The microbiome of diabetic foot ulcers: a comparison of swab and tissue biopsy wound sampling techniques using 16S rRNA gene sequencing.

BACKGROUND: Health-care professionals need to collect wound samples to identify potential pathogens that contribute to wound infection. Obtaining appropriate samples from diabetic foot ulcers (DFUs) where there is a suspicion of infection is of high importance. Paired swabs and tissue biopsies were collected from DFUs and both sampling techniques were compared using 16S rRNA gene sequencing. RESULTS: Mean bacterial abundance determined using quantitative polymerase chain reaction (qPCR) was significantly lower in tissue biopsies (p = 0.03). The mean number of reads across all samples was significantly higher in wound swabs [Formula: see text] = 32,014) compared to tissue ([Formula: see text] = 15,256, p = 0.001). Tissue biopsies exhibited greater overall diversity of bacteria relative to swabs (Shannon's H diversity p = 0.009). However, based on a presence/absence analysis of all paired samples, the frequency of occurrence of bacteria from genera of known and potential pathogens was generally higher in wound swabs than tissue biopsies. Multivariate analysis identified significantly different bacterial communities in swabs compared to tissue (p = 0.001). There was minimal correlation between paired wound swabs and tissue biopsies in the number and types of microorganisms. RELATE analysis revealed low concordance between paired DFU swab and tissue biopsy samples (Rho = 0.043, p = 0.34). CONCLUSIONS: Using 16S rRNA gene sequencing this study identifies the potential for using less invasive swabs to recover high relative abundances of known and potential pathogen genera from DFUs when compared to the gold standard collection method of tissue biopsy.

Providers' beliefs about the effectiveness of the HPV vaccine in preventing cancer and their recommended age groups for vaccination: Findings from a provider survey, 2012.

BACKGROUND: The human papillomavirus (HPV) vaccine was recommended in 2007 by the Advisory Committee on Immunization Practices (ACIP) to preadolescent and adolescent girls. Vaccination initiation was recommended at age 11-12 years with the option to start at age 9. Catchup vaccination was recommended to females aged 13-26 previously not vaccinated. However, vaccination coverage remains low. Studies show that the HPV vaccine can prevent cervical, vulvar, vaginal, anal and some oropharyngeal cancers and that provider recommendation of vaccines can improve low vaccination rates. METHODS: Using data from 2012 DocStyles, an annual, web-based survey of U.S. healthcare professionals including physicians and nurse practitioners (n=1753), we examined providers' knowledge about the effectiveness of the HPV vaccine in preventing cancer and their vaccine recommendation to all age-eligible females (9-26 years). Descriptive statistics and Chi-square tests were used to assess differences across specialties. RESULTS: Knowledge about HPV vaccine effectiveness in preventing cervical cancer was highly prevalent (96.9%), but less so for anal, vaginal, vulvar and oropharyngeal cancers. Only 14.5% of providers recommended the vaccine to all age-eligible females and 20.2% recommended it to females aged 11-26 years. Knowledge assessment of cancers associated with HPV and vaccination recommendations varied significantly among providers (p<0.01). Providers more frequently recommended the vaccine to girls older than 11-12 years. CONCLUSIONS: Improving providers' knowledge about HPV-associated cancers and the age for vaccination initiation, communicating messages focusing on the vaccine safety and benefits in cancer prevention and on the importance of its delivery prior to sexual onset, may improve HPV vaccine coverage.

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies.

BACKGROUND: AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). METHODS: In study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a once daily (QD) oral schedule (A). In study 1, pharmacokinetic assessments led to twice daily (BID) dosing (schedule B) to increase exposure. Study 2 explored a once daily schedule. RESULTS: In study 1, 49 pts were treated with escalating doses of AZD3514 (A 35 pts, B 14 pts). Starting doses were 100 mg (A) and 1000 mg (B). The AZD3514 formulation was switched from capsules to tablets at 1000 mg QD. 2000 mg BID was considered non-tolerable due to grade (G) 2 toxicities (nausea [N], vomiting [V]). No adverse events (AEs) met the dose-limiting toxicity (DLT) definition. Thirteen pts received AZD3514 in study 2, with starting doses of 250 mg QD. The most frequent drug-related AEs were N: G1/2 in 55/70 pts (79 %); G3 in 1 pt (1.4 %); & V: G1/2 in 34/70 pts (49 %) & G3 in 1 pt (1.4 %). PSA declines (≥50 %) were documented in 9/70 patients (13 %). Objective soft tissue responses per RECIST1.1 were observed in 4/24 (17 %) pts in study 1. CONCLUSION: AZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds.

The effect of diabetes mellitus on costs and length of stay in patients with peripheral arterial disease undergoing vascular surgery.

OBJECTIVE: To determine the impact of diabetes mellitus (DM) and other comorbidities on length of stay (LOS) and costs in patients with peripheral arterial disease (PAD) admitted to a vascular surgical unit. METHODS: A retrospective study was conducted between January 2011 and July 2012 at a tertiary referral hospital in Sydney. Demographic, laboratory, and operative data were obtained from the Australasian Vascular Audit database and hospital diagnostic-related group (DRG) reports. Patients with confirmed PAD with or without DM requiring hospital admission for a diagnosis of claudication, rest pain, ulcer/gangrene, and infection that required lower limb surgical intervention were included. Associations between LOS, surgical procedure, and DRG were explored. RESULTS: Five hundred and sixty-eight admissions (492 patients) were identified: 292 admissions with PAD and 276 admissions with PAD in conjunction with DM (PADDM). Mean LOS for patients with PAD was 10 ± 13.7 days compared with 15 ± 18.2 days for PADDM (p < .01; 95% confidence interval 2.7-8.0). LOS and costs were greatest in patients with PADDM undergoing major amputation (37 ± 13.7 days; US$42,236; p < .01). Analysis of variance indicated that the best predictors of LOS were the presence of DM, bypass surgery, amputation, chronic kidney disease (CKD) stage V, infection, and emergency admission. Over 18 months, the estimated total inpatient costs associated with lower limb intervention for PAD with and without DM amounted to US$7,598,597. People with DM incurred greater inpatient costs, averaging US$1,912 more per episode of admission and a total of US$528,029 over 18 months. CONCLUSION: The impact of diabetes as a comorbid condition in patients with PAD is significant, both clinically and economically. Factors that predict increased LOS in patients with PAD are DM, bypass surgery, amputation, CKD stage V, infection, and emergency admission.

Pedal osteomyelitis in patients with diabetes: a retrospective audit from Saudi Arabia.

OBJECTIVE: To examine the characteristics of patients presenting to the emergency room and the specialist diabetes foot clinic with pedal osteomyelitis (PO). METHOD: A retrospective study was conducted at a regional hospital. The charts of patients with suspected PO who presented during the period 1 January to 31 December 2011 were analysed. Demographics, biochemistry and microbiological data were obtained. Bone biopsies were performed by the attending clinician either during surgical removal of infected bone, or percutaneously under guided fluoroscopy through non-infected tissue. RESULTS: Sixty-six cases of osteomyelitis affecting 102 joints were noted. The study population consisted of 44 men, mean age 62.9 +/- 1.3 years, and 22 women, mean age of 57.6 +/- 10.6 years. Gram-positive bacteria were the predominating pathogens (p < 0.05). Staphylococcus aureus was cultured in 36% of all bone biopsy cases. A predictive trend in HbA1c was observed,where every increase of 1% from the recommended level of 7% was associated with a 10% increase in the likelihood of receiving surgical intervention. CONCLUSION: S. aureus infection is a major cause of osteomyelitis in interphalangeal joints of the feet of diabetic patients.There is an apparent association with patients who present with diabetic foot osteomyelitis and sub-optimal glycaemic control, requiring surgical intervention.

Deep wound cultures correlate well with bone biopsy culture in diabetic foot osteomyelitis.

BACKGROUND: Osteomyelitis is a major complication in patients with diabetic foot ulceration. Accurate pathogenic identification of organisms can aid the clinician to a specific antibiotic therapy thereby preventing the need for amputation. METHODS: All diabetic patients with bone biopsy-confirmed osteomyelitis were included into the study: biopsies were performed either during surgical removal of infected bone or percutaneously under guided fluoroscopy through non-infected tissue. The depth and extent of the ulcer was assessed using a sterile blunt metal probe. Deep wound cultures were taken from the wound base after sharp debridement. RESULTS: Of 66 cases of suspected osteomyelitis in 102 joints, 34 patients had both bone biopsies and deep wound cultures over the study period. Thirty two of 34 (94%), had a history of preceding foot ulceration, and in 25 of the cases a positive probe to bone test was recorded. In a high proportion of patients, at least one similar organism was isolated from both the deep wound culture and bone biopsy procedures (25 of 34 cases, 73.5%, p<0.001). When organisms were isolated from both wound cultures and bone biopsies, the identical strain was identified in both procedures in a significant proportion of cases (16 of 25 cases, 64%, p<0.001, total sample analysis in 16 of 34 cases, 47%). CONCLUSIONS: Deep wound cultures correlate well with osseous cultures and provide a sensitive method in assessing and targeting likely pathogens that cause osseous infections. This will help aid the clinician in guiding antibiotic therapy in centers where bone biopsies may not be readily available.

An extensive primary nodular melanoma of the foot with associated distant metastases: a case report.

A Nodular Melanoma of the foot is a relatively uncommon disease, which accounts for the dearth of literature. The anatomical location of a primary malignant melanoma is of prognostic importance as primary lesions of the foot and ankle have poorer prognostic outcomes. This single case reports a life-threatening presentation, of a primary nodular melanoma of the foot with associated distant metastases of the skeletal system, organs and lymph nodes.

Circulating melanoma cells and survival in metastatic melanoma.

A validated assay for the enumeration of circulating melanoma cells (CMCs) may facilitate the development of more effective therapies for metastatic melanoma patients. In this study CD146+ cells were immunomagnetically enriched from 7.5 ml of blood. Isolated cells were fluorescently stained with DAPI, anti-molecular weight melanoma-associated antigen (HMW-MAA), anti-CD45 and CD34 and Ki67. CMCs were identified as CD146+, HMW-MAA+, CD45-, CD34-, Ki67-/+ cells. Eighty-eight percent of spiked SK-MEL28 cells in 7.5 ml blood were recovered. In all 55 healthy donors ≤1 CMCs were detected in 7.5 ml of blood. A retrospective analysis was conducted comparing CMC counts and overall survival in 79 blood samples from 44 melanoma patients. CMCs ranged from 0 to 8,042 per 7.5 ml. Two or more CMCs were detected in 18 (23%) of the patients and 30-100% (mean 84%) of the CMCs expressed the proliferation marker Ki67. Patients with ≥2 CMCs per 7.5 ml of whole blood, as compared with the group with <2 CMCs, had a shorter overall survival (2.0 months vs. 12.1 months, P=0.001).

Virological investigations in sudden unexpected deaths in infancy (SUDI).

Previous studies have implicated viral infections in the pathogenesis of sudden unexpected death in infancy (SUDI), and routine virological investigations are recommended by current SUDI autopsy protocols. The aim of this study is to determine the role of post-mortem virology in establishing a cause of death. A retrospective review of 546 SUDI autopsies was carried out as part of a larger series of >1,500 consecutive paediatric autopsies performed over a 10-year period, 1996-2005, in a single specialist centre. Virological tests were performed as part of the post-mortem examination in 490 (90%) of the 546 SUDI autopsies, comprising 4,639 individual virological tests, of which 79% were performed on lung tissue samples. Diagnostic methods included immunofluorescence assays (using a routine respiratory virus panel; 98% of cases), cell culture (61%), rapid culture techniques such as the DEAFF test for CMV (55%), PCR (13%), electron microscopy (10%), and others. Virus was identified in only 18 cases (4%), viz. five cases of enterovirus, four of RSV, three of HSV and CMV, and one each of adenovirus, influenza virus and HIV. In seven of the 18 cases the death was classified as due to viral infection, whilst of the remaining 11 cases, death was due to bacterial infection in five, a non-infective cause in one and unexplained in five. Virus was identified in 33% of deaths due to probable viral infections, but also in 6% of SUDI due to bacterial infections, and in 2% of SUDI due to known non-infective causes and unexplained SUDI. When predominantly using immunofluorescence, virus is identified in only a small proportion of SUDI autopsies, resulting in a contribution to the final cause of death in <2% of SUDI post-mortem examinations. Routine post-mortem virological analysis by means of an immunofluorescence respiratory virus panel appears to be of limited benefit in SUDI for the purposes of determining cause of death. Application of a broader panel using more sensitive detection techniques may reveal more viruses, although their contribution to the final cause of death requires further exploration.

Remission of paroxysmal atrial fibrillation with iron reduction in haemophilia A.

SUMMARY: Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12-15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing.

Preoperative binge eating status and gastric bypass surgery: a long-term outcome study.

BACKGROUND: The primary purpose of the study was to evaluate the effect of preoperative binge status on long-term weight loss outcomes. METHODS: IRB approval was obtained. This prospective study was initiated in 1997 at a large teaching hospital. Adult patients who participated in the study and attended post-surgery clinic visits for at least 12 months were included. Patients completed the gormally binge eating scale (BES), the beck depression inventory (BDI), and the SF-36 at baseline prior to surgery. All data are expressed as mean +/- SD. Data were analyzed using a Student's t test, pairwise correlation and regression analysis as appropriate. RESULTS: A total of 157 patients (135 women) aged 45 +/- 10 years were recruited. Their preoperative BMI was 50.7 +/- 8.0 kg/m(2). Thirty-seven patients were classified as severe binge eaters (BES >or= 27) prior to surgery. There was no significant difference in their weight loss compared to the rest of the group at any time point up to 6 years after surgery. Patients with significant depressive symptoms (BDI >13) had no significant difference in their weight loss outcomes compared to the rest of the group. Pre-surgery SF-36 scores did not predict differences in weight loss outcome. CONCLUSION: Pre-surgical binge status, incidence of depressive symptoms and health related quality of life were not predictive of poor weight loss outcomes in patients up to 6 years after gastric bypass surgery, who were able to make lifestyle changes in preparation for surgery and who adhered to scheduled post surgery clinic visits.

Capillary apposition and density in the diagnosis of alveolar capillary dysplasia.

AIM: Alveolar capillary dysplasia (ACD) is a rare disorder, typically presenting with persistent pulmonary hypertension of the newborn. The aim was to characterise further the histological features of patients suspected of having ACD and to correlate histopathological features with outcome. METHODS AND RESULTS: Three pathologists retrospectively reviewed 21 surgical lung biopsy specimens (SLBx) where ACD entered the differential diagnosis. Semi-quantitative assessment showed that there was a spectrum of muscular arterial hypertrophy, capillary apposition to epithelium and capillary density within the interstitium, with the latter being more disordered in ACD. Misalignment of pulmonary vessels was also frequently seen. Four of 19 patients survived beyond the neonatal period, these having higher degrees of capillary apposition and density. Associated extrapulmonary abnormalities were common, most frequently with ACD. CONCLUSION: Poor capillary apposition and density, allied with medial arterial hypertrophy and misalignment of pulmonary vessels are the strongest diagnostic features of ACD. Of the four patients alive, all had high capillary apposition and density, suggesting that these features may be of prognostic value. SLBx remains useful in such cases as it may help predict patients who survive the neonatal period and also identify patients with disorders that are not primarily vascular anomalies.

Electron microscopy of chorionic villus samples for prenatal diagnosis of lysosomal storage disorders.

Some lysosomal storage disorders cause progressive prenatal accumulation of undegradable metabolites that manifest as membrane-bound vacuoles in endothelial cells, fibroblasts, and trophoblast, identifiable by electron microscopic examination of chorionic villus samples (CVS). There were 111 CVS, which had ultrastructural examination for suspected storage disorders at Great Ormond Street Hospital (1988-2005). There were 31 positive diagnoses, including glycogen storage disease type II, gangliosidosis type 1, mucopolysaccharidosis type 1, MPS not specified, Niemann-Pick type A, sialidosis/mucolipidosis type 1, neuronal ceroid lipofuscinoses (including variant forms), Wolman disease, sialic acid storage disease, and storage disease not specified. In most of these cases the indication was a previously affected individual. Seventy-seven cases showed no evidence of storage disease; 3 samples were inadequate for ultrastructural diagnosis. In selected cases, one-third of CVS may demonstrate distinctive ultrastructural features allowing prenatal diagnosis of a range of storage diseases.

Primary thoracic myxoid variant of extrarenal rhabdoid tumor in childhood.

Primary extrarenal rhabdoid tumors (RT) are now recognized as a specific entity in pediatric oncological pathology practice. We present an unusual case of a small cell myxoid variant of a thoracic RT in an infant and highlight the importance of recent molecular developments in the diagnosis of these tumors. An 8-month-old child presented with a short history of cough and shortness of breath. Imaging demonstrated a large mass occupying the majority of the thoracic cavity on the right side. A percutaneous needle biopsy of the mass showed fragments of tissue composed of malignant tumor with a predominant "small ovoid cell" phenotype and extensive myxoid change, with small nests and islands of tumor cells; occasional cells demonstrated open vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasmic inclusions. Immunohistochemical staining revealed focal strong cytoplasmic positivity for cytokeratin, focal strong paranuclear cytoplasmic vimentin positivity, and INI1 staining showed normal nuclear positivity in control tissues but was negative in tumor cell nuclei. Electron microscopy demonstrated characteristic paranuclear whorls of intermediate filaments confirming the diagnosis of extrarenal malignant RT. The diagnosis of malignant rhabdoid tumor may be difficult, particularly in cases, such as the present, with a predominant small-cell myxoid phenotype. The characteristic expression patterns of cytokeratin and vimentin provide strong clues to the diagnosis, and the use of INI1 antibody now makes definitive diagnosis possible even on needle core biopsies.

Congenital alveolar capillary dysplasia and associated gastrointestinal anomalies.

Congenital alveolar capillary dysplasia is a rare cause of irreversible pulmonary hypertension with 100% mortality. We present three cases of congenital alveolar capillary dysplasia with associated gastrointestinal abnormalities. Three full-term neonates presented with pulmonary hypertension needing ventilatory support by oscillation. Of the three, two neonates subsequently needed extracorporeal membrane oxygenation. Abdominal distension associated with bilious aspirates was the gastrointestinal manifestation. One child had duodenal atresia and anorectal anomaly, one with intestinal malrotation and the other with a rare combination of intestinal malrotaion and total colonic Hirschsprung's disease. All three infants succumbed to pulmonary hypertension at mean age 34 days. The etiopathogenesis and pathology of this condition are discussed with a comprehensive review of the literature.

Melanotic neuroectodermal tumor of infancy: clinical, radiological, and pathological features.

We present a case of a 4-month-old female infant with a maxillary melanotic neuroectodermal tumor of infancy (MNTI) and review the pooled data from previous publications on this entity. The literature to date comprises 378 reported cases from 1918 to the present, from which data on the presence or absence of metastatic disease was available in 311, and on the presence or absence of local recurrence in 165. These pooled data suggest a local recurrence rate of 36% with metastasis occurring in 7% of cases. At present, the optimal management includes complete surgical excision with clear margins, but there are no reliable histopathological or molecular features to predict the biological behavior in individual cases.

Risk of germ cell malignancy in children with XY intersex versus isolated cryptorchidism by immunohistochemistry.

The risk of subsequent development of testicular germ cell neoplasia is related to presence of underlying developmental defects such as cryptorchidism, in which the risk is around 0.5%, and XY intersex with abdominal testes, in which the risk may be as high as 20-25%. We examined the hypothesis that the increased risk of germ cell malignancy in intersex testes with Y chromosome was a direct consequence of an abnormal increase in number of PLAP/CD117+ immature germ cells into postnatal life. Archival cases of uncomplicated cryptorchidism (CO) and XY intersex (INT) were identified and anonymized, and a subgroup of aged-matched cases had sections immunostained with placental alkaline phosphatase (PLAP) and CD117. From a total of 89 intersex and 105 cryptorchid cases identified, a power calculation to detect a 20% difference in expression between groups (alpha = 0.05, power = 80%) determined that 18 intersex and 36 cryptorchid cases were required. Thus, 58 cases were examined, median age 3 (range birth-11) years, including 39 CO and 19 INT. The prevalence of any PLAP+ germ cells was 2/39 (5.1%) versus 3/19 (15.7%), respectively. (Z = 1.4, p = 0.17). In contrast, 94% of cases showed presence of any CD117+ germ cells, but the frequency of CD117+ cells was not significantly different between groups (t = 0.56, p = 0.58). CD117 and PLAP identify different populations of germ cells in pediatric testes. The extent of increased risk of malignancy in XY INT is not simply related to increased numbers of immature PLAP+/CD117+ germ cells present; additional factors play a pathogenic role.

Histopathological features of testicular regression syndrome: relation to patient age and implications for management.

Testicular regression syndrome (TRS) represents a congenital condition in which no normal testicular tissue can be identified following exploration for a clinically impalpable testis. A spectrum of pathological findings may be present but there is little literature systematically examining these features. We searched a pediatric histopathology database to identify cases of TRS, and the histopathological findings were reviewed and pooled with those of all previously published smaller series. A total of 117 cases were identified during the period (1989-2004), median age 2 (range birth-12) years. In 52 (44%) a nodule was identified macroscopically, median maximum diameter 0.5 (range 0.1-2.0) cm. Microscopic hemosiderin-laden macrophages were present in 85 (73%), dystrophic calcification in 52 (44%), residual testicular tubules in 12 (10%), vas deferens in 71 (61%), and epididymal tissue in 39 (33%). The prevalence of hemosiderin laden macrophages and dystrophic calcification were significantly greater in cases < or =3 years (84% versus 64% and 55% versus 32%, respectively). But there was no significant difference in the frequency of other findings between the younger and older age groups; in particular, the presence of residual testicular tubules was similar (7% versus 13%, respectively). Furthermore, there was no significant correlation between identification of a macroscopically distinct nodule and presence of residual tubular structures, tubules being identified in 6 of the 65 cases in which no clearly identifiable nodule was seen macroscopically. The presence of hemosiderin-laden macrophages and foci of dystrophic calcification showed a positive association. TRS is associated with specific histopathological features, the findings being consistent with changes secondary to intrauterine testicular torsion. Residual testicular tubules are found in 10% of cases regardless of the presence or absence of a macroscopically identifiable nodule.

Histopathological reporting of paediatric cutaneous vascular anomalies in relation to proposed multidisciplinary classification system.

BACKGROUND: The terminology applied to vascular anomalies has been variable in previously published literature making interpretation suboptimal. The International Society for the Study of Vascular Anomalies (ISSVA) has proposed a revised classification based on clinical features and histopathological findings. This classification is increasingly being accepted as clinically useful and a platform for future studies. AIMS: To examine the extent to which the ISSVA classification can be practically applied to diagnostic histopathological specimens. METHODS: Cutaneous vascular lesions received in a single paediatric pathology unit during a 2-year period (2004-5) were reviewed, including glucose transporter protein 1 (GLUT1) immunostaining where required, and lesions were reclassified according to the ISSVA classification. RESULTS: 144 specimens were identified. Appropriate full clinical information was provided in only 17% of cases at submission. Infantile haemangiomas comprised 46% of cases, 18% of which were regressive type, initially inaccurately identified as vascular malformations before GLUT1 immunostaining. 30% of lymphatic malformations and all lymphovenous malformations were previously classified as vascular malformations, not otherwise specified. CONCLUSIONS: The ISSVA classification of vascular anomalies provides a useful framework for histopathologists to classify vascular anomalies. However, meaningful and appropriate use of such a system is dependent on the adequacy of clinical information provided and routine use of immunohistochemical markers.

Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis.

Glucocorticoid hormones induce apoptosis in lymphoid cells. This process is transcriptionally regulated and requires de novo RNA/protein synthesis. However, the full spectrum of glucocorticoid-regulated genes mediating this cell death process is unknown. Through gene expression profiling we discovered that the expression of thioredoxin-intereacting protein (txnip) mRNA is significantly induced by the glucocorticoid hormone dexamethasone not only in the murine T-cell lymphoma line WEHI7.2, but also in normal mouse thymocytes. This result was confirmed by Northern blot analysis in multiple models of dexamethasone-induced apoptosis. The induction of txnip mRNA by dexamethasone appears to be mediated through the glucocorticoid receptor as it is blocked in the presence of RU486, a glucocorticoid receptor antagonist. Deletion and mutation analysis of the txnip promoter identified a functional glucocorticoid response element in the txnip promoter. Reporter assays demonstrated that this glucocorticoid response element was necessary and sufficient for induction of txnip by dexamethasone. Expression of a GFP-TXNIP fusion protein was sufficient to induce apoptosis in WEHI7.2 cells, and repression of endogenous txnip by RNA interference inhibited dexamethasone-induced apoptosis in WEHI7.2 cells. Together, these findings indicate that txnip is a novel glucocorticoid-induced primary target gene involved in mediating glucocorticoid-induced apoptosis.