Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

Autologous bone marrow transplantation as adjuvant treatment for high-risk Hodgkin's disease in first complete remission after MOPP/ABVD protocol.

Fifteen patients with very poor prognosis Hodgkin's disease in remission after MOPP/ABVD regimen, were treated with high-dose chemotherapy (HDC) and autologous marrow transplantation (ABMT) immediately after achieving complete remission (CR). Thirteen patients (86.6%) remain alive in unmaintained CR at a median time of 36 months (range 10-64 months) post-transplant. In the other two patients reasons for failure included relapse of Hodgkin's disease (one patient) and death due to interstitial pneumonitis secondary to carmustine therapy. These patients were compared with a historical control group consisting of 24 patients with the same poor prognostic factors, who achieved CR with MOPP/ABVD and did not receive other treatment. Eight out of 24 patients (33%) remain alive and well in unmaintained CR at a median time of 42 months (range 19-83 months). The administration of MOPP/ABVD combined with HDC and ABMT was not associated with an increased incidence of major toxicity. The results achieved support the early sequential treatment of a highly effective drug combination followed by HDC/ABMT that can substantially improve the likelihood of cure in these advanced stage very poor prognosis Hodgkin's disease patients.     

Variable dystrophin expression in different muscles of a Duchenne muscular dystrophy carrier

The majority of Duchenne muscular dystrophy (DMD) female carriers show dystrophin immunostaining abnormalities, although a significant proportion of clinically non-manifesting carriers are normal following this analysis. We had the opportunity to study dystrophin immunostaining in two different muscles, the vastus lateralis and the rectus abdominis of a possible DMD carrier. While the vastus showed normal dystrophin immunostaining, pathological staining was detected in her rectus abdominis. These findings seem to indicate that dystrophin expression can vary in different muscle groups of a DMD carrier. The implications of these findings in DMD carrier detection and possible dystrophin function are discussed.     

Determination of the human salivary peptides histatins 1, 3, 5 and statherin by high-performance liquid chromatography and by diode-array detection

A reversed-phase high-performance liquid chromatography (HPLC) method with diode-array detection for the quantification of several human salivary peptides is described. Sample pretreatment consisted of the acidification of whole saliva by phosphate buffer. This treatment produced precipitation of mucins, alpha-amylases and other high-molecular-mass salivary proteins, simultaneous inhibition of intrinsic protease activities and reduction of sample viscosity. Direct HPLC analysis by diode-array detection of the resulting acidic sample allowed one to quantify histatin 1, histatin 3, histatin 5, statherin, as well as uric acid, in normal subjects. Moreover, the groups of peaks pertaining to proline-rich proteins and cystatins were tentatively identified. The method can be useful in assessing the concentration of salivary peptides from normal subjects and from patients suffering oral and/or periodontal diseases.     

The intracellular structure of secretory and ductal epithelia of human major salivary glands. A scanning electron microscopic study

The secretory and ductal cells of human salivary glands have been studied at Scanning Electron Microscopy (SEM) by our modification of the Aldehyde-Osmium-DMSO-Osmium (A-ODO) maceration method which enables the analytical study of human bioptical specimens. The most interesting results are those concerning the visualization of the cytoplasmic aspect of intercellular canaliculi of serous cells and of mitochondria of ductal cells. The canaliculi appear as elongated cylindrical structures fenestrated by holes correspohding to the bases of microvilli deprived of the cytoskeleton. Mitochondria of principal cells are longer and more complex than previously reported.     

Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.

BACKGROUND: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. PATIENTS AND METHODS: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). RESULTS: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT.     

Lipid peroxidation induced by N-acetylcysteine in isolated rat hepatocytes

In isolated rat hepatocytes N-acetylcysteine induces an increase of lipid peroxidation, as evaluated by the malondialdehyde production and diene conjugation. Lipid peroxidation did not result in increased cell mortality. Antioxidants and free radicals scavengers completely protect toward lipid peroxidation induced by N-acetylcysteine.     

Association study of the I/D polymorphism and plasma angiotensin-converting enzyme (ACE) as risk factors for stent restenosis

The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95%). Restenosis rates among genotypes were 31.2% DD, 25.5% ID and 28.8% II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7+/-18.6 units/l compared with 22.8+/-12.8 units/l; P=0.0001) and a strong independent predictor of ISR [OR (odds ratio)=3.70; 95% CI (confidence interval), 2.40-5.71; P<0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR=0.16; 95% CI, 0.04-0.69; P=0.014; and patients with AMI, OR=0.21; 95% CI, 0.061-0.749; P=0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7% DD, 24.3% ID and 17.6% II (P=0.02; DD compared with non-DD OR=1.57; 95% CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.     

Dopamine genes and migraine

Migraine is a common chronic disorder with an etiology still mostly unknown. Several neurotransmitters such as dopamine and serotonin are considered to be involved in the pathogenesis of the disease and the study of their systems is crucial in the understanding of migraine. Dopaminergic receptors are variously represented in human CNS and periphery. The hypothesis that a hypersensitivity of the dopaminergic system may have a role in migraine is based on clinical and genetic data. Genetic data are represented by association studies using dopaminergic genes as candidate genes which show that the D2 receptor gene appears to be involved in the pathogenesis of migraine.