Clinical and microscopic characteristics of canine toxic epidermal necrolysis.

Canine toxic epidermal necrosis (TEN), a rare and life-threatening cutaneous drug reaction, traditionally has been described as full-thickness devitalization of the epidermis with minimal dermal inflammation; however, few reports detail the histologic findings. We characterize the clinical features and histologic variations of 3 canine TEN patients. Clinically, irregular erythematous and purpuric macules evolved into widespread and severely painful erosions. The number of eroded mucosae varied; however, periocular and perilabial mucocutaneous junctions frequently were affected. Thirteen of 17 biopsies were evaluated. Apoptosis at multiple epidermal levels was the most common pattern of epidermal necrosis (12/13 biopsies, 92%). In contrast, full-thickness coagulation necrosis was present less often (7/13 biopsies, 52%). Lymphocytic interface dermatitis was the predominant inflammatory pattern, and intraepidermal lymphocytes, along with fewer histiocytes, were present to some degree in all samples along with lymphocytic satellitosis of apoptotic keratinocytes. The sequence of changes points to lymphocyte-mediated keratinocyte apoptosis as an early step in lesion development with subsequent variation in progression to coagulation necrosis among patients. Histopathologic changes overlapped with those reported for erythema multiforme, in contrast to traditional histologic descriptions of canine TEN. A specific algorithm for assessment of drug causality in epidermal necrolysis (ALDEN) was applied for each patient; carprofen was associated with a probable score for causality in 1 dog. Clinicians should be encouraged to take multiple biopsies in TEN suspect cases as nearly 25% of all biopsies lacked epithelium and were not diagnostic.

Adverse events associated with chloramphenicol use in dogs: a retrospective study (2007-2013).

Chloramphenicol is a broad spectrum antibiotic that has been increasingly utilised since the emergence of methicillin-resistant staphylococcal infections. Due to toxicities in humans, use of the drug has been limited. In dogs, gastrointestinal signs are common adverse events described, and bone marrow suppression is possible. The aim of this study was to evaluate the adverse events associated with chloramphenicol in dogs seen by one specialty practice from January 2007 through June 2013. The database was searched for all dogs prescribed chloramphenicol during the time period. Dosage, length of treatment, age and body weight of the dogs were recorded as well as any adverse events that occurred during treatment. A total of 105 cases were evaluated. Thirty-nine dogs experienced at least one adverse event while on the medication. The most commonly noted were gastrointestinal signs and hindlimb weakness. The mean body weight for dogs with hindlimb weakness was 35.3 kg, which was significant. Resolution was documented in 54 per cent of cases when the drug was discontinued. Methicillin-resistant Staphylococcus pseudintermedius on bacterial culture was listed as the reason for chloramphenicol use in 76 per cent of the cases. Based on this information, further prospective studies are recommended to evaluate the reproducibility of this report.

[Evaluation of time, attendance of medical staff, and resources during stereotactic radiotherapy/radiosurgery : QUIRO-DEGRO Trial].

BACKGROUND: The German Society of Radiation Oncology ("Deutsche Gesellschaft für Radioonkologie", DEGRO) initiated a multicenter trial to develop and evaluate adequate modules to assert core processes and subprocesses in radiotherapy. The aim of this prospective evaluation was to methodical assess the required resources (technical equipment and medical staff) for stereotactic radiotherapy/radiosurgery. MATERIAL AND METHODS: At two radiotherapy centers of excellence (University Hospitals of Heidelberg and Marburg/Giessen), the manpower and time required for the implementation of intra- and extracranial stereotactic radiotherapy was prospectively collected consistently over a 3-month period. The data were collected using specifically developed process acquisition tools and standard forms and were evaluated using specific process analysis tools. RESULTS: For intracranial (extracranial) fractionated stereotactic radiotherapy (FSRT) and radiosurgery (RS), a total of 1,925 (270) and 199 (36) records, respectively, could be evaluated. The approximate time needed to customize the immobilization device was median 37 min (89 min) for FRST and 31 min (26 min) for RS, for the contrast enhanced planning studies 22 and 27 min (25 and 28 min), for physical treatment planning 122 and 59 min (187 and 27 min), for the first and routine radiotherapy sessions for FSRT 40 and 13 min (58 and 31 min), respectively. The median time needed for the RS session was 58 min (45 min). The corresponding minimal manpower needed was 2 technicians for customization of the immobilization device, 2.5 technicians and 1 consultant for the contrast-enhanced planning studies, 1 consultant, 0.5 resident and 0.67 medical physics expert (MPE) for physical treatment planning, as well as 1 consultant, 0.5 resident, and 2.5 technicians for the first radiotherapy treatment and 2.33 technicians for routine radiotherapy sessions. CONCLUSION: For the first time, the resource requirements for a radiotherapy department for the maintenance, protection and optimization of operational readiness for the application of intra- and extracranial stereotactic radiotherapy was determined methodically.

Dosimetric integration of daily mega-voltage cone-beam CT for image-guided intensity-modulated radiotherapy.

PURPOSE: The goal of this work was to compare different methods of incorporating the additional dose of mega-voltage cone-beam CT (MV-CBCT) for image-guided intensity modulated radiotherapy (IMRT) of different tumor entities. MATERIAL AND METHODS: The absolute dose delivered by the MV-CBCT was calculated and considered by creating a scaled IMRT plan (scIMRT) by renormalizing the clinically approved plan (orgIMRT) so that the sum with the MV-CBCT dose yields the same prescribed dose. In the other case, a newly optimized plan (optIMRT) was generated by including the dose distribution of the MV-CBCT as pre-irradiation. Both plans were compared with the orgIMRT plan and a plan where the last fraction was skipped. RESULTS: No significant changes were observed regarding the 95% conformity index of the target volume. The mean dose of the organs at risk (OAR) increased by approx. 7% for the scIMRT plan and 5% for the optIMRT plan. A significant increase of the mean dose to the outline contour was observed, ranging from 3.1 ± 1.3% (optIMRT) to 13.0 ± 6.1% (scIMRT) for both methods over all entities. If the dose of daily MV-CBCT would have been ignored, the additional dose accumulated to nearly a whole treatment fraction with a general increase of approx. 10% to the OARs and approx. 4% to the target volume. CONCLUSION: Both methods of incorporating the additional MV-CBCT dose into the treatment plan are suitable for clinical practice. The dose distribution of the target volume could be achieved as conformal as with the orgIMRT plan, while only a moderate increase of mean dose to OAR was observed.

Breed and site predispositions of dogs with atopic dermatitis: a comparison of five locations in three continents.

The objectives of this multicentre study were to analyse and compare breed predispositions and lesion distributions of 552 dogs diagnosed with atopic dermatitis from five different dermatologic referral centres located in Australia, Germany (2) and the United States (2). Breeds were compared with the canine population in the respective locations. Breed predispositions varied from geographical site, although golden retrievers and German shepherd dogs were predisposed in three of five practices. Lesions were present most commonly on the paws (62%), ventrum (51%), ears (48%) and face (39%). Various breeds had specific site predilections. Based on this study, breed predispositions can vary greatly both between continents and also between different locations on the same continent. In addition, some breeds showed predispositions for certain body sites which also varied in some instances with the geographical location.

[Postoperative radiotherapy of the chest wall in patients with male breast cancer]. / Postoperative Strahlentherapie der Thoraxwand beim Mammakarzinom des Mannes.

INTRODUCTION: We analysed our long-term results with postoperative radiotherapy of the chest wall in male breast cancer patients with respect to local control and survival. METHODS: Twenty-five patients with 26 histological proven carcinomas of the male breast underwent postoperative radiotherapy of the chest wall with (n = 15) or without regional lymphatics after mastectomy. Additionally 13 patients received adjuvant hormones and 3 patients adjuvant chemotherapy. Median age at treatment was 62.2 years (45.9-78.5 years). Median follow-up was 15.3 years (7.7-27.5 years). RESULTS: Overall survival after radiotherapy was 28 %, disease-specific survival was 64 %. Actuarial 3-, 5- and 10-year survival was 72 %, 56 % and 35 %. Median survival time was 6.1 years. Actuarial progression-free survival was 80 %, 52 % and 43 % after 3, 5 and 10 years, respectively. Local tumor control was 92 % (24 / 26). Survival was significantly affected by the presence of lymph node metastases (p < 0.01) and localisation of the tumor in the right breast (p < 0.04). CONCLUSION: Postoperative radiotherapy is an important part of the management of male breast cancer to improve local control and progression-free survival. The presence of lymph node metastases significantly impairs survival.

Moraxella catarrhalis induces ERK- and NF-kappaB-dependent COX-2 and prostaglandin E2 in lung epithelium.

Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. Cyclooxygenase (COX)-derived prostaglandins, such as prostaglandin E(2) (PGE(2)), are considered to be important regulators of lung function. The present authors tested the hypothesis that M. catarrhalis induces COX-2-dependent PGE(2) production in pulmonary epithelial cells. In the present study, the authors demonstrate that M. catarrhalis specifically induces COX-2 expression and subsequent PGE(2) release in pulmonary epithelial cells. Furthermore, the prostanoid receptor subtypes EP2 and EP4 were also upregulated in these cells. The M. catarrhalis-specific ubiquitous cell surface protein A1 was important for the induction of COX-2 and PGE(2). Moreover, M. catarrhalis-induced COX-2 and PGE(2) expression was dependent on extracellular signal-regulated kinase 1/2-driven activation of nuclear factor-kappaB, but not on the activation of p38 mitogen-activated protein kinase. In conclusion, the present data suggest that ubiquitous cell surface protein A1 of Moraxella catarrhalis, extracellular signal-regulated kinase 1/2 and nuclear factor-kappaB control cyclooxygenase-2 expression and subsequent prostaglandin E(2) release by lung epithelial cells. Moraxella catarrhalis-induced prostaglandin E(2) expression might counteract lung inflammation promoting colonisation of the respiratory tract in chronic obstructive pulmonary disease patients.

Concentrations of progesterone, prolactin and relaxin in the luteal phase and pregnancy in normal and short-cycling German Shepherd dogs.

Twenty-two nonpregnant and 19 pregnant German Shepherd dogs were assigned to either a control group or a suspected short-cycling group, based on the interestrous interval (> or = 6 month and < 5 month, respectively) and data from previous pregnancies. Blood serum concentrations of progesterone and prolactin were determined from days 5 to 60 (day 0 = ovulation) for characterization of luteal function. In pregnant bitches, placental integrity was additionally assessed by relaxin concentrations. The nonpregnant, suspected short-cycling bitches had significantly lower progesterone concentrations than the controls, indicating decreased luteal activity both in the autonomous and prolactin-dependent period. In the pregnant suspected short-cycling bitches, unavoidable progesterone supplementation prevented assessment of luteal function; it may have suppressed prolactin secretion (significantly lower prolactin concentrations from days 20 to 60, compared with the pregnant control group), but deficient prolactin secretion affecting luteal function cannot be excluded. The significantly lower relaxin concentrations, together with a high incidence of embryonic death found in the pregnant, suspected short-cycling group, may indicate loss of placental integrity and may have caused decreased prolactin concentrations.

Review of 15 cases of pemphigus foliaceus in horses and a survey of the literature.

The records of 15 horses with pemphigus foliaceus diagnosed on the basis of their history, clinical signs, histopathology and the exclusion of differential diagnoses were evaluated with respect to the age of onset, the clinical signs and the diagnostic tests used. There was no apparent breed predisposition. The horses' mean age was nine years, with a range from three months to 25.5 years, three were foals up to six months old and eight were nine years old or older. The most frequent lesions were scaling in 11, crusting in 10 and alopecia in 10, and they appeared most commonly on the face, neck and trunk, in 10 horses for each of these sites. The extremities were involved in nine of the horses, pruritus occurred in seven, and four of the horses had pustules. The clinical signs mostly corresponded with those described in previous reports, but signs of pain were not a prominent feature. Acantholytic cells were identified cytologically in four of six of the horses.

Effect of omega-3 fatty acids on canine atopic dermatitis.

Twenty-nine dogs were included in a double-blinded, placebo-controlled, randomised trial and were orally supplemented for 10 weeks with either flax oil (200 mg/kg/day), eicosapentaenoic acid (50 mg/kg/day) and docosahexaenoic acid (35 mg/kg/day) in a commercial preparation, or mineral oil as a placebo. For each dog, clinical scores were determined based on a scoring system developed prior to the trial. Total omega-6 and omega-3 intake and the ratio of omega-6:omega-3 (omega-6:3) were calculated before and after the trial. The dogs' clinical scores improved in those supplemented with flax oil and the commercial preparation, but not in the placebo group. No correlation was identified between total fatty acid intake or omega-6:3 ratio and clinical scores. Based on the results of this study, the total intake of fatty acids or the omega-6:3 ratio do not seem to be the main factors in determining the clinical response.

Calcification in coronary arteries as quantified by CT scans correlated with tobacco consumption in patients with inoperable non-small cell lung cancer treated with three-dimensional radiotherapy.

It has been shown that radiological manifestations of coronary artery sclerosis are an indirect measure of co-morbidity and predictive of survival. The aim of the present study is to evaluate the outcome and side effects after three-dimensional (3D) radiotherapy in patients with unresectable non-small cell lung cancer (NSCLC) stage I, II and IIIA, depending on coronary artery calcification, Karnofsky performance index (KI) and co-morbidity. Between 1993 and 1999, 89 patients with unresectable NSCLC were treated with 3D-radiotherapy. The median age was 66.6 years and median KI 80%. All patients had 3D-treatment planning, based on CT scans. The median total dose was 60 Gy in 2 Gy fractions five times a week. The mean follow-up period was 13.2 months and mean survival time 12.2 months. Significant prognostic factors for improved survival were KI and tumour stage. Patients with a KI<90% had a median survival of 6.5 months compared with 14 months, in patients with KI>/==" BORDER="0">90% (p<0.001). NSCLC stage I+II showed a significantly longer median survival than patients with NSCLC stage IIIA (16.5 months versus 7 months, p<0.004). A significant correlation was seen between pack-years and coronary artery calcification (p<0.05) and between age and marked coronary artery calcification. The incidence of calcification was 67% in smokers (>/==" BORDER="0">20 pack-years) and 43/58 in patients >60 years (p<0.007). Side effects, e.g. pneumonitis, did not correlate with coronary artery calcification but correlated with chronic obstructive lung disease in 19/89 patients. Conventional CT scans for 3D-treatment planning are able to detect coronary artery calcification. There is a significant correlation between age, KI, tobacco consumption and vascular calcification. Although there was a trend to worse overall survival, coronary artery calcification was not a significant predictor of progression-free and overall survival.

Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland.

PURPOSE: We evaluated survival rates and side effects after fractionated stereotactically guided radiotherapy (SCRT) and radiosurgery in patients with pituitary adenoma. METHODS AND MATERIALS: Between 1989 and 1998, 68 patients were treated with FSRT (n = 63) or radiosurgery (n = 5) for pituitary adenomas. Twenty-six had functional and 42 had nonfunctional adenomas. Follow-up included CT/MRI, endocrinologic, and ophthalmologic examinations. Mean follow-up was 38.7 months. Seven patients received radiotherapy as primary treatment and 39 patients received it postoperatively for residual disease. Twenty-two patients were treated for recurrent disease after surgery. Mean total dose was 52.2 Gy for SCRT, and 15 Gy for radiosurgery. RESULTS: Overall local tumor control was 93% (60/65 patients). Forty-three patients had stable disease based on CT/MRI, while 15 had a reduction of tumor volume. After FSRT, 26% with a functional adenoma had a complete remission and 19% had a reduction of hormonal overproduction after 34 months' mean. Two patients with STH-secreting adenomas had an endocrinologic recurrence, one with an ACTH-secreting adenoma radiologic recurrence, within 54 months. Reduction of visual acuity was seen in 4 patients and partial hypopituitarism in 3 patients. None of the patients developed brain radionecrosis or radiation-induced gliomas. CONCLUSION: Stereotactically guided radiotherapy is effective and safe in the treatment of pituitary adenomas to improve local control and reduce hormonal overproduction.

Allele-specific losses of heterozygosity on chromosomes 1 and 17 revealed by whole genome scan of ethylnitrosourea-induced BDIX x BDIV hybrid rat gliomas.

The induction of neural tumors by N-ethyl-N-nitrosourea (EtNU) in inbred strains of rats has evolved as a valuable model system of developmental stage- and cell type-dependent oncogenesis. Tumor yield and latency times are strongly influenced by genetic background. Compared with BDIX rats, BDIV rats are relatively resistant to the induction of brain tumors by EtNU, with a lower tumor incidence and latency periods prolonged by a factor of 3. To characterize genetic abnormalities associated with impaired tumor suppressor gene function in neuro-oncogenesis, losses of heterozygosity (LOHs) and microsatellite instability (MI) were investigated in brain tumors induced by EtNU in (BDIV x BDIX) F(1) and F(2) rats. The polymerase chain reaction was used to amplify 55 polymorphic microsatellite markers spanning the entire rat genome. The tumors displayed different histologies and grades of malignancy, corresponding to part of the spectrum of human gliomas. MI was not observed in any of the tumors. LOH of rat chromosome 1q was predominantly detected in oligodendrogliomas and mixed gliomas, with a 30% incidence in informative cases. 11p15.5, the human genome region syntenic to the consensus region of LOHs observed on rat chromosome 1, has been shown to be involved in the formation of gliomas in humans. Furthermore, rat brain tumors of different histologies often showed allelic imbalances on chromosome 17p. In both cases of LOH, there was a clear bias in favor of the parental BDIV allele, suggesting the involvement of tumor suppressor genes functionally polymorphic between the two rat strains.

Multicompartment analysis of gadolinium chelate kinetics: blood-tissue exchange in mammary tumors as monitored by dynamic MR imaging.

The blood-tissue exchange kinetics of gadopentetate were studied in 49 malignant and benign mammary tumors. Signal enhancement was monitored simultaneously in the aorta and in tumor for 10.5 minutes after the beginning of a 1 minute i.v. infusion of the contrast medium (CM). Kinetic analysis was based on a model with two compartments for systemic pharmacokinetics and up to three kinetically distinct compartments for tumor. Kinetic heterogeneity, ie, two or more compartments with different exchange rate constants in a given tumor, was found in 85% of carcinomas, 38% of fibroadenomas, and 14% of mastopathic tumors. The within-tumor average of CM exchange rates was 1.22 (0.62-1.65) min(-1) in carcinomas, 0.38 (0.26-0.60) min(-1) in fibroadenomas, and 0.16 (0. 12-0.20) min(-1) in mastopathies (median and interquartile distances). The area under the signal enhancement-time curve of the aorta varied 4.5-fold between individuals. It is concluded that individual CM kinetics in arterial blood should be taken into account when CM exchange rates between blood and tumor are to be determined and that a kinetic model for potentially malignant tumors should allow for kinetic heterogeneity.

Transformed cells trigger induction of their own apoptosis in coculture with normal cells.

In vitro, transforming growth factor type betal triggers normal cells to induce apoptosis in transformed cells. We show that in the absence of exogenous transforming growth factor type betal, induction of apoptosis of transformed cells in coculture with normal cells is dependent on the number of transformed cells per assay and is abrogated by antibodies against TGF-beta 1. Therefore, transforming growth factor type betal produced by transformed cells seems to be responsible for triggering a mechanism that leads to the induction of their apoptosis. This mechanism may be crucial for the control of carcinogenesis in vivo.