Microbiological environmental monitoring in high-risk departments during building activities in a hospital site.

BACKGROUND: This study examines the microbial and fungal contamination associated with the presence of renovation works in a hospital site in Sardinia (Italy). METHODS: Microbiological environmental monitoring was carried out before, during and at the conclusion of the works in the Ophthalmology Department in view of a risk assessment procedure. RESULTS: Although the median values of microbial and fungal counts were found raised during the works, protective measures set out by the internal procedures limited the contamination level. CONCLUSIONS: This study emphasizes the benefits of environmental surveillance for airborne contamination to help prevent outbreaks of nosocomial mycosis associated with construction work.

Serum lipoproteins and cancer.

BACKGROUND AND AIMS: In haematological and solid tumours the blood lipoprotein profile has been reported to be altered; while decreased levels of total cholesterol and increased values of triglycerides have been observed. The mechanism and meaning of these changes are, however, not fully understood. The aim of the present study was to determine relationships between cancer progression and serum lipoproteins. METHODS AND RESULTS: We performed a case-control study. We included cancer patients admitted to the 1st Division of Medical Oncology, Businco Hospital of Cagliari, Italy, between 1984 and 1998; 519 patients with any type of solid tumours and 928 healthy controls. We considered total cholesterol (C), high-density lipoprotein (HDL)-C, low-density lipoprotein (LDL)-C, triglycerides and apolipoprotein A-1; other parameters examined were glycaemia, insulinaemia, body mass index (BMI), homeostasis model assessment-estimated insulin resistance (HOMA-IR), C reactive protein (CRP) and tumour necrosis factor-alpha (TNF-alpha). In the cancer group HDL-C and apolipoprotein A-1 were lower (p<0.05) and triglycerides were higher (p<0.05) than in controls; HDL-C (mg/dl) females: 48 vs. 64; males, 40 vs. 52; Apo-A-1 (mg/dl) females: 125 vs. 173; males, 120 vs. 152; triglycerides (mg/dl) females: 133 vs. 96; males, 152 vs. 117. Glucose (mg/dl) was lower in the cancer group (p<0.05); females, 72.3 vs. 80.0; males, 75.7 vs. 78.4. CONCLUSION: Using multivariate analysis we were able to rule out cardiovascular and inflammatory diseases as causes of low HDL-C, and also demonstrate that these alterations can be shown as a specific consequence of the presence of a malignant tumour with a diagnostic and prognostic significance.

Hck inhibitors as potential therapeutic agents in cancer and HIV infection.

Hematopoietic cell kinase (Hck) is a member of the Src-family of non-receptor tyrosine kinases, which plays many roles in signalling pathways involved in the regulation of cell processes. Hck is expressed in cells of hematopoietic origin, specifically myelomonocytic cells and B lymphocytes. It participates in phagocytosis, adhesion, migration, regulation of protrusion formation on cell membrane, lysosome exocytosis, podosome formation and actin polymerization. More importantly from a medicinal chemistry point of view, high levels of Hck are involved in chronic myeloid leukemia and other hematologic tumors. Furthermore, Hck activity has been associated with virus infections including HIV-1. In particular, Hck is activated by the HIV-1 accessory protein Nef, a multifunctional HIV-1 protein that accelerates progression to AIDS and enhances the infectivity of progeny viruses. Nef binding to Hck leads to kinase activation which is important in AIDS pathogenesis. For these reasons, Hck represents a potentially good therapeutic target for the treatment of both specific cancers and HIV infection. This article summarizes Hck biological activities connected with malignancies and HIV infection, many of which have been only recently reported, and presents an overview of the compounds endowed with Hck inhibitory activity, especially focusing on the medicinal chemistry aspect.

Click chemistry, a potent tool in medicinal sciences.

This review focuses on the application of click chemistry in medicinal sciences, and particularly on its role in drug discovery. Because of its high modularity, click chemistry helps to accelerate the current drug discovery process, which relies on massive screening of chemical libraries. This article describes examples of click chemistry applications that are aimed at finding new lead candidates against pathologies such as cancer, AIDS and Alzheimer's disease, and explores the impact that the technique could have in therapy and prevention in the near future, through application in drug delivery systems, bioconjugation and diagnostic. An introduction, addressed to researchers who intend to use this methodology, examines the opportunities to perform click reactions according to the most common and best studied techniques, such as synthesis in water, on solid phase, and under microwave or ultrasound irradiation. Every topic is furnished with examples which have appeared in the literature in the last five years and is clarified by schemes and figures.

Sequential treatment with interferon and chemotherapy of metastatic malignant melanoma. Total remission of cutaneous and visceral metastasis, but not of cerebral metastasis.

A woman 35 years of age suffering from cutaneous and visceral metastatic melanoma was treated with recombinant Interferon alpha 2b (rIFN alpha 2b) subcutaneously 3 X 10(6) U/m2 3 times a week for 3 months with no apparent effect on the course of the illness. Two months after IFN therapy the patient developed cerebral metastasis. A cycle of carmustine, 100 mg/day for 3 days, was given, and complete disappearance of the cutaneous and visceral, but not of the cerebral manifestations was observed. Two consolidation cycles based on vincristine, dacarbazine and lomustine were then administered. The patient died 26 months after beginning treatment with IFN and 18 months after chemotherapy for the cerebral metastasis. No trace of tumor at the cutaneous or visceral level was found at autopsy.

[Hormonal therapy with androgenic steroids in diffuse malignant neoplasms of the breast]. / Sulla ormonoterapia con steroidi androgeni delle neoplasie maligne diffuse della mammella

2-alpha-methyl-17-beta hydroxy-androstan-3-one was given to advanced breast cancer patients whose general condition (preterminal in many cases) or haematological picture precluded other cytostatic management. Rapid progression of the tumour was noted in 65%, improvement in 15% and no change in 20%. It is felt that androgens alone should only be given where other more effective treatments are contraindicated. They can be associated with polychemotherapeutic courses to exploit their anabolising and antianaemic activity.

[Estrogen therapy of advanced breast cancer]. / Terapia estrogenica del cancro avanzato della mammella.

The results obtained with oestrogen treatment of diffuse malignant cancer of the breast are reported. Improvement was obtained in 50% of cases, 23.3% remained stationary and 26.6% worsened. Side effects were confined essentially to liver trouble of colostatic type, a disturbance that was temporary and closely linked with the drug dose employed. Some aspects of high dose antitumour hormone treatment are examined in detail: hormone dose in the induction phase and during maintenance, latency time before the appearance of the first signs of improvement, relationship between age, sexual endocrinal state and therapeutic result, correlation between time of onset of the disease, free interval and result obtained.

High-level production of heterologous protein by engineered yeasts grown in cottage cheese whey.

Cottage cheese whey is a cheese industry by-product still rich in proteins and lactose. Its recycling is seldom cost-effective. In this work we show that the lactose-utilizing yeast Kluyveromyces lactis, engineered for production of recombinant human lysozyme, can be grown in cottage cheese whey, resulting in high-level production of the heterologous protein (125 microg/ml).

Vinorelbine, cisplatin, and 5-fluorouracil as initial treatment for previously untreated, unresectable squamous cell carcinoma of the head and neck: results of a phase II multicenter study.

BACKGROUND: The combination of vinorelbine (VNR), cisplatin (CDDP), and 5-fluorouracil (5-FU) has previously been shown to be active in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCHNC). This multicenter Phase II study was carried out with the aim of evaluating the effectiveness of this combination in patients with previously untreated, unresectable locally advanced SCHNC. METHODS: Sixty patients with previously untreated, unresectable SCHNC were treated with CDDP 80 mg/m2 on Days 1, 5-FU 600 mg/m2 as a 4-hour infusion on Days 2-5, and VNR 25 mg/m2 i.v. bolus on Days 2 and 8. There were 15 patients with laryngeal carcinoma, 19 patients with oropharyngeal carcinoma, 15 with carcinoma in the oral cavity, 5 with carcinoma in the hypopharynx, and 4 with carcinoma in the maxillary sinus. Most patients (78%) had Stage IV disease. After achievement of the best possible objective response, patients were subjected to definitive locoregional treatment, i.e., radiotherapy and/or surgery, as appropriate. RESULTS: All patients completed the induction chemotherapy. After a mean of 3.86 cycles per patient, the overall response rate was 88% (95% confidence interval [CI], 82-94%), with a complete response rate of 23% (95% CI, 14-26%). Complete responses were more frequently seen in patients with N0-1 disease than in those with N2-3 disease (P = 0.037). No other statistically significant correlation between type of response and extent of disease was noted. Toxicity consisted mainly of myelosuppression and gastrointestinal side effects. After definitive locoregional treatment, 58% of patients were clinically free of disease. These patients included those who had complete response after induction chemotherapy, 19 of 39 patients who had partial response, and 2 with stable disease. Median disease free survival was 16 months, and median overall survival was 23 months. CONCLUSIONS: The combination regimen of CDDP, 5-FU, and VNR was very active in previously untreated SCHNC. It was well tolerated in most cases, and neurotoxicity was not a major side effect. This regimen, which does not require hospitalization, should be compared with standard chemotherapy, such as the combination of CDDP and continuous-infusion 5-FU.