorganism that has been isolated in various regions of the vascular system and its prevalence is about 10% in the patient population. This study involved a group of 43 patients (27 men, 16 women, mean age 68 years) who underwent carotid endarterectomy. About 9.3% of the patients yielded plaques that tested positive for the DNA genome of Chlamydia pneumoniae.

Aged↗

A rare complication of surgical management for esophageal tumor: a non neoplastic belated fistula between stomach and main right bronchus.

The fistula between stomach and bronchus after surgery for cancer of the esophagus is a rare occurrence. We describe a gastric non neoplastic ulceration that arose late after six years from an esophagectomy, with an end-side cervical esophagogastrostomy, for a spino-cellular carcinoma. After the partial failure of surgical technique, of the endoscopic treatment and for the bad general conditions of patient we decided to treat the fistula by transluminal drainage. This technique involved a progressive resolution of the fistula, becoming, nowadays, in our division, the preferred treatment for these kinds of postoperative complications.

Bronchial Fistula↗

Cultures of astrocytes and microglia express interleukin 18.

Interleukin 18 (IL-18 or interferon-gamma inducing factor) is a recently discovered pro-inflammatory cytokine and powerful stimulator of the cell-mediated immune response. IL-18 is produced by several sources including monocytes/macrophages, keratinocytes and the zona reticularis and zona fasciculata of the adrenal cortex. IL-18 occurs in brain but its cellular source in the CNS has never been investigated. The presence of IL-18 and its response to stimulation in the brain was tested with primary cultures of microglia, astrocytes and hippocampal neurons. IL-18 mRNA was present in astrocytes and microglia, but not in neurons. The endotoxin lipopolysaccharide (LPS) did not affect IL-18 in astrocytes, but LPS robustly increased IL-18 mRNA in microglia. IL-18 protein was constitutively expressed in astrocytes and induced in microglia by LPS. The levels of interleukin-1beta converting enzyme (ICE), an activating enzyme, and caspase 3 (CPP32), an inactivating enzyme, were assessed to investigate the presence of the appropriate processing enzymes in the cultured cells. ICE was present at constitutive levels in microglia and astrocytes suggesting that these cell types may produce and secrete matured IL-18. Active forms of CPP32 were not detectable in either cell type indicating the absence of a degradative pathway of IL-18. The present results demonstrate that microglia and astrocytes are sources of brain IL-18 and add a new member to the family of cytokines produced in the brain.

Animals↗