Urogenital manifestations in Wegener granulomatosis: a study of 11 cases and review of the literature

We describe the main characteristics and treatment of urogenital manifestations in patients with Wegener granulomatosis (WG). We conducted a retrospective review of the charts of 11 patients with WG. All patients were men, and their median age at WG diagnosis was 53 years (range, 21-70 yr). Urogenital involvement was present at onset of WG in 9 cases (81%), it was the first clinical evidence of WG in 2 cases (18%), and was a symptom of WG relapse in 6 cases (54%). Symptomatic urogenital involvement included prostatitis (n = 4) (with suspicion of an abscess in 1 case), orchitis (n = 4), epididymitis (n = 1), a renal pseudotumor (n = 2), ureteral stenosis (n = 1), and penile ulceration (n = 1). Urogenital symptoms rapidly resolved after therapy with glucocorticoids and immunosuppressive agents. Several patients underwent a surgical procedure, either at the time of diagnosis (n = 3) (consisting of an open nephrectomy and radical prostatectomy for suspicion of carcinoma, suprapubic cystostomy for acute urinary retention), or during follow-up (n = 3) (consisting of ureteral double J stents for ureteral stenosis, and prostate transurethral resection because of dysuria). After a mean follow-up of 56 months, urogenital relapse occurred in 4 patients (36%). Urogenital involvement can be the first clinical evidence of WG. Some presentations, such as a renal or prostate mass that mimics cancer or an abscess, should be assessed to avoid unnecessary radical surgery. Urogenital symptoms can be promptly resolved with glucocorticoids and immunosuppressive agents. However, surgical procedures, such as prostatic transurethral resection, may be mandatory in patients with persistent symptoms.

Ungual melanoma - controversies in diagnosis and treatment

Ungual melanomas are considered rare, being difficult to diagnose, and having a poor prognosis. The aim of the present study was to discuss the epidemiology, potential causes, treatment options, and outcome of ungual melanomas. In contrast to assumptions in many articles, ungual melanomas are not rare when calculated for the cumulative size of the nail apparatus of both the fingers and toes. The prognosis is not worse than that of melanomas with the same thickness, mitotic rate, or presence of ulceration on other sites. Melanomas of the nail apparatus behave similar to melanomas in other localizations. What makes them enigmatic is the high rate of misdiagnoses and very late diagnoses.

Detection of surfactant proteins A and D in human tear fluid and the human lacrimal system

PURPOSE: To evaluate the expression and presence of surfactant protein (SP) A and SP-D in the lacrimal apparatus, at the ocular surface, and in tears in healthy and pathologic states. METHODS: Expression of mRNA for SP-A and SP-D was analyzed by RT-PCR in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal ducts as well as in a spontaneously immortalized conjunctival epithelial cell line (HCjE; IOBA-NHC) and a SV40-transfected cornea epithelial cell line (HCE). Deposition of SP-A and SP-D was determined by Western blot, dot blot, and immunohistochemistry in healthy tissues, in tears, aqueous humor, and in sections of different corneal abnormalities (keratoconus, herpetic keratitis, and Staphylococcus aureus-based ulceration). Cell lines were stimulated with different cytokines and bacterial components and were analyzed for the production of SP-A and SP-D by immunohistochemistry. RESULTS: The presence of SP-A and SP-D on mRNA and protein levels was evidenced in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal duct samples. Moreover, both proteins were present in tears but were absent in aqueous humor. Immunohistochemistry revealed the production of both peptides by acinar epithelial cells of the lacrimal gland and epithelial cells of the conjunctiva and nasolacrimal ducts, whereas goblet cells revealed no reactivity. Healthy cornea revealed weak reactivity on epithelial surface cells only. In contrast, SP-A and SP-D revealed strong reactivity in patients with herpetic keratitis and corneal ulceration surrounding lesions and in several immigrated defense cells. Reactivity in corneal epithelium and endothelium was also seen in patients with keratoconus. Cell culture experiments revealed that SP-A and SP-D are produced by both epithelial cell lines without and after stimulation with cytokines and bacterial components. CONCLUSIONS: These results show that SP-A, in addition to SP-D, is a peptide of the tear film. Based on the known direct and indirect antimicrobial effects of collectins, the surfactant-associated proteins A and D seem to be involved in several ocular surface diseases.

The "flap-shaft" prosthesis for insensate feet with Chopart or Lisfranc amputations

BACKGROUND: The inevitable detachment of tendons and the loss of the forefoot in Chopart and Lisfranc amputations result in equinus and varus of the residual foot. In an insensate foot these deformities can lead to keratotic lesions and ulcerations. The currently available prostheses cannot safely counteract the deforming forces and the resulting complications. METHODS: A new below-knee prosthesis was developed, combining a soft socket with a rigid shaft. The mold is taken with the foot in the corrected position. After manufacturing the shaft, the lateral third of the circumference of the shaft is cut away and reattached distally with a hinge, creating a lateral flap. By closing this flap the hindfoot is gently levered from the varus position into valgus. Ten patients (seven amputations at the Chopart-level, three amputations at the Lisfranc-level) with insensate feet were fitted with this prosthesis at an average of 3 (range 1.5 to 9) months after amputation. The handling, comfort, time of daily use, mobility, correction of malposition and complications were recorded to the latest followup (average 31 months, range 24 to 37 months after amputation). RESULTS: Eight patients evaluated the handling as easy, two as difficult. No patient felt discomfort in the prosthesis. The average time of daily use was 12 hours, and all patients were able to walk. All varus deformities were corrected in the prosthesis. Sagittal alignment was kept neutral. Complications were two minor skin lesions and one small ulcer, all of which responded to conservative treatment, and one ulcer healed after debridement and lengthening of the Achilles tendon. CONCLUSIONS: The "flap-shaft" prosthesis is a valuable option for primary or secondary prosthetic fitting of Chopart-level and Lisfranc-level amputees with insensate feet and flexible equinus and varus deformity at risk for recurrent ulceration. It provided safe and sufficient correction of malpositions and enabled the patients to walk as much as their general condition permitted.

Outcome of transmetatarsal amputations in diabetics using antibiotic beads

BACKGROUND: Diabetic patients with transmetatarsal amputation (TMA) for chronic forefoot ulceration or necrosis are at high risk for postoperative skin breakdown and subsequent amputation. Locally applied antibiotics may reduce the revision rate and improve the outcome. MATERIAL AND METHODS: In a retrospective comparative study, 60 diabetic patients (65 feet) with forefoot ulceration or necrosis were treated with TMA by three surgeons in three hospitals. In the "beads group'' (46 patients, 49 feet) TMA was combined with local application of bioabsorbable, tobramycin impregnated calcium sulphate beads (OsteoSet-T beads, Wright Medical, Memphis, TN) as a single-stage procedure. The remaining 16 patients had transmetatarsal amputation without beads at the surgeon's discretion and acted as a control group. For all patients, time to healing, length of hospital stay, number of revisions for wound breakdown and conversions to a higher-level amputation were retrospectively reviewed. Of the 60 patients 17 had died and three were lost to followup, leaving 40 patients available for latest followup at 29 months. The Foot ; Ankle Outcome Score, Foot Function index, SF-36, and Comorbidity score were recorded. RESULTS: The revision rate for wound breakdown after TMA was 8.2% (4/49) in the beads group, and 25% (4/16) in the control group (p<0.05). At latest followup, 27% (13/49) in the beads group, and 25% (4/16) in the control group had to be converted to transtibial amputation. Patients in the beads group scored worse for activities of daily living in the FAOS and SF-36 (p < 0.05), and demonstrated more health problems in the Comorbidity scores (not significant), indicating sicker individuals in the beads group. CONCLUSION: Bioabsorbable calcium sulphate antibiotic beads may be a useful addition for TMA for patients with non-healing diabetic ulcerations of the forefoot. The single-stage procedure could have a significant impact on the management of diabetic forefoot ulcerations by preventing additional hospital stays, improving the patient's quality of life and minimizing cost.

Keratitis resulting from Thielavia subthermophila Mouchacca

PURPOSE: The purpose of this study was to report the first case of fungal keratitis resulting from Thielavia sp. METHODS: We conducted a retrospective chart review. RESULTS: A 10-year old girl presented 2 weeks after ocular plant injury with pain and corneal stromal infiltration with central ulceration and ill-defined margins. Cultures of corneal scrapings and biopsy sequence analysis of the ribosomal internal transcribed spacer region isolated Thielavia subthermophila Mouchacca. Clinically, the organism appeared to respond to topical amphotericin B and oral voriconazole. Best-corrected visual acuity at last follow-up visit counted 0.5. CONCLUSIONS: A rare case of Thielavia sp. keratitis was successfully treated with topical amphotericin B and oral voriconazole. Newly developed molecular diagnostic tools contribute to the recognition of a widening spectrum of emerging fungal pathogens capable of causing serious ocular infections.

Outbreaks of an ulcerative and haemorrhagic disease in Arctic char Salvelinus alpinus caused by Aeromonas salmonicida subsp. smithia

Arctic char Salvelinus alpinus farmed in different places in Austria and free of the viral diseases viral haemorrhagic septcaemia (VHS), infectious haematopoietic necrosis (IHN) and infectious pancreatic necrosis (IPN) experienced disease and mortality. Diseased fish showed skin ulceration and pathological signs of sepsis. Aeromonas sp. was isolated as pure culture from the kidney of freshly euthanized diseased fish. Three independent isolates from outbreaks that occurred on 2 of the affected farms were analyzed phylogenetically by DNA sequence analysis of the rrs and gyrB genes and phenotypically with biochemical reactions. All 3 isolates were identified as Aeromonas salmonicida subsp. smithia. Analysis of virulence genes in these isolates revealed the presence of a Type III secretion system as well as several related virulence effector genes including aexT, encoding the Aeromonas exotoxin AexT, aopP and aopH. These genes are characteristic for virulent strains of typical and atypical subspecies of A. salmonicida.

Ankle dorsiflexion arthrodesis to salvage Chopart's amputation with anterior skin insufficiency

BACKGROUND In Chopart-level amputations the heel often deviates into equinus and varus when, due to the lack of healthy anterior soft tissue, rebalancing tendon transfers to the talar head are not possible. Consequently, anterior and lateral wound dehiscence and ulceration may occur requiring higher-level amputation to achieve wound closure, with considerable loss of function for the patients. METHODS Twenty-four consecutive patients (15 diabetes, 6 trauma, and 3 tumor) had Chopart's amputation and simultaneous or delayed additional ankle dorsiflexion arthrodesis to allow for tension-free wound closure or soft tissue reconstruction, or to treat secondary recurrent ulcerations. Percutaneous Achilles tendon lengthening and subtalar arthrodesis were added as needed. Wound healing problems, time to fusion and full weight-bearing in the prosthesis, complications in the prosthesis, and the ambulatory status were assessed. Satisfaction and function were evaluated by the AmpuPro score and the validated Prosthesis Evaluation Questionnaire scale. RESULTS Five patients had successful soft tissue healing and fusions but died of their underlying disease 2 to 46 months after the operation. Two diabetic patients required a transtibial amputation. The other 17 patients were followed for 27 months (range, 13-63). The average age of the 4 women and 13 men was 53.9 years (range, 16-87). Postoperative complications included minor wound healing problems in 8 patients, wound breakdown requiring revision in 4, phantom pain in 3, residual equinus in 1, and adjacent scar carcinoma in 1 patient. The time to full weight-bearing in the prosthesis ranged from 6 to 24 weeks (mean 10). The mean AmpuPro score was 107 points (of 120), and the mean Prosthesis Evaluation Questionnaire scale was 147 points (of 200). No complications occurred with the prosthesis. Twelve patients lost 1 to 2 mobility classes (mean 0.9). The arthrodeses all healed within 2.5 months (range, 1.5 to 5 months). CONCLUSION Adding an ankle arthrodesis to a Chopart's amputation either immediately or in a delayed fashion to treat anterior soft tissue complications was a successful salvage in most patients at this amputation level. It enabled the patients to preserve the advantages of a full-length limb with terminal weight-bearing. LEVEL OF EVIDENCE Level IV, retrospective case series.

Factors influencing the onset and progression of pododermatitis in captive flamingos (Phoenicopteridae).

Pododermatitis is a worldwide problem in captive flamingos. We performed an evaluation of different influence factors (age, sex, weight, origin, breeding status) and a comparison of foot lesions between several zoological institutions and the feet of free-ranging Greater flamingos (Phoenicopterus roseus). A scoring system was used to determine the prevalence and types of lesions and severity. Cracks and nodules developed as early as 3 months of age and papillomatous growths as early as 6 to 7 months of age in captivity. Nodules with ulceration occurred significantly more often in birds older than 31 years and heavier than 4 kg. The comparison of different institutions revealed that birds kept in enclosures with natural-floored water ponds had significantly less severe lesions than birds kept in concrete water ponds. None of the free-ranging flamingos, which live on a muddy underground, showed any lesion. This study demonstrates that flooring, weight and age are important in the onset and progression of pododermatitis in flamingos.

Excision of fascia in melanoma thicker than 2 mm: no evidence for improved clinical outcome.

BACKGROUND Lack of evidence-based data causes significant variation among surgeons concerning the depth of wide excision for primary cutaneous melanomas. OBJECTIVES To evaluate the clinical effect of excision of the deep fascia in melanomas thicker than 2 mm on patient outcome. METHODS We performed a retrospective cohort review (1996-2012) of patients with melanomas thicker than 2 mm. Included patients underwent excision with a 1-cm margin. Data collected included the patients' sex, age, tumour location, tumour type, Breslow depth and presence of ulceration. Local recurrences, locoregional and distant metastases, and disease-free and overall survival were compared between the fascia-excised and the fascia-preserved groups. RESULTS Out of 2182 patients with malignant melanomas, 213 melanomas thicker than 2 mm, with a median follow-up of 1547 days, were included. The mean age of the patients was 62·6 years and the mean Breslow depth was 4·2 mm. Analysis of data for death attributable to melanoma (P = 0·72), local recurrence (P = 0·71), and locoregional (P = 0·87) and distant metastases (P = 0·34) were not significantly different between the study groups. Furthermore, Kaplan-Meier and Cox regression analysis of both groups showed no evidence of significant difference regarding disease-free [P = 0·35; hazard ratio (HR) 1·25; 95% confidence interval (CI) 0·79-1·97] and overall survival (P = 0·63; HR 1·18; 95% CI 0·61-2·27). CONCLUSIONS We believe that excision of the deep fascia does not improve the outcome of melanomas thicker than 2 mm.

Experimental infection of the pig with Mycobacterium ulcerans: a novel model for studying the pathogenesis of Buruli ulcer disease.

BACKGROUND Buruli ulcer (BU) is a slowly progressing, necrotising disease of the skin caused by infection with Mycobacterium ulcerans. Non-ulcerative manifestations are nodules, plaques and oedema, which may progress to ulceration of large parts of the skin. Histopathologically, BU is characterized by coagulative necrosis, fat cell ghosts, epidermal hyperplasia, clusters of extracellular acid fast bacilli (AFB) in the subcutaneous tissue and lack of major inflammatory infiltration. The mode of transmission of BU is not clear and there is only limited information on the early pathogenesis of the disease available. METHODOLOGY/PRINCIPAL FINDINGS For evaluating the potential of the pig as experimental infection model for BU, we infected pigs subcutaneously with different doses of M. ulcerans. The infected skin sites were excised 2.5 or 6.5 weeks after infection and processed for histopathological analysis. With doses of 2 × 10(7) and 2 × 10(6) colony forming units (CFU) we observed the development of nodular lesions that subsequently progressed to ulcerative or plaque-like lesions. At lower inoculation doses signs of infection found after 2.5 weeks had spontaneously resolved at 6.5 weeks. The observed macroscopic and histopathological changes closely resembled those found in M. ulcerans disease in humans. CONCLUSION/SIGNIFICANCE Our results demonstrate that the pig can be infected with M. ulcerans. Productive infection leads to the development of lesions that closely resemble human BU lesions. The pig infection model therefore has great potential for studying the early pathogenesis of BU and for the development of new therapeutic and prophylactic interventions.

Epidermolysis bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene.

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock.

Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host.

Salmonella enterica subspecies 1 serovar Typhimurium is a principal cause of human enterocolitis. For unknown reasons, in mice serovar Typhimurium does not provoke intestinal inflammation but rather targets the gut-associated lymphatic tissues and causes a systemic typhoid-like infection. The lack of a suitable murine model has limited the analysis of the pathogenetic mechanisms of intestinal salmonellosis. We describe here how streptomycin-pretreated mice provide a mouse model for serovar Typhimurium colitis. Serovar Typhimurium colitis in streptomycin-pretreated mice resembles many aspects of the human infection, including epithelial ulceration, edema, induction of intercellular adhesion molecule 1, and massive infiltration of PMN/CD18(+) cells. This pathology is strongly dependent on protein translocation via the serovar Typhimurium SPI1 type III secretion system. Using a lymphotoxin beta-receptor knockout mouse strain that lacks all lymph nodes and organized gut-associated lymphatic tissues, we demonstrate that Peyer's patches and mesenteric lymph nodes are dispensable for the initiation of murine serovar Typhimurium colitis. Our results demonstrate that streptomycin-pretreated mice offer a unique infection model that allows for the first time to use mutants of both the pathogen and the host to study the molecular mechanisms of enteric salmonellosis.

Outbreak of severe foot rot associated with benign Dichelobacter nodosus in an Alpine ibex colony in the Swiss Prealps.

An outbreak of foot rot occurred in the ibex colony "Vanil Noir" in Switzerland from May to December 2014. This article describes field observations and the analyses carried out on the limbs of 3 animals submitted for postmortem examination. Disease signs observed in the field included lameness, poor body condition and overgrown hooves. Macroscopic examination of selected limbs revealed severe lesions in all of them, including interdigital inflammation with ulceration and malodorous exudation. Histological changes were consistent with chronic laminitis with bone resorption, which was not detected at radiographical examination. Grocott-positive organisms compatible with Dichelobacternodosus were detected in the lesions. Samples collected from the lesions were positive by polymerase chain reaction for benign D. nodosus, which is typically associated with only mild lesions in domestic sheep. Whether D. nodosus is endemic in the colony or had previously been transmitted from sympatric domestic livestock is unclear. The unusual warm and humid weather conditions in 2014 may well have contributed to the outbreak.