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Biomedical subjects

A Morabito

Publications and source records attributed to A Morabito.

At least 55 records · Page 3Linked to original sources
PubMed2001

Do patients with tumor-positive sentinel nodes constitute a homogeneous group?

From January 1993 to May 2000, 1062 patients with primary cutaneous melanoma and no evidence of clinically detectable regional node metastases underwent sentinel node (SN) dissection to microscopically define the tumor status of the regional lymph nodes. A total of 1165 biopsies were performed. The SN identification rate was 89.6%. In 62.2% of the cases, only one SN was detected; 26.4% of patients had two SNs; and 11.4% had three or more SNs. Analysis of survival indicated that the tumor status of the nodes was the most important prognostic factor. Breslow's thickness had a significant impact on survival in tumors 4 mm or thicker, and ulceration dropped to a borderline-significant P value. To assess the tumor burden in positive SNs, all slides for patients at the Istituto Nazionale Tumori and S. Pio X Hospital were reviewed. Of 658 patients in this series, 90 had positive SNs. Eighteen of these patients had evidence of metastasis in other nodes. Of the remaining 72 with a single tumor-involved SN, 62% had a single metastatic deposit. Preliminary data from this study indicate that several subgroups may be identified among patients with positive nodes, but adequate analysis of survival requires a larger number of patients and a multicenter study.

Female↗
PubMed2001

Thalidomide: an old sedative-hypnotic with anticancer activity?

Thalidomide is a synthetic derivative of glutamic acid with sedative-hypnotic activity, which caused devastating teratogenic effects in the 1960s. This paper reviews the possible mechanisms of its teratogenic effect, its new therapeutic indications, the proposed mechanisms for its antitumor activity and, finally, reviews published studies of its application in oncology. Current data demonstrates that thalidomide is clinically promising in multiple myeloma, glioblastoma multiforme and renal cell cancer. Furthermore, a beneficial effect of the drug has been proposed in cancer-related cachexia, which merits further investigation. Well-designed, randomized studies are warranted to establish the possible indications of thalidomide as an antitumor compound.

Animals↗
PubMed2000

Effect of recombinant human erythropoietin on cerebral ischemia following experimental subarachnoid hemorrhage.

Erythropoietin exerts a neuroprotective effect during cerebral ischemia. We investigated the effect of systemic administration of recombinant human erythropoietin in a rabbit model of subarachnoid hemorrhage-induced acute cerebral ischemia. The animals were divided into three groups: group 1, subarachnoid hemorrhage; group 2, subarachnoid hemorrhage plus placebo; group 3, subarachnoid hemorrhage plus recombinant human erythropoietin (each group, n=8). Experimental subarachnoid hemorrhage was produced by injecting autologous blood into the cisterna magna. Treatment with recombinant human erythropoietin and placebo was started 5 min after subarachnoid hemorrhage and was continued every 8 h for 24 h. Before the animals were killed, erythropoietin concentration was measured in the cerebrospinal fluid. The rabbits were killed 24 h after subarachnoid hemorrhage and ischemic brain injury was histologically evaluated. In group 3, the concentration of erythropoietin in the cerebrospinal fluid was significantly increased and a significant reduction in cortical necrotic neuron count was also observed. These findings may encourage the use of erythropoietin in the treatment of cerebral ischemia that often occurs in the early stage of subarachnoid hemorrhage.

Animals↗
PubMed2000

Behaviour of metastasis in relation to vascular index in patients with node-positive breast cancer treated with adjuvant tamoxifen.

Some experimental studies suggested that one possible oestrogen-receptor-unrelated mechanism of action of tamoxifen involves inhibition of angiogenesis. We evaluated the correlation of the degree of vascularisation of the primary tumour and we assessed it by using the panendothelial marker anti-CD31 and immunohistochemistry with microvessels count, performed at the vascular 'hot spot' of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast cancer treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median follow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observation. The study of the hazard function for metastasis was performed by a generalized linear modelling approach with a binomial error according to Efron. The risk of first recurrence was strictly associated with vascular index, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an interaction of vascularity with oestrogen receptor (ER) status. However, in the subgroup of patients with ER-positive tumours the hazard of metastasis was almost constant in time, while in that with ER-negative tumours it increased rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascularized breast cancers may gain poor benefit of adjuvant tamoxifen and, therefore. that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial.

Antineoplastic Agents, Hormonal↗
PubMed2000

Identification of a new DRB3*02 allelic variant (DRB3*0209) by high-resolution sequence-based typing.

The HLA-DRB3/B4/B5 sequence-based typing method developed in this study in combination with PCR-SSP, enabled us to identify a new DRB3*02 allele, that was named as DRB3*0209 (GenBank accession number AF148518). This name has been officially assigned by the WHO Nomenclature Committee in May 1999. The new allele differs from DRB3*0207 by one substitution in codon 51 from AGG to ACG and another in codon 60 from TAC to TCC, resulting in aminoacid changes from Arg-->Thr (codon 51) and from Tyr-->Ser (codon 60). The DRB3*0209 allele was discovered in two related North Italian families. The fact that it was present in an hemizygous situation in three members of the paternal family and in one member of the secondary related family enabled us to isolate and sequence the new DRB3 allele without cloning, to identify its association with the DRB1 locus, and to generate an Epstein-Barr virus (EBV)-transformed cell line, now present in our ECBR (European Collection for Biomedical Research) Cell Line Bank.

Alleles↗
PubMed2000

The anterior mediastinal approach for management of tracheomalacia.

BACKGROUND: Tracheomalacia occurs as a primary developmental defect or may be secondary to vascular compression. It is common in association with esophageal atresia and tracheoesophageal fistula. Collapse of the weak trachea is a cause of recurrent respiratory symptoms but may be severe and life threatening. METHODS: Between 1978 and 1999 at Sheffield Children's Hospital and The Royal Manchester Children's Hospital, of 16 children with clinically significant symptoms of tracheomalacia 8 underwent combined aortopexy and tracheopexy, 1 had aortopexy alone, 4 only had a tracheopexy, and 3 had tracheal reinforcement with free costal cartilage ring grafts. The surgical approach was limited to a low cervical skin crease incision with a midline manubrial split providing extrapleural access to the anterior mediastinum and allowing for all surgery under direct unimpaired vision. RESULTS: Ten children did not require postoperative ventilatory support. Four underwent ventilation for a few hours or days. One child required CPAP for 4 months for residual tracheomalacia and a further child, who had 3 operations to insert 11 costal cartilage ring grafts, underwent ventilation intermittently for 6 months. Adequate tracheal patency could be verified by intraoperative tracheoscopy and was sustained postoperatively so that only 1 child with associated bilateral vocal cord paralysis came to tracheostomy. Four children required prolonged hospitalization because of residual tracheomalacia, 2 for bronchomalacia and 2 because of esophageal narrowing leading to further surgery. All other children were fit for discharge within 10 to 30 days of surgery. Long-term follow-up has confirmed sustained tracheal improvement and resolution of the life-threatening features of tracheomalacia. CONCLUSIONS: The authors recommend the low skin crease transmanubrial approach, as described by Vaishnav and MacKinnon, for tracheopexy, aortopexy and for tracheal reconstruction for tracheomalacia. The approach gives excellent access for surgery under direct vision through a relatively avascular plane. It is associated with less morbidity than a conventional thoracotomy and leaves a more acceptable aesthetic scar.

Child, Preschool↗
PubMed2000

Laparoscopic repair of Morgagni-Larrey hernia in a child.

Primary laparoscopic repair of Morgagni-Larrey hernia has been described in adult patients but not in children. This is the first report of primary laparoscopic correction in the pediatric age group without using a prosthesis. A Morgagni-Larrey hernia was found incidentally in a 3-year-old-girl. Laparoscopic correction of the defect was performed. After 6 months the patient is doing well. The chest radiograph shows complete resolution of the hernia. The laparoscopic approach allowed repair the hernia with minimal invasiveness. Laparoscopic correction is not difficult except for those hernias in which dense adhesions are present.

Child, Preschool↗
PubMed2000

Detection of haemoglobins with abnormal oxygen affinity by single blood gas analysis and 2,3-diphosphoglycerate measurement.

The aim is to determine if a single measurement of blood 2,3-diphosphoglycerate combined with gas analysis (pH, PCO2, PO2 and saturation) can identify the cause of an altered blood-oxygen affinity: the presence of an abnormal haemoglobin or a red cell disorder. The population (n=94) was divided into healthy controls (A, n=14), carriers of red cell disorders (B, n=72) and carriers of high oxygen affinity haemoglobins (C, n=8). Those variables were measured both in samples equilibrated at selected PCO2 and PO2 and in venous blood. In the univariable approach applied to equilibrated samples, we correctly identified C subjects in 93.6% or 96.8% of the cases depending on the selected variable, the standard P50 (PO2 at which 50% of haemoglobin is oxygenated) or a composite variable calculated from the above measurements. After introducing the haemoglobin concentration as a further discriminating variable, the A and B subjects were correctly identified in 91.9% or 94.2% of the cases, respectively. These figures become 93.0% or 86.1%, and 93.7% or 94.9% of the cases when using direct readings from venous blood, thereby avoiding the blood equilibration step. This test is feasible also in blood samples stored at 4 degrees C for 48 h, or at room temperature for 8 h.

2,3-Diphosphoglycerate↗
PubMed2000

Effectiveness and safety of a nonremovable fiberglass off-bearing cast versus a therapeutic shoe in the treatment of neuropathic foot ulcers: a randomized study.

OBJECTIVE: To evaluate and compare the rate of reduction of the surface area of neuropathic plantar ulcers in diabetic patients treated with nonremovable rigidity-differentiated fiberglass off-bearing casts or a cloth shoe with a rigid sole with unloading alkaform insoles. The secondary aim was to evaluate the side effects and degree of patient acceptance of treatment. RESEARCH DESIGN AND METHODS: Fifty diabetic patients with neuropathic plantar ulcers were consecutively enrolled and randomized to one of two treatment groups. Of the 50 patients, 24 were treated with a specialized cloth shoe with a rigid sole and an unloading alkaform insole (shoe group), and 26 patients were treated with a nonremovable off-bearing fiberglass cast (cast group). All patients in both study groups returned to the clinic for weekly control visits. Their ulcers were treated with a standard dressing. Tracings of the ulcer area using a transparent dressing were performed on the day of entry to the study and after 30 days of treatment. The presence of new ulcerations caused by the use of the pressure-relief apparatus was recorded. Patient acceptance of the treatment was measured using a visual analog scale. RESULTS: At the end of the treatment period, an 8.3% increase of the ulcer area was observed in two patients in the shoe group, whereas in the cast group, no patient presented an increase. The reduction of the ulcer area was statistically more rapid in the cast group (Mann-Whitney test, P = 0.0004). Furthermore, the number of ulcers completely healed at the 30-day time point was 13 (50%) in the cast group and 5 (20.8%) in the shoe group (P = 0.03). In both groups, no side effects were recorded. The average score +/- SD of patient acceptance was 91.15 +/- 9.9 in the shoe group and 88.33 +/- 17.3 (NS) in the cast group. CONCLUSIONS: Our study has shown a significant difference in the speed of the reduction of neuropathic plantar ulcers treated with a fiberglass cast compared with a specialized cloth shoe. The use of fiberglass material with variable rigidity has also shown two important results: the elimination of side effects including ulcers caused by the cast, and high patient acceptance. These data show that the use of off-bearing casts made with fiberglass bandages of variable rigidity is the elective treatment of neuropathic plantar ulcers.

Aged↗
PubMed2000

Percutaneous transluminal coronary revascularization in women: higher risk of dissection and need for stenting.

BACKGROUND: Even though success rates of percutaneous transluminal coronary angioplasty (PTCA) are influenced by gender, women are at higher risk for adverse procedural events. Plaque dissection has been demonstrated to cause more adverse cardiac events during PTCA in the female gender than the male, but it is not clear how much it could influence stent implantation and procedural complications in the stent era. This study sought to evaluate whether the prevalence of dissection is equal in men and women with similar vessel size, which factors are associated with the risk of this complication and whether stenting has modified the immediate outcome. METHODS: Three hundred thirty-nine lesions were studied in 100 consecutive women and 128 men with a vessel diameter < or = 3.5 mm, who underwent PTCA in our catheterization laboratory between March 1998 and March 1999. RESULTS: Procedural success rates were similar in the two groups (93.9% women vs 97.6% men). Complications were one coronary artery bypass graft and five acute myocardial infarctions. In the group of women, however, there was a significant increase in the incidence of plaque dissection during the procedure (37.9 vs 21.7%, p = 0.001), with consequent increased need for stenting (70.4 vs 52.2%, p < 0.05) to achieve adequate final results. Moreover, dissection was strongly associated (p = 0.03) with procedural complications. Multivariate analysis of the whole patient cohort showed the risk of dissection to be associated only with the female gender (p = 0.009), diabetes (p = 0.029), and type C lesion morphology (p = 0.019). CONCLUSIONS: Women are at higher risk of plaque dissection, which is associated with adverse procedural events and an increased need for stenting.

Aged↗
PubMed2000

Lumbosacral congenital dermal sinus presenting in a 52-year-old man. Case report.

Spinal congenital dermal sinus is a rare entity which results from failure of the neuroectoderm to separate from cutaneous ectoderm during the process of neurulation. This epithelium-lined tract forms a potential communication between the skin surface in the midline along the spine and the deeper tissues. We describe a case of an asymptomatic lumbosacral congenital dermal sinus in a 52-year-old man. Microsurgical excision of dermal tract was performed with no postoperative complications and with a satisfactory cosmetic result. The authors stress the importance of an early neuroradiological and neurosurgical management of the lesion. The embryogenesis of this pathological condition and the possible complications are also discussed.

Congenital Abnormalities↗
PubMed1999

Low prevalence of selective human leukocyte antigen (HLA)-A and HLA-B epitope losses in early-passage tumor cell lines.

The down-regulation of human leukocyte antigen (HLA) class I molecules, especially the selective down-regulation of certain allelic products, is believed to represent a major mechanism of tumor escape from immune surveillance. In the present report, an original approach is described to precisely evaluate and classify HLA class I epitope losses in 30 cancer patients with malignant melanoma and lung, breast, endometrium, ovary, and colon carcinoma tumors. Early-passage tumor cell lines were established in culture from the corresponding metastatic tumor lesions obtained in each patient. Both the cell lines and the tumor lesions were compared, in their HLA-A and -B expression, to the peripheral blood mononuclear cells (PBMCs) obtained from the same patient (autologous PBMCs). On the basis of HLA-genotyping data, the appropriate monoclonal antibodies identifying mono- and poly-morphic HLA-A and HLA-B epitopes were selected from a panel of 34 antibodies for a total of 24 testable alleles. The selected antibodies were used not only in immunohistochemical assays on cryostatic tumor sections and cytospins of PBMCs but also in quantitative, sensitive flow cytometry assays on early-passage tumor cells and PBMC suspensions. With this latter method, a low overall HLA expression was detected in 26 tumor cell explants and a complete, generalized HLA-A, HLA-B, HLA-C loss in the remaining 4 cases. However, no complete, selective loss of any of the 45 tested HLA-A and HLA-B allomorphs was observed. Sequences from all of the HLA class I alleles could be detected at the genomic DNA level in tumor cells and tissues. At variance from the literature and the results of immunohistochemical experiments performed in parallel on the corresponding tumor lesions, the relative proportions of the various HLA epitopes were relatively preserved in each early-passage cell line/PBMC pair, and selective increases, rather than decreases, in the expression of polymorphic HLA epitopes had the highest prevalence and greatest magnitude. Our data suggest an alternative tumor stealth strategy in which up- and down-regulation are equally important. This alternative model of tumor-host interaction better fits the available models of tumor cell recognition by CTLs and natural killer cells bearing activatory and inhibitory receptors for HLA-A, HLA-B, HLA-C molecules.

Antibodies, Monoclonal↗
PubMed1999

Alcoholism as a complex trait: comparison of genetic models and role of epidemiological risk factors.

A genetic component for alcoholism appears likely, but the genes involved have yet to be identified. The mode of inheritance is probably more complex than for traditional mendelian disorders. In particular, there are marked differences in alcoholism by gender, parent-of-origin effects, ethnicity, and other epidemiological factors. We investigated the evidence for the presence of susceptibility genes for alcohol dependence in the Collaborative Study on the Genetics of Alcoholism data set.

Adolescent↗
PubMed1999

A phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: Gemcitabine and docetaxel have been claimed to be active single agents in advanced pancreatic cancer. We determined the maximum tolerable dose of docetaxel combined with a weekly fixed dose of gemcitabine and assessed the activity of this combination in advanced pancreatic cancer. PATIENTS AND METHODS: Phase I. Patients were treated with gemcitabine on days 1 and 8, every three weeks, at a fixed dose of 1,000 mg/m2; docetaxel was given at escalating doses starting from 70 mg/m2 on day 8. Phase II. In accord with the optimal two-stage phase II study design, 18 patients were treated with gemcitabine (1000 mg/m2) and the maximum tolerable dose of docetaxel (70 mg/m2). RESULTS: Phase I. Dose-limiting toxicities occurred at the second dose level of docetaxel (80 mg/m2), with all three patients developing grades 3 or 4 neutropenia. Consequently, the dose tested in the phase II study was 70 mg/m2. Phase II. In the 18 patients enrolled in the study, we registered only one partial response. The time to progression was 3 months, and the median treatment survival was 5.4 months. Grade 3-4 toxicities consisted of neutropenia (three episodes) and thrombocytopenia (two episodes). Furthermore, 10 patients complained of grade 3 fatigue. CONCLUSIONS: The addition of docetaxel to gemcitabine does not appear to be useful in advanced pancreatic cancer, since gemcitabine alone achieves similar results.

Adenocarcinoma↗
PubMed1999

Myelinolytic lesions in spinal cord of cobalamin-deficient rats are TNF-alpha-mediated.

Repeated intracerebroventricular (i.c.v.)microinjection of tumor necrosis factor-alpha (TNF-alpha) into normal rats causes intramyelin and interstitial edema in the white matter of the spinal cord (SC). This response is identical to that observed in the SC white matter of rats made cobalamin (Cbl) deficient by total gastrectomy (TG). Immunoblot analysis showed that: 1) the level of the biologically active form of the TNF-alpha protein (17 kDa) is higher in the SC of totally gastrectomized (TGX) rats 2 months after TG, i.e., at the postoperative time when edema is observed; 2) SC levels of TNF-alpha protein (17 kDa) in 2-mo-TGX-, Cbl-treated rats are reduced to control. Repeated i.c.v. microinjections of anti-TNF-alpha antibodies, transforming growth factor-beta1 (TGF-beta1) or interleukin-6 (IL-6) into TGX rats, begun shortly after TG, substantially reduced both intramyelin and interstitial edema in the SC white matter. This study provides the first evidence that the hallmark myelin damage of Cbl-deficient central neuropathy, which is a pure myelinolytic disease, is not caused directly by the withdrawal of the vitamin itself, but reflects enhanced production of the biologically active form of TNF-alpha by SC cells. This study thus supports the view that TGF-beta1 and IL-6 may act as neuroprotective agents in Cbl deficiency central neuropathy.

Animals↗
PubMed1999

HLA-A, -B, -C genotyping and expression in human nonlymphoid tumor cell lines.

A combination of molecular genotyping and protein biochemistry methods was used to assess the HLA-A, -B, -C genotyping and expression of six tumor cell lines. Four cell lines had been previously HLA typed by conventional serologic methods. Two could not be typed by serology because deficient in the surface expression of HLA-A, -B, -C molecules. As shown herein, all the 25 alleles carried by the six tested cell lines were typed at the DNA level. In addition, discrepancies between the previous serologic and the present DNA typing results were detected in 9 of the 21 tested serologic specificities. Typing at the protein level by isoelectric focusing and allele-specific monoclonal antibodies confirmed the DNA typing data. Our results exemplify the limits of the serologic typing procedures and demonstrate that molecular methods are highly desirable to conduct functional experiments and identify HLA losses in neoplastic cells at single allele level.

Alleles↗
PubMed1999

Multi-institutional phase II randomized trial of integrated therapy with cisplatin, dacarbazine, vindesine, subcutaneous interleukin-2, interferon alpha2a and tamoxifen in metastatic melanoma. BREMIM (Biological Response Modifiers in Melanoma).

The aim of this study was to evaluate the toxicity and efficacy of a monochemotherapy regimen of dacarbazine (DTIC), tamoxifen , interferon-alpha2a and interleukin-2 (IL-2) and two polychemotherapy regimens of cisplatin, DTIC, vindesine, tamoxifen, interferon-alpha2a with or without IL-2 in patients with metastatic melanoma. Consecutive patients with metastatic melanoma were enrolled in this trial and were randomized to arm A, consisting of DTIC 800 mg/m2 every 21 days, IL-2 9 MIU subcutaneously days 1-5 and 8-12, arm B, consisting of cisplatin 30 mg/m2 days 1-3, DTIC 250 mg/m2 days 1-3 and vindesine 2.5 mg/m2 day 1 every 28 days (CVD), or arm C, consisting of CVD plus IL-2 6 MIU days 1-5 and 8-12 every 28 days. In all three arms Interferon 3 MU subcutaneously three times a week and tamoxifen 20 mg orally were given throughout. Ninety-two patients were included in this study. Patient characteristics in the three groups were well balanced. The three regimens were delivered on an outpatient basis without major toxicity. The toxicities that did occur consisted primarily of flu-like symptoms in the IL-2 arms (A and C) and haematological toxicities in the CVD arms (B and C). No grade IV toxicities were encountered and no treatment-related deaths occurred. The total response rate was 13% in arm A, 35% in arm B and 37% in arm C. The median duration of response was 6 months and the median survival was 11 months. According to this phase II randomized trial polychemoimmunotherapy with CVD has an objective response rate of 35-36%, while monochemoimmunotherapy with DTIC has a response rate of 13%.

Antineoplastic Combined Chemotherapy Protocols↗