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Biomedical subjects

F Barbieri

Publications and source records attributed to F Barbieri.

At least 55 records · Page 3Linked to original sources

Antiproliferative effect of DNA polymerase alpha antisense oligodeoxynucleotides on breast cancer cells.

Antisense oligonucleotides appear to offer considerable promise as sequence-specific inhibitors of gene expression. Different cellular targets for oligodeoxynucleotides with oncologic interest have been identified such as oncogenes, growth factors, and cell cycle-related genes. DNA polymerase alpha (pol alpha) plays a relevant role in DNA synthesis and cell proliferation. Pol alpha gene expression is constitutive throughout the cell cycle and its mRNA content and activity are related to the growth rate and neoplastic phenotype. The effects of a 18-mer pol alpha antisense oligomer on the proliferation of the MDA-MB 231 breast cancer cell line have been investigated. After 48 h in culture with oligomers (10 microM), about 50% growth inhibition was observed in antisense-treated cells, as evaluated by 3-(4,5-dimethythiazol-2yl)-2,5-diphenyltetrazolium bromide assay and cell count. [3H]Thymidine incorporation exhibited a 90% inhibition of DNA synthesis associated to 64% accumulation of cells at the G1-S border of the cycle as by flow cytometry, at 24 h. Northern hybridization and SDS-PAGE of immunoprecipitated MDA-MB 231 cell lysates revealed a decreased expression of pol alpha mRNA and a reduction of the 180-kDa polypeptide, respectively. Collectively, the data further confirm the relevance of pol alpha in the replicative cycle, as well as strengthen the potentiality of the antisense strategy for the control of gene expression and cell growth.

Adenocarcinoma↗

Biological monitoring of human exposure to atrazine.

Atrazine exposure was evaluated in six manufacturing workers by personal and biological monitoring. Total atrazine exposure varied from 10 to 700 mumol per workshift and total urinary atrazine excretion accounted for 1-2% of the external dose. The spectrum of the urinary atrazine metabolites comprises bi-dealkylated (80%), deisopropylated (10%), deethylated (8%) and unmodified atrazine (2%). The metabolites are eliminated in urine in slightly longer than 24 h: 50% of the amount is excreted in the first 8 h following the workshift.

Adult↗

Soluble interleukin-2 receptor and urinary neopterin concentrations in malignant lymphoma.

The serum concentrations of soluble interleukin-2 receptors and urine neopterin were studied in 82 patients with malignant lymphomas (25 patients with Hodgkin's disease and 57 patients with non-Hodgkin's lymphoma. Increases in soluble interleukin-2 receptors and in urinary neopterin were significantly correlated with the clinical phase of the disease. The average values in both Hodgkin's disease and non-Hodgkin's lymphoma patients suffering from the disease in its active phase were significantly higher than those of patients in complete remission. Neopterin concentrations (but not soluble interleukin-2 receptor concentrations) were also elevated in clinical stages III-IV of each disease. Urinary neopterin correlated directly and significantly with the erythrocyte sedimentation rate and inversely with haemoglobin. Finally, a longitudinal analysis showed a general tendency for the markers to return to normal values, in accordance with the favourable outcome of therapy; this was more evident for urinary neopterin than for soluble interleukin-2 receptors. These findings seem to confirm that soluble interleukin-2 receptors and especially urinary neopterin can be useful markers for monitoring and prognosis of malignant lymphomas.

Adult↗

Amiodarone-induced experimental acute neuropathy in rats.

Amiodarone was injected endoneurially at increasing doses into the exposed tibial nerve of rats to study its electrophysiologic and pathologic effects on peripheral nerve fibers. Forty-five male Wistar rats were used, and each of the following concentrations was injected into 15 nerves: 25 micrograms/mL, 50 micrograms/mL, and 100 micrograms/mL. Microinjection of a 25 micrograms/mL concentration of amiodarone resulted in a subacute, incomplete conduction block evident at day 3 postinjection. This conduction block remained stable until day 10 and recovery was complete at day 35. Microinjection of a 50 micrograms/mL concentration of amiodarone produced a faster evolving conduction block, and significant axon degeneration (approximately 40% of fibers). Injection of a 100 micrograms/mL concentration resulted in severe acute motor axon degeneration followed by complete but delayed regeneration. Results of morphological studies closely correlated with electrophysiological findings. Amiodarone thus seems to have a direct toxic effect on axons at high concentrations in the peripheral nerve, and we suggest that different pathological changes described in human amiodarone neuropathy could be related to different concentrations of the drug in the nerve, perhaps due to variability of blood-nerve barrier efficacy.

Amiodarone↗

Is early onset cerebellar ataxia with retained tendon reflexes identifiable by electrophysiologic and histologic profile? A comparison with Friedreich's ataxia.

An electrophysiologic and histologic study was performed on 18 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Sensory and motor conduction velocity (SCV, MCV) was measured along peripheral nerves in all patients, somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) were recorded in 13; cortical stimulation (CS) in 12, and sural nerve biopsy in 4 patients were also performed. The results as a whole allow a division of EOCA patients into 2 groups: with (7 patients) and without (11 patients) peripheral neuropathy. Among EOCA patients with neuropathy a differential diagnosis with Friedreich's disease patients was not possible according to BAEPs and CS, while SSEPs could differentiate 2 out 5 patients in whom they were performed.

Adolescent↗

POEMS syndrome: follow-up study of a case.

We report here the case of a 20-year-old man with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M proteins, skin changes). This rare syndrome followed a 3-year history of a syndrome that mimics a chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment with cyclophosphamide induced regression of the syndrome and improved peripheral nerve conduction.

Adult↗

Methotrexate, vinblastine, epidoxorubicin and cisplatin (M-VEC) in patients with locally advanced transitional bladder cancer.

M-VEC (methotrexate, vinblastine, epidoxorubicin and cisplatin), a new combined drug regimen in which epidoxorubicin has been substituted to adriamycin to reduce the toxicity of the original M-VAC chemotherapy, has been tested in 23 patients with locally advanced transitional cell bladder cancer (TCBC) (stage T2-T4 No Mo). After two to four courses, an objective response was observed in 19 patients, with 13 clinical complete responses. Seven patients underwent cystectomy after chemotherapy: one patient had no residual tumor on bladder specimens, five patients had a surgical eradication of the disease, while one patient had only a partial resection. Eight relapses of bladder carcinoma were observed, three among the surgically treated patients and five among patients who did not undergo cystectomy, with a median time-to-relapse of 9.7 months. Progression-free survival at 24 months was 52.3%. M-VEC regimen appears to be effective in locally advanced TCBC, with acceptable toxicity.

Adult↗

The use of antisense oligodeoxynucleotides (aODNs) for the therapy of cancer.

Although specific cancer targets are difficult to identify, the recent development of antisense oligodeoxynucleotides (aODNs) as inhibitors of gene expression has been shown to provide a new and useful tool in antiblastic management. aODNs are able to specifically interact with gene or mRNA sequences and inhibit the expression of relevant molecules for cancer pathogenesis and progression. Since alpha-DNA polymerase (pol-alpha) plays an essential role in cell proliferation, aODNs to pol-alpha have been synthesized in order to block mRNA translation and affect the growth of MDA-MB 231, human breast cancer cell line and SW626 ovarian cancer cells. A rapid colorimetric test (MTT assay) which measures cell growth and survival has been employed to evaluate the effects induced by ODN treatment. The present experimental results demonstrate that the aODNs to pol-alpha are able to significantly affect cell proliferation. This study provides an encouraging basis for the exploitation of ODNs as therapeutic agents in vitro and in future clinical application.

Cell Division↗

Pyridoxine neuropathy. A four-year electrophysiological and clinical follow-up of a severe case.

In a 54-year-old male a severe sensory neuropathy was observed during treatment for pulmonary tuberculosis with isoniazid (400 mg/day) and pyridoxine (600 mg/day). Eight months after withdrawal from isoniazid the sensory symptomatology was still progressing, although muscle strength was never reduced. A sural nerve biopsy revealed marked loss of large myelinated fibres. Only when pyridoxine treatment was interrupted did a slow improvement begin. A clinical and electrophysiologic follow-up showed a very slow and still incomplete recovery after four years. The possibility of an unusual individual susceptibility to toxic effects of pyridoxine is considered.

Electrophysiology↗

The role of surgery in the multimodal treatment of primary gastric non-Hodgkin's lymphomas. A report of 76 cases and review of the literature.

Seventy-six patients with primary gastric non-Hodgkin's lymphomas (PGL) were diagnosed, and 75 were treated between 1975 and 1985. According to the Working Formulation 22 patients had low-grade malignant histologic subtypes, 27 intermediate-grade, and 27 high-grade. Twenty-four cases were diagnosed by endoscopic biopsies, 52 through laparotomy biopsies. Forty-five underwent subtotal or total gastric resection; seven were considered unresectable at laparotomy; 23 did not undergo surgery because of the high operative risk, mainly due to advanced age and coexisting diseases; and one died of myocardial infarction a few days after admission, before starting therapy. All patients who did not undergo laparotomy were staged with bipedal lymphangiography or abdominal ultrasonography and/or computed tomography. Stage, evaluated according to the criteria of Musshoff, was I or II1 in 16 cases, II2 in five, and IV in the remaining 55. Treatment modalities included surgery (S), chemotherapy (CT), radiotherapy (RT), and combinations thereof in the following proportions: only S in ten cases, S + CT in 32 cases, S + RT in one case, S + CT + RT in two cases, CT only in 25 cases, CT + RT in five cases. No substantial differences in response to therapy and in survival were found in relation to the different treatments. Ten-year survival was 43% in Stage I or II and 20% in Stage IV. Of the 45 resected patients, five postoperative deaths were recorded (11%). No bleeding or perforations were observed in the 30 unresected patients, and survival of such cases compared with that of the resected ones. These findings, together with data from the literature, suggest that some of the advantages claimed for surgery in PGL (debulking and abatement of the risk of perforation or hemorrhage during CT or RT) have been overestimated in relation to the intrinsic surgical risk and to the possibility of anticancer therapy. Gastric resection may still be unavoidable as a diagnostic procedure in a minority of cases and may represent the primary therapeutic procedure in clinically assessed early-stage and low-risk patients, but it cannot be considered mandatory whenever possible merely for debulking purposes or to obviate possible perforation or hemorrhage. The CT and/or RT can be effective in unresected and even bulky cases, providing minimal risk of severe hemorrhage or perforation.

Adolescent↗

Thymidine labelling index as prognostic factor in resected non-small cell lung cancer.

To assess the prognostic value of tumor proliferative activity, 89 patients with operable non-small cell lung cancer were studied. Tumor samples were obtained during surgery and cell kinetics were analyzed by the in vitro thymidine labelling index (TLI). The overall median TLI (2.9) was used to identify two subsets of patients with high and low proliferating tumors. In univariate analysis survival was significantly longer in patients with lower TLI (P = 0.047) and with stage I-II (P = 0.003) and T1-T2 tumors (P = 0.043). In multivariate analysis, stage was the most important prognostic parameter (P = 0.004). The risk of death for patients with TLI higher than 2.9 was increased (hazard ratio = 2.01, CI = 0.96-4.27).

Adult↗

Cerebellar ataxia and hypogonadism. A clinicopathological report.

A female showed primary amenorrhea and slowly progressive ataxia of limbs and gait, that had started when she was 18 years old. Endocrine data were consistent with hypogonadotropic hypogonadism. She died at 35 years of age. Post mortem examination showed mucinous carcinoma of the lung, hypoplastic uterus, atrophic ovaries. The cerebellum was small, with the atrophy most marked in the vermis, and the pons was shrinked. There was almost complete Purkinje cell disappearance and neuronal loss in the granular layer and the inferior olives.

Adult↗

A family with tomaculous neuropathy mimicking Charcot-Marie-Tooth disease.

The appearance of Guillain-Barré syndrome in a 9-year-old girl led to the detection of a hereditary neuropathy in her family. This neuropathy showed clinical and electrophysiological characteristics of Charcot-Marie-Tooth disease. Only nerve biopsy performed in a sister of the proband allowed diagnosis of tomaculous neuropathy which presented unusual clinical, electrophysiological and bioptic aspects.

Biopsy↗

Clinical and genetic heterogeneity in early onset cerebellar ataxia with retained tendon reflexes.

A clinical and genetic study was performed on 20 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Mean age at onset was 8.8 (SD 6.0) years. The frequency distribution of age of onset significantly differed from the normal distribution. Consanguinity rate was 16.7% and segregation ratio 0.164. As well as ataxia, which was a constant feature, there were signs of involvement of the cortico-spinal tracts and/or peripheral nerves in most patients. Results of neurophysiological studies were not homogeneous, nor were morphological findings of the sural nerve biopsy. The data suggest that EOCA may be genetically and clinically heterogeneous.

Adolescent↗

Neurocutaneous melanosis, neurofibromatosis and spinal meningioma: an unusual association.

The case of 38-year-old woman bearer of a congenital giant naevus "en pélerine" with numerous neurofibromas and other satellite naevi was reported: the patient was afflicted by spastic tetraparesis, more pronounced on the right side. MRIscan of the spine revealed the presence of a cervical spinal tumor shown histologically to be a psammomatous meningioma. The skin picture was consistent with neurocutaneous melanosis; the rarity of its association with neurofibromatosis and spinal meningioma is discussed in the light of embryologic arguments.

Adult↗