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Biomedical subjects

S Spada

Publications and source records attributed to S Spada.

At least 19 recordsLinked to original sources
PubMed2005

Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study.

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.

Adult↗
PubMed2005

[Exercise-induced left arm pain and thrombocytosis].

We describe the case of a 45-year-old male smoker who presented with an acute anterior wall myocardial infarction and a platelet count on admission of 1030000/mm3. Emergent coronary angiography revealead left anterior wall akinesia caused by a spontaneously resolved thrombosis of the left anterior descending artery with residual stenosis. Primary percutaneous coronary angioplasty and stenting were performed. Postangioplasty course was uneventful. He was diagnosed with essential thrombocythemia based on the findings of marked thrombocytosis of 1,030,000/mm3, splenomegaly and numerous clumping giant megakaryocytes on bone marrow biopsy. In addition to standard therapy with aspirin, heparin, betablocking agent, ACE-inhibitor and statine he received additional anti-platelet therapy with Clopidogrel. Cytoreductive therapy was not necessary.

Angioplasty, Balloon, Coronary↗
PubMed2005

Acroparesthesia and acral arterial occlusions as first manifestations of essential thrombocythemia.

Thrombocytosis is either caused by a reactive process (secondary thrombocytosis) or by a clonal bone marrow disorder The latter category includes essential thrombocythemia with bleedings and thrombotic complications as major causes of illness and death in this patients. We describe a 43-year-old man with a 6 months history of acroparesthesia in his toes. Half a year after onset of these symptoms, he noticed a bluish discoloration of digit V of his left foot. On first presentation physical examination revealed a bluish discoloration of all toes and a cold and blue digit V of the left foot. Peripheral pulses were all palpable, normal ankle systolic pressure measurements and normal pulse volume recordings except for digit V of the left foot were found. Laboratory tests revealed thrombocytosis of 800000/microliter. On treatment with acetylsalicylacid, prostanoids intravenously and low molecular weight heparin, the patient became asymptomatic and pulse volume recording of digit V was normalized. After exclusion of cardial or vascular sources of embolism by utrasonography bone marrow aspirate and biopsy supported the diagnosis of essential thrombocythemia.

Adult↗
PubMed2003

Functional changes of human quadriceps muscle injured by eccentric exercise.

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5 /s; range of motion from 40 to 110 of knee flexion). The isometric torque of the quadriceps (knee at 90 flexion) decreased 52% immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63%) and VMO (66%) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109% on the 2nd day and were still increased by 32% on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals.

Adult↗
PubMed2003

Cancer precursor lesions in intact stomach Helicobacter pylori gastritis and in resected stomach gastritis.

Hemigastrectomy for benign disease and Helicobacter pylori infection are risk conditions for the development of gastric cancer. Aim of the study was to compare gastric histology and precursor lesions of malignancy in these two conditions. The hemigastrectomy group included 351 consecutively endoscoped subjects operated for gastroduodenal benign disease. Six to ten biopsy specimens were routinely taken from the residual gastric mucosa. The intact stomach group included 2097 consecutively endoscoped symptomatic subjects, who did not receive eradication therapy against H. pylori. The histological findings were classified as normal mucosa (NM), chronic non atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS). One thousand and three intact stomachs were H. pylori negative, and 1094 showed H. pylori colonization. The age over fifty was a significant risk factor for the occurrence of IM (OR 2.52, P < or = 0.001) and DYS (OR 3.46, P < or = 0.001), while Hp-positivity was a risk factor for CNAG (OR 1.81, P < or = 0.001) and CAG (OR 3.88, P < or = 0.001). Gastroresection was associated to higher risk for CNAG (OR 1.53, P < or = 0.001) and DYS (OR 4.31, P < or = 0.001) and to a lower risk of CAG (OR 0.49, P < or = 0.001). Both in males and females the risk for CNAG was significantly higher in Hp-positive (males OR 1.92, P=0.000; females OR 1.70, P=0.000) and gastrectomized subjects (males OR 2.06, P=0.000; females OR 2.43, P=0.000). Gastrectomized males, furthermore, showed an increased risk for DYS (OR 5.82, P=0.000). The aged Hp-negative and Hp-positive subjects evidenced a significant risk for IM (respectively OR's 3.42, P=0.000 and 4.85, P=0.000); the risk for DYS was significant in aged Hp-negative subjects (OR 4.09 P < or = 0.020). The Hp-positive individuals evidenced a significant risk for metaplastic mucosal changes (OR 38.17, P=0.000). Subjects aged over forty at the time of surgery and those with a longer postoperative follow up endoscopy presented an increased risk for CNAG of the residual mucosa (respectively OR's 2.75, P=0.000 and 5.25, P=0.000). CNAG and IM were the most frequently observed mucosal lesions both in subjects operated for duodenal and gastric ulcer (respectively OR's 4.02, P=0.000 and 3.00, P=0.000). Our data support that hemigastrectomy for benign disease and H. pylori infection may induce an increased incidence for histological precursor lesions for gastric malignancy and suggest that carcinogenesis in a resected stomach may be different from that in the intact stomach.

Adolescent↗
PubMed2002

Co-occurrence of psoriatic arthritis with collagenous colitis: clinicopathologic findings of a case.

A 58-year-old man developed psoriatic arthritis and, after 6 months, persistent watery diarrhoea. Biopsies from the colorectal mucosa showed thickened subepithelial collagen consistent with collagenous colitis. There also was an inflammatory cell infiltration (mainly lymphocytes and monocytes) in the chorion. These findings and the parallel course of articular and bowel complaints suggest a clinicopathologic correlation between arthritis and colic involvement.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Case control study on health-related quality of life in adult coeliac disease.

AIMS: To evaluate whether health-related quality of life in adult coeliac disease is related to: 1) adhesion to gluten-free diet; 2) manifestation of clinical features; and 3) associated diseases. PATIENTS AND METHODS: A total of 68 coeliac patients (54 female and 14 male) aged between 18 and 74 years, on gluten-free diet for at least two years were studied. The subjective health status was measured by means of the Short Form 36 Health Survey. A series of 136 subjects, matched according to sex, age and ethnic group, were evaluated as control group. RESULTS: Patients obtained worse scores with respect to healthy controls at all domains of Short Form 36 Health Survey (p<0.05); compliers showed better results than non-compliers. The lowest scores were obtained in patients with more than six symptoms, mostly in non-compliers, the highest in compliers with less than six symptoms. Patients with two or more associated diseases presented significantly worse scores than patients with only one associated disease. CONCLUSIONS: The importance of gluten-free diet in clinical management of coeliac disease is confirmed by results of the present study; moreover, the results seem to indicate that a complex interplay of factors should be taken into account in evaluating health-related quality of life in adult coeliac disease. Accordingly, our data show that health-related quality of life of coeliac patients is impaired not only by poor compliance but also by different negative factors such as severity of illness (in terms of number of symptoms) at diagnosis and comorbidity.

Adolescent↗
PubMed2001

Isolation and characterisation of the ylmE homologue of Thermus thermophilus.

Screening of a Thermus thermophilus genomic library led to the identification of a homologue of the ylmE gene. ylmE is highly conserved in widely divergent organisms from prokaryotes to mammals, suggesting an important, albeit currently unknown, cellular function. The 633 bp gene has a GC content of 69.2% overall and 90% in the third nucleotide position, while the gene product is predicted to be a soluble cytoplasmic protein of 23,441 Da. It belongs to a family of conserved proteins of unknown function and exhibits amino acid identities ranging from 45% to 28% to the Aquifex aeolicus and Saccharomyces cerevisiae family members, respectively. We speculate that the gene product may be involved in a cellular stress response in T. thermophilus.

Amino Acid Sequence↗
PubMed2001

Cloning and characterisation of the Hint homologue of the thermophile Thermus thermophilus.

Screening of a genomic library of the thermophile Thermus thermophilus revealed a novel thermophilic hint gene, homologues of which are highly conserved in genera from archaea to mammals. Hint belongs to the HIT protein super-family, which contains two broad groups, Fhit, associated with tumour suppression in eukaryotes and Hint with putatitively protein kinase C inhibitory activity. In T. thermophilus the 321 bp gene has a GC content of 67% overall and 94.4% in the third nucleotide position, with unusually no thymine as a wobble base. The gene product, a small highly conserved 11,996 Da predicted soluble cytoplasmic protein, offers an ideal opportunity to investigate thermostabilising amino acid substitutions. Here we report on the characterisation of the novel hint sequence.

Amino Acid Sequence↗
PubMed2001

[Predictive variables of mortality in elderly patients after hospitalization. Significance of multidimensional evaluation].

Functional status evaluation in the elderly is stronger predictor of hospital outcomes than type and number of pathology. Multidimensional and functional assessment among hospitalized elderly allows to identify, as well as acute and chronic illness, disabilities of sanitary problems and socio-economical aspects that in the elderly can complicate illness. Our study has identified six-month mortality post hospitalization of 20.2%. The high mortality observed in our follow-up agrees with the literature and it is a marker of considerable frailty among elderly patients. The independent predictor variables of six month post hospital mortality in the study were: male gender, dependence DMI score, low serum albumin (2.8 g/dl), impaired IADL score, cancer illness and APACHE score < 13.7. These measures represent distinct domains: demographic, functional and clinical. Identifying predictors of high-risk patients is an important way in accurate targeting.

Age Factors↗
PubMed1999

[Polypharmacy in the ambulatory care of aged patients].

The aim of this study was to assess the prevalence and possible predictors of polypharmacy in a sample of the general population. The sample consisted of 638 subjects (267 males, mean age 54.7, and 371 females, mean age 55) taken from the records of three general practitioners in the city of Turin, Italy. The prevalence of polypharmacy, for prescription drugs, was 12.5% (80 subjects). The prevalence of polypharmacy, for non prescription drugs, was 17.4% (111 subjects). The number of prescription drugs per patient rises progressively with age, averaging 2.28 and 2.5 respectively in males and in female aged older than 80 years. The number of non prescription drugs was observed to decrease with age: in women, subjects that used two or more non prescription drugs were 35% in those aged under 50 years, 20% in subjects aged from 65 to 80 years and 12.5% in those aged older than 80 years. Subjects aged older than 65 years, an IADL score < 10, more than 20 physical exams performed by practitioner in the last year, a recent hospitalisation, presence of cardiovascular disease, and presence of genito-urinary disease, were significantly and independently associated to polypharmacy for prescription drugs. Only female sex was significantly associated to polypharmacy for non prescription drugs. Our conclusion is that although age should not be involved in polypharmacy as a variable, several phenomena that influence medical treatment goals become more prevalent with increasing age and explain the high drugs consumption in the elderly. A rational, essential therapy, helped by guidelines could reduce potential problems associated with polypharmacy in the elderly.

Activities of Daily Living↗
PubMed1998

Reproducing the natural evolution of protein structural features with the selectively infective phage (SIP) technology. The kink in the first strand of antibody kappa domains.

The beta-sandwich structure of immunoglobulin variable domains is characterized by a typical kink in the first strand, which allows the first part of the strand to hydrogen bond to the outer beta-sheet (away from the VH-VL interface) and the second part to the inner beta-sheet. This kink differs in length and sequence between the Vkappa, Vlambda and VH domains and yet is involved in several almost perfectly conserved interactions with framework residues. We have used the selectively infective phage (SIP) system to select the optimal kink region from several defined libraries, using an anti-hemagglutinin single-chain Fv (scFv) fragment as a model system. Both for the kink with the Vkappa domain length and that with the Vlambda length, a sequence distribution was selected that coincides remarkably well with the sequence distribution of natural antibodies. The selected scFv fragments were purified and characterized, and thermodynamic stability was found to be the prime factor responsible for selection. These data show that the SIP technology can be used for optimizing protein structural features by evolutionary approaches.

Bacteriophages↗
PubMed1998

5-Fluorouracil plus interferon alpha-2a compared to 5-fluorouracil alone in the treatment of advanced colon carcinoma: a multicentric randomized study.

Biochemical modulation is one of the most interesting fields in cancer chemotherapy. Interferon-alpha (IFNalpha) is a cytokine that is able to influence the pharmacodynamics of 5-fluorouracil (5FU) through a number of mechanisms. With the aim of confirming some data emerging from the literature, we initiated a multicentric randomized study comparing the combination of 5FU and IFNalpha-2a with 5FU alone in the treatment of advanced or metastatic colon cancer. A group of 205 colon cancer patients (104 in the 5FU arm and 101 in the 5FU + IFNapha-2a arm) were included in the final intention-to-treat analysis. Rectal cancers were not considered eligible. All patients had measurable disease, were aged 75 years or less, had a Karnofsky index of at least 60 and had good bone marrow, renal, liver and cardiac functions. No previous chemo-immunotherapy was allowed. The treatment was 750 mg/m2 5FU (4 h i.v. infusion) on days 1 5 and then i.v. bolus weekly, starting from day 12, with or without IFNalpha-2a given s.c. three times weekly (starting dose 3 x 10(6) IU rising to 9 x 10(6) IU, if tolerated). Patients were treated until progression or, if responsive, for a maximum of 48 weeks and then observed for a period of 2 years. The primary end-point of the study was objective clinical response (OR); secondary parameters were time to progression, overall survival, and time to death after progression. WHO criteria were used for both clinical response and toxicity measurements. Dose reduction was planned a priori in the event of significant toxicity due to 5FU, IFNalpha-2a or both. Association between primary and secondary end-points and treatment was studied by univariate and multivariate analysis. Altogether, 47 patients achieved a documented response. A 25% OR was observed in the combination arm while a 21% OR was seen in the 5FU arm; this difference is not statistically significant (P = 0.6). Patients with a small tumour burden (below 5 cm2) showed a higher probability of response in both arms. Patients in the experimental arm had a higher but not statistically significant cumulative progression-free probability. Median survival was 47.1 weeks overall, while it was 43.7 and 48.5 weeks in the control and experimental arms, respectively. The combination was clearly more toxic than 5FU alone, leukopenia being the most frequent side-effect in the experimental arm and nausea and vomiting in the control arm. In conclusion these results are quite disappointing and 5FU + IFNalpha-2a can not be considered a standard treatment for advanced colon cancer.

Aged↗
PubMed1998

[Acute confusion in the geriatric patient].

During 1996, 585 patients, aged 55 to 96, were admitted into hospital at the Geriatric Department of Ospedale Maggiore (Turin). Acute confusion was seen in 22.2% of these patients who tended to have more serious clinical condition, were more likely to have chronic cognitive impairment, were treated with a greater number of drugs and suffered more from immobility with pressure ulcer. The confusional state, manifested at admission to Geriatric department, was mostly related with the patient's clinical severity, while the one which developed during hospital stay was linked to situations of physical frailty, as pressure ulcer and low albumin values. The most frequent causes of acute confusional state were acute infectious diseases, heart failure, gastro-intestinal bleeding with secondary anaemia, stroke and dehydration. In many cases the very cause of the acute confusional state could not be identified. Falls, more than 31 days length of stay in hospital and death were more frequent in patients suffering from confusional state. Chronic cognitive impairment, functional dependence, clinical severity and treatment involving a great number of drugs, are the main contributing factors in this syndrome. Thus, a multi-dimensional evaluation which takes into account both clinical-functional and socio-economical aspects, is useful for a correct preventive and diagnostic approach of acute confusional state.

Acute Disease↗
PubMed1997

Selectively-infective phage (SIP): a mechanistic dissection of a novel in vivo selection for protein-ligand interactions.

Selectively-infective phage (SIP) is a novel methodology for the in vivo selection of interacting protein-ligand pairs. It consists of two components, (1) a phage particle made non-infective by replacing its N-terminal domains of geneIII protein (gIIIp) with a ligand-binding protein, and (2) an "adapter" molecule in which the ligand is linked to those N-terminal domains of gIIIp which are missing from the phage particle. Infectivity is restored when the displayed protein binds to the ligand and thereby attaches the missing N-terminal domains of gIIIp to the phage particle. Phage propagation is thus strictly dependent on the protein-ligand interaction. We have shown that the insertion of beta-lactamase into different positions of gIIIp, mimicking the insertion of a protein-ligand pair, led to highly infective phage particles. Any phages lacking the first N-terminal domain were not infective at all. In contrast, those lacking only the second N-terminal domain showed low infectivity irrespective of the presence or absence of the F-pilus on the recipient cell, which could be enhanced by addition of calcium. An anti-fluorescein scFv antibody and its antigen fluorescein were examined as a protein-ligand model system for SIP experiments. Adapter molecules, synthesized by chemical coupling of fluorescein to the purified N-terminal domains, were mixed with non-infective anti-fluorescein scFv-displaying phages. Infection events were strictly dependent on fluorescein being coupled to the N-terminal domains and showed a strong dependence on the adapter concentration. Up to 10(6) antigen-specific events could be obtained from 10(10) input phages, compared to only one antigen-independent event. Since no separation of binders and non-binders is necessary, SIP is promising as a rapid procedure to select for high affinity interactions.

Calcium Chloride↗
PubMed1997

Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice.

We have generated a transgenic mouse model for astrocytoma by expressing the v-src kinase under control of the glial fibrillary acidic protein (GFAP) gene regulatory elements in astrocytes. Abnormal astrogliosis was observed in all transgenic animals already at 2 weeks postnatally, frequently followed by the development of dysplastic changes. Later, small proliferative foci arose, and overt astrocytoma developed in the brain and spinal cord in 14.4% of mice after a follow up time of 65 weeks. While early lesions were histologically consistent with low-grade astrocytoma, at later stages most tumors were highly mitotic and frankly malignant. Vascular endothelial growth factor (VEGF) was expressed by tumor cells already at early stages, suggesting induction by v-src, and it was most pronounced in pseudopalisading cells surrounding necrotic areas, implying additional upregulation by hypoxia. In larger lesions, mitotic activity and expression of flk-1, the cognate receptor of VEGF were induced in endothelial cells. Therefore, end-stage tumors mimicked the morphological and molecular characteristics of human glioblastoma multiforme. Time course and stochastic nature of the process indicate that v-src did not suffice for malignant transformation, and that astrocytomas were the result of a multistep process necessitating co-operation of additional genetic events.

Animals↗
PubMed1997

Selectively infective phages (SIP).

We review here advances in the selectively infective phage (SIP) technology, a novel method for the in vivo selection of interacting protein-ligand pairs. A 'selectively infective phage' consists of two components, a filamentous phage particle made non-infective by replacing its N-terminal domains of gene3 protein (g3p) with a ligand-binding protein, and an 'adapter' molecule in which the ligand is linked to those N-terminal domains of g3p which are missing from the phage particle. Infectivity is restored when the displayed protein binds the ligand and thereby attaches the missing N-terminal domains of g3p to the phage particle. Phage propagation becomes strictly dependent on the protein-ligand interaction. This method shows promise both in the area of library screening and in the optimization of peptides or proteins.

Bacteriophages↗