Quercetin decreases proliferation of orbital fibroblasts and their release of hyaluronic acid.

BACKGROUND: Inhibition of fibroblast (FB) proliferation and hyaluronic acid (HA) production may be a therapeutic approach to Graves' ophthalmopathy (GO). The flavonoid quercetin has a wide range of activities, including reduction of FB growth. AIM: To investigate the effects of quercetin in orbital FB from GO patients and control subjects. METHODS: Primary cultures of orbital FB were treated with quercetin or with its glycosides rutin and quercitrin. Cell proliferation, necrosis, apoptosis, HA production, and cell cycle were measured. RESULTS: Beginning at a 30 µM concentration, quercetin, but not rutin and quercitrin, reduced cell proliferation, with no difference between GO and control FB. The effect of quercetin on proliferation was due to necrosis and cell cycle blockade, whereas apoptosis was unaffected. Quercetin reduced HA in the cell media, with no difference between GO and control FB. CONCLUSIONS: Quercetin reduces cell proliferation and HA release in orbital FB. Whether these initial findings have any potential for the use of quercetin in the clinical practice remains to be established.

Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation.

Early onset of primary hyperparathyroidism (PHPT) and multiglandular involvement suggest a familial form in which germline mutation of a PHPT-related gene(s) and a somatic event at the same locus can be often demonstrated. We investigated the involvement of multiple endocrine neoplasia type 1 (MEN1) and HRPT2 genes in a 39-year-old man with recurrent PHPT. PHPT was firstly diagnosed at the age of 21 and the patient had two recurrences separated by extended periods of normocalcemia. This unusual history prompted us to investigate other family members and study the MEN1 and HRPT2 genes. An HRPT2 germline missense mutation in exon 3 (R91P) was found in the index case, which was associated with different HRPT2 somatic alterations in each of the three examined parathyroid tumors. These findings are consistent with Knudson's 'two hit' concept of biallelic inactivation of classical tumor suppressor genes. Screening of 15 asymptomatic relatives was negative for the R91P germline mutation. All the three abnormal parathyroid specimens showed cystic features at histology and were negative for parafibromin immunostaining. In one specimen, diffuse parafibromin staining was evident in a rim of normal parathyroid tissue surrounding the adenomatous lesion. Our study shows that different somatic genetic events at the HRPT2 locus are responsible for the asynchronous occurrence of multiple adenomas in a patient carrying an HRPT2 germline mutation. The finding of diffuse parafibromin staining in a rim of normal parathyroid tissue, but not in the contiguous adenomatous lesion, reinforces the concept that loss of parafibromin expression is responsible for the development of parathyroid tumors in this setting.

[Epidemiologic surveillance in occupational bladder cancer: a Tuscan experience]. / Intervento di ricerca attiva delle neoplasie vescicali di origine professionale: una esperienza toscana.

The percentage of bladder cancer as occupational disease in West-Europe is of 5/10%, but only a few amount of them are recognized as occupational disease from INAIL. The above mentioned research project is realized in order to decrease the gap between expected and claimed cases of occupational disease and it is conducted with the collaboration of ASL of Pisa, ASL of Empoli, Azienda Ospedaliera Universitaria Pisana and INAIL. 677 patients with bladder cancer were interviewed by phone, among them 64 subjects had a working experience compatible with neoplastic risks because had a previous occupational exposure to aromatic amines and metal working fluids. These cases were discussed into a Medical Staff and 40 cases were considered "probable" for occupational disease, 18 "possible", 3 cases are suspended for more research, 3 cases are considered "no professional disease". The research allows finding out a great number of bladder cancer, increasing the total amount of workers with occupational disease. The integrated approach with the collaboration among different institutions is surely the best way to allow and guarantee a suitable and right protection of workers with occupational disease.

Asthma-like symptoms, atopy, and bronchial responsiveness in furniture workers.

OBJECTIVES: To study the role of individual and occupational risk factors for asthma in furniture workers. METHODS: 296 workers were examined (258 men, 38 women) with a questionnaire of respiratory symptoms and diseases, baseline spirometry, bronchial provocative test with methacholine, and skin prick tests. Non-specific bronchial hyperreactivity was defined as when a provocative dose with a fall of 20% in forced expiratory volume in 1 second (PD20FEV1) was < 0.8 mg and atopy in the presence of at least one positive response to skin prick tests. Workers were subdivided into spray painters (exposed to low concentrations of diisocyanates and solvents), woodworkers (exposed to wood dusts), and assemblers (control group). RESULTS: The prevalences of attacks of shortness of breath with wheezing and dyspnoea were higher in spray painters (13.5% and 11.5% respectively) than in woodworkers (7.7% and 6.3%) or in assemblers (1.6% and 1.6%); prevalences of chronic cough, asthma, and rhinitis were also slightly but not significantly higher in spray painters and in woodworkers than in assemblers. The difference in the prevalence of respiratory symptoms among the job titles was due to the atopic subjects, who showed a higher prevalence of chronic cough, wheeze, shortness of breath with wheeze, dyspnoea, and asthma in spray painters than in the other groups. The prevalence of non-specific bronchial hyperreactivity in subjects who performed bronchial provocative tests was 17.7%, with no significant difference among groups. Asthma symptoms were significantly associated with non-specific bronchial hyperreactivity. Asthma-like symptoms plus non-specific bronchial hyperreactivity was found in 4% of assemblers, 10% of woodworkers, and 13.3% of spray painters (chi 2 = 2.6, NS). Multiple logistic analysis taking into account individual (smoke, atopy, age) and occupational (job titles) risk factors confirmed that spray painters had higher prevalence of chronic cough than assemblers, and a trend in increasing the prevalence of shortness of breath with wheeze, dyspnoea, and asthma. CONCLUSIONS: Painters in the furniture industry, particularly atopic subjects, are at higher risk of asthma-like symptoms than other job titles. In these workers asthma-like symptoms are more sensitive than non-specific bronchial hyperreactivity in detecting a negative effect of the occupational exposure.

[Early neonatal manifestations of group B Streptococcus infection: case series and preventive strategy]. / Manifestazioni neonatali precoci da GBS: casistica e strategie preventive.

Group B Streptococcus (GBS) is, so far, one of the most important causes of neonatal morbidity and mortality. In order to elucidate the extent of this problem a screening for GBS has been performed on a group of pregnant women and their neonates. Maternal vaginal and rectal swabs were obtained on admission to the labor area. In these infants throat swabs at birth and throat and rectal swabs on day 4th and 6th were obtained. In the 14,248 pairs mother/infant examined, the rate of colonization was, respectively, 9 (7%) and 4 (1%). 6 among 569 colonized newborn show evidence of the early onset type infection (respiratory form: 2 cases; meningitic form: 4 cases). Fatal outcome and severe neurologic impairment were observed respectively in 3 and 1 patient. Risk factors (prematurity) were present only in two patients. In all cases clinic evidence was observed before that laboratory findings were disposable. The Authors remark the importance of the bacteriological screening in pregnancy, and of antibiotic therapy intrapartum in women with risk factors and in colonized newborn in the first hour of life when acute phase reactants are positive.

[Rhodococcus equi infections in AIDS: personal cases]. / Sepsi da Rhodococcus equi in corso di AIDS: osservazioni personali.

We report on the occurrence of an uncommon pathogen, Rhodococcus equi (R.e.) in HIV infection. In the period february 1990-July 1991 we performed the diagnosis of R.e. infection (lung, lung-central nervous system) in two infected patients, aged 27 and 31 years, both males, drug addicts, classified as CDC IV. In the first of them an cavitating right bronchopneumonia (bpm) was diagnosed as of tuberculous origin, on the ground of the microscopic demonstration of an acid-fast, gram-positive strain in b.a.l.. A standard antituberculous regimen was uneffective and R.e. was eventually isolated in three blood culture taken shortly before the exitus and at post-mortem examination of the lungs. In the second patient a subclavian right bpm developed without microbiological evidence of any common pathogen. A third-generation cephalosporin course was only partially successful (clinical amelioration, incomplete clearing of radiological findings). After 3 months the patient relapsed and an aseptic meningitis developed. Cultures of blood and csf yielded a R.e. strain; post-mortem examination revealed a diffuse, cavitating bpm. Our personal experience underlines the difficulty in recognizing R.e. infections in compromised host, because of similarity to other entities (i.e. tuberculosis) and the absence of pathognomonic hints.

Treatment of choroidal melanoma: MR imaging in the assessment of radioactive plaque position.

Verification of the position of an episcleral iodine-125 gold plaque in relation to underlying choroidal melanoma is essential during early radiation therapy to ensure accurate plaque placement and thus optimum dose delivery. The authors used magnetic resonance (MR) imaging to examine 15 patients with choroidal melanoma after plaque placement to assess tumor coverage. The relationship of the plaque to the tumor was well defined in all cases, including two tumors anterior to the ora serrata. MR imaging measurements of the plaques were within 1 mm of the actual plaque sizes, while tumor measurements were within 2 mm of the preoperative ultrasound estimations of tumor dimensions. Tumors as small as 3 mm thick were readily visualized with MR imaging. Associated subretinal effusion was demonstrated in seven cases.

Use of MR imaging to assess results of chemotherapy for Ewing sarcoma.

MR imaging was used to monitor the results of initial chemotherapy of primary Ewing sarcoma of bone. The signal intensities of the soft-tissue and marrow components of the tumor were evaluated on T2-weighted images obtained in 10 patients (nine with responsive tumors) at presentation and during and immediately after completion of two cycles of chemotherapy. MR evidence of marrow and soft-tissue involvement was seen in all tumors at presentation. After treatment, the bone-marrow component of the nine drug-sensitive tumors showed an increase in signal intensity that in eight cases became comparable to that of water. Changes in signal intensity of the soft-tissue component were variable, consisting of increases in two of the responsive lesions, no change in three, a decrease in two, and complete resolution of the soft-tissue mass in two. There was no increase in signal intensity of either the bone-marrow or the soft-tissue component of the single nonresponsive tumor. All of the responsive tumors showed advanced healing, and abundant bony sclerosis was apparent on CT. Bone-marrow examinations, performed in seven of the nine patients with responsive lesions, disclosed no evidence of tumor in four. Two patients had residual extramedullary tumor; the nonresponsive lesion contained sheets of tumor cells. The increase in marrow signal intensity on T2-weighted images was associated with replacement of marrow elements by a loose, hypocellular myxoid matrix containing modest amounts of collagen, consistent with response to chemotherapy and eradication of disease. Therefore, an increase in the T2-weighted signal intensity of the bone-marrow component of Ewing sarcoma of bone reflected a favorable response to chemotherapy. MR signal changes, however, were not predictive of resolution of malignant disease within adjacent soft tissue.

Seborrheic dermatitis in otherwise healthy patients and in patients with lymphadenopathy syndrome/AIDS-related complex: treatment with 1% bifonazole cream.

Recent studies reported in the literature have repeatedly pointed out the utility of imidazole derivatives, one of which is bifonazole, in the therapy of seborrheic dermatitis (SD). The cause of this pathological situation is still under discussion but the therapeutic success obtained with antimycotics speaks in favor of the pathogenetic importance of Malassezia ovale in this context. There is a high frequency of SD type complaints in patients with HIV infections in whom immune defenses against various pathogens, including yeasts, are deficient. We therefore verified the clinical efficacy of 1% bifonazole cream on 15 subjects with SD of the face, 9 of whom were affected with lymphadenopathy syndrome/AIDS-related complex (LAS/ARC). The treatment was administered over a four-week period and gave good results in 12 patients. The best results, however, were observed in those suffering from LAS/ARC.

[Yersinia enterocolitica sepsis in splenectomized thalassemic subjects. Description of 2 cases]. / La sepsi da Yersinia enterocolitica nei soggetti talassemici splenectomizzati. Descrizione di due casi.

Two cases of Yersinia enterocolitica septicemia in two splenectomized children with thalassemia major are reported. Human Yersinia enterocolitica septicemia is an uncommon condition, but its frequency may increase in patients having debilitating diseases or blood disorders, as well as a consequence of the splenectomy. Some brief considerations on the pathogenetic factors yielding, to severe infections in splenectomized thalassemic children are discussed. The high number of thalassemic people in Italy makes necessary an early diagnosis in case of septicemia. Particularly important is the blood culture, because of the slowness of the microbic development in stools.