Exposure to moxifloxacin and cytomegalovirus replication is associated with skin squamous cell carcinoma development in lung transplant recipients.

BACKGROUND: Lung transplant recipients (LTR) are at increased risk for squamous cell carcinoma of the skin (SCC), but risk factors (RF) are incompletely understood. OBJECTIVE: To assess associations between exposure to certain medications and viral infections, and subsequent SCC development. METHODS: Retrospective study examining incidence and potential RF for SCC in LTR transplanted from 1992 to 2010 followed up at one centre. Cumulative incidence and Cox proportional hazards regression models were used to evaluate RF in the first year post-transplant for SCC formation during the follow-up. RESULTS: In 205 analysed LTR, 46 patients were diagnosed with SCC during a median follow-up of 4.9 years. The cumulative incidences of first SCC were 16.7% and 34.1%, for 5 and 10 years post-transplantation respectively. Multivariable analysis identified CMV replication (HR 7.69, 95% CI 2.93-20.2, P < 0.001) and moxifloxacin exposure (HR 2.35, 95% CI 1.15-4.81, P = 0.020) during the first year post-transplantation as independent RF for SCC development during follow-up. CONCLUSION: In our cohort, moxifloxacin use and CMV replication during the first year post-transplantation were associated with increased risk for SCC. These two factors could be indicators of over-immunosuppression. Their role in SCC development requires investigations in larger cohorts and prospective studies.

[Results of the Czech National Colorectal Cancer screening programme -  faecal occult blood tests]. / Výsledky Národního programu screeningu kolorektálního karcinomu v Ceské republice -  testy na okultní krvácení do stolice.

INTRODUCTION: The nationwide Colorectal Cancer Screening Programme was introduced in the Czech Republic in 2000. The aim of this article is to describe the employment of faecal occult blood tests (FOBTs) by the Czech population within the screening programme, and to provide information on the latest results of the programme. MATERIAL AND METHODS: Data on the development of the colorectal cancer (CRC) burden in the Czech population is obtained from the Czech National Cancer Registry, a database required by the Czech law that has been collecting comprehensive data on cancer patients since 1977. Data on FOBT employment can be obtained from health care payers, and was provided by the Czech National Reference Centre. RESULTS: Around 8,000 patients are diagnosed with colorectal cancer in the Czech Republic each year, and the number of CRC deaths is about 4,000. Despite the ongoing screening programme, significant improvements in the proportional representation of cancer stages (i.e., improvements in early detection of CRC cases) have yet to be seen. Although the number of FOBTs performed in the Czech Republic has significantly grown in the long term (which is accompanied by an increase in coverage by this screening test), the total coverage of the Czech population aged over 50 was only 25.5% in 2012. The Olomouc Region, the Zlin region, and the Usti nad Labem region had the highest coverage rates by CRC screening based on FOBT (over 28%), while the Capital of Prague had the lowest coverage rate (18%). Since 2008, FOBT positivity rates have seen a continuous and significant increase, reaching 6.9% in 2012. Between 13 to 14% of FOBTs in women are performed by practical gynaecologists. CONCLUSION: Despite a significant increase in the participation rate in recent years, which was partially improved by the involvement of practical gynaecologists, the programme unfortunately still covers only a quarter of the eligible population. Implementation of effective measures aimed at getting people interested in preventive examinations (including the recently introduced programme of personalized invitations) is therefore essential; otherwise, the screening programme will not be successful on the population level.

[Results of the Czech National Colorectal Cancer Screening Programme - colonoscopy examinations]. / Výsledky Národního programu screeningu kolorektálního karcinomu v Ceské republice - kolonoskopická vysetrení

INTRODUCTION: Colorectal cancer (CRC) is one of the most common cancers, and the Central European countries have the highest CRC burden worldwide. CRC screening has repeatedly been proven capable of decreasing CRC mortality and incidence rates. The nationwide Colorectal Cancer Screening Programme in the Czech Republic involves the colonoscopic examination as a diagnostic method (for patients with a positive FOBT result -  screening colonoscopy -  SC), or as a screening method (primary screening colonoscopy -  PSC). The aim of this article is to present the results of colonoscopic examinations performed as part of the Czech screening programme. MATERIAL AND METHODS: For the purpose of quality assurance, the Czech programme has been equipped since 2006 with an information system called the Colorectal Cancer Screening Registry, which collects and evaluates data on preventive colonoscopies performed in the colonoscopy screening centres. Performance indicators, as specified in the European Guidelines (and adapted for the Czech programme), are employed to assess preventive colonoscopies performed in the Czech Republic. RESULTS: Since 2006, more than 110,000 SCs and almost 20,000 PSCs were recorded. Approximately 95% of SCs and almost 98% of PSC were classified as total, i.e. examining the entire colonic mucosa up to the caecum. The positive predictive value of FOBT for adenomas has increased slightly and continuously over time, and was 39.7% in 2013. In PSC, the adenoma detection rate (ADR) has recently increased compared to previous years, and was 27.3% in 2013. CRC was detected in 3.7% of individuals undergoing an SC examination and in 1.0% of individuals undergoing a PSC examination. The programme safety is controlled based on the monitoring of complications during colonoscopies; these can occur either during diagnostic colonoscopy (perforation in 0.03% of cases since 2006) or during endoscopic polypectomy (perforation in 0.12% of cases, bleeding in 0.73% of cases since 2006). CONCLUSION: Our results confirm that the quality of colonoscopic examinations corresponds to the international standards and that this is not an obstacle to a positive impact of CRC screening on the Czech population, which has a high colorectal cancer burden.

Volumetry: an alternative to assess therapy response for malignant pleural mesothelioma?

The purpose of our study was to assess robustness of volumetric measurement of malignant pleural mesothelioma (MPM) before and after chemotherapy to modified RECIST (response evaluation criteria in solid tumours) criteria. 30 patients with digitally available chest computed tomography (CT) scans before and after three cycles of chemotherapy were included. Three readers independently assessed tumour response using two different methods: 1) the modified RECIST criteria; and 2) the tumour volumetric approach using dedicated software (Myrian; Intrasense, Paris, France). Inter-rater reliability of unidimensional and volumetric measurements was assessed using intraclass correlation. Tumour response classification for modified RECIST was compared to the volumetric approach applying unidimensional RECIST volumetric equivalent criteria. The determination of unidimensional tumour measurement (RECIST) revealed a low inter-rater reliability (0.55) and a low interobserver agreement for tumour response classification (general κ 0.33). Only 14 patients were classified equally. A high inter-rater reliability (0.99) and interobserver agreement (general κ 0.9) were found for absolute tumour volumes (volumetric measurements). 27 cases were classified equally. The number of cases classified as "stable disease" was higher for the volumetric approach using tumour-equivalent criteria compared to modified RECIST. Volumetric measurement of MPM on CT using Myrian software is a reliable, reproducible and sensitive method to measure tumour volume and, thus, therapy response after induction chemotherapy.

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure.

We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving.

High dose N-acetylcysteine to prevent pulmonary complications in partial or total transthoracic esophagectomy: results of a prospective observational study.

Cancer of the esophagus has a poor long-term prognosis and a high peri-operative morbidity in which pulmonary complications play a major role. The combination of the surgical approach, pre-existing pulmonary disorders, poor nutritional status and the release of pro-inflammatory cytokines may be contributing factors. N-acetylcysteine ((NAC) has been shown to have oxygen scavenging abilities. In severe sepsis and acute respiratory distress syndrome, positive effects of NAC on morbidity and mortality were discovered. In this observational study peri-operative high dose NAC was administered in 22 patients. The effects of this treatment on respiratory function, morbidity and survival were studied. These prospectively collected data were compared with data of a matched, retrospective group without NAC treatment. There were no significant differences between the groups in terms of socio-demographic data, preoperative pulmonary function, intra-operative course and oncologic characteristics. The oxygenation indices at the postoperative hours 2 (P = 0.019), 4 (P < 0.001), 8 (P = 0.035), 12 (P = 0.035) and 24 (P = 0.046) were significantly higher in the NAC group. After 36 h, the difference between groups was no longer significant (P = 0.064). NAC-treated patients showed significant lower overall pulmonary morbidity, 45.5% versus 81.8% (P = 0.027). Surgical morbidity, intensive care unit and hospital stay were not significantly different between groups, mortality was zero. Kaplan-Meier curves showed no significant difference in survival 12 months postoperatively. These data indicate that postoperative oxygenation can be improved and rate of overall pulmonary complications is reduced using peri-operative high dose NAC in transthoracic esophagectomy.

Combination of 308-nm xenon chloride excimer laser and topical calcipotriol in vitiligo.

BACKGROUND: A large variety of therapeutic agents are being used for the treatment of vitiligo, but treatment remains a challenge. Recently, monochromatic phototherapies such as 311-nm narrowband ultraviolet B therapy and 308-nm xenon chloride excimer laser have been reported to be an effective and safe therapeutic option in children and adult patients with vitiligo. Single reports stipulate that the addition of topically applied calcipotriol to phototherapy increases its effectiveness. OBJECTIVE: The purpose of the present pilot study was to determine if the addition of topical calcipotriol increases the efficacy of the 308-nm xenon chloride excimer in the treatment of vitiligo. METHODS: Ten patients with vitiligo with essentially bilateral symmetrical lesions were enrolled in this prospective right/left comparative, single-blinded trial conducted over a 15-month period. All patients received 308-nm XeCl excimer laser therapy three times weekly. Calcipotriol ointment (Daivonex) was applied to lesions on one side of the body twice daily. RESULTS: After 24 treatments (8 weeks), nine patients were evaluated. Eight patients showed evidence of repigmentation on both body sides, with no significant difference between the body side treated with calcipotriol and excimer laser and the side treated with excimer laser alone. The mean repigmentation rate was 22.4% (1-37%). CONCLUSION: The addition of calcipotriol ointment to 308-nm xenon chloride excimer laser phototherapy does not significantly enhance its efficacy. Small additive effects must be investigated in a larger trial.

Oral premedication for operations on the face under local anesthesia: a placebo-controlled double-blind trial.

Modern strategies for preventing or controlling pain and anxiety demand a premedication for operations using local anesthesia and for those using sedation or general anesthesia. For optimal patient care, the premedication should be given orally and, with respect to the outpatient basis of the operations, should have a short recovery period. Midazolam, one of the most favored premedications for general anesthesia, has been recommended as a premedication for operations using local anesthesia as well. However, midazolam has only sedative-anxiolytic effects and does not reduce pain sensation, which should be mandatory for operations using local anesthesia. A further requirement is the maintenance of stable hemodynamics for the prevention of postoperative hematomas, especially in the face. For these reasons, another premedication meeting all requirements (anxiolysis, analgesia, and stable hemodynamics) was researched. A randomized, double-blind prospective study was performed from March of 1997 to June of 1998. Five groups totalling 150 patients were included in the study; each group contained 30 patients who had operations performed solely on the face. In the first four groups, the effect of midazolam (0.15 mg/kg(-1)), morphine (0.3 mg/kg(-1)), and clonidine (1.5 microg/kg(-1)) administered orally was compared with a placebo. The fifth group was the control group and received no premedication. To evaluate the effects of the premedications, a corresponding questionnaire was completed independently by the patient and surgeon. With regard to the anxiolytic or analgesic properties of the premedication, 61 percent of the patients preferred pain reduction to anxiety control, and 24 percent of patients preferred reduction of anxiety. The remainder insisted on a reduction of both properties (8 percent) or had no preference (7 percent). Reduction of anxiety was largest in the midazolam and the clonidine groups, but the difference was not significant. The least pain during the application of local anesthesia was experienced by the morphine group (37 percent) and the clonidine group (33 percent), in contrast to the midazolam group (60 percent) (p = 0.04). Morphine and clonidine met the requirements of pain reduction equally well. Nevertheless, considering the rate and intensity of adverse effects with respect to hemodynamic compromises, nausea, and emesis, clonidine is even better suited as an oral premedication for operations on the face using local anesthesia.

Increased expression of integrin and receptor tyrosine kinase genes during autograft fusion in the sponge Geodia cydonium.

Recently cDNAs coding for cell surface molecules have been isolated from sponges. The molecules for alpha-integrin, galectin, and receptor tyrosine kinase (RTK), obtained from the marine sponge, Geodia cydonium, have been described earlier. In the present study also the cDNA for one putative beta-integrin has been identified from G. cydonium. The deduced aa sequence comprises the characteristic signatures, found in other metazoan beta-integrin molecules; the estimated size is 95,215 Da. To obtain first insights into the molecular events which proceed during autograft fusion, the expressions of these genes were determined on transcriptional and translational level. The cDNAs as well as antibodies raised against the recombinant sponge proteins alpha-integrin, RTK and galectin were used and Northern blot experiments and immunocytochemical analyses have been performed. The results show that transcription of the two subunits of an integrin receptor as well as of the RTK are strongly upregulated after grafting; levels of > 10-fold have been determined in the fusion zone of the grafts after a 10 days incubation. Immunofluorescence studies of sections through the fusion zone support these data. In contrast the transcription of the gene encoding galectin is drastically downregulated after grafting. In a parallel series of experiments the level of the heat-shock protein-70 was determined and it was found that it remained unchanged after grafting. We conclude that integrin subunits and the RTK molecule are involved in self-self recognition of sponge.

The effect of potato starch derived and corn starch derived hydroxyethyl starch on in vitro blood coagulation.

We have compared the effects of progressive in vitro haemodilution (30% and 60%) with potato starch derived hydroxyethyl starch and corn starch derived hydroxyethyl starch on blood coagulation in 80 patients using thrombelastography. Both solutions significantly compromised blood coagulation as evidenced by an increase in coagulation time and decrease in angle alpha, maximum amplitude and coagulation index (p < 0.05). Blood coagulation was more compromised during haemodilution with potato starch derived hydroxyethyl starch as compared with corn starch derived hydroxyethyl starch (p < 0.05). When taking the effect of haemodilution with 0.9% saline into account, haemodilution with both hydroxyethyl starch solutions also augmented clot lysis (p < 0.05), with potato starch derived hydroxyethyl starch having a greater effect than corn starch derived hydroxyethyl starch (p < 0.05). We conclude that potato starch derived hydroxyethyl starch compromises in vitro blood coagulation more than corn starch derived hydroxyethyl starch.

[Hypocalcemia as a rare cause of acute left heart failure. Case report and review of the literature]. / Hypokalzämie als seltene Ursache einer akuten Linksherzinsuffizienz. Fallbeschreibung und Literaturübersicht.

We report the case of a 50-year-old female in whom the connection between hypocalcemia and heart failure was not made until a second hospital admission for left ventricular failure. Under appropriate calcium supplementation the symptoms were relieved within 2 days and the patient remained well thereafter. The hypocalcemia was found to be caused by autoimmune hypoparathyroidism. Heart failure due to hypocalcemia has been rarely reported, and even in textbooks the subject is poorly documented. The physiologic functions of calcium and the implications of deficiency for heart muscle are outlined, with a review of the literature. A treatment regimen for hypocalcemia is recommended.

Incidence and in-vivo relevance of anti-interferon antibodies during treatment of low-grade cutaneous T-cell lymphomas with interferon alpha-2a combined with acitretin or PUVA.

Interferon-alpha combined with retinoid or PUVA is used for the treatment of cutaneous T-cell lymphoma. Anti-IFN-alpha antibodies (IFN ab) occur regularly during IFN-alpha treatment. We investigated the incidence of neutralizing and binding IFN ab and analysed their relationship with clinical and immunological parameters. A group of 17 CTCL patients were treated with IFN alpha-2a three times weekly subcutaneously at a dose of 3 Mill. I.U. combined either with retinoid (acitretin, Neotigason; 0.5 mg/kg bodyweight) daily or with 5-methoxypsoralen (1.2 mg/kg bodyweight) plus UVA radiation three times weekly. Prior to and during treatment we monitored stage, skin involvement by a tumour burden index, serum levels of beta 2-microglobulin, neopterin, binding and neutralizing IFN ab, Interleukin-6 (IL-6), soluble IL-2 receptors (sIL-2r) and the CD4/CD8 ratio of peripheral blood mononuclear cells. We observed two complete, two partial and six minor responses, four patients with stable disease and three patients with progressive disease. Of the 17 patients, 7 developed binding IFN ab, but only 2 had neutralizing IFN ab which were associated with high titres of binding IFN ab. IFN ab formation was more frequent in patients with normal CD4/CD8 ratios and a high tumour burden index and showed a trend to be more frequent in PUVA-cotreated patients than in retinoid-cotreated patients. Responses were more frequently seen in IFN ab-negative patients. IFN ab developed in patients treated with PUVA or retinoid combined with IFN. Binding as well as neutralizing IFN ab may have an impact on the treatment success in CTCL patients.

[Quantitative assessment of heliotherapy in psoriasis vulgaris in high altitude climate]. / Quantitative Erfassung der Heliotherapie bei Psoriasis vulgaris im Hochgebirgsklima.

At the Davos Clinic for Dermatology and Allergy (Alexanderhausklinik), patients suffering from psoriasis were treated with natural UV irradiation over 6 weeks in 1987: the average doses applied amounted to 1.042 J/cm2 UVB (= 41.7 sunburn units (SU] and 41.511 J/cm2 UVA. These doses were far below those of artificial UV sources usually required in the treatment of psoriasis. The doses were also far below those which statistically increase the incidence of non-melanotic skin cancer.

[Interdisciplinary diagnosis and therapy concepts in climacteric osteoporosis]. / Interdisziplinäres Diagnostik- und Therapiekonzept der klimakterischen Osteoporose.

50 patients with signs of osteoporosis have been selected from special outpatient clinics for climacteric or rheumatic complaints for a complex interdisciplinary programme concerning diagnostics and therapy. 46 patients could be treated successfully for one year with estrogens and progestogens, fluoride and calcium preparations as well as physiotherapeutic treatments including electrotherapy and dietetic advice. X-ray examinations done after this period did not show any progression of the osteoporosis. But only in 4 patients an increase of bone density could be demonstrated. In the other patients health conditions were stabilized. Good results could be obtained with regard to climacteric complaints and improvement of fitness and efficiency. In 2 patients a long-time disablement could be stopped.