Describing readmissions to an Ebola case management centre (CMC), Sierra Leone, 2014.

Case management centres (CMCs) are part of the outbreak control plan for Ebola virus disease (EVD). A CMC in Sierra Leone had 33% (138/419) of primary admissions discharged as EVD negative (not a case). Fifteen of these were readmitted within 21 days, nine of which were EVD positive. All readmissions had contact with an Ebola case in the community in the previous 21 days indicating that the infection was likely acquired outside the CMC.

Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study.

BACKGROUND: The aim of the study was to evaluate tolerance and efficacy of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally advanced, resectable, rectal cancer. PATIENTS AND METHODS: Fifty-three patients with potentially resectable T3, N0-2 (87%) and T4, N0-2 (13%) rectal cancer were treated with capecitabine (825 mg/m2, twice daily for 7 days/week) and concomitant RT (50.4 Gy/28 fractions). Patients underwent surgery after 6-8 weeks followed, upon physician's indications, by 4-months adjuvant capecitabine. The primary end point was to determine the rate of pathologic complete response. Secondary end points were to assess the rate of clinical response and the safety profile. RESULTS: All patients but two completed the RT programme and 47 (89%) received 81%-100% of the capecitabine dose (100% of dose in 72% patients, 81%-95% in 17% patients and 48%-74% in 11% of patients). No patient had grade 4 toxicity. Grade 3 toxicity occurred in six patients (11%) and consisted mainly of leucopenia (4%) and hand-foot syndrome (4%). Mild or moderate toxicity was common and included leucopenia (72%), diarrhea (40%), proctitis (34%) and skin toxicity (20%). The overall clinical response rate was 58% and the downstaging rate was 57%, with a pathologic complete response rate of 24%. Among 34 patients with low-lying tumors (

Diosmectite (DIOSMECTAL) in preventive anti-diarrheic therapy in patients subjected to pelvic radiation.

BACKGROUND: The radiation therapy of abdominal-pelvic tumors, determining diarrhea and cramps, could reduce the compliance of the patient and compromise his quality of life. This study attempts to assess the effects of adjuvant therapy with diosmectite (Diosmectal) on the above mentioned side effects from radiotherapy. METHODS: From August 1998 to September 1999, 40 patients (mean age 68) at the Oncological Radiotherapy Division of the Azienda Policlinico of Modena took part in the study: 21 forming the group of patients treated with diosmectite and 19 forming the control group. The radiotherapy was administered with total doses varying from 45 to 70 Gy in both groups with daily doses of 1.8-2 Gy. From the beginning of the therapy the patients in the group treated with Diosmectal, received 6 g daily doses of the drug split into two administrations. The diarrhea was assessed by referring to the Lent Soma score. RESULTS: In the group of patients not in therapy, an incidence of diarrhea was observed in 77% of subjects while in the group in therapy the incidence of diarrhea dropped to 25% of the cases (p<0.005), with an increase in the latency of the appearance of any diarrhoeic symptoms. CONCLUSIONS: Our data suggests that the administration of diosmectite in a prophylactic manner is capable of reducing the incidence of gastroenteric symptomatology (diarrhea and cramps).

[Preoperative radiotherapy in cancer of the rectum. Our 5-year experience]. / La radioterapia preoperatoria nel cancro del retto. La nostra esperienza di 5 anni.

Since 1990, 41 patients with rectal carcinoma have been submitted to preoperative radiotherapy, which induced a shrinkage of the tumor, favouring its surgical resection. Besides, in 3 cases the operative specimens were tumor free, and a higher incidence of A and B 1 categories was found. Surgical results have been compared with an analogous group of 20 patients, where surgery was performed as a first procedure, then followed by radiotherapy in 9. No increase of postoperative complications was observed. While analysis of follow-up results demonstrates a decrease of tumour recurrence in patients with preoperative radiotherapy, no difference in survival was registered, because of the development of extra-pelvic metastases.

Epidermal Langerhans cells are resistant to the permeabilizing effects of extracellular ATP: in vitro evidence supporting a protective role of membrane ATPase.

Extracellular adenosine 5'-triphosphate (ATPo) can induce pore formation in cell membranes, leading to cell permeabilization and eventual cell death. In this study, we examined the sensitivity of human epidermal Langerhans cells to ATP-induced permeabilization and tested the possibility that the Mg(++)- or Ca(++)-dependent plasma membrane ectonucleotidase (mATPase) on Langerhans cells provides protection against the cytotoxic effects of ATPo. Membrane permeability was assessed by using the fluorescent tracer propidium iodide, which confers red nuclear fluorescence to permeabilized cells. Langerhans cells were identified within human epidermal cell suspensions with fluorescein isothiocyanate-conjugated MoAb against CD1a or human leukocyte antigen-DR (HLA-DR) antigens. Cultured human keratinocytes and J774 macrophages were both highly sensitive to permeabilization induced by incubation with ATP (0.5 to 20 mM at 37 degrees C), whereas Langerhans cells were relatively resistant. The non-hydrolyzable ATP analog, adenosine 5'-(beta,gamma-imido) triphosphate, but not other nucleotides such as ADP, AMP, GTP, or UTP, was also able to induce permeabilization comparable to that of ATP, thereby suggesting that ATP hydrolysis is not required for this effect. ATP4- is the moiety most likely responsible for permeabilization, because propidium iodide uptake occurred only when the pH of the medium was > or = 7.4. Permeabilization induced by ATP was augmented by chelation of divalent cations with ethylene-diamine-tetraacetic acid and by the addition of lanthanum or cerium (0.01 to 1 mM). Finally, incubation with the adenosine analog, 5'-p-fluorosulfonylbenzoyl-adenosine (1 mM), inhibited mATPase staining of Langerhans cells in human epidermal sheets, but markedly augmented ATP-induced permeabilization of Langerhans cells. The results indicate that epidermal LC are resistant to the lytic effects of ATPo and that mATPase is involved in such resistance.

Membrane ecto-ATPase on epidermal Langerhans cells.

Epidermal Langerhans cells (LC) possess a plasma membrane Mg(++)- or Ca(++)-dependent ecto-ATPase (mATPase), the function of which is not known. On the other hand, extracellular ATP (ATPo) has been shown to cause a rapid increase in cell-membrane permeability for selected cells, thus inducing the entry of exogenous substances, leading eventually to cell death. ATPo has also been shown to be a mediator of T cell-mediated cytotoxicity. We have observed human LC to be resistant to the permeabilizing effects of ATPo when compared to cultured human keratinocytes and J774 macrophages. In addition, our preliminary evidence in vitro suggests that mATPase on LC may provide protection against the lytic effects of ATPo. Finally, we propose that this latter mechanism may also operate in vivo.

Effect of low frequency low energy pulsing electromagnetic fields on mice injected with cyclophosphamide.

C3H mice have been used to investigate the effect of a combination of cyclophosphamide (CY) and electromagnetic fields (PEMF). Mice were injected i.p. with a single dose of 200 mg/kg body weight of CY and then exposed to PEMF 24 h per day. In an initial series of experiments immediately after CY injection mice were exposed to PEMF until sacrifice. WBC counts in the peripheral blood demonstrated a quicker decline in WBC at days 1 and 2 in mice exposed to PEMF. Groups of mice were sacrificed at days 1, 4, 6, 8, and 10 after CY injection. In mice exposed to PEMF the spleen weight was less than in controls at days 6, 8, and 10. Autoradiographic studies demonstrated that the labeling index of bone marrow smears did not significantly differ between controls and experimental mice exposed to PEMF, whereas the spleen labeling index proved to be higher among control mice versus mice exposed to PEMF at day 6, and higher among mice exposed to PEMF versus controls at day 8. In a second series of experiments mice were exposed to PEMF only over the 24 h following CY injection. We found that the spleens of mice exposed to PEMF weighed less than those of controls at days 6 and 8. The labeling index of bone marrow did evidence a slight decrease among mice exposed to PEMF at days 8 and 10 after CY injection versus control mice. The spleen labeling index proved to be lower in experimental mice exposed to PEMF than in controls at days 4, 6, and 8. Mice were then injected with CY, half were exposed to PEMF, and 24 h later bone marrow was recovered from both groups of animals. The same number of bone marrow cells was injected via the tail vein into recipient mice irradiated to 8.5 Gy. The grafting efficiency of the bone marrow was evaluated by examining the number of spleen colonies and the spleen and bone marrow labeling indices at day 8; all parameters proved to be significantly lower among mice grafted with the bone marrow of mice injected with CY and exposed to PEMF than among controls injected with CY only. Finally, we found th at the effect of PEMF is evident only if mice are exposed during the 24 h following CY injection. The data reported here indicates that PEMF exposure after CY injection increases the damage induced in mice by CY.

VLA protein expression on epidermal cells (keratinocytes, Langerhans cells, melanocytes): a light and electron microscopic immunohistochemical study.

The very late antigens, or VLA proteins, are a family of cell surface heterodimers (alpha 1-b beta 1) that mediate cell adhesion to specific components of the extracellular matrix (collagens, fibronectin, laminin). In normal human epidermis, the common VLA beta 1 subunit is expressed on basal keratinocytes (BK). Langerhans cells (LC) and melanocytes. By means of light and electron microscopic immunostaining procedures, we have investigated the distribution of VLA alpha 1,2,3,4,6 subunits on normal human adult and foetal epidermal cells. alpha 1 antigen expression was not observed on any epidermal cell type. Both during foetal development and in adult epidermis, alpha 2 and alpha 3 were strongly expressed on the cell membrane BK, while alpha 6 was mainly expressed at their dermal pole. These different patterns of distribution suggest that the alpha 6 subunit may mediate BK anchorage to the basement membrane zone, while the alpha 2 and alpha 3 subunits may also be involved in intracellular adhesion. Moreover, with immunoelectron microscopy, LC were seen to be weakly alpha 5 and alpha 6 positive and melanocytes were alpha 3 and alpha 6 positive. Thus, VLA proteins are expressed by epidermal cells in a cell-type-specific pattern that could be related to particular functional roles of these proteins.

[Culture of human normal keratinocytes. Main models and clinical applications]. / Colture di cheratinociti umani normali. Principali modelli ed applicazioni cliniche.

In the last fifteen years various epidermal cell (EC) culture systems have been developed suitable both for investigation purposes and for clinical applications. In organ and explant cultures skin pieces are grown to obtain in the first case vertical proliferation of epidermis and in the second outward migration and proliferation of EC. In isolated EC cultures, EC suspensions are seeded on plastic or specific substrates (collagens, fibronectin, 3T3 fibroblasts). EC attach to the substrate, proliferate to form a confluent multilayered epithelium and can be subcultured. Using a serum-free medium (MCDB 153) EC can be grown in culture free of any undefined supplement. In organotypical culture systems, EC are seeded on a biological matrix (dermis, dermal equivalent) and lifted at the air-liquid interface. Under these conditions a high level of differentiation of the cultured epidermis can be obtained. The availability of a culture-grown epithelium, similar to the in vivo epidermis, has led to the use of cultured epidermal sheets for the treatment of wounds, in particular burns. The therapeutic results have been quite promising.