Biomedical subjects
Publications and source records attributed to F Porta.
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From January 1984 to December 1994, ABMT was performed on 154 children (101 males, 53 females; median age 10, range 3-21 years) with ALL and registered for BMT by the AIEOP (Italian Association of Paediatric Haemato-Oncology). All patients were in CR: 98 were in 2nd CR and 56 were in >2nd CR. Fifteen children (9.7%) died of transplant-related mortality. Ninety-five patients (61.6%) relapsed at a median of 5 (range 1-42) months after ABMT. The 8-year EFS according to pre-BMT status was 34.6% (s.e. 4.9) for 2nd CR patients and 10.6% (s.e. 5.6) for patients in >2nd CR. By univariate analysis, site of relapse (isolated extramedullary (IE) vs BM: EFS = 68.5% vs 18.2%; P < 0.0001) and TBI containing regimen (TBI vs no TBI: EFS = 48.1 vs 15.4%; P = 0.0023) were significant factors for 2nd CR patients. When the 2nd CR subset with BM involvement was analysed, TBI became insignificant (EFS = 25.4 vs 11.8%). No factors influenced EFS in patients in >2nd CR. By multivariate analysis, site of relapse was the only significant factor in 2nd CR patients (P < 0.0001). In conclusion, ABMT is an effective treatment after one early IE relapse. Few patients can be rescued after BM relapse.
OBJECTIVE: A new surgical approach to foraminal disc herniation is proposed. METHODS: The procedure was performed in 28 patients during a span of 3 years. The herniation was purely foraminal in 18 patients and mainly foraminal with a definite extraforaminal component in the other 10 patients. Surgical treatment was offered only after 6 weeks of therapy with anti-inflammatory drugs and strict bed rest had proved to be ineffective. SURGICAL TECHNIQUE: To unroof the foraminal compartment, an ovoid fenestration (10 x 5 mm) is cut, with its major longitudinal axis at the level of the pars interarticularis, just medially and slightly off-center under the lateral isthmic notch, i.e., below the pedicle projection. This fenestration exposes the foraminal root compressed by the herniated disc, which can be easily removed. RESULTS: Treatment was successful in all patients, with swift remission of pain and only mild postoperative discomfort. All patients resumed their occupations as usual within 10 to 30 days after the operation, according to type of work. Mean follow-up is 24 months (range, 12-36 mo), without any return of pain. CONCLUSION: We propose pars interarticularis fenestration because it spares, with minimal bone removal, the facet joints and the anatomic continuity of the pars interarticularis, yet properly exposes the foraminal compartment both medially and laterally and thereby permits optimal removal of the disc herniation.
Bone Marrow transplantation (BMT) is the treatment of choice in a large number of primary immunodeficiencies, for which this treatment is potentially curative. BMT needs to be considered as soon as possible after diagnosis because these disorders usually run an unpredictable course and may be rapidly fatal. Beside conventional HLA-matched donor BMT, there is growing and increasingly favourable experience with alternative, in particular HLA-haploidentical donors. In this review, current results of BMT are presented.
From December 1989 to December 1997 40 children aged 1 year to 19 years with inborn errors other than severe combined immunodeficiencies underwent unrelated donor (UD) bone marrow transplantation (BMT) in one of 10 institutions of the Italian Bone Marrow Transplant Group participating in this program. The diseases leading to BMT included Fanconi Anemia (10), Thalassemia (8), Wiskott Aldrich syndrome (5), haemophagocytic lymphohystiocytosis (6), osteopetrosis (3), storage diseases (6), Chediak Higashi syndrome (1), Schwachman syndrome (1). Thirty-three pairs were A, B, DRB1 matched. Three pairs were one antigen mismatched and one pair was two antigens mismatched. The remaining three pairs lacked information on molecular biology. Twelve children underwent a preparative regimen including radiotherapy. The remaining 28 children were conditioned with a chemotherapy regimen which included Busulfan. GvHD disease prophylaxis included CSA and MTX alone (9) or associated with ALG (17) or in vivo Campath 1G (12). The remaining two children received CSA alone. Thirty-five children showed donor engraftment; three children with thalassemia and one with osteopetrosis failed to engraft. Five children developed secondary graft failure. Actuarial 5 year disease-free survival was 62%; grade III-IV acute GvHD developed in seven of 38 evaluable children (18%); chronic GvHD developed in seven of 27 evaluable children (26%). We confirm that Wiskott Aldrich syndrome, HLH, and osteopetrosis represent an absolute indication for UD-BMT. Prognosis of UD-BMT for FA could improve in children grafted in an early phase, but a better preparative regimen has to be identified. UD-BMT in thalassemia is acceptable only in a restricted subset of patients selected for poor compliance to therapy.
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We report a case of a gastric carcinoid tumor in an anemic woman with chronic atrophic gastritis and hypergastrinemia. An antrectomy with excision of a carcinoid tumor was performed; afterwards, gastrinemia was normal. Gastric carcinoids were considered uncommon gastric cancers; however, in recent years they have been studied with increasing interest because, as in chronic atrophic gastritis, it has been suggested that they might be produced by prolonged hypergastrinemia associated with therapeutic use of gastric acid supressors. We discuss the gastrin hypothesis, the different clinical types of gastric carcinoids and its therapeutical management.
BACKGROUND: X-linked severe combined immunodeficiency (SCIDXI) is an inherited immune defect which leads to death in infancy from severe infections. The defect is caused by mutations of the IL-2RG gene that encodes for the common gamma chain shared by several cytokine receptors. The disease is characterised by lack of T and NK cells with normal numbers of B cells. SCIDXI can be cured by bone marrow transplantation (BMT) or prevented by abortion after prenatal diagnosis. METHODS: A male fetus was diagnosed as having SCIDXI by molecular, immunophenotypic, and functional analyses. The fetus was injected intraperitoneally under ultrasound guidance with CD34 haematopoietic progenitor cells purified from paternal bone marrow and T-cell depleted by E rosetting. Chimerism analysis was by HLA-DQ alpha typing and gamma-chain staining on cord blood. FINDINGS: A healthy 3.6 kg boy was delivered by caesarean section at 38 weeks of gestation with no clinical or laboratory signs of graft-versus-host disease. Engraftment of donor-derived CD2 cells was found at birth. At 3.5 months of age the infant is well and his T-cell counts and function are normal. INTERPRETATION: In-utero transplantation of haematopoietic progenitor cells allowed immune reconstitution of a fetus with SCIDXI and may be an alternative to elective abortion. Our report should encourage applications of this method to other inherited disorders curable by BMT.
We report on two sisters affected by congenital alopecia, nail dystrophy, and a severe T-cell immunodeficiency, presumably inherited as an autosomal-recessive disorder. The T-cell defect was characterized by severe functional impairment, as shown by the lack of proliferative response and upregulation of activation markers following mitogen stimulation. The functional abnormality occurred in spite of the presence of phenotypically mature of the defect. This is the first observation reported on an ectodermal disorder, characterized by alopecia and nail dystrophy, observed at birth, in association with a primary immunodeficiency. The hypothesis that these two events may be casually related is discussed.
From 1 September 1988 to 30 September 1993, a search for an unrelated donor (URD) was started for 633 Italian patients. Eighty-five of them (13%) were transplanted. Despite the introduction of more strict criteria for the selection of compatible donors, the percentage of patients who reached transplant increased significantly after December 1992. For patients who started a search before and after January 1993, respectively the probability of transplant by 8 and 16 months from search activation was 4 and 10%, compared to 22 and 37% (P = 0.0001). The average intervals between search activation and graft were 15 and 8 months respectively, for the first and second group (P = 0.0001). Data of 75 consecutive transplants performed up to March 1994 were analyzed. Actuarial 2-year survival was 15% for patients grafted before 1992 and 40% for those grafted after January 1992. In this latter period, survival of patients with malignant and non-malignant disorders was 32 and 67%, respectively. In univariate analysis, patients younger than 16 years (P = 0.01), patients grafted after 1992 (P = 0.01) and patients receiving the marrow from a 6-antigen matched donor (P = 0.01) showed a higher survival probability. Multivariate analysis did not show any difference, probably due to the low number of patients and to short follow-up. The adoption of stricter and more accurate HLA-matching criteria and the consequent reduction of deaths related to acute GVHD were the main reasons for the improvement of survival observed in patients grafted after 1992.
The role of autologous bone marrow transplantation (ABMT) in childhood ALL after an isolated extramedullary (IE) relapse is controversial. Between December 1984 and November 1995, 52 children underwent ABMT because of an IE relapse. The data were stored in the AIEOP-BMT Registry. Thirty four children were transplanted in 2nd CR; eighteen > 2nd CR. The median duration of 1st CR was 24 (range 3-69) and 18 (range 3-59) months, respectively. The median interval from last CR to ABMT was 6 (range 1-28) and 3 (range 1-81) months, respectively. The 5 year EFS for patients transplanted in 2nd CR was 67.7%, while the 3 year EFS for patients in > 2nd CR was 16.7%. In conclusion, ABMT was an effective treatment in early IE relapse only if performed in 2nd CR.
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Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma c), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID, which is usually associated with a lack of circulating T cells and the presence of B lymphocytes (T- B+ SCID). The gene(s) responsible for autosomal recessive T- B+ SCID is still unknown. The Jak-3 protein kinase has been found to associate with the gamma c-chain-containing cytokine receptors. Therefore Jak-3 or other STAT proteins with which it interacts are candidate genes for autosomal recessive T- B+ SCID. Here we investigate two unrelated T- B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100-->Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.
We studied antibiotic resistance patterns and extended-spectrum beta-lactamases (ES beta Ls) production in Serratia marcescens strains isolated in our hospital during 1993. We examined 210 S. marcescens isolates. Of these, 172 were obtained from 49 patients admitted to an intensive care ward; 157 out of 172 were obtained from February to October and presented the same pattern of antibiotic resistance, including monobactams and oxyimino-cephalosporins. The remaining 15 out of 172 isolates (obtained from September to December) were susceptible to all drugs tested, with the exception of first generation cephalosporins. Thirty-eight additional isolates were recovered, during the same period, from 28 patients admitted to wards other than the intensive care unit; also these strains showed the high susceptibility pattern reported above. Epidemic strains of S. marcescens produced three different types of beta-lactamase with pI 5.4, 5.5, and 8.4. In contrast, non-epidemic strains produced only one type of beta-lactamase with pI 8.4. Conjugation experiments showed that the beta-lactamases having a pI of 5.4 and 5.5 (but not the one with pI 8.4) were plasmid-mediated. Since the beta-lactamase with pI 5.5 was capable of hydrolyzing monobactams and oxyimino-cephalosporins it was classified as ES beta L. Electrophoretic analysis showed that plasmids obtained from multiresistant strains were of about 54 kb; these plasmids appeared also to code for aminoglycoside resistance. Our data indicate that the plasmid-mediated production of ES beta Ls may contribute to the epidemic spread of Serratia marcescens in high-risk wards.
We conducted a phase II study on 19 children with AML in first (10 patients) or second (nine patients) complete remission (CR) treated with ABMT, evaluating the combination of total body irradiation (TBI, 12 Gy in six divided fractions) and high-dose melphalan (140 mg/m2 in single dose) in an attempt to improve antitumour efficacy of conditioning regimen. All patients received cryopreserved and in vitro purged (mafosfamide at a dose of 100 micrograms/ml) bone marrow. The median time from first CR to ABMT was 5 months compared with a median time of 3 months for patients in second remission. One of the 19 patients, transplanted in second CR, died of transplant-related complication 10 days after transplant and another second CR patient relapsed on day +28, before engraftment. Three further patients in second CR relapsed at 6, 6 and 18 months after marrow transplant, respectively, and this determined a relapse rate of 43% in children given ABMT in second CR and 0% for patients transplanted in first remission (P < 0.05). Seventy-two per cent of all patients are projected to be alive and disease-free at 6 years, whereas the event-free survival of patients in first and in second CR is 100 and 44%, respectively (P < 0.05). Although the number of patients does not allow us to draw any firm conclusion, our results are encouraging and suggest that the association of TBI and high-dose melphalan appears to be safe and valuable.