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Low-molecular-weight antioxidants are some of the most efficient agents of the skin defense mechanism against environmental factors, such as cosmic rays, smoke, and pollutants. The total skin concentrations of hydrophilic ascorbic and uric acids, as well as lipophilic α-tocopherol, β-carotene, and ubiquinol-10 antioxidants were determined by an HPLC-EC detector from 18 biopsies of human nonmelanoma skin carcinomas and 18 biopsies from skin areas adjacent to carcinomas. No significant differences in the concentrations of lipophilic antioxidants in both carcinomas and normal-looking skin areas adjacent to carcinomas were observed. On the contrary, ascorbic and uric acid concentrations were found to be 18 and 36% lower in carcinomas than in normal-looking skin areas, respectively. No statistical significance was observed between antioxidant concentrations and age, sex, phototype, profession, site of tumor, frequency, and time of UV light exposure either. Accordingly the antioxidant concentrations in both cancerous skin and adjacent normal-looking areas were found to be much higher than in normal skin, in contrast to literature data. © 2017 S. Karger AG, Basel. Copyright: All rights reserved.

Low-molecular-weight antioxidants are some of the most efficient agents of the skin defense mechanism against environmental factors, such as cosmic rays, smoke, and pollutants. The total skin concentrations of hydrophilic ascorbic and uric acids, as well as lipophilic α-tocopherol, β-carotene, and ubiquinol-10 antioxidants were determined by an HPLC-EC detector from 18 biopsies of human nonmelanoma skin carcinomas and 18 biopsies from skin areas adjacent to carcinomas. No significant differences in the concentrations of lipophilic antioxidants in both carcinomas and normal-looking skin areas adjacent to carcinomas were observed. On the contrary, ascorbic and uric acid concentrations were found to be 18 and 36% lower in carcinomas than in normal-looking skin areas, respectively. No statistical significance was observed between antioxidant concentrations and age, sex, phototype, profession, site of tumor, frequency, and time of UV light exposure either. Accordingly the antioxidant concentrations in both cancerous skin and adjacent normal-looking areas were found to be much higher than in normal skin, in contrast to literature data.

Heat shock protein 27 (Hsp27), apart from its protective function in response to stress, is implicated in the regulation of cell growth, differentiation and apoptosis. Data on the expression of Hsp27 in the developing human epidermis are sparse and partially conflicting. Thus, the purpose of the present study was to investigate Hsp27 expression during the morphogenesis of human epidermis. Skin biopsies and dispase-separated epidermal sheets obtained from 7 human embryos (7 and 8 weeks estimated gestational age, EGA), from 79 human fetuses (9-23 weeks EGA) and from 10 healthy adult volunteers were investigated by immunohistochemistry and Western blotting, respectively. The earliest detection of Hsp27 expression was found by immunohistochemistry at the 12th week EGA (basal and intermediate layer) and by Western blotting at the 9th week EGA. From the 16th to the 23rd week EGA immunoreactivity was not detectable in the basal layer, whereas in the overlying layers it revealed a differentiation-related pattern. The simultaneous onset of epidermal stratification and Hsp27 expression (9th week EGA) and the alterations of the latter in the subsequent stages of development, suggest that this stress protein may be involved in the molecular events underlying human epidermal morphogenesis.

Trends in rates of asthma admissions among children have shown a variety of patterns in different countries in the last decades. We undertook the present study to determine the time trends in asthma admissions and readmissions of children in Athens, Greece. Data were obtained retrospectively from hospital registries of the three main children's hospitals in Athens from 1978 to 2000. Children admitted with the diagnoses of asthma, asthmatic bronchitis or wheezy bronchitis were included. Hospital admission rate for asthma among children 0–14 yr from 1978 to 2000 rose by 271% (p

In-band crosstalk noise can pose important limitations in wavelength-division-multiplexing (WDM) optical networks. This paper describes a model that takes into account the statistical behavior of in-band crosstalk noise accurately and that can be used to estimate the error probability (EP) in a WDM receiver. It is based on the formulation of the moment-generating function of the decision variable in terms of a double integral, which allows the inclusion of the crosstalk-crosstalk noise, which was previously neglected in the literature. The optical amplifier noise and the electrical receiver noise are also incorporated, and the model is used to assess the implications of the crosstalk-crosstalk contribution. With the aid of some examples, it is shown that the crosstalk-crosstalk noise can influence the value of the EP, change the optimum receiver threshold, and introduce some power penalty.

The purpose of this double-blind randomised parallel-group study was to compare the efficacy and safety of short-contact treatment with dithranol ointment (2%) with its combination with calcipotriol ointment (50 µg/g) in 2 groups of in-patients with chronic plaque psoriasis. The patients of the first group (n = 23) topically applied dithranol once daily for 30 min and the vehicle of calcipotriol twice daily. The patients of the second group (n = 23) used a single topical application of dithranol for 30 min daily and additionally applied calcipotriol twice daily. The extent and the severity of psoriasis were assessed by means of psoriasis area and severity index score (PASI score) before the onset of the 6-week therapy and weekly thereafter. The difference between the two groups with regard to the mean PASI score became statistically significant already after the first week of treatment and remained so until the end of the trial. No significant differences were observed between the two groups with respect to the cutaneous adverse events. These findings indicate that the addition of calcipotriol ointment to short-contact dithranol markedly augments the therapeutic efficacy of the latter in chronic plaque psoriasis and impressively accelerates the response of psoriatic plaques to this well-tolerated regimen.

Background: Perirectal abscess is encountered commonly in surgical practice, and simple incision and drainage usually is sufficient. However, life-threatening sepsis may occur. In such instances, the high morbidity and mortality rates from the severe systemic inflammatory response syndrome (SIRS) associated with rapidly evolving necrotizing and gas-forming soft tissue infections are of major concern. Methods: Case report and review of pertinent literature. Results: A rare case of extensive necrotizing fasciitis of the torso arising from a perirectal abscess, in which the principles of radical surgical debridement were adhered to while minimizing disfigurement, is reported in a 19-year-old female. In some cases, despite the life-threatening nature of necrotizing fasciitis, it is possible to minimize tissue loss without compromising patient survival. Conclusion: Planning of the patient's site rehabilitation for maximum cosmetic outcome commences at the time of surgical debridement and is especially...

Locally invasive colonic carcinomas are seldom complicated by the formation of gastro-colic fistula. The authors present a case of a 52-year-old man with malignant gastro-colic fistula presenting with upper extremity deep vein thrombosis posing operative challenges.

The aim of this study was to determine whether imiquimod, a Toll-like receptor-7/8 agonist, in addition to its well-known topical action on the cutaneous immune response, might also induce alterations in the peripheral blood lymphocytes. A 62.5 mg quantity of imiquimod (5% cream) was applied topically under occlusion once daily every second day for 3 weeks to the skin of 10 healthy volunteers, age range 30–57 years. Ten sex- and age-matched healthy controls applied corresponding quantities of the vehicle under occlusion. Before, and one and 3 weeks after the start of treatment, peripheral blood lymphocyte subpopulations were measured by flow cytometry. Statistically significant alterations in the percentage or absolute numbers of peripheral blood lymphocyte subpopulations were found in the imiquimod-treated group compared with the control group. These alterations indicate for the first time that topical application of imiquimod induces alterations in peripheral blood lympho cyte subsets in healthy individuals, which may be of importance in the immunotherapy of neoplastic and infectious disorders and should be taken into careful consideration in patients who are treated with imiquimod.

Accumulating evidence suggests the involvement of neurogenic inflammation in the pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral neuropathy has been reported in several psoriatic patients. Thus, the aim of the present study was to answer the question whether an impairment of peripheral large nerve fibre function may exist in psoriasis. Thirty-two patients with severe and generalized chronic plaque psoriasis and 32 sex- and age-matched healthy controls were evaluated by detailed clinical neurological and standard neurophysiological examination. The latter included motor nerve conduction study of one nerve in the upper and one in the lower extremities and sensory nerve conduction study of one nerve in the upper and two in the lower extremities. Neurological examination failed to demonstrate any clinical evidence of large fibre neuropathy. Furthermore, all values of the examined neurophysiological parameters were within normal limits; comparisons of the corresponding mean values in the patient and the control group showed no statistically significant differences. These findings demonstrate no measurable abnormalities of the peripheral large nerve fibres in psoriatic patients and therefore an association of psoriasis with peripheral large fibre neuropathy cannot be suggested.

Background International guidelines recommend the long-acting anticholinergic , tiotropium , or long-acting β2 -agonists as maintenance therapy in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The efficacy of long-acting β2 -agonists combined with inhaled corticosteroids (ICS) in the treatment of COPD has also been confirmed for severe and very severe COPD, but data comparing tiotropium with the combination of a long-acting β2-agonist and an ICS are lacking. Methods This 6-week multicentre, randomised, double-blind, triple-dummy pilot study compared the bronchodilator effects of tiotropium 18 μg once daily (n =56) vs. the combination of salmeterol 50 μg plus fluticasone 250 μg twice daily (n =51) in patients with moderate-to-very severe COPD. Serial spirometry was performed over 12 h after 6 weeks of treatment. The primary endpoint was forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 12 h (AUC0−12 h) on Day 43. Results Randomization failed to provide treatment groups with comparable baseline characteristics for smoking history, current smokers, duration of COPD, FEV1, forced vital capacity (FVC) and reversibility. Mean±SD FEV1 was 1.31±0.47 l in the tiotropium group vs. 1.46±0.53 l in the salmeterol plus fluticasone group. Fewer patients in the tiotropium showed a 12% and 200 ml acute increase to short-acting bronchodilators at baseline. However, treatment with tiotropium alone resulted in comparable bronchodilation compared with salmeterol plus fluticasone, as measured by all the spirometric parameters at the end of the 6-week study period. FEV 1 AUC0–12 h was 1.55±0.03 l in the tiotropium group vs. 1.57±0.04 l in the salmeterol plus fluticasone groups (p=0.63). Trough (predose) FEV1 was 1.54±0.03 l in the tiotropium group vs. 1.46±0.03 l in the combination group (p=0.07), and peak FEV1 was 1.68±0.04 l vs. 1.66±0.04 l, respectively, (p=0.77). FVC AUC0–12 h, trough and peak were also comparable between groups at study end (p >0.05, for all). Further, rescue salbutamol use was similar in the tiotropium and combination groups and both treatment regimens were well tolerated. Conclusions Six weeks of treatment with tiotropium resulted in comparable bronchodilation compared with salmeterol plus fluticasone in patients with moderate-to-very severe COPD, despite tiotropium patients having lower lung function and fewer patients considered reversible at baseline. The results of this pilot study will aid planning for further large-scale comparative studies.

Trends in rates of asthma admissions among children have shown a variety of patterns in different countries in the last decades. We undertook the present study to determine the time trends in asthma admissions and readmissions of children in Athens, Greece. Data were obtained retrospectively from hospital registries of the three main children's hospitals in Athens from 1978 to 2000. Children admitted with the diagnoses of asthma, asthmatic bronchitis or wheezy bronchitis were included. Hospital admission rate for asthma among children 0-14 yr from 1978 to 2000 rose by 271% (p < 0.001). The rise in rates among those aged 0-4 and 5-15 yr were 250% and 276%, respectively. The mean annual increase in admission rate was 12.2% for 1978-1987, 4.7% for 1988-1993 and 0.6% for 1994-2000. The readmission rate among children 0-14 yr was increased from 15.3% to 23.3%. A positive correlation between admission and readmission rates in all age groups was observed. In conclusion, our findings show an increase in the childhood asthma admission rate in Athens in late 1970's and during the 1980's, which has decelerated in the 1990's, particularly in the second-half of the decade. The readmission rate paralleled that of admissions over the entire study period. © 2005 Blackwell Munksgaard.

The purpose of this study was to investigate the carbohydrate residue composition of cell surface in the developing epidermis and to define the chronological sequence of its alterations in human fetuses from the 10th to the 20th weeks of gestation and at the 23rd week of gestation, using a panel of six biotinylated lectins: Concanavalin A, Ulex europaeus agglutinin-I, Ricinus communis agglutinin-I, Peanut agglutinin, Wheat germ agglutinin, and Dolichos biflorus agglutinin. Distinct qualitative and quantitative alterations in the expression of cell surface carbohydrate residues were found during epidermal morphogenesis prior to keratinization (10th to 20th weeks). At the 23rd week of gestation, the already keratinized fetal human epidermis revealed a pattern of cell surface glycosylation very similar to that of the adult human epidermis. Further studies are now warranted to answer the question regarding whether the glycosylation pattern in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatally diagnosing the latter.

Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small cell lung cancer, but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), a radioprotector, could reduce the incidence of RCT-induced acute and late toxicities. Between October 1997 and August 1999, 73 patients with previously untreated stage IIIa–IIIb non-small cell lung cancer were randomized to treatment with RCT alone or RCT plus amifostine (300 mg/m2 daily intravenous infusion). Chemotherapy consisted of either paclitaxel (60 mg/m2) or carboplatin (area under the concentration-curve of 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy daily fraction, 5 days a week to a total dose of 55 to 60 Gy. Esophagitis and acute lung toxicity were evaluated during treatment; late lung toxicity was assessed at 3 and 6 months after RCT and was graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria. Esophageal endoscopy was performed the fourth week during RCT and 1 month after the end of RCT. Endoscopic findings of radiation esophagitis were scored from 0 to 3. There was no significant difference between treatment arms in baseline patient characteristics. A total of 68 patients were evaluable for toxicity and efficacy (RCT group, n = 32; RCT plus amifostine, n = 36). The incidence of grade ≥ 3 esophagitis during RCT was significantly lower for patients receiving amifostine than for those receiving RCT alone (38.9% v 84.4%; P < .001). The incidence of grade ≥ 3 acute pulmonary toxicity was also significantly reduced in amifostine-treated patients (19.4% v 56.3%; P = .002). At 3 months following RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than those who received RCT alone (P = .009). Endoscopic grade ≥ 2 esophagitis was observed in eight of 15 patients in the RCT group and in three of 18 patients in the RCT plus amifostine group (P = .061). No significant differences in response rates were noted between patients receiving RCT with or without amifostine (P = .498). Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced non-small cell lung cancer without compromising antitumor efficacy.

Radiochemotherapy (RCT) is an effective treatment for locally advanced non-small-cell lung cancer (NSCLC), but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine, a radioprotector, could reduce the incidence of radiochemotherapy-induced acute and late toxicities.Between October 1997 and August 1999, 73 patients with previously untreated Stage IIIa-IIIb NSCLC were randomized to treatment with RCT alone (n = 36) or RCT plus amifostine (300 mg/m(2) daily i.v. infusion, n = 37). RCT consisted of either paclitaxel (60 mg/m(2)) or carboplatin (AUC 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy/5 days/week to a total dose of 55 to 60 Gy. Blood cell counts were measured weekly; esophagitis and acute lung toxicity were evaluated during the treatment course. Treatment efficacy was assessed following World Health Organization criteria for response. Late lung toxicity was assessed at 3 and 6 months after RCT and was graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria.A total of 68 patients were evaluable for toxicity analysis (RCT group, n = 32; RCT + amifostine, n = 36). There was no significant difference between treatment arms in patient baseline characteristics. The incidence of Gradeor=3 esophagitis during RCT was significantly lower for patients receiving amifostine than for patients receiving RCT alone (38.9% vs. 84.4%%, p0.001). Furthermore, the incidence of Gradeor=3 acute pulmonary toxicity was significantly reduced in patients treated with RCT plus amifostine compared to patients who received RCT alone (19.4% vs. 56.3%, p = 0.002). At 3 months after RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than patients who received RCT alone (p = 0.009). Combined response rates (complete plus partial responses) were 82.2% in the RCT group and 88.8% in the RCT plus amifostine group (p = 0.498). Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced NSCLC without compromising antitumor efficacy.

In-band crosstalk noise can pose important limitations in wavelength-division-multiplexing (WDM) optical networks. This paper describes a model that takes into account the statistical behavior of in-band crosstalk noise accurately and that can be used to estimate the error probability (EP) in a WDM receiver. It is based on the formulation of the moment-generating function of the decision variable in terms of a double integral, which allows the inclusion of the crosstalk-crosstalk noise, which was previously neglected in the literature. The optical amplifier noise and the electrical receiver noise are also incorporated, and the model is used to assess the implications of the crosstalk-crosstalk contribution. With the aid of some examples, it is shown that the crosstalk-crosstalk noise can influence the value of the EP, change the optimum receiver threshold, and introduce some power penalty.

The multidrug resistance (MDR) transporter-proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance protein (LRP) have been associated with treatment failure. The aim of this study was to investigate prospectively the clinical significance of expression and function of the MDR proteins, considering other prognostic factors, such as age, immunophenotype, and cytogenetics. Mononuclear cells of peripheral blood or bone marrow from 61 patients with de novo acute myelogenous leukemia (AML) were analyzed. The monoclonal antibodies JSB1, MRPm6 and LRP56 were used for expression studies. Accumulation and retention studies were performed using the substrates Daunorubicin, Calcein-AM, Rhodamine-123 and DiOC2 in the presence or absence of the modifiers Verapamil, Genistein, Probenecid, BIBW22S and PSC833. Induction treatment consisted of a 3 +7 combination of Ida/Ara-C for patients 60 years of age and a 3 + 5 Ida/VP-16 combination per OS for patients 60. MDR function was expressed as the ratio of mean fluorescence intensity substrate in the presence of modifier over the substrate alone (resistance index, RI). Patients with advanced age, low CD15 expression and high RI for accumulation of DiOC2 in the presence of BIBW22S had significantly lower complete remission (CR) rates. No factor was prognostic for event-free survival analysis, which was limited to remitters only. Overall survival was shorter in patients with advanced age, poor prognosis cytogenetics, high CD7 expression, and high RI for Daunorubicin efflux modulated by Verapamil. These results suggest that MDR transporter-proteins have a limited role in the treatment failure of patients treated with Idarubicin-based regimens. © 2002 Elsevier Science Ltd. All rights reserved.

The multidrug resistance (MDR) transporter-proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance protein (LRP) have been associated with treatment failure. The aim of this study was to investigate prospectively the clinical significance of expression and function of the MDR proteins, considering other prognostic factors, such as age, immunophenotype, and cytogenetics. Mononuclear cells of peripheral blood or bone marrow from 61 patients with de novo acute myelogenous leukemia (AML) were analyzed. The monoclonal antibodies JSB1, MRPm6 and LRP56 were used for expression studies. Accumulation and retention studies were performed using the substrates Daunorubicin, Calcein-AM, Rhodamine-123 and DiOC(2) in the presence or absence of the modifiers Verapamil, Genistein, Probenecid, BIBW22S and PSC833. Induction treatment consisted of a 3 + 7 combination of Ida/Ara-C for patients less than or equal to 60 years of age and a 3 + 5 Ida/VP-16 combination per OS for patients > 60. MDR function was expressed as the ratio of mean fluorescence intensity substrate in the presence of modifier over the substrate alone (resistance index, RI). Patients with advanced age, low CD15 expression and high RI for accumulation of DiOC(2) in the presence of BIBW22S had significantly lower complete remission (CR) rates. No factor was prognostic for event-free survival analysis, which was limited to remitters only. Overall survival was shorter in patients with advanced age, poor prognosis cytogenetics, high CD7 expression, and high RI for Daunorubicin efflux modulated by Verapamil. These results suggest that MDR transporter-proteins have a limited role in the treatment failure of patients treated with Idarubicin-based regimens. (C) 2002 Elsevier Science Ltd. All rights reserved.

Hyperglycaemia is a strong risk factor for the development of renal disease in insulin dependent diabetes mellitus but it is uncertain whether it contributes to the progression of incipient or established nephropathy. The rigorous treatment of blood pressure in recent years may help uncover the contribution of hyperglycaemia, if any, to the progression of renal failure. Our aim therefore, was to assess in a current cohort of insulin dependent diabetic patients with diabetic nephropathy the relative importance of glycaemic control and blood pressure on disease progression.All insulin dependent diabetic patients with persistent albuminuria (300 mg/24 h) attending the diabetic clinic at Guy's Hospital between 1977 and 1993 were recruited. Serial measurements of blood pressure, HbA1 and GFR were performed every 6 months until end-stage renal disease or death. Only patients with at least 1 year of follow up were analysed. The mean follow up period was 8 years (range 1.5-15.5 years). Baseline and time dependent variables were related to the rate of change of GFR using weighted linear regression and stepwise multiple regression analysis. The impact of each variable on the change of GFR with time was adjusted for the effect of other potentially confounding variables by analysis of co-variance.Patients had well-controlled blood pressure throughout the observation period (mean arterial pressure 97 +/- 8 mmHg) and the average rate of decline of GFR was 4.32 +/- 4.08 ml/min/year. In univariate analysis baseline and mean HbA1 were linearly related to the rate of decline of GFR (baseline r5-0.565, P0.001; mean r-0.5107, P0.001) with those with a higher HbA1 having a faster rate of progression. In stepwise multivariate analysis both mean HbA1 mean diastolic blood pressure (P0.0001 and P = 0.019, respectively) was significantly and independently related with a faster rate of decline of GFR.Worse glycaemic control is associated with a faster rate of progression of diabetic nephropathy once blood pressure is controlled. Thus improvement of glycaemic control in patients where good blood pressure control has been achieved may potentially further delay the progression of nephropathy.