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Biomedical subjects

M Lazzaro

Publications and source records attributed to M Lazzaro.

15 recordsLinked to original sources

[Comparative immunogenicity of 2 antirabies vaccines in a 2-1-1 post-exposure vaccination schedule].

Few trials have compared the Purified Duck Embryo Vaccine (PDEV) and the Human Diploid Cell Vaccine (HDCV) in a post-exposure immunization schedule of 4 shots (2 on day 0 and 1 each on day 7 and 21, or 2-1-1 schedule). A retrospective analysis compared 10 patients with PEDV and 20 with HDCV, who had received the 2-1-1 schedule as well as 20 UI mg/kg of immune globulins on day 0. The median neutralizing antibody titers on day 21 (after 3 doses) and the median of maximum titers until day 90 were higher for HDCV than for PEDV (0.6 IU/ml versus 3.5 IU/ml [p < 0.04] and 2.5 IU/ml versus 5.8 IU/ml [p < 0.03] respectively). Seven patients had not reached the seroconversion titer of 0.5 IU/ml after 3 doses (day 21). These results differ from previous studies showing a 100% seroconversion rate on day 21, and suggest that more studies are required before these 2 vaccines can be used in the 2-1-1 schedule after severe exposure.

Adult↗

Cyclosporin A resistance of herpes simplex virus-induced "fusion from within" as a phenotypical marker of mutations in the Syn 3 locus of the glycoprotein B gene.

We here report research in which nine strains of Herpes simplex virus (HSV) with fusing activity were investigated in order to establish precise phenotypical markers of mutations in the carboxy terminus of glycoprotein B (gB). The gene region encoding the carboxy terminus of gB was isolated, then cloned, and finally sequenced. Our investigation showed that seven strains have different mutations in the syn 3 locus. We observed no base difference in the gB gene region encoding the carboxy terminus of gB of two other strains. Strains with a mutation in the carboxy terminus of gB induced fusion from within (FFWI) in the presence of Cyclosporin A (CyA) at a concentration up to 150 microM. There are two clusters of mutations correlated with the syn 3 locus and selected in the presence of CyA: One group comprised of amino acid substitutions at position 816, the other of changes at positions 853, 854, and 857. In contrast, the fusion induced by strains with mutations in other syn loci is CyA sensitive. CyA inhibits the FFWI at concentrations of 20-60 microM. The results demonstrate the CyA resistance of HSV-induced FFWI should serve as a phenotypical marker of mutations in the carboxy terminus of gB. Moreover, our investigations revealed that fusion from without (FFWO) does not always serve as a phenotypical marker of mutations in the syn 3 locus. On the one hand, all FFWO-positive strains possess a syn 3 locus mutation, whilst, on the other hand, five strains with mutations in the carboxy terminus of gB are FFWO negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The carbamyl phosphate synthetase promoter contains multiple binding sites for C/EBP-related proteins.

The promoter of the gene (CPS) encoding rat carbamyl phosphate synthetase I has been mapped 5' to a segment of about 525 nucleotides upstream from the transcription start point and, when analyzed in liver nuclear extracts, contained six well-defined protein-recognition elements, designated CPS sites I-VI. All six elements were recognized, with varying affinities, by CAAT and enhancer-binding protein (C/EBP alpha) produced in bacteria. Oligodeoxyribonucleotides corresponding to CPS site II or to the C/EBP alpha-recognition element of the ALB promoter, site D, competed with the six CPS-promoter elements in footprinting assays. However, mutagenesis of the C/EBP alpha-recognition element, 5'-GTTGCAAC, at the core of site II was sufficient to abolish transactivation of the CPS promoter by C/EBP alpha in co-transfected HepG2 cells. These findings indicate that the CPS promoter contains multiple recognition elements for factors with DNA-binding specificities similar to C/EBP proteins. Activation by C/EBP alpha, however, requires promoter site II.

Animals↗

Palytoxin: an extraordinarily potent stimulator of prostaglandin production and bone resorption in cultured mouse calvariae.

Palytoxin, a nonphorbol ester-type tumor promoter, stimulated the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvariae in organ culture. The action of palytoxin on bone resorption occurred at extraordinarily low concentrations; enhanced resorption was regularly observed at 0.5 pg/ml, and the ED50 was 1-2 pg/ml (approximately 3 X 10(-13) M). Palytoxin-induced formation of PGE2 and bone resorption were inhibited completely by indomethacin (200 ng/ml). Concentrations of palytoxin above 10 pg/ml led to progressively decreasing enhancement of bone resorption; by 100-250 pg/ml no stimulation of resorption was observed despite continued high production of PGE2. Treatment with high concentrations of palytoxin (100 or 250 pg/ml) for 24-72 h inhibited cAMP accumulation stimulated by exogenous PGE2 or PTH and inhibited bone resorption induced by PGE2, PTH, or an analog of cAMP. Thus, palytoxin exhibited a biphasic dose-response curve for enhanced bone resorption, with stimulation at low concentrations (0.5-10 pg/ml) and toxic inhibition at high concentrations (greater than 50 pg/ml). Palytoxin is one of the most potent stimulators of bone resorption yet identified.

1-Methyl-3-isobutylxanthine↗

Tumor necrosis factor-alpha (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism.

Recombinant human (h) and murine (m) tumor necrosis factor (TNF)-alpha stimulated bone resorption and the production of prostaglandin (PG) E2 in neonatal mouse calvaria in organ culture. In experiments of 72-h duration, the effect on bone resorption was of large magnitude (an average increase in medium calcium of 3.3 mg/dl above control values in 11 separate experiments) and occurred over a concentration range of 0.1-20 ng/ml mTNF and 0.5-50 ng/ml hTNF. Accompanying the TNF-enhanced release of bone calcium there was enhanced accumulation of PGE2 in the culture medium. The increases in medium calcium and PGE2 were both inhibited completely by nontoxic concentrations of 4 different PG cyclooxygenase inhibitors (indomethacin, piroxicam, ibuprofen, and acetylsalicylic acid) but not by the noncyclooxygenase inhibitor salicylic acid. The magnitude of the PGE2 response, but not the calcium release, was less for bones treated with TNF than for those treated with equipotent doses of epidermal growth factor or human transforming growth factors-alpha or -beta, suggesting that the local site of production of PGE2 in bone may be different for TNF than for the other factors. Repeated sc injections of hTNF to intact mice for a 48-h period produced a statistically significant elevation of the plasma calcium concentration. Because TNF is produced by cells of the monocyte/macrophage lineage in response to invasive stimuli such as the presence of tumor, our findings indicate that a host factor produced in response to malignant cells can cause enhanced bone resorption. Thus, the concept of the humoral hypercalcemias of malignancy must be expanded to include mediators not produced by the tumor cells themselves.

Animals↗

Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria.

Human alpha and beta transforming growth factors (TGF-alpha and TGF-beta) stimulated the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvaria in organ culture. Significant stimulation of bone resorption by TGF-alpha was observed with a concentration of 0.2 ng/ml (35 pM) and by TGF-beta with 0.2 ng/ml (8.0 pM). Enhanced production of PGE2 and bone resorption stimulated by either TGF-alpha or TGF-beta were both inhibited by indomethacin. We conclude that TGF-alpha and TGF-beta are potent and powerful stimulators of the resorption of mouse bone by a mechanism that involves the enhanced local production of PGE2.

6-Ketoprostaglandin F1 alpha↗

Polyaromatic hydrocarbons administered in humans by dermal route increase total IgE.

Inhalation of polyaromatic hydrocarbons (PAHs) extracted from diesel exhaust particles (DEP) enhances local (nasal) production of IgE in humans. The aim of the present research is to investigate whether in humans dermal exposure to PAHs which are not extracted from DEPs increases serum IgE, and whether host factors modify the immunologic effect. In thirty-two patients with acute psoriatic lesions, a cream containing 3% of coal tar (which holds a variety of PAHs) was applied to the skin for 24 hours. Serum IgE were measured before (IgE0) and four (IgE4) and eight (IgE8) days after application. Replicated means were compared by analysis of variance for repeated measures and by the Newman-Keuls' test. IgE0, IgE4 and IgE8 were 151.19, 159.69 (a 6% excess) and 170.90 kU/L (a 13% excess) respectively; pairwise comparison showed IgE8 was significantly higher than IgE0 (p<0.05). At multiple linear regression analysis, the percentage increase in serum IgE across observation days was the dependent variable against age, sex, cigarettes/day, urinary 1-pyrenol, atopy, skin area treated, and grams of cream. Of the independent variables, only age had a significant (p<0.028) influence: the younger the age, the higher the IgE response to PAHs. We conclude that whatever the source and the route of entry (skin or respiratory tract), PAHs increase total serum IgE, mainly in younger age groups.

Administration, Cutaneous↗

Lung microcytoma: a multidisciplinary therapeutic approach.

This report is of 26 patients diagnosed with microcytoma of the lung in stages I, II, and IIIa. All patients received surgical treatment as well as postoperative chemoradiotherapy when indicated by stage. Mean survival rates were 16 months for stage 1, 10 months for stage II and 6 months for stage IIIa disease. For many years surgery was considered contraindicated in the treatment of pulmonary microcytoma. Now a multidisciplinary approach is being used in which surgery has a crucial role. Microcytoma of the lung has a poor prognosis due to its early metastasis and rapid growth. It is crucial to have early diagnosis and accurate, consistent staging as the basis for treatment. A review of literature shows that the use of surgery, chemotherapy and radiotherapy are all important in treatment of microcytoma. Chemotherapy is successfully utilized preoperatively to improve local control, decrease neoplastic mass, induce histological regression and as postoperative adjuvant therapy. Radiotherapy has been shown to be effective preoperatively to reduce local mass and prophylactically for cerebral metastasis. Surgery is crucial to irradicate the neoplastic mass, improve staging accuracy, decrease the possible selection of neoplastic clones resistant to postoperative therapy, decrease local recurrence and allow less aggressive chemoradiotherapy. We feel the most effective protocol for pulmonary microcytoma includes preoperative chemotherapy and radiotherapy when indicated followed by surgical intervention and finally successive adjuvant therapy. The limited number of our cases does not consent a statistically significative conclusion. Our data confirm the importance of the surgical procedure in stages I and II, where according also to other authors, the best results are obtained. Surgical indication in stage IIIa is still discussed due to precocius lymphnode dissemination that significantly affects long-term survival.

Carcinoma, Small Cell↗

[Benign thyroid disease: 20-year experience in surgical therapy].

This retrospective study compares recurrence and postoperative complication rates after isthmo-lobectomy and subtotal thyroidectomy (group I) vs near-total and total thyroidectomy (group II) for benign thyroid disease. Seven hundred and forty-three patients were operated on for thyroid diseases over the period from 1977 to 1998. We considered 202 patients operated on for benign thyroid disease from 1988 to 1998. The follow-up ranged from 1 to 10 years (mean: 3.4 yrs). One hundred and thirty-two patients (65.3%) were operated on for bilateral nodular goitre, 35 (17.3%) for unilateral nodular goitre, 14 (6.9%) for toxic goitre and 21 (10.4%) for thyroiditis. Over the period 1988-1992, 19 patients underwent isthmo-lobectomy and 71 subtotal thyroidectomy (group I). From 1993 to 1998, 39 patients underwent near-total thyroidectomy and 61 total thyroidectomy (group II). The relapse rate was 14.4% in group I, while there were no recurrences in group II (p = 0.000064). Temporary hypocalcaemia was significantly higher (p = 0.000001) in group II (29%) than in group I (2.2%). Within group II, the rate was significantly higher (p = 0.0013) after total thyroidectomy (37.7%) than after near-total thyroidectomy (15.4%). In our experience, near-total and total thyroidectomy are an appropriate approach for preventing recurrence in patients with benign thyroid disease despite the fact that the risk of temporary hypocalcaemia is higher than after less radical surgery. Near-total thyroidectomy and the exercise of all due care in the surgical technique may help to reduce its incidence.

Adult↗

A multidisciplinary approach to the treatment of small-cell lung cancer: the role played by surgery.

The authors report their data on 344 cases of small-cell lung cancer treated according to indications with combined chemoradiotherapy and in selected cases with surgical intervention. In patients with limited disease, the results of pharmacologic therapy significantly improve the prognosis only in association with surgery. The role of surgery has been reappraised in the treatment of small-cell lung cancer which appears, nowadays, multidisciplinary.

Carcinoma, Small Cell↗

Sentinel node role in breast cancer surgery.

Radical surgery of breast cancer includes lymphadenectomy of axilla as well as the dissection of the neoplastic tissue. However recently many works have raised doubts on the opportunity of performing routinary axillary dissection, which elevates morbidity risk, in absence of axillary metastases. However, unfortunately, information on axillary lymph node pathology, is not available with any other technique excluding complete dissection and istopathological examination. Sentinel node technique is a new methodology that consents evaluation of lymph node status in the operating theatre. It allows the surgeon to judge on the opportunity of carrying out the lymphadenectomy or not.

Aged↗

Wernicke's encephalopathy post subtotal extended gastrectomy.

Wernicke's encephalopathy, neuropathy caused by a deficiency of thiamine is a syndrome characterized by memory troubles, mental confusion, ophthalmoplegia and nystagmus. The authors present a case that came up in a patient who underwent a subtotal gastrectomy because of malignant neoplasm of the stomach. More or less three months after the intervention the patient's general conditions were considerably declined and characterised by alimentary vomit, sensory obnubilation and neuromuscular deficit. After appropriate diagnostic ascertainments a repetition of the neoplastic disease was to be excluded locally and at a distance. So the authors analysed the different etiopathogenic possibilities to get a better clinical view of the syndrome in the surgical patient.

Gastrectomy↗

Update on prostate cancer screening.

Prostate cancer is the second most common cause of death in men; it is diagnosed in about 1 in 10 men. Significant risk factors include, but are not limited to, race and age; the peak age at diagnosis is the seventh decade. A through screening program, sensitive to the risk factors and targeted to patients with curable prostate cancer, can decrease the rates of mortality and morbidity associated with this disease, without overtreating patients who have latent cancer. Screening methods include annual digital rectal examinations and prostate-specific antigen tests. Staging is important when treatment options are considered and treatment morbidity rate is weighed against disease mortality rate. Research concerning genetics changes and chemoprevention trials of vitamins and hormonal agents are targeted toward primary prevention. Implications for practice should include primary prevention, screening and detection, public education, and monitoring of the disease.

Aged↗