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P Sala

Publications and source records attributed to P Sala.

89 records · Page 5Linked to original sources
PubMedDate not supplied

A novel protocol that allows short-term stem cell expansion of both committed and pluripotent hematopoietic progenitor cells suitable for clinical use.

To obtain long-term engraftment and hematopoiesis in myeloablated patients, the cell population used for hematopoietic reconstitution should include a sufficient number of early pluripotent hematopoietic stem cells (HSCs), along with committed cells from the various lineages. For this purpose, the small subset of CD34+ cells purified from different sources must be expanded ex vivo. Since cytokines may induce both proliferation and differentiation, expansion would provide a cell population comprising committed as well as uncommitted cells. Optimization of HSC expansion methods could be obtained by a combination of cytokines able to sustain renewal of pluripotent cells yet endowed with poor differentiation potential. We used variations of the combinations of cytokines described by Brugger et al. [W. Brugger, S. Heimfels, R. J. Berenson, R. Mertelsmann, and L. Kanz (1995) N. Engl. J. Med. 333, 283-287] and Piacibello et al. [W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta (1997) Blood 89, 2644-2653] to expand UCB CD34+ cells and monitored proliferation rate and phenotype after 14 days of culture. Several hematopoietic lineage-associated surface antigens were evaluated. Our data show that flt3L and thrombopoietin in combination with IL-3, while sustaining a high CD34+ proliferation rate, provide a relatively low enrichment in very early uncommitted CD34+/CD38- cells. Conversely, in the absence of IL-3, they are less effective in inducing proliferation yet significantly increase the number of CD34+/CD38- cells. A combination of the above protocols, applied simultaneously to aliquots of the same sample, would allow expansion of both committed and pluripotent HSC. This strategy may represent a significant improvement for clinical applications.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

Pharmacokinetics in rats of n-dimethylaminoacetyl-partricin a 2-dimethylaminoethylamide diascorbate (spk-843).

Single- and multiple-administration trials in rats were performed in this study to assess the serum and tissue concentrations of SPK-843 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate), a new polyene antibiotic with a heptaene structure. A dose of 1.25 mg/kg (roughly 1 mg/kg of free base) by intravenous route was used both for the single- and multiple-administration trials. The single-administration trial was carried out in comparison with amphotericin B (AmB) at intravenous doses of 1 mg/kg. Plasma samples were drawn at intervals from 15 min to 96 h after injection. The elimination half-lives were 22.15 and 18.15 h, and the area under the curve to infinity (AUC(0-infinity)) values were 35.52 and 10.33 microg.h.ml(-1), respectively, for SPK-843 and AmB. Both drugs showed an extensive tissue distribution, with higher uptake by the kidneys, followed by the liver, spleen and lungs for SPK-843, and higher uptake by the spleen, followed by the lungs, liver and kidneys for AmB. The multiple-administration trial (1.25 mg/kg/day for 7 days) led to sustained serum and tissue concentrations. On the seventh day, the rats were bled at intervals from 5 min to 96 h after dosing. The serum elimination half-life and AUC(0-infinity) values were roughly twice those of the single-dose study (41.4 h and 72.1 microg.h.ml(-1), respectively). Also, the half-lifes and AUCs from 0 to infinity of tissues were greater than those in the single-dose trial.

Amphotericin B↗
PubMedDate not supplied

Different expressivity of two adjacent mutations of the APC gene.

AIMS AND BACKGROUND: The phenotypic expression of different APC mutations in familial adenomatous polyposis (FAP) is variable: two to three variants of the disease have been defined based on the severity of colonic manifestations. Age of onset and number of polypectomies per person-year of post-surgical follow-up were compared in two FAP families with very close mutation sites in the APC gene, in order to ascertain mutation-specific variation of expressivity. FAMILIES AND APC MUTATIONS: Family A (5 patients) carried a newly characterized mutation, a four bp deletion at codon 843. Family B (5 patients) carried a previously identified mutation at codon 835. RESULTS: Mean age of onset was 49.7 years in family A and 30.5 years in family B; number of polypectomies per person-year of follow-up was 1.05 for family A and 10.1 for family B (P < 0.001). CONCLUSIONS: There is significant variation of expressivity (allelic heterogeneity) in FAP between two mutations separated by only eight codons, located at the 5' extremity of APC gene exon 15.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Risk of colorectal cancer following colonoscopic polypectomy.

AIMS AND BACKGROUND: To follow a cohort of patients who had undergone polypectomies in order to assess the overall risk of subsequent colorectal cancer in relation with various adenomas characteristics. METHODS: A total of 1,063 patients with adenomatous polyps of the large intestine were treated between 1979 and 1996 at the National Cancer Institute of Milan, during a screening program for colorectal carcinoma. Data on patients who had undergone colonoscopies were collected prospectively. The relation between colorectal cancer and adenomas characteristics was assessed by computing the hazard ratio (HR) values and corresponding confidence intervals (95% CI), according to Cox. RESULTS: Of the 1,063 patients who met the eligibility requirements, 672 had single adenomas (63.2%) and 391 had multiple adenomas (36.8%). Histological examination revealed 743 cases of tubular adenoma, 196 cases of tubulo-villous adenoma, and 96 cases of villous adenoma. High-grade dysplasia was found in 3.1% of the cases. During the 8,906 persons/year of follow-up, adenocarcinomas of the large bowel developed in 11 patients. Several adenomas' characteristics at index polypectomy were significant predictors of colorectal cancer occurrence. In univariate analysis the risk of colon cancer was significantly related with multiple adenomas (HR 4.2, 95% CI 1.1-6.5), high-grade dysplasia adenomas (HR 10.0, 95% CI 2.6-38.1) and with adenomas larger than 2 cm (HR 5.0, 95% CI 1.2-20.4). A multivariate stepwise procedure confirmed that the presence of multiple adenomas and presence of high-grade dysplasia are the most important predictors of carcinomas. Hazard ratios for colorectal cancer occurrence, from multivariate Cox's model, were 5.1 (95% CI 1.2-19.9) for multiple compared to single adenomas, and 13.0 (95% CI 3.6-50.7) for adenomas with high-grade dysplasia compared to those with low-grade dysplasia. CONCLUSIONS: High-grade dysplasia, number and size of adenomas were confirmed as the major cancer predictors. Based on this conclusion, a subgroup of patients, who may benefit from intensive surveillance colonoscopy, can be identifiable.

Adenoma↗
PubMedDate not supplied

Treatment of malignant polyps.

From 1975 to 1993, at the Division of Diagnostics and Endoscopic Surgery of the Istituto Nazionale Tumori in Milan, 191 malignant adenomas of colon-rectum have been endoscopically removed. On the basis of histopathologic criteria, endoscopic treatment has been judged adequate in 102 cases (53%), not adequate in 44 (23%), doubtfully adequate in 45 (24%). In 84 patients (44%) endoscopic polypectomy has been followed by surgical resection of the involved intestinal tract, 107 patients (56%) have been treated only by endoscopy. Results have been evaluated on the basis of surgical specimen, clinical follow-up and survival, showing that criteria we have adopted for the adequacy of the endoscopic treatment have a high negative predictive value (96%) and a low positive predictive value (32%). Actuarial survival of patients treated only endoscopically is 97% at 5 years and 95% at 10 years.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Simultaneous transplantation.

1. Thoracic organ transplantation requires extensive preparation with little advance notice. 2. A single organ transplant requires a team of various staff members, and may include one or two circulating nurses, two scrub technologists or nurses, one perfusionist, one surgeon's assistant, two surgeons, and one anesthesiologist. 3. Timing is important in organ transplantation because thoracic organs ideally should be transplanted within four hours after cross-clamping the aorta of the donor. 4. The dedication, expertise, and thorough follow-up care provided by transplant surgeons, nurse transplant coordinators, organ procurement coordinators, and the CICU and coronary care nurses/departments directly relate to the success of a thoracic organ transplant program.

Heart Transplantation↗
PubMedDate not supplied

Monitoring clonal expansion in the laboratory.

The definitive demonstration of the clonal origin of an expanded B or T cell population is achieved by the molecular analysis of B or T cell receptor gene rearrangement. However, in recent years techniques that are both sensitive and relatively easy to carry out have been introduced as the first step to the diagnosis of clonality. These include immunochemical analysis of serum and urine to characterize their monoclonal immunoglobulin components, and immunophenotypic studies of peripheral blood or tissue cells. The most widely used techniques are reviewed here, with particular emphasis on the clinical applications of immunofixation electrophoresis and multiparametric cytofluorimetric procedures.

B-Lymphocytes↗
PubMedDate not supplied

CD4 cytopenia and occasional expansion of CD4+CD8+lymphocytes in Sjögren's syndrome.

OBJECTIVES: To define whether Sjögren's syndrome (SS) patients have lymphocytopenia compared to healthy controls, and to assess which lymphocyte subset might be involved. The presence of any concurrent infection was recorded. METHODS: A cohort of ten consecutive patients with SS was studied, and the results were compared with ten sex- and age-matched controls (C). RESULTS: In SS, a significant cytopenia of CD4+ (679 +/- 339 vs 1110 +/- 222 cells/mm3, p < 0.005) and an even more impressive decrease in the CD4+CD45 RA+ (242 +/- 154 vs 491 +/- 190 cells/mm3, p < 0.005) subset was observed. An absolute CD4 lymphocytopenia (CD4+ < 300 cells/mm3) was seen in two patients. In one patient an unusual finding was the expansion of a double positive population of CD4+CD8+ lymphocytes. No striking relationship with any particular infection was shown. A retrospective review of the absolute CD4+ cytopenia in 54 consecutive SS cases revealed a prevalence of 5.5%. CONCLUSION: Some SS patients have T lymphocytopenia which mainly affects the CD4+CD45 RA+ subset. Occasional cases with absolute CD4 lymphocytopenia may also be observed. These patients show some evidence of mild recurrent or chronic, but never severe, opportunistic infections.

Adult↗
PubMedDate not supplied

[Etiology and epidemiology of 547 episodes of acute viral hepatitis diagnosed in adults in a general hospital (1983-1994)].

The etiology and epidemiology of 547 consecutive episodes of acute viral hepatitis in adults and diagnosed in a general hospital over 12 years (1983-1994) were prospectively analyzed as were the changes observed during the two halves of the study period. Of the 547 episodes, 25.4% were of type A, 41.1% type B, 21.9% type C, 6.6% non A, non B, non C, 2.4% type D, 1.1% by cytomegalovirus and 1.4% by the Epstein-Barr virus. The proportion of hepatitis A increased from 21.5% from 1983-1988 to 34.1% from 1989-1994 (p = 0.002), while hepatitis C decreased from 24.9% to 15.3% (p = 0.01) during the same periods. The proportion of hepatitis B observed in intravenous drug addicts fell from 56.1% in the first period to 39.3% in the second period (p = 0.03), while sexually transmitted hepatitis B rose from 7.3% to 22.9% (p = 0.002). A decrease was observed in the cases of hepatitis C in both periods in the intravenous drug addict cases (60.6% vs. 34.6%; p = 0.03) with an increase being observed in the C virus transmitted by unapparent mechanisms (2.1% vs. 23.1%; p = 0.001). These results suggest that modifications may currently be observed in the epidemiology of the viral hepatitis in Spain and that these trends should be taken into account when planning preventive strategies.

Adolescent↗
PubMedDate not supplied

[Epidemiology, natural history and indications for carotid thromboendarterectomy].

Stroke is the third most common cause of death in the occidental population and most important cause of disability. The average annual incidence of cerebral ischemia is increasing linked to population's mean age that is growing together with risk factors for cerebrovascular disease. There are many multicentre randomised trials (NASCET, ECST, Vet. Adm. SCT, CASANOVA, ACSV Adm. Study, ACAS, ACST) that identify surgical therapy as a prevention for stroke in symptomatic and asymptomatic patients. In discussing about all these studies it appears the necessity to follow the surgical guide-line proposed by multicentre trials in order to uniform indications for surgical or conservative therapy and to obtain data and results good enough to be effective in preventing really efficaciously stroke.

Arteriosclerosis↗