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Biomedical subjects

F Tucci

Publications and source records attributed to F Tucci.

At least 19 recordsLinked to original sources

Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine.

PURPOSE: To assess thiopurine S-methyltransferase (TPMT) phenotype and genotype in patients who were intolerant to treatment with mercaptopurine (MP) or azathioprine (AZA), and to evaluate their clinical management. PATIENTS AND METHODS: TPMT phenotype and thiopurine metabolism were assessed in all patients referred between 1994 and 1999 for evaluation of excessive toxicity while receiving MP or AZA. TPMT activity was measured by radiochemical analysis, TPMT genotype was determined by mutation-specific polymerase chain reaction restriction fragment length polymorphism analyses for the TPMT*2, *3A, *3B, and *3C alleles, and thiopurine metabolites were measured by high-performance liquid chromatography. RESULTS: Of 23 patients evaluated, six had TPMT deficiency (activity < 5 U/mL of packed RBCs [pRBCs]; homozygous mutant), nine had intermediate TPMT activity (5 to 13 U/mL of pRBCs; heterozygotes), and eight had high TPMT activity (> 13.5 U/mL of pRBCs; homozygous wildtype). The 65.2% frequency of TPMT-deficient and heterozygous individuals among these toxic patients is significantly greater than the expected 10% frequency in the general population (P <.001, chi(2)). TPMT phenotype and genotype were concordant in all TPMT-deficient and all homozygous-wildtype patients, whereas five patients with heterozygous phenotypes did not have a TPMT mutation detected. Before thiopurine dosage adjustments, TPMT-deficient patients experienced more frequent hospitalization, more platelet transfusions, and more missed doses of chemotherapy. Hematologic toxicity occurred in more than 90% of patients, whereas hepatotoxicity occurred in six patients (26%). Both patients who presented with only hepatic toxicity had a homozygous-wildtype TPMT phenotype. After adjustment of thiopurine dosages, the TPMT-deficient and heterozygous patients tolerated therapy without acute toxicity. CONCLUSION: There is a significant (> six-fold) overrepresentation of TPMT deficiency or heterozygosity among patients developing dose-limiting hematopoietic toxicity from therapy containing thiopurines. However, with appropriate dosage adjustments, TPMT-deficient and heterozygous patients can be treated with thiopurines, without acute dose-limiting toxicity.

Adolescent↗

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

Bacteremia↗

G-CSF serum pharmacokinetics during peripheral blood progenitor cell mobilization: neutrophil count-adjusted dosage might potentially improve mobilization and be more cost-effective.

The optimal dosing schedule of G-CSF for peripheral blood progenitor cell (PBPC) mobilization is still under investigation although many centers use 10 microg/kg/day in a single subcutaneous dose. However, G-CSF clearance increases with increasing absolute neutrophil count (ANC). Hence a G-CSF dosage adjusted to ANC might be a reasonable approach. We measured G-CSF trough serum levels by sandwich ELISA assay at different ANCs in eight patients undergoing treatment with filgrastim at 10 microg/kg/day in a single subcutaneous dose. A total of 26 samples were analyzed, and a strong correlation between increasing ANC and decreasing G-CSF levels was found by linear regression analysis (P < 0.0003, r2 = 0.4199). For ANC values above 5000/microl the trough serum levels, ie 24 h after administration, were consistently below the level that provides maximal clonogenic precursor stimulation in vitro (10 ng/ml). Serial serum G-CSF measurements performed in three patients at 0, 3, 6, 9 and 24 h after G-CSF administration, showed a reduction of the area under the curve (AUC) with increasing ANC. For an ANC of 20000/microl or greater, the G-CSF serum level fell under the maximal in vitro stimulation threshold of 10 ng/ml within 12 h. This preliminary pharmacokinetic data seems to suggest that an ANC-adjusted G-CSF dosing schedule might improve the design of PBPC mobilization regimens.

Adolescent↗

Pediatric peripheral blood progenitor cell collection: haemonetics MCS 3P versus COBE Spectra versus Fresenius AS104.

BACKGROUND: An increasing number of apheresis machines are becoming available for peripheral blood progenitor cell (PBPC) collection in children. STUDY DESIGN AND METHODS: At the Children's Hospital of Florence (Italy), three apheresis machines were evaluated: MCS 3P (Haemonetics) (10 procedures in 4 patients, aged 10-12 years, weight 23.5-64 kg), Spectra, (COBE) (8 procedures in 3 patients, aged 4-17 years, weight 19-59 kg), and AS104 (Fresenius) (24 procedures in 9 patients, aged 2-16 years, weight 13.6-60 kg). For PBPC quantitative analysis, CD34 cytofluorimetry was employed. Relevant variables analyzed included efficiency of CD34+ cell extraction and enrichment, mononuclear cell purity and red cell contamination of the apheresis components, and platelet count decreases after leukapheresis. RESULTS: No significant differences in CD34+ cell-extraction abilities were found. However, the AS104 provided consistently purer leukapheresis components in terms of mononuclear cell and CD34+ cell enrichment (441 +/- 59%, vs. 240 +/- 35% and 290 +/- 42% for MCS 3P and Spectra, respectively). Postapheresis platelet counts dropped the least with the AS104. The smallest patient who underwent apheresis with MCS 3P (the only machine working on discontinuous flow and hence with greater volume shifts) weighed 23.5 kg and tolerated the procedure well, with no signs of hemodynamic instability. No significant complications were observed. CONCLUSION: All machines seem to have comparable PBPC extraction efficiency, but the AS104 seems to give the component with the greatest PBPC enrichment. This feature might be relevant for further ex vivo cell processing (CD34+ cell selection, expansion, and so on).

Adolescent↗

High-sensitivity immunocytologic analysis of neuroblastoma cells in paired blood and marrow samples.

High-sensitivity immunocytochemistry was used to evaluate the relative frequency of neuroblastoma cells in bone marrow and peripheral blood in patients with neuroblastoma (NB). A total of 51 concomitant paired blood and marrow samples (102 total) from 35 patients with NB (age 4 months-31 years; stage 29 stage IV, 4 stage III, 2 stage IVS; 14 at diagnosis, 18 in relapse, 12 during treatment, and 7 off-therapy) were analyzed. Cytospins containing up to 10(6) cells each were prepared using the mononuclear cell (MNC) fraction. For immunocytologic staining, a primary mouse monoclonal anti-GD2 antibody (3F8), a secondary antimouse biotinylated antibody, and a streptavidin-alkaline phosphatase complex were used. A minimum of two cytospins containing a mean of 1.4 x 10(6) total MNCs was analyzed in addition to a negative and a positive control. No circulating tumor cells were detected when the concomitant marrow samples were negative or had <10 positive cells per 106 MNC (23 of 51 samples). Of the 18 marrow samples positive at 10-10,000 cells per 106 MNC, 6 had detectable NB cells in the corresponding blood sample, whereas for marrow samples with >10,000 NB cells per 10(6) MNC (1%), the concomitant blood sample was positive for 9 of the 10. When both marrow and blood samples were positive (15 BM-PB pairs), NB cell frequency was significantly lower in blood, with a mean difference of 2.14 logs (median 2.22, range -0.16-4.8, standard error 0.38). In patients with NB, circulating tumor cell frequencies seem to be substantially lower than in concomitant marrow samples, with a mean difference of >2 logs.

Adolescent↗

Gastroesophageal reflux and bronchial asthma: prevalence and effect of cisapride therapy.

We evaluated the prevalence of gastroesophageal reflux in 36 children, 22 (61.2%) male and 14 (38.8%) female (median age, 75.5 months; range, 18-178), with noncontrolled asthma by means of prolonged (22-24 h) esophageal pH monitoring. None of the children had gastrointestinal symptoms suggesting gastroesophageal reflux. Atopy was seen in 21 of 36 (58.3%) patients. Pathological gastroesophageal reflux was present in 27 (75%) children. All patients were given cisapride (0.2 mg/kg q.i.d.) for 3 months. A clinical and pharmacological score was determined, and a second pH-metric study was made at the end of the follow-up period. The following pH-metric parameters were evaluated: the total percentage of time pH was < 4, the number of reflux episodes, the number of reflux episodes lasting > 5 min, the length of the longest single reflux episode, and the percentage of time the esophageal pH was < 4 during sleep. The study was completed in 11 of 27 children. The percentage of time that esophageal pH was < 4 improved in nine of 11 (81.8%) patients (p = 0.013). The percentage of time that esophageal pH was < 4 during sleep showed the most significant decrease (p = 0.002) after treatment. Improvement in both clinical and pharmacological scores was highly significant (p < 0.0001) in 19 of 27 patients, eight of whom did not want to repeat the pH study. We conclude therefore that gastroesophageal reflux is frequently associated with noncontrolled asthma and that medical therapy for reflux may improve the further course of respiratory disease.

Adolescent↗

Five-year follow-up of vaccination against hepatitis B virus in newborns vaccinated with a reduced number of doses.

The protective efficacy and long-term immunogenicity of a schedule with a reduced number of vaccinations in infants born to mothers positive for hepatitis B surface antigen (HBsAg) has been investigated: 494 infants immunized with a plasma derived hepatitis B vaccine (Hevac B Pasteur) at day 20 after birth and 2 months later were studied. Anti-HBs seroconversion rate was 96% after the second dose, a value similar to that obtained in older children. At 5 years of life anti-HBs at protective levels was still 95.8%. In conclusion, we suggest that this effective and economical reduced vaccination schedule, which before this study was applied to older children, can be used in newborns from HBsAg positive mothers with good protective efficacy shifting the beginning of active immunization from birth to day 20.

Age Factors↗

False diagnosis of non-A/non-B hepatitis hiding two cases of cystic fibrosis.

We report two cases of children followed for many years with an original diagnosis of non-A/non-B hepatitis. One child developed serious cirrhosis with portal hypertension. Long-term observation of the course of their hepatic disease provided the diagnosis of cystic fibrosis. These cases demonstrate that cystic fibrosis though rarely presenting with initial hepatic signs, can manifest itself with only long-term hepatic symptoms. We therefore strongly recommend analysis of sweat chloride concentration in cases of hepatic disease of unknown origin.

Adolescent↗

[Value of a rational postoperative treatment protocol in cardiac surgery].

The postoperative course of 76 patients, who underwent valve and/or coronary surgery during a period of 18 months, was analyzed to determine the influence of the overall non-surgical management on the results of the operations. We used an approach (System analysis) based upon analysis of the cardiac, pulmonary, renal, general metabolic, neurologic, and gastrointestinal subsystems. The use of inotropic support and the incidence of postoperative arrhythmias were lower. The permanence in intensive care unit and the hospital postoperative course were shorter in comparison with all series of patients who had the same type of surgery over the same period in our unit. These results indicate that the postoperative care after cardiac surgery needs accurate analysis, precise deductions and effective treatment.

Cardiac Surgical Procedures↗

[Hyperbaric oxygenation in cerebral air embolism occurring during open-heart surgery (author's transl)].

Hyperbaric oxygenation was used in two patients with extensive neurologic damage from cerebral air embolism occurring during open-heart surgery. One patient made a full recovery. The use of hyperbaric oxygenation produces the most direct relief of the mechanical obstruction and provides the definitive treatment for cerebral air embolism. First consideration must be given to the prevention of this complication, but once an embolus has occurred, hyperbaric treatment should be instituted promptly and early. Therefore every team engaged in open-heart operations should be familiar with the diagnosis and the therapy of air embolism.

Cardiac Surgical Procedures↗

[Relationship between the platelet aggregation of the newborn and mother (author's transl)].

The platelets function of newborn aroused great interest in these last years. On this line, AA. made the stretching test according to Breddin K. and Burck K. H., and. Breddin's Aggregation test on blood coming from 30 couples mother-newborn, drawn immediately after the birth. 22 newborns (73.3%) showed a stretching less than 65%, as well as 21 mothers (70%). The average stretching of mothers resulted 59.5% (+/- 2.26), whereas the average of newborns resulted 55.03% (+/- 2.71). Student's T, calculated on these values, did not result statistically meaningfull. Data-difference of Aggregation test according to Breddin and Burck, pertinent the couples mother-newborn gave on contrary satisfactory statistical information (p less than 0.0001). The explanatory characteristics of stretching test did not allow further issues, whereas Aggregation test results allow to come to the conclusion that newborn's platelets show a less capacity, as to mother's platelets, to aggregata under a mechanical standardized stimulation.

Adult↗

Acute onset of X-linked adrenoleukodystrophy mimicking encephalitis.

We report the case of a 6-year-old boy with X-linked adrenoleukodystrophy (ALD). In view of the acute onset of vomiting, fever, and coma, encephalitis was initially suspected. However, brain magnetic resonance imaging demonstrated a pattern of demyelination that was consistent with ALD; this diagnosis was confirmed by the finding of elevated plasma very long-chain fatty acids levels. At presentation, the patient was hyponatremic. That this metabolic disturbance and the coma resolved within hours of the initiation of corticosteroid therapy suggests that the presenting symptoms were secondary to adrenal cortical insufficiency. Primary adrenal failure was confirmed by endocrinologic evaluation. Thrombocytopenia, hepatic transaminase abnormalities, anemia and leukopenia developed during the subsequent course of therapy with oleic acid and erucic acid.

Acute Disease↗

[Recent acquisitions on viral hepatitis].

In the last years the research on viral hepatitis let to better understand the biological, molecular, immunological and epidemiologic characteristics of the viruses that are responsible for hepatitis. The first studied virus was hepatitis B virus (HBv). The scientific attention is still, today, focused on that virus since new markers of infectivity and biological importance in early diagnosis and in disease evolution have been found. The most important result in the last years in the field of viral hepatitis has been, however, the identification of agents responsible for Non-A-Non-B hepatitis. Its epidemiology and clinical importance are discussed in the present paper. Virus C is the most important parenteral agent of NANB hepatitis. Its epidemiology in at risk populations and its role in post-transfusional and cryptogenetic hepatitis are here discussed. The research of new markers of HCV infection is today considered a main goal since the role of the only marker now available is still under discussion.

Adult↗

[Urinary tract infections in childhood: importance of immediate urine culture. Personal experience with 4176 tests].

Since infections of the urinary tract in children often present diagnostic difficulties, it is essential to be able to identify these patients with simple, reliable methods. After a clinical-laboratory study on 4176 urine cultures, the Authors affirm that the reliability of this test is much greater when the parents have been instructed in the correct way of collection the urine specimen, and when in the laboratory the "slide" is carried out within three hours of taking the sample.

Adolescent↗

[The behaviour of platelets in some viral infectious diseases in childhood (author's transl)].

To evidentiate a participation clinically not evident of thrombocytes during viral infections, the Authors performed platelets count in 207 children of age varying 7 months to 12 years from the diagnosis and during the course of the illness. A subclinical thrombocytopenia was revealed in 55% of children affected by measles, in 25% of mumps, in 45% of varicella, in 30% of german measles and in 55% of infectious mononucleosis. In all the cases we didn't observe hemorrhagic manifestations and platelets count has come back to normal and higher levels spontaneously. Previously the Authors discuss pathogenetic ways which may have a role in subclinically thrombocytopenia during viral infectious diseases.

Chickenpox↗