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Biomedical subjects

C Farina

Publications and source records attributed to C Farina.

At least 19 recordsLinked to original sources

Cytotoxic T-lymphocyte clones from different patients display limited T-cell-receptor variable-region gene usage in HLA-A2-restricted recognition of the melanoma antigen Melan-A/MART-1.

To determine whether T-cell-receptor (TCR) usage by T cells recognizing a defined human tumor antigen in the context of the same HLA molecule is conserved, we analyzed the TCR diversity of autologous HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones derived from five patients with metastatic melanoma and specific for the common melanoma antigen Melan-A/MART-1. These clones were first identified among HLA-A2-restricted anti-melanoma CTL clones by their ability to specifically release tumor necrosis factor in response to HLA-A2.1+ COS-7 cells expressing this tumor antigen. A PCR with variable (V)-region gene subfamily-specific primers was performed on cDNA from each clone followed by DNA sequencing. TCRAV2S1 was the predominant alpha-chain V region, being transcribed in 6 out of 9 Melan-A/MART-1-specific CTL clones obtained from the five patients. beta-chain V-region usage was also restricted, with either TCRBV14 or TCRBV7 expressed by all but one clone. In addition, a conserved TCRAV2S1/TCRBV14 combination was expressed in four CTL clones from three patients. None of these V-region genes was found in a group of four HLA-A2-restricted CTL clones recognizing different antigens (e.g., tyrosinase) on the autologous tumor. TCR joining regions were heterogeneous, although conserved structural features were observed in the complementarity-determining region 3 sequences. These results indicate that a selective repertoire of TCR genes is used in anti-melanoma responses when the response is narrowed to major histocompatibility complex-restricted antigen-specific interactions.

Amino Acid Sequence

Epidemiological characteristics of Pseudomonas aeruginosa strains causing infection in an Italian general hospital. A one-year surveillance.

During the 1989 calendar year, P. aeruginosa caused clinical infections in 0.46% of patients admitted to Ospedali Riuniti (a general hospital), Bergamo, Italy. Strains (n = 267) of P. aeruginosa were collected during this period, and epidemiological characteristics were studied. The mean prevalence of P. aeruginosa infection in inpatients was 1.1% (range 0.06-7.3), whereas outpatients showed a significantly lower prevalence of infection (0.05%). Strains were recovered from inpatients of surgical wards (n = 126; 47.2%), and outpatients (n = 15; 5.6%). Males were more often affected than females (2.7:1). Infection of the urinary tract was the most common (34.1%). Pseudomonas aeruginosa was also involved in lower respiratory tract infections (18.7%) and septicaemia (17.6%). Four typing methods were performed, i.e. serotyping, antibiotyping, pyocin typing, and restriction endonuclease analysis (REA). Serotypes O:11 and O:6 were endemic in the hospital. Some serotypes correlated with specific clinical wards. Pyocin typing was an unreliable epidemiological tool. However, antibiotyping showed the presence of some epidemic clusters, probably related to the antibiotic consumption of the patients. REA suggested the circulation of edemic P. aeruginosa strains in both the obstetrics and neurosurgery wards.

Cross Infection

Pharmacologic evaluation of the calcitonin analogue SB 205614 in models of osteoclastic bone resorption in vitro and in vivo: comparison with salmon calcitonin and elcatonin.

The activity of a novel calcitonin SB 205614 was compared with salmon calcitonin (sCT) and (Asu1,7)-eel calcitonin (ELC) in six different models of osteoclastic bone resorption in vitro and in vivo. SB 205614 is an ELC analogue that has an acetylenic bridge instead of the natural disulphide bridge, rendering the molecule more stable biologically than sCT and equally stable to ELC. Our aim was to determine whether this structural change compromised biologic activity, and if not, whether the increased stability could be used to exploit novel modes of administration. In the in vitro assays of pit formation by disaggregated rat osteoclasts on cortical bone slices (DROcA) and PTH stimulation of 45Ca-release from prelabeled fetal rat bone, no significant differences in activity were observed between the three calcitonins. In the DROcA, IC50s of 0.003, 0.015 and 0.064 pg/ml for sCT, ELC, and SB 205614, respectively, were determined, with total or near complete inhibition observed at 1 pg/ml (0.3 pM). In the assay of PTH-stimulation of 45Ca release, IC50s were measured of 5.5, 4.8, and 12.9 pM for sCT, ELC, and SB 205614, respectively; in every case maximal inhibition (ca. 80%) was observed at 30 and 100 pM. The internationally approved U.S. Pharmacopoeia bioassay of hypocalcemia in the rat following intravenous (IV) administration indicated that SB 205614 had a greater potency than ELC or sCT. More important, a full dose-hypocalcemic response curve demonstrated significantly increased potency compared to sCT or ELC, as the doses causing 15% lowering of serum calcium (approximately 50% of the maximum effect) were 33.9, 25.2, and 12.9 mg/kg for sCT, ELC, and SB 205614, respectively. As a preliminary means of investigating alternative delivery forms of calcitonin, the time course of the hypocalcemic effect was investigated in the rat and rabbit following IV administration, and was compared with that following intranasal (IN) administration (rat and rabbit), and following intracolonic administration (rat only). Maximal effects were similar, whereas in general the hypocalcemic effect of SB 205614 was of a longer duration than the other two calcitonins; this was reflected in a larger area over the curve (AOC). However, following IN administration in the rabbit, where an aerosol delivery device similar to that used in the clinic was used to administer the calcitonins, SB 205614 (100 IU/kg) induced a highly significant two-fold increase in the AOC compared to ELC or sCT. The calcitonins were also compared in assays designed to measure therapeutic efficacy in the rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence

Long-term outcome after transaxillary approach for thoracic outlet syndrome.

BACKGROUND: Recurrence or persistence of neurologic symptoms after surgical treatment of patients with thoracic outlet syndrome (TOS) are reported to be as high as 25%. To identify factors affecting the long-term outcome of surgical treatment of patients with TOS, we reviewed our 20-year experience. METHODS: One hundred thirty-four transaxillary first rib resections were performed on 118 patients (43 men, 75 women, mean age 38 +/- 13 years). Eighty-three operations (61.9%) were undertaken to relieve symptoms resulting from compression of the lower roots of the brachial plexus, 37 (27.6%) for compression of both lower and upper roots, and 14 (10.5%) for lower root and vascular symptoms. All patients underwent a transaxillary extraperiosteal first rib resection with transection of the scalene muscles. In 73 cases (54.5%) a resection of the anterior scalene muscle was also performed. A cervical rib was removed in 28 cases (20.1%), and anomalous fibrous bands adjacent to the neurovascular bundle were resected in 41 cases (30.6%). RESULTS: No major complications were observed. Of 105 patients (118 procedures) followed up (mean follow-up, 99 +/- 72 months), good to excellent results were obtained in 96 cases (81.4%) and fair to poor results were recorded in 22 cases (18.6%). The presence of a long posterior first rib stump, measured from the chest x ray films, was the strongest determinant of the long-term results among the variables examined (p < 0.0001). Reoperation, consisting of neurolysis and resection of the stump, was performed in 16 patients. The results were excellent in all cases at a mean follow-up of 66 +/- 46 months. Primary and secondary 10-year, actuarial freedom rates from recurrent symptoms were 80.9% and 93.1%, respectively. CONCLUSIONS: Our results suggest that the long-term outcome after surgery for TOS was strongly influenced by the extent of the first rib resection.

Adolescent

Human nocardiosis in northern Italy from 1982 to 1992. Northern Italy Collaborative Group on Nocardiosis.

We conducted a retrospective survey of nocardiosis in 9 city hospitals in northern Italy from 1982 to 1992. The medical records of 30 patients with documented nocardiosis were reviewed. Microbiological data included morphology, biochemical characteristics, serology and in vitro susceptibility testing. The 29 isolates (1 case was diagnosed on the basis of serological results) were Nocardia asteroides (n = 25) and Nocardia farcinica (n = 4). Predisposing factors including immunosuppression for organ transplant rejection prophylaxis, lung disease (silicotuberculosis and pulmonary fibrosis), solid tumours and hematological malignancies, and AIDS. Three patients had no identified risk factors. 20 cases of pulmonary nocardiosis were observed. Sites of infection in patients without previous pulmonary involvement were: brain abscesses, soft tissues, pericardium, blood, and cerebrospinal fluid. Most strains tested were susceptible to amikacin and imipenem. Resistance to several antimicrobial agents was found, particularly erythromycin, fosfomycin, pefloxacin, sulphonamides and trimethoprim. Antimicrobial chemotherapy included sulphonamides, amikacin, ceftriaxone, imipenem and minocycline. 21 patients survived, although 2 relapsed transiently. Nocardiosis appears to be more common than generally realised by physicians in northern Italy. The local species distribution and disease spectrum are similar to those described elsewhere. Nocardiosis should be part of the differential diagnosis in patients with pulmonary infiltrates or brain abscess, particularly those with predisposing factors.

AIDS-Related Opportunistic Infections

Community-acquired pneumonia: is there difference in etiology between hospitalized and out-patients?

Since March 1991 a prospective 1-year study of patients with community-acquired, radiologically verified, pneumonia (CAP) was performed at the Divisione Pneumologica, Ospedali Riuniti Bergamo, and at the Centro Pneumo-Allergologico, Bergamo, Italy. The study included 119 out-patients and 60 in-patients, with a median age of 37.4 and 49.8 years respectively. There were not statistically significant differences between the patients included with respect to the various months. The most common underlying illnesses were: chronic obstructive pulmonary disease (20.7%), diabetes (7.3%) and malignancy (3.4%). We found a quite different etiology of CAP between out- and in-patients. By far the most common etiologic agent in out-patients was Mycoplasma pneumoniae (32.8%), while in in-patients was Legionella pneumophila (11.7%). 5 patients had a double infection. There were no distinctive clinical and radiological features found to be diagnostic for any etiologic agent. Hospital stay averaged 12.1 days. 35% of the patients included in the study were been treated by beta-lactam, often parenterally, nevertheless 88 pathogens of the 100 identified were resistant to this antimicrobial therapy. We believe that there should always be a macrolide, erythromycin or the latest ones such as azythromycin, in the treatment of CAP, owing to their efficiency, ease of use and lower cost.

Adult

[Local recurrence after gastrectomy for cancer. Presentation of 2 clinical cases].

The Authors report two cases with local recurrence after partial gastrectomy for advanced gastric carcinoma. The Authors suggest that chemo and/or radiotherapy associated with surgical treatment can improve the prognosis in some patients with recurrence. Response to chemotherapy and time elapsing before recurrence appears may select this group of patients.

Adenocarcinoma

Comparative results of carotid-subclavian bypass and axillo-axillary bypass in patients with symptomatic subclavian disease.

The results of 26 carotid-subclavian bypass (CSB) and 17 axillo-axillary bypass (AAB) procedures, performed to treat symptomatic lesions of the proximal subclavian artery, were reviewed. Nine graft failures (seven CSB and two AAB) occurred (mean follow-up: CSB = 60.5 +/- 41 months; AAB = 67.8 +/- 48 months). All CSB graft thromboses were observed in patients with an associated ipsilateral carotid lesion, surgically treated or not (p less than 0.05). Cumulative 5- and 10-year patency rates were 78.3 and 62.9% for the CSB group and 87.9% for the AAB group (N.S.). In patients with an associated ipsilateral carotid lesion, 5- and 10-year patency rates were 66.0% and 40.8% for the CSB group and 100% for the AAB group (p less than 0.05). Both the surgical procedures were safe and effective with excellent results in terms of operative mortality, major morbidity and long-term patency. CSB is the procedure of choice for the treatment of proximal subclavian artery disease for its physiological characteristics and for graft shortness. However AAB must be considered a suitable alternative and preferred when a concomitant ipsilateral carotid lesion is present. Recurrence of carotid stenosis or carotid lesion progression may cause the carotid-subclavian failure.

Aged

Verotoxin glycolipid receptors determine the localization of microangiopathic process in rabbits given verotoxin-1.

Infection with verotoxin-producing Escherichia coli has been implicated in the cause of hemolytic-uremic syndrome. Cases of thrombotic thrombocytopenic purpura and verotoxin infections have been also described. In this study we sought to determine the following: (1) whether verotoxin induces microvascular lesions in the rabbit, (2) the organ distribution of such lesions, and (3) the distribution of verotoxin glycolipid receptors in the various organs. Rabbits challenged with verotoxin-1 purified from E. coli O157:H7 had anorexia, lethargia, and limb paralysis; renal function, however, was normal. Central nervous system lesions found included pericellular and perivascular edema, focal hemorrhage, vascular lesions, and severe alterations of Purkinje cells. Histologic changes were also seen in the colon, with mucosal and submucosal edema and hemorrhage, and in the lung, with interstitial fibrosis and focal lymphohistiocitic infiltration. No lesions were detected in kidney, heart, liver, and spleen. Screening of various tissues for the presence of the verotoxin receptors revealed galabiosyl ceramide in the central nervous system and globotriosyl ceramide in the gastrointestinal tract, lung, and spleen. No receptors for verotoxin were found in the heart, liver, and kidney. These results indicate that organ localization of the disease in rabbits is dependent on the distribution of verotoxin receptors.

Administration, Oral

Healing of high-porosity polytetrafluoroethylene arterial grafts is influenced by the nature of the surrounding tissue.

The aim of this study was to determine the influence of the nature of the perigraft tissue in the healing pattern of high-porosity polytetrafluoroethylene (PTFE) vascular grafts. Nine-centimeter long segments of unreinforced experimental high-porosity (60 microns) PTFE grafts were placed as abdominal aortic interposition in mongrel dogs. Three grafts served as controls (group A); in five dogs (group B) a 25 x 25 cm piece of devascularized omentum was wrapped around the graft. In five dogs (group C) the omentum with its own vascular supply was completely wrapped around the graft. Animals were killed 4 weeks after surgery. The percentage of thrombus-free area was 31% in group A grafts, 39% in group B grafts, and 79% in group C grafts (p less than 0.01). Scanning electron microscopy showed many confluent areas of endothelium-like cells in the midportion of group C grafts, corresponding to capillary ingrowth. Transmural endothelial migration was more evident in group C grafts. We conclude that the nature of the perigraft tissue influences transmural capillary migration and the endothelialization rate of high-porosity PTFE grafts in dogs. Agents able to increase capillary formation in the perigraft tissue might improve endothelialization of vascular grafts.

Animals

Some chemical and biological properties of the low molecular weight heparan sulfate alpha-idosane.

A low molecular weight heparan sulfate derivative, alpha-idosane was separated from a mixture of glycosaminoglycans extracted from porcine mucosa. Its molecular weight, sulfur, uronic acid and hexosamine contents, C-NMR spectrum and electrophoretic properties are reported in this paper. The pharmacological effects of a-idosane were investigated "ex vivo" in dogs and rats. At doses of 10-50 mg/kg p.o., a-idosane shows fibrinolytic activity but it is devoid of anticoagulant action. At the dose of 100 mg/kg p.o. a-idosane exertes a significant anti-inflammatory effect but is unable to protect the rats against arachidonate-induced sudden death.

Animals

Effects of a new aldose reductase inhibitor on diabetic complications in rats.

The effects of a new aldose reductase inhibitor, 7-fluoro-2-(N-methyl-N-carboxymethyl)sulfamoyl xanthone (BAL-ARI8, CAS 124066-40-6), on the diabetic complications of streptozotocin-induced diabetic rats were studied. The daily administration of BAL-ARI8 throughout the 8-week course of the experiment sharply decreased the sorbitol accumulation in the lens of the diabetic rats. The incidence of cataract formation was also reduced, being detected in only 45% of BAL-ARI8 treated animals, against the 100% of diabetic controls showing cataract after 8 weeks from diabetes onset. On the other hand, the serum glucose levels remained unchanged. In diabetic controls, there was about a 2.5-fold increase of the total protein urinary excretion during the 24 h. Treatment with BAL-ARI8 prevented up to 70% of this increase. Individual protein components were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins with molecular weight in the range 30,000-60,000 D, together with an increase of albumin (25% of the total excretion) and the presence of new higher molecular weight proteins (greater than 66,000 D). BAL-ARI8 administration resulted in a shift of the protein profile back toward normality i.e. 73% of proteins with molecular weight below 30,000 D, 7.5% albumin and no proteins above 66,000 D. These results suggest that BAL-ARI8 may represent a therapeutic approach for the management of diabetic complications.

Aldehyde Reductase

[Prevention of infection and improvement of cenesthesia with thymostimulin during chemotherapy following mastectomy].

Eighty-five breast cancer patients who had been operated for mastectomy and were currently undergoing adjuvant or therapeutic chemotherapy were included in the study. Patients were divided into two matching groups of 50 (A) and 35 (B) subjects; group A was treated with CT and thymostimulin Serono and group B with CT alone. The difference between the two groups in relation to first-degree (24% vs 57%) and second-degree leucopenia (8% vs 14%), in addition to the difference in relation to infections and the regularity of chemotherapy cycles confirmed the value of immunotherapy with thymostimulin during chemotherapy for breast cancer.

Adjuvants, Immunologic

[Visceral toxocariasis. Description of 3 cases].

Three cases of visceral toxocariasis in adult patients are here described. Toxocariasis is a not uncommon, probably underestimated infection and the diagnosis should be considered also in adults who present clinical signs and it must be confirmed by serological tests.

Adult

"In vitro" fibrinolytic activity of a new low molecular weight heparan sulfate.

The fibrinolytic activity, effect on the fibrinolytic activity of plasmin, anticoagulant activity and anti platelet aggregation activity of a low molecular weight heparan sulfate (LMW HS Bal) were investigated "in vitro" on blood plasma obtained from rats and rabbits. LMW HS Bal at concentrations as low as 0.25-2 micrograms/ml prevented thrombin-induced platelet aggregation. At concentrations 25 to 50 times larger it showed no significant anticoagulant activity but a marked fibrinolytic effect. At still larger concentrations LMW HS Bal also potentiated the fibrinolytic activity of plasmin. Conversely, unfractionated heparan sulfate (UHS) at concentrations of 25 to 50 micrograms/ml, only showed anticoagulant activity with no fibrinolytic activity.

Animals

Epidemiology of digestive tract mycoses in immunocompromised patients--a review.

Systemic fungal infections are diseases of increasing incidence in immunocompromised patients. They are an important cause of morbidity and mortality in patients with severe granulocytopenia caused by hematological malignancies or high-dose corticosteroid treatments. Systemic candidiasis is usually attributed to colonization of the patient's digestive mucosa or central venous/peritoneal catheters by endogenous Candida spp. Esophageal candidiasis can be a serious problem in predisposed individuals, and it can be the first opportunistic infection suggesting overt AIDS in HIV-seropositive patients. The aim of this review is to assess the epidemiology of alimentary tract mycoses in "at risk" groups because of iatrogenous or pathological reasons, such as in-patients undergoing solid organ and bone marrow transplantation, peritoneal dialysis and enteral/parenteral nutrition and in HIV infected patients.

Acquired Immunodeficiency Syndrome