[New melanoma immunotherapies: mechanisms of action, efficiency and management of toxicities]. / Nouvelles immunotherapies du mélanome: mécanismes d'action, efficacité et prise en charge des toxicities.

In recent years the therapy of metastatic melanoma has been revolutionized from a disease with very few efficient treatment options to one with access to multiple therapies which can impact on patient survival. Two main classes of therapies have been developed: 1. Immunotherapy by immune checkpoint inhibitors and 2. Small molecule inhibitors of the MAPK pathway. Immunotherapies achieved by either inhibition of CTLA-4 or the PD1/PD-Ll axes are impacting the overall survival in an important fraction of patients. In addition, the side effects of these immune therapy approaches require early detection by all the specialists involved as well as early management according to precise guidelines for optimal outcome.

Effects of benzoic Acid and dietary calcium:phosphorus ratio on performance and mineral metabolism of weanling pigs.

In a 2×2 factorial experiment the hypotheses tested were that the metabolic acid load caused by benzoic acid (BA) added to the feed affects bone mineralization of weanling pigs, and that a wide dietary calcium (Ca) to phosphorus (P) ratio in phytase-supplemented feeds with a marginal P concentration has a positive effect on bone mineralization. The four experimental diets, which contained 0.4% P and were supplemented with 1,000 FTU phytase/kg, contained either 5 g BA/kg or no BA and either 0.77% Ca or 0.57% Ca. The 68 four-week-old Large White pigs were fed the experimental diets ad libitum for six weeks and were then slaughtered. Benzoic acid increased feed intake (p = 0.009) and growth rate (p = 0.051), but did not influence the feed conversion ratio (p>0.10). Benzoic acid decreased the pH of the urine (p = 0.031), but did not affect breaking strength and mineralization of the tibia (p>0.10). The wide Ca:P ratio decreased feed intake (p = 0.034) and growth rate (p = 0.007) and impaired feed the conversion ratio (p = 0.027), but increased the mineral concentration in the fat-free DM of the tibia (p = 0.013) without influencing its breaking strength (p>0.10). The observed positive effect of the wide Ca:P ratio on bone mineralization may be attributed, at least in part, to the impaired feed conversion ratio, i.e. to the higher feed intake and consequently to the higher mineral intake per kg BW gain. The negative impact on animal performance of the wide dietary Ca:P ratio outweighs its potentially positive effect on bone mineralization, precluding its implementation under practical feeding conditions.

[Melanoma: a new therapeutic era]. / Mélanome: une nouvette ère thérapeutique.

Melanoma is the cancer with the fastest incidence increase in Switzerland. 30% of the cases arise before the age of 50 years. Once metastatic, the median survival under current systemic therapies is about 8 months, with less than 5% of patients alive at 5 years. Many efforts in the understanding of cellular biology, intracellular signaling pathways, as well as the role of cellular immunity have been made in the recent years. This has resulted in the development of novel and very promising therapies. In this review, we will cover the results obtained with targeted therapies such as "tyrosin kinase inhibitors" (TKI), as well as those obtained with a monoclonal antibody directed against the CTLA-4 receptor of lymphocytes.

Influence of a raised slatted area in front of the nest on leg health, mating behaviour and floor eggs in broiler breeders.

European farms for broiler breeders often have raised slatted areas in front of the nests, but in other regions of the world no raised slatted areas are provided. This study aimed to investigate the effects of a raised slatted area on leg health, mating behaviour and floor laying behaviour. Ten groups of 33 broiler breeder hens and three males were housed in two pen types: with or without a raised slatted area in front of the nests. Each pen had one plastic and one wooden nest. Between 25 and 31 weeks of age, ten marked hens per pen were weighed and assessed weekly on foot pad dermatitis, hock burn and wounds. At the end of week 31, animals were euthanized and bone strength of the tibia and humerus of these individuals was assessed. At 24, 27 and 30 weeks of age, mating behaviour was observed for an hour per pen, noting both numbers of successful and unsuccessful copulations. The number of eggs laid in the nests and on the floor was recorded daily between 20 and 31 weeks of age. Foot pad dermatitis scores were affected by age, but not by pen type. Generally, there were only minor issues with foot pad dermatitis (scores <11 on a 0-100 scale), probably due to the young age of the hens. Body weight was not affected by pen type, while the prevalence of hock burns was too low to analyse and no difference in bone strength was found for the tibia and the humerus. Overall, mating behaviour was less frequent in pens with raised slats than in pens without raised slats (29 ±â€¯2 vs 35 ±â€¯3 times/h) and more frequent at 27 weeks of age than at 24 and 30 weeks of age (38 ±â€¯1 vs 31 ±â€¯4 and 27 ±â€¯2 times/h). The pens with raised slats had a lower percentage of floor eggs than pens without raised slats (11.2 ±â€¯0.4 vs 19.3 ±â€¯0.5%). The wooden nest was preferred over the plastic nest as on average 63% of the eggs were laid in the wooden nest. This study shows that providing raised slats decreases mating behaviour and percentage of floor eggs, although its effects on leg health remain inconclusive.

Effect of fat score on the quality of various meat products.

In the larger Swiss abattoirs the fat score (FS) is determined by default as an indicator of fat quality. The FS refers to the iodine number and is related to the degree of unsaturation of the outer layer of backfat. In a feeding trial with Large White gilts, the FS was determined in 47 carcasses. Meat and fat tissues were prepared for the production of salami (SAL), raw-cured bacon (RCB), pork hamburger (PHB) and Vienna sausage (VIS). In the different meat products, the FS was closely related to the percentage of saturated (SFA: r=-0.49 to -0.79) and polyunsaturated fatty acids (PUFA, r=0.36 to 0.79) for RCB, SAL and PHB (p⩽0.05), but not for VIS. For RCB, significant correlations with FS were seen for the meat:fat-ratio (r=0.39), fat firmness (r=-0.31) and one fat oxidation marker (1-octen-3-ol: r=0.51). The texture (r=-0.60), a(w)-value (r=0.63) and one fat oxidation marker (1-octen-3-ol: r=0.46) were significantly correlated with FS in SAL. On the whole, only a few variables correlated significantly with FS for SAL and RCB and the corresponding relationships were always linear. No significant correlation between FS and any of the technological and sensorial parameters were found for VIS or PHB.

Sentinel lymph node involvement and a high Breslow index are independent factors of risk for early relapse of melanoma.

AIM: The clinical relevance of sentinel lymph node (SLN) analysis was evaluated prospectively and compared with other known risk factors of relapse in early stage melanoma. METHODS: Surgery was guided by lymphoscintigraphy, blue dye and gamma probe detection. SLN were analysed by haematoxylin eosin (HE) histochemistry and multimarker immunohistochemistry (IHC). Disease free survival (DFS) was evaluated with Kaplan-Meier plots according to different parameters and Cox analyses of variance. RESULTS: From 210 patients a total of 381 SLN were excised. Lymphoscintigraphy identified all excised SLN with only 2 false positive lymphatic lakes. Fifty patients (24%) had tumour positive SLN. With a mean follow-up of 31.3 months, 29 tumour recurrences were observed, 19 (38%) in 50 SLN positive and 10 (6%) in 160 SLN negative patients. Strong predictive factors for early relapse (p < 0.0005) were SLN positivity and a high Breslow index. CONCLUSION: SLN tumour positivity is an independent factor of high risk for early relapse with a higher power of discrimination than the Breslow index.

Tolerance to 1,25 dihydroxyvitamin D3 glycosides from Solanum glaucophyllum by the growing pig.

Solanum glaucophyllum leaves contain high levels of glycosidically bound 1,25 dihydroxyvitamin D3, the most important vitamin D metabolite. The tolerance to this source was evaluated during six weeks with fifty weaned pigs fed increasing levels (0, 2.5, 5, 10 and 20µg 1,25(OH)2D3/kg diet). The diet contained, per kg, 9.7g Ca, 3.5g digestible P and 2000IU cholecalciferol. Ten additional pigs were fed a diet containing 1000IU cholecalciferol/kg, without 1,25(OH)2D3. Weekly plasma and final kidney, bone and urinary mineral contents, bone density and breaking strength served as indicators for possible adverse effects of the supplement. All animals grew well and remained clinically healthy. The measured parameters remained unchanged when 1000 replaced 2000IU cholecalciferol/kg and when 1,25(OH)2D3 was fed up to 10µg/kg. Twenty µg 1,25(OH)2D3 increased plasma Ca and decreased plasma P from the 2nd and the 4th experimental week onwards, respectively. Twenty µg 1,25(OH)2D3 increased final plasma Ca and 1,25(OH)2D3 and reduced final plasma P by respectively 19, 56 and 13%. Twenty µg 1,25(OH)2D3 also increased kidney Ca and urinary Ca by 43 and 69%, respectively, reduced bone breaking strength by 12% and tended to decrease bone ash by 3%. To conclude, 2000IU D3 was not beneficial compared to 1000IU cholecalciferol; up to 10µg 1,25(OH)2D3 per kg diet did not lead to observed adverse effects; 20µg 1,25(OH)2D3 altered the homeostatic regulation of Ca and P thus, may lead to first signs of possible adverse effects, such as soft tissue calcification.

Sunscreen use and duration of sun exposure: a double-blind, randomized trial.

BACKGROUND: In epidemiologic studies, sunscreen use is associated with increased risk of cutaneous melanoma, basal cell skin cancer, and higher numbers of nevi. It has been proposed that sunscreens may encourage prolonged sun exposure because they delay sunburn occurrence. We examined whether, under habitual conditions of sunscreen use, the sun-protection factor (SPF) had an influence on sun-exposure duration. METHODS: Before the 1997 summer holidays, we randomly assigned 87 French and Swiss participants who were 18-24 years of age to receive an SPF 10 or an SPF 30 sunscreen. Neither medical personnel nor study participants were aware of their sunscreen assignment. Participants were asked to complete daily records of their sun exposure. To avoid influencing the recreational sun-exposure habits of the study participants, no recommendation was made about sun exposure or sun protection. Furthermore, participants were told that the trial end point was the number of pigmented skin lesions before and after the holidays. One subject was lost to follow-up. All statistical tests were two-sided. RESULTS: The SPF 10 (n = 44) and SPF 30 (n = 42) groups had equivalent mean holiday durations (19.4 days versus 20.2 days) and mean quantities of sunscreen used (72.3 g versus 71.6 g). The mean cumulative sun exposures for the two groups were 58.2 hours and 72.6 hours, respectively (P =.011). The mean daily durations of sunbathing were 2.6 and 3.1 hours, respectively (P =.0013), and, for outdoor activities, they were 3.6 and 3.8 hours, respectively (P =.62). There was no difference in sunburn experience between the two groups. CONCLUSIONS: Use of higher SPF sunscreen seems to increase the duration of recreational sun exposure of young white Europeans.

[Acute generalized exanthematous pustulosis: first case associated with a Chlamydia pneumoniae infection]. / Pustulose exanthématique aiguë généralisée: premier cas décrit en relation avec une infection à Chlamydia pneumoniae.

UNLABELLED: Skin reactions to drugs or infections can be very important. CASE REPORT: A 14-year-old boy developed fever, a diffuse pustular rash and a respiratory distress. Chest X-rays and serology were consistent with an acute Chlamydia pneumoniae infection. A skin biopsy revealed an acute generalized exanthematous pustulosis. CONCLUSION: Acute generalized exanthematous pustulosis (AGEP) is a disease manifested by a diffuse eruption of follicular sterile pustules. Most of the cases are drug induced, but they may be secondary to viral or bacterial infections. We report the first case of AGEP in a child with an acute C. pneumoniae infection.

Chorioretinal vascular abnormalities associated with angioid streaks and pseudoxanthoma elasticum.

OBJECTIVE: To analyze the retinal and choroidal vascular abnormalities in eyes with angioid streaks (AS) associated with pseudoxanthoma elasticum (PXE). METHODS: Color photographs and fluorescein angiograms of 54 eyes of 27 consecutive patients with AS and PXE were examined retrospectively. RESULTS: Four (7%) of the 54 eyes had a major vascular abnormality at the level of the disc; this took the form of a large vascular loop corresponding to an arteriovenous communication between retina and choroid in 3 eyes (6%) and an anastomosis between 2 retinal arteries in 1 eye (2%). CONCLUSION: Analysis of the vascular network in these eyes showed several vascular abnormalities, among which chorioretinal arteriovenous communications appear to be the most dramatic.

[Erythema migrans with multiple lesions]. / Erythème chronique migrant avec lésions multiples.

INTRODUCTION: Erythema migrans with multiple lesions is observed in Europe in only 5-20 p. 100 of Borrelia infections. The number of lesions observed simultaneously in one patient is less than 7, considering all the cases published in the literature to date. CASE REPORTS: We report three patients who presented multiple macular, erythematous and centrifugal lesions localized on the trunk and the limbs. The first patient presented about thirty lesions, the second more than seventy, and the third about twenty. Serology investigation and immunoblots allowed to establish the diagnosis of a recent Borrelia Burgdorferi infection, with multiples lesions of erythema migrans. PCR performed on a skin biopsy of one of the patients confirmed the presence of Borrelia burgdorferi. Response to antibiotic therapy was immediate in all 3 patients. DISCUSSION: These 3 cases are of particular interest because the number of simultaneous lesions is much higher than what is reported in the European literature. These observations remind the clinician that the diagnosis of erythema migrans with multiple lesions should be included, in Europe as well, in the differential diagnosis of multiple annular dermatoses.

[Clinical aspects and pathology of melanoma]. / Klinik und Pathologie des Melanoms.

The annual incidence of melanoma is continually increasing. Melanomas can easily be diagnosed because they are readily visible on the skin. The prognosis is excellent for melanoma when it is diagnosed in an early stage. The clinical diagnosis of melanomas is made by the simple A-B-C-D-E-rule. Clinically, we distinguish the following melanoma types by the order of frequency: the melanoma of the superficial spreading type (SSM), the melanoma with nodular type (NM), the lentigo maligna melanoma (LMM) and the acro-lentiginous melanoma (ALM). Other clinical subtypes of melanoma are congenital giant nevus and melanoma of the mucous membranes. With help of histogenesis, we can distinguish similar forms for melanoma of the SSM-type, melanoma of the NM-type, the lentigo maligna melanoma (LMM) and the melanoma of the ALM-type. In this case, it is preferable to use the terminology acanthotic-lentiginous melanoma since acro-lentiginous is the clinical expression and not a histopathological one. Further subtypes can be distinguished histopathologically such as the desmoplasic melanoma which has been recently described as melanoma from a dysplasic nevus as well as melanoma of the lichen cleanness type. Furthermore, due to histopathology other particular forms can be distinguished such as the melanoma of the nevus Spitz type and melanoma originating from a blue nevus. Most important for the histopathological report is the thickness of the melanoma in millimeters related to the Breslow index as well as the invasion level in the skin by the Clark classification since the melanoma thickness is the most important risk factor for the melanoma patient.

Determination of Vitamin B12 in meat products by RP-HPLC after enrichment and purification on an immunoaffinity column.

A quantitative method for the determination of Vitamin B12 in meat products by RP-HPLC and UV detection was developed and compared to the reference method (microbiological assay, MBA). Vitamin B12 was extracted with 50mM sodium acetate buffer in the presence of sodium cyanide. For the quantification of total Vitamin B12, it was necessary to release protein-bound Vitamin B12 by pepsin treatment. Cyanocobalamin was detected as total Vitamin B12 after purification and enrichment on an immunoaffinity column. The calibration with five concentrations of Vitamin B12 was linear with a regression coefficient r2>0.99. The method was validated at three different concentration levels (5-15 ng/g) with salami showing good recovery rates between 80 and 108% and low relative standard deviations between 1.50 and 7.26% (n = 6). The detection limit was found to be 2 ng/g. The Vitamin B12 levels of 50 meat products measured by the developed procedure were similar or significantly lower than those determined by the MBA.

Intraepidermal IgA pustulosis preceding a CD30+ anaplastic large T-cell lymphoma.

We report the case of a 62-year-old patient with an extracutaneous CD30+ anaplastic large T-cell lymphoma which was preceded by intraepidermal IgA pustulosis (IEAP). The clinical picture was identical to Sneddon-Wilkinson disease and histologic examination showed subcorneal pustules with slight acantholysis. Direct immunofluorescence exclusively revealed IgAK deposits on the plasma membrane of suprabasal keratinocytes. Indirect immunofluorescence and immunoelectrophoresis showed no evidence of monoclonal IgA gammopathy. IEAP responded to dapsone treatment (100 mg/day). Two months after disappearance of active cutaneous lesions, the patient developed generalized lymphadenopathy due to CD30+ anaplastic T-cell lymphoma.

Severe, chronic anorexia and extensive leg ulcerations as presenting signs of primary Sjögren's syndrome.

We report the case of a 75-year-old woman with a 15-year history of inappetance resulting in weight loss of approximately 40 kg. On physical examination, the skin of the lower extremities was markedly hyperpigmented with a brown-greyish hue. In addition, the skin of the legs was infiltrated, erythematous, riddled with erosions and necrotic ulcers. Clinical and laboratory evaluation revealed sicca syndrome, a pronounced polyclonal hypergammaglobulinemia (60 g/l), high levels of antinuclear, anti-SSA and anti-SSB antibodies. Histological examination of involved skin demonstrated a leukocytoclastic vasculitis.

Methods for the determination of sulphonamides in meat.

Sulphonamides, due to their important antibacterial effects, are widely used in veterinary practice and animal husbandry. Residues arising from administration without observing withdrawal time sufficiently are normally the parent compounds and the N4-acetyl derivatives, the latter being hydrolyzed to the parent compounds only during extraction under acidic conditions. It is therefore quite conceivable that many authors concentrate on determining these metabolites. In the past decade, we have witnessed a considerable increase in new analytical techniques dealing with the determination of sulphonamides. Among these procedures, especially the so-called multimethods using high-performance liquid chromatography--though sometimes including toilsome clean-up steps--can be mentioned. However, current approaches also utilize gas chromatography, gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, supercritical fluid chromatography-mass spectrometry, thin-layer chromatography and immunological methods. For most of these techniques, a strong trend towards lowering the level of detectability (down to the sub-ppb range) and improving accuracy and reproducibility can be established.

Meleda disease: report of two cases investigated by electron microscopy.

We report 2 cases of clinically typical Meleda disease in a family from Herzegovina. Electron microscopy did not reveal major ultrastructural anomalies of keratinization; however, the transition from stratum granulosum to stratum corneum appeared to occur less abruptly than normally by a stepwise process suggesting a slowing down of terminal cornification.

Drug-induced linear IgA bullous dermatosis probably induced by furosemide.

Linear IgA bullous dermatosis (LABD) is an autoimmune disease, characterized by linear deposition of IgA along the basement membrane zone. Drug-induced LABD is rare but increasing in frequency. A new case of drug-induced LABD associated with the administration of furosemide is described.

Monosymptomatic Loa loa infection.

We report the case of a 17-year-old student from Cameroon who presented an atypical, mono-symptomatic form of Loa loa infection, characterized only by rare subcutaneous movements of adult worms.

Norwegian scabies in a patient with acquired immunodeficiency syndrome.

We report the case of a 42-year-old man with symptomatic HIV infection (C3 CDC stage) who presented widespread hyperkeratotic skin lesions diagnosed as Norwegian scabies. The CD4 count was 87 cells/mm3. The patient has been the source of a nosocomial outbreak (20 individuals affected). He was treated successfully with combined topical treatment (permethrin 5% cream plus keratolytic agents) and oral ivermectin.