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Biomedical subjects

D Carbone

Publications and source records attributed to D Carbone.

At least 19 recordsLinked to original sources

A novel method for preparing and characterizing alcoholic EPD suspensions.

Ceramic suspensions composed of alumina and mixtures of alumina and zirconia powders in ethyl alcohol were prepared. A solution of citric acid and triethylamine was used as dispersant. The citric acid, which usually is used as dispersant in water alumina suspensions, gave excellent results in ethyl alcohol also if it was used in conjunction with triethylamine. A novel method consisting of combined measurements of grain size, zeta potential, and transmittance was optimized to study the dispersion and stability properties of the ceramic suspensions; by using this method the optimal dispersant amount was determined. The suspensions based on alumina and alumina-zirconia powders were used to coat stainless steel plates by electrophoretic deposition (EPD); the optimal composition of suspensions and the used EPD parameters made it possible to obtain coatings with uniform thickness and composition.

Journal Article↗

Hormonal control of inhibin B in men.

Serum inhibin B (IB) and testosterone (T) levels, secreted by Sertoli cells (SC) and Leydig cells (LC), respectively, are parameters of the functional state of these cells. Whereas LC activity and, consequently, T secretion are regulated by serum LH, factors regulating IB secretion by SC are still partially unknown. There is evidence that under certain conditions such as puberty, aging or some spermatogenesis defects, LH levels or Gn-independent factors might contribute to regulating SC activity and IB secretion. Among these factors, GH and IGF-I as well as PRL might have a role. Therefore, in order to explore the possible effects of either LH alone and FSH alone or a combination of both Gn, respectively, on SC function, IB plasma levels and spermatogenesis, we studied their effects in 6 patients with hypogonadotropic hypogonadism (HH), whereas the effects of GH on these parameters were studied in 6 men with panhypopituitarism (PH). Finally, the possible effects of PRL on SC function and spermatogenesis were studied in 6 patients with hyperprolactinemia (HPRL); 24 normal, fertile adults served as control group. In men with HH, neither human chorionic Gn (hCG) nor FSH, respectively, were able to increase serum IB after 3 months of therapy, whereas combined Gn therapy for 24 months increased IB plasma levels and stimulated spermatogenesis in 4 out of 6 hypogonadal men. In panhypopituitaric men, GH added to the classical Gn therapy did not have an additional effect on serum IB levels or spermatogenesis. Surprisingly, in our hyperprolactemic men, IB plasma levels were increased and positively correlated (p<0.01) with serum PRL levels, whereas normalization of the latter by cabergoline treatment caused a decrease of IB levels and a moderate increase in T, LH and FSH. In conclusion, the lack of SC response to FSH therapy alone, as opposed to the response to combined Gn therapy, might indicate that normalization of serum T by hCG is required to obtain IB secretion by SC. Addition of GH did not affect SC function, serum IB levels or spermatogenesis. Finally, our data suggest that PRL plasma levels might have a direct role on IB secretion, suggesting that the hypogonadism found in patients with HPRL might be a consequence of both central (inhibition of Gn secretion) and peripheral (stimulation of IB secretion) origin.

Adult↗

Order parameter segregation in Ce0.7La0.3B6: 4f octopole and 5d dipole magnetic order.

The intriguing thermophysical properties of CeB6 have been subject to investigation for more than 20 years. In particular, an exotic ground state, phase IV, emerges under doping with La. We report resonant x-ray scattering results on the order parameter symmetries in phase IV of Ce0.7La0.3B6, which condenses below T(IV)=1.5 K. The results reveal a degree of mesoscopic 5d dipole antiferromagnetic order, with propagation vector Q0=(1/2 1/2 1/2), both below and above T(IV). Below T(IV), this polarization coexists with long-range 4f antiferro-octupole (AFO) order also at Q0. The marked differences in temperature dependence and spatial correlation suggest a state of order parameter segregation at low temperature. A simple model of AFO order, consistent with the polarization dependent azimuth symmetries, the Bragg angle, and temperature dependence is given.

Journal Article↗

Screening a coastal population in Southern Italy: iodine deficiency and prevalence of goitre, nutritional aspects and cardiovascular risk factors.

BACKGROUND AND AIM: To evaluate the prevalence of goitre by means of urinary iodine excretion, palpatory and ultrasonographic thyroid examinations in a heterogeneous population living by the sea. METHODS AND RESULTS: We used a special self-administered questionnaire to evaluate thyroid size, iodine intake, eating habits and cardiovascular risk factors in 600 subjects with a mean age of 45 +/- 17 years: 253 men (42.3%) and 347 women (57.7%). Urinary iodine excretion was low (72.1 +/- 15.7 microg/L; median 71.2) and associated with ultrasonographic evidence of an enlarged thyroid (16%) or structural thyroid abnormalities (30%), thus allowing us to define the Salerno Gulf as a mild-moderate area of endemic goitre. All of the subjects ate a Mediterranean diet, with a mean of two portions of fish/week. The cardiovascular risk factors considered were obesity, cigarette smoking, hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes, the prevalences of which were in line with those reported in other studies of similar age-matched populations. CONCLUSIONS: The moderate intake of fish and the consumption of a Mediterranean diet did not prevent goitre. Iodine deficiency and subsequent goitre endemia are also present at sea level, probably because of a diet based on local products grown on soil with a low iodine content or possible seawater, soil and air environmental pollution that may interfere with the availability of iodine. The assessment of iodine deficiency should therefore involve the entire population and not only subjects living far from the sea.

Adult↗

Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung cancer.

BACKGROUND: Neoadjuvant chemotherapy before resection is the standard of care for stage IIIA non-small cell lung cancer in many institutions. Further, neoadjuvant therapy is being studied in earlier stage lung cancer and may be applied more broadly in the future. There is little information about the effect of preoperative chemotherapy on the perioperative complications and mortality after lung resection. METHODS: All patients undergoing anatomic resection after neoadjuvant chemotherapy by a single surgeon at a single institution were compared with patients undergoing similar resections without preoperative chemotherapy. Complications were analyzed as life-threatening (pneumonia, emergency surgery, transfer to the intensive care unit, or intubation), major (prolonging hospital stay but not necessarily dangerous), and minor. The incidence of life-threatening complications, major complications, reintubation, tracheostomy, and mortality were analyzed to determine whether neoadjuvant chemotherapy might have an effect on these complications. Mortality was defined as hospital mortality. Two-tailed Student's t test was used to analyze differences in means and chi2 to determine differences in proportions. Differences less than 0.05 were considered significant. RESULTS: Thirty-four patients underwent resection after neoadjuvant chemotherapy, and 67 patients underwent resection without preoperative therapy. No differences between the two groups in age, pulmonary function, or comorbid diseases were found. The patients receiving chemotherapy did have a more advanced stage (2.52 versus 1.55, p < 0.0001). Striking increases were found in incidence of life-threatening complications (6.0% versus 26.5%, p = 0.0036), major complications (19.4% versus 47.1%, p = 0.0037), reintubation (3.0% versus 17.6%, p = 0.0093), and tracheostomy (0% versus 11.8%, p = 0.0042) in those patients who received preoperative chemotherapy. There was no hospital mortality. However, 2 (neoadjuvant) patients died within 90 days after discharge from the hospital of pneumonia and pulmonary embolus. This difference was also significant (0% versus 5.89%, p = 0.045). CONCLUSIONS: Neoadjuvant carboplatin and Taxol increased the perioperative life-threatening complications in this cohort of patients compared with a similar cohort undergoing operations by the same surgeon in the same institution. The most common life-threatening complication in patients receiving induction chemotherapy was the failure to respond to antibiotics given for pneumonia. Strategies to prevent these complications will be important, especially if chemotherapy before resection becomes the standard for earlier stages of non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Activity of docetaxel in platinum-treated non-small-cell lung cancer: results of a phase II multicenter trial.

PURPOSE: Although several new chemotherapeutic agents are promising as primary therapy in non-small-cell lung cancer (NSCLC), few have demonstrated activity in platinum-refractory disease. Based on encouraging results reported in two single-institution studies of docetaxel in this setting, we performed a multicenter phase II trial evaluating this novel taxane in previously treated NSCLC patients prospectively categorized by platinum response status. PATIENTS AND METHODS: Eighty patients with NSCLC previously treated with platinum-based chemotherapy received docetaxel at a dose of 100 mg/m(2) intravenously over 1 hour, repeated every 21 days, accompanied by dexamethasone 8 mg orally twice daily for 5 days. Forty-seven patients (59%) were defined as platinum-refractory based on response status to prior therapy. RESULTS: The median number of cycles delivered per patient was four (range, one to 21 cycles). Partial response was observed in 13 (16%) of 80 of patients, with similar response rates in platinum-sensitive and platinum-refractory patients. The median survival time was 7 months, and the 1-year survival rate was 25%. Docetaxel was relatively well tolerated in this previously treated population. Grade IV neutropenia was common in patients (77%) but typically of brief duration. Febrile neutropenia was observed in 11 patients (14%), with no fatal infections. Severe fluid retention was rare (4% of patients). CONCLUSIONS: This multicenter phase II trial confirms antitumor activity and encouraging survival with docetaxel therapy in platinum-treated and platinum-refractory NSCLC. To validate these results, a phase III trial randomizing platinum-treated patients to docetaxel or best supportive care is underway.

Adult↗

[Physical training and low-dose heparin-calcium in patients suffering from chronic obliterating arteriopathy of the lower limbs with intermittent claudication].

In the treatment of peripheral obliterating arteriopathy (POA) physical training provides clear results in terms of increased walking autonomy; it is still not fully clear whether the positive effects of physical training can be further improved by concomitant back-up drug therapy. For this purpose 374 patients of both sexes, with a mean age of 64 years, suffering from chronic peripheral obliterating arteriopathy of the lower limbs were enrolled in a controlled open clinical trial, instructed to follow a programme of physical training and randomly allocated to low dose treatment with heparin calcium (12,500 IU/day) for 6 months. An improvement in the claudicometric parameters (free gait interval, absolute gait interval and recovery time) measured at constant speed and in the resting Winsor ankle/arm index of the most severely damaged limb were observed in both groups. These improvements were significantly greater in the group receiving pharmacological treatment (p < 0.01) and efficacy increased in line with basal deambulatory impairment. The results obtained and the good tolerance of the drug underline the clinical efficacy of heparin calcium at low doses in association with a physical training programme in patients suffering from Fontaine's stage II peripheral obliterating arteriopathy.

Analysis of Variance↗

Stab avulsion of the short saphenous vein. Technique and duplex evaluation.

BACKGROUND: Stab avulsion, largely employed for removal of superficial collateral varicosities, is generally considered unsuited for surgical removal of the varicose short saphenous vein. OBJECTIVE: To describe the technique of stab avulsion of the short saphenous vein and objectively validate it by demonstrating the exact site of short saphenous vein division in the popliteal fossa. METHODS: Postoperative duplex scan of popliteal fossa in 18 limbs, 3.5 months after stab avulsion of the short saphenous vein. RESULTS: No short saphenous vein stump in 4 limbs (22%). An average 1.7-cm (range 1 to 4 cm) stump in the remaining 14 limbs. CONCLUSIONS: High (not flush) ligation of the standard short saphenous vein, considered adequate by experts who practice traditional (open field) surgery, can also be achieved by stab avulsion without a large incision, and dissection in the popliteal fossa. The stab avulsion technique is therefore adequate for removal of the standard short saphenous vein. However, because of the short-term follow-up of this study, in which cases high ligation is as efficacious as flush ligation cannot be indicated.

Adult↗

Smoking and cancer.

An extensive body of epidemiologic data has linked cigarette smoking to a wide variety of neoplastic diseases. Smokers have been found to incur an increased relative risk of mortality from cancer of the lung, head and neck, urinary tract, pancreas, and bladder. Recent work has also implicated smoking in the risk of leukemia and myeloma. The magnitude of these risks has prompted research aimed at identifying the carcinogens involved in specific smoking-related neoplasms, as well as potential genetic predispositions to the effects of these toxins. Mutations in tumor suppressor genes have been identified in both small-cell and non-small-cell lung cancer, and mutations in dominant oncogenes have been noted in the latter disease. A growing understanding of the molecular genetics of smoking-related cancers may translate into improved diagnosis and treatment. Detection of mutations in oncogenes or tumor suppressor genes in premalignant tissues might facilitate identification of individuals who have a hereditary predisposition to smoking-related carcinomas. In the future, tumor growth may be halted by replacement or substitution of mutated tumor suppressor gene functions or biochemical modulation of oncogene products. New forms of immunotherapy may also be targeted specifically toward mutant oncogenes in cancer cells.

Adult↗

Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions.

Accumulating evidence indicates that lung cancer arises due to multiple genetic changes in both dominant oncogenes, such as ras, and tumor suppressor genes, such as p53. In this report we examined whether the wild-type p53 gene is able to suppress in vitro and/or in vivo cellular growth of lung cancer cell lines which carry multiple genetic abnormalities. Introduction of a wild-type p53 complementary DNA expression vector into lung cancer cell lines carrying either a homozygous deletion (NCI-H358) or a missense mutation (NCI-H23) in the p53 gene greatly suppressed tumor cell growth. In contrast, p53 expression vectors bearing lung cancer derived mutations affecting single amino acids had lost this growth suppressing ability.

Animals↗

p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features.

We screened 77 non-small-cell lung cancer (NSCLC) cell lines for mutations of the p53 gene using a single-strand conformation polymorphism (SSCP) assay. We found that 57 cell lines (74%) had mutations of the p53 gene. Three cell lines had a deletion of the p53 gene. Of the remaining 54 cell lines, 49 cell lines were sequenced and 52 mutations were confirmed. In contrast to previously published p53 mutations in other human tumors, the p53 gene mutations in NSCLC were diverse with regard to the location and nature of the mutations. The region corresponding to codons 144-166, which is outside the evolutionarily conserved regions, was a frequent site of p53 gene mutations in NSCLC. The presence of a p53 gene mutation was not associated with age, sex, histological types, culture site, treatment intent, presence of prior cytotoxic treatment, neuroendocrine differentiation, median culture time or patient survival. The prevalence of p53 mutations in cell lines with ras mutations did not differ from that in cell lines without ras mutations. However, p53 gene mutations in NSCLC cell lines with ras mutations tended to cluster in exon 8, suggesting the presence of a functional domain of the p53 gene relating to interaction with the ras gene. We conclude that p53 and ras mutations are frequent and apparently independent genetic alterations which play different roles in the pathogenesis, progression and prognosis of NSCLC.

Amino Acid Sequence↗

High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors.

We analysed the p53 open reading frame (ORF) in 16 small-cell lung cancer (SCLC) cell lines by direct sequencing of cDNA/PCR products and in 20 SCLC tumors by chemical cleavage and single-strand conformation polymorphism analyses of genomic DNA/PCR products. Abnormalities of p53 were found in 16/16 cell lines (100%) and in 16/20 tumors (80%). In the SCLC cell lines, mutations (59% missense, 18% nonsense and 23% splicing) changing the coding sequence were dispersed between amino acids 68 and 342. In the tumor samples, while the mutations occurred predominantly in exons 5-8, other mutations were located outside these regions. G to T transversions were common, occurring in 32% of the cases. We found no p53 mutations in the corresponding normal tissue from 19 patients whose tumors had p53 lesions, indicating that the mutations were all somatically acquired. In analysing the clinical data of the patients we found no correlation between tumor response to therapy or survival and the location or type of mutations. We conclude from these data that: (1) p53 mutations are found in SCLC with high frequency; (2) p53 mutations in a significant fraction of cases generate cDNAs with nonsense or splicing mutations; and (3) to date, these mutations have all been somatically acquired events.

Base Sequence↗

[Cardiac rhabdomyoma in tuberous sclerosis. Presentation of a case].

We report of a case of cardiac tumor in a three months old infant, examined with echocardiography because a murmur was noted on routine examination. Further investigations brought out the diagnosis of tuberous sclerosis. Spontaneous regression of the tumor mass occurred in the following months. No signs of cardiac dysfunction of CNS involvement appeared. The peculiarity of rhabdomyoma as an early manifestation of tuberous sclerosis is emphasized.

Echocardiography↗

Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation.

We investigated the immunocytochemical staining and immunoblotting characteristics of 33 different p53 mutant proteins identified in lung cancer cell lines (18 small-cell lung cancer and 15 non-small-cell lung cancer) using monoclonal antibodies pAbs 240, 421 and 1801. The p53 mutants studied were representative of those found in lung cancer and included three deletions, four nonsense, seven splicing and 19 missense lesions. Control cell lines included six B-lymphoblastoid cell lines and two lung cancer cell lines without p53 mutations. Immunocytochemistry demonstrated 16 cell lines (48%) with definite overexpression of p53 protein (the high-expresser group of mutants), while in the remainder of cases either no p53 expression or low levels of p53 protein expression were found (the low-expresser group of mutants). The type of p53 mutation correlated with the expresser group. High expressers all had p53 missense mutations in exons 5-8, and immunocytochemistry identified 16/17 (94%) of these mutants. Several classes of p53 mutations occur in the low-expresser groups: deletions, splicing mutants, nonsense mutants and missense mutations outside of exons 5-8 all resulted in very low or undetectable levels of p53 protein. We conclude that there are low- and high-expression groups of p53 mutants in lung cancer and that the detection of protein expression in tumor cells by immunocytochemistry and immunoblotting is dependent upon the type of mutation of the p53 tumor-suppressor gene.

Blotting, Western↗