The Geriatric Nutritional Risk Index is Independently Associated with Prognosis in Patients with Critical Limb Ischemia Following Endovascular Therapy.

OBJECTIVES: Patients with critical limb ischemia (CLI) have poor overall and limb prognosis. Although nutritional status influences overall prognosis, and the Geriatric Nutritional Risk Index (GNRI) is a widely used, simple and well established nutritional status screening method, the association between the GNRI and the overall and limb prognosis of patients with CLI following endovascular therapy (EVT) has not been explored. METHODS: Clinical outcomes were retrospectively evaluated in 473 consecutive patients (74 ± 10 years; 59% male) with CLI who underwent EVT. The GNRI on admission was calculated as follows: [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)]. Cox proportional hazard analysis was performed to explore the independent association between the GNRI and mortality and major amputation. RESULTS: Patients (53% ambulatory, 38% wheelchair bound, and 9% bedridden) were divided into two groups based on the median GNRI: the higher group (GNRI ≥ 91.2, n = 237) and the lower group (GNRI < 91.2, n = 236). Median follow up duration after EVT was 11.3 months. Three years after EVT, the survival rate (74% in the higher GNRI, and 48% in the lower GNRI, respectively), and limb salvage rate (92% in the higher GNRI, and 84% in the lower GNRI) were significantly lower in the lower GNRI group. GNRI (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05), along with being wheelchair bound (HR, 1.87; 95% CI 1.17-2.97; vs. ambulatory status), being bedridden (HR, 3.10; 95% CI, 1.63-2.97; vs. ambulatory status), being on hemodialysis (HR, 2.33; 95% CI, 1.49-3.64), and having chronic heart failure (HR, 2.22; 95% CI, 1.44-3.43) were the independent predictors of mortality. The GNRI (HR, 1.04; 95% CI, 1.01-1.07), being bedridden (HR, 4.15; 95% CI, 1.67-10.3; vs. ambulatory status), isolated below knee disease (HR, 2.49; 95% CI, 1.30-4.77), and hemodialysis (HR, 2.44; 95% CI, 1.23-4.85) were independently associated with major amputation. CONCLUSIONS: The GNRI on admission was independently associated with mortality and major amputation after EVT in patients with CLI.

Predictors of delayed wound healing after endovascular therapy of isolated infrapopliteal lesions underlying critical limb ischemia in patients with high prevalence of diabetes mellitus and hemodialysis.

OBJECTIVES: Acceptable limb salvage rates underlie the widespread use of endovascular therapy (EVT) for patients with critical limb ischemia (CLI) secondary to isolated infrapopliteal lesions; however, post-EVT delayed wound healing remains a challenge. Predictors of delayed wound healing and their use in risk stratification of EVT in patients with CLI due to isolated infrapopliteal lesions are explored. METHODS: This was a retrospective multicenter study. 871 consecutive critically ischemic limbs were studied. There was tissue loss in 734 patients (age: 71 ± 10 years old; 71% male) who had undergone EVT between April 2004 and December 2012. The wound healing rate after EVT was estimated by the Kaplan-Meier method. The association between baseline characteristics and delayed wound healing was assessed by the Cox proportional hazard model. RESULTS: Diabetes mellitus and regular dialysis were present in 75% (553/734) and 64% (476/734) of patients, respectively; 67% of limbs (585/871) had Rutherford class 5 CLI; 8% (67/871) of wounds were located in the heel only; 25% (219/871) of limbs had Rutherford 6 (involving not only the heel); and 42% (354/871) of wounds were complicated by infection. The rate of freedom from major amputation at 1 year reached 88%, whereas the wound healing rate was 67%. Median time to wound healing was 146 days. By multivariate analysis, non-ambulatory status (hazard ratio [HR], 1.58; 95% confidence interval [CI] 1.31-1.91) serum albumin <3 g/dL (HR 1.42; 95% CI 1.08-1.86), Rutherford 6 (not only heel) (HR 1.68; 95% CI 1.33-2.14), wound infection (HR 1.24; 95% CI 1.03-1.50), EVT not based on angiosome concept (HR 1.28; 95% CI 1.06-1.55), and below the ankle (BTA) 0 vessel runoff after EVT (HR 1.45; 95% CI 1.14-1.86) were independent predictors of delayed wound healing. CONCLUSIONS: Non-ambulatory status, low albumin level, Rutherford 6 (not only heel), wound infection, indirect intervention, and poor BTA runoff were independent predictors for delayed wound healing after EVT in patients with CLI secondary to infrapopliteal lesions, and their use in risk stratification allows estimation of the wound healing rate.

Galactomyces fermentation filtrate prevents T helper 2-mediated reduction of filaggrin in an aryl hydrocarbon receptor-dependent manner.

BACKGROUND: The aryl hydrocarbon receptor (AhR) recognizes diverse small molecules such as dioxins, tryptophan photoproducts and phytochemicals. It also plays crucial roles in epidermal homeostasis by upregulating epidermal barrier proteins. In preliminary screening, we found that Galactomyces fermentation filtrate (GFF), a cosmetic compound, was capable of activating AhR. AIM: To examine whether GFF upregulates the expression of the filaggrin and loricrin genes, FLG and LOR, in an AhR-dependent manner. METHODS: The activation (cytoplasmic to nuclear translocation) of AhR was confirmed by immunofluorescence study and by upregulation of an AhR-specific marker, cytochrome P450-1A1 (CYP1A1). Gene expression levels were compared by quantitative reverse transcription PCR with or without GFF, interleukin (IL)-4 or IL-13 in normal human keratinocytes. AhR or control knockdown was carried out by transfection with AhR or control small interfering RNA. The protein expression of FLG and LOR was examined by immunohistochemistry using a three-dimensional epidermal equivalent treated with or without GFF or T helper (Th)2 cytokines. RESULTS: GFF induced the nuclear translocation of AhR with significant and dose-dependent upregulation of CYP1A1, FLG and LOR gene expression. The enhancing effects of GFF were abolished in AhR-knockdown keratinocytes. Th2 cytokines decreased expression of genes for FLG and LOR, and this expression was completely restored in the presence of GFF. The downregulated expression of the FLG gene with its restoration by GFF was also evident in the epidermal equivalent. GFF also upregulated the gene expression of genes encoding occludin, claudin-1 and 4, and kallikrein 5 and 7. CONCLUSIONS: Use of GFF is feasible to prevent the Th2-mediated reduction of FLG in an AhR-dependent fashion.

Perioperative complications after aorto-iliac stenting: associated factors and impact on follow-up cardiovascular prognosis.

OBJECTIVES: To investigate factors associated with 30-day perioperative complications (POC) after aorto-iliac (AI) stenting, and to compare follow-up cardiovascular prognosis between patients with and without POC. MATERIALS AND METHODS: This was a retrospective multicenter study. We used a multicenter database of 2012 consecutive patients who successfully underwent AI stenting for peripheral arterial disease in 18 centers in Japan from January 2005 to December 2009 to analyze independent predictors of POC and impact of POC on prognosis by logistic regression and a Cox proportional hazard regression model, respectively. RESULTS: Mean age was 71 ± 9 years (median: 72 years; range: 37-98 years), and 1,636 patients (81%) were men. POC occurred in 126 patients (6.3%). In multivariate logistic regression analysis, old age (≥80 years), critical limb ischemia (CLI), and Trans Atlantic Inter-Societal Consensus (TASC) II class C/D were independently associated with POC with adjusted odds ratios and 95% confidence intervals (CI) of 1.9 (1.3-2.9), 2.3 (1.5-3.4), and 2.4 (1.6-3.4), respectively. Out of 2012 patients, 1995 were followed up for more than 30 days (mean: 2.6 ± 1.5 years; range: 2-2,393 days). In a Cox hazard regression model adjusted for baseline clinical characteristics, POC was positively and independently associated with follow-up major adverse cardiac events (adjusted hazard ratio [HR]: 1.9; 95% CI: 1.3-2.8; p = .002), but not with major adverse limb events and target lesion revascularization (adjusted HR: 1.4; 95% CI: 0.7-2.7; p = .25; and adjusted HR: 1.2; 95% CI 0.6-2.6; p = .568), respectively. CONCLUSIONS: Age >80 years, CLI, and TASC C/D lesion were positively associated with POC after AI stenting. Occurrence of POC appears to adversely affect follow-up cardiovascular, but not limb and vessel prognosis.

One-year follow-up of zoster-associated pain in 764 immunocompetent patients with acute herpes zoster treated with famciclovir (FAMILIAR study).

BACKGROUND: Herpes zoster (HZ), a reactivation of varicella zoster virus manifested by skin blisters and neuralgia, can lead to postherpetic neuralgia in 10-20% of affected subjects. METHOD: In this study, a cohort of 764 patients with HZ was treated with 1500 mg/day of famciclovir for 7 days, and zoster-associated pain (ZAP) was monitored monthly thereafter for up to 12 months until pain resolution was achieved. Patients were questioned monthly by telephone, and pain was recorded using a numerical rating scale (NRS, 0-10). KEY RESULTS: A total of 751 of 764 (98.3%) patients completed follow-up. The percentage of patients with ZAP was 12.4% at day 90, 7.1% at 6 months and 4.0% at 1 year. After the third month, the NRS were 3 or less in most of the remaining patients with ZAP. Stratified analysis revealed significant persistence of ZAP in patients aged ≥50 years and in those aged ≥65 years, and in patients with either moderate-to-severe skin symptoms or severe pain at the initial consultation.Stratified analyses unexpectedly showed patients who commenced famciclovir at 0-2 days after onset of the eruption had a higher prevalence of ZAP at day 90 than those treated at 3-5 days or ≥6 days after rash onset (P = 0.0164, log-rank test). On further analysis, a higher proportion of patients (45.4%) treated at 0-2 days had moderate to severe symptoms compared with those treated at 3-5 days (40.5%) or ≥6 days (37.0%) (P = 0.0987, Cochran-Armitage test). CONCLUSION & INFERENCE: This study, with an exceptionally high follow-up rate, revealed several new findings, including the influence of disease severity on the delay between the onset of symptoms and seeking medical attention. Six adverse drug reactions were reported in five of 721 patients in the safety analysis, including two severe cases of vomiting and convulsions.

Worse limb prognosis for indirect versus direct endovascular revascularization only in patients with critical limb ischemia complicated with wound infection and diabetes mellitus.

OBJECTIVES: To investigate factors in patients with critical limb ischemia (CLI) and isolated infrapopliteal lesions that adversely affect outcomes of endovascular therapy (EVT) with or without angiosome-oriented revascularization. METHODS: This was a retrospective multicenter study. We used a database of 718 consecutive CLI patients (70 ± 11 years, 75% diabetics, 68% on hemodialysis, 24% Rutherford class 6) with ischemic tissue loss due to isolated infrapopliteal lesions undergoing primary EVT. Primary outcome was MALE (major adverse limb event). Association between indirect EVT (recanalization of a non-angiosome-based artery) and outcome was assessed by Cox proportional hazard regression model. RESULTS: C-reactive protein (CRP) level was >3 mg/dL in 32% of cases. Indirect EVT (in 307 CLI patients, 43%), was associated with MALE (p = .04, hazard ratio [95% confidence interval] 1.25 [1.01, 1.55]), and interacted with CRP >3 mg/dL (p < .004) but not with other baseline characteristics. Indirect EVT with CRP >3 mg/dL had higher MALE risk (HR 2.08), and interacted with diabetes mellitus (DM) presence. Indirect EVT with CRP >3 mg/dL and DM had higher MALE risk (HR 2.17). CONCLUSION: Limb prognosis was equivalent for direct and indirect endovascular revascularization except in the presence of both diabetes and wound infection, when indirect revascularization has a poorer outcome.

Angiographic restenosis and its clinical impact after infrapopliteal angioplasty.

OBJECTIVE: To assess 3- and 12-month angiographic restenosis rates and their clinical impact after infrapopliteal angioplasty. DESIGN: Prospective multicenter study. MATERIALS AND METHODS: We analyzed 68 critical ischemic limbs (tissue loss: 58 limbs) from 63 consecutive patients due to isolated infrapopliteal lesions who underwent angioplasty alone. Primary endpoint was 3-month angiographic restenosis rate; secondary endpoints were 12-month angiographic restenosis rate, and 3- and 12-month rates of mortality, major amputation and reintervention. Three- and 12-month frequency of ambulatory status and of freedom from ischemic symptoms, and time to wound healing in the ischemic wound group, were compared between restenotic and non-restenotic groups. Angiographic restenosis predictors were assessed by multivariable analysis. RESULTS: 95% of cases had 3-month angiography; restenosis rate was 73%: 40% restenosis and 33% re-occlusion. Twelve-month follow-up angiography was conducted for the patients without 3-month angiographic restenosis, and restenosis rate at 12 months was 82%. Non-administration of cilostazol and statin, and chronic total occlusion were 3-month angiographic restenosis predictors. Three- and 12-month mortality was 5% and 12%, respectively. Despite no patients having undergone amputation, 15% had persistent ischemic symptoms, and 48% of limbs underwent reintervention within 12 months. During the same study period, ambulatory status and limbs with complete healing were more frequently observed in the non-restenosis group than in the restenosis group. In the tissue loss group, time to wound healing in the restenosis group was longer than in the non-restenosis group (127 days vs. 66 days, p = 0.02). CONCLUSION: The extremely high angiographic restenosis rate after infrapopliteal angioplasty may adversely impact clinical status improvement.

Anatomical predictors of major adverse limb events after infrapopliteal angioplasty for patients with critical limb ischaemia due to pure isolated infrapopliteal lesions.

OBJECTIVE: To identify anatomical factors associated with major adverse limb events (MALE) after angioplasty as the basis for a novel morphology-driven classification of infrapopliteal lesions. DESIGN: Retrospective-multicenter study. MATERIALS AND METHODS: Between March 2004 and October 2010, 1057 limbs from 884 patients with CLI due to isolated infrapopliteal lesions were studied. Freedom-from MALE, defined as major amputation or any reintervention, was assessed out to 2 years by the Kaplan-Meier methods. Anatomical predictors and risk stratification for MALE were analyzed by multivariate analysis. RESULTS: Freedom-from MALE was 47 ± 1% at 2 years. Lesion calcification, target vessel diameter<3.0 mm, lesion length>300 mm and no below-the-ankle (BA) run-off were positively associated with MALE by multivariate-analysis. The total number of risk factors was used to calculate the risk score for each limbs for subsequent categorization into 3 groups with 0 or 1 (low-risk), 2 (moderate-risk) and 3 or 4 (high-risk) factors. Freedom-from MALE at 2 year-rates was 59% in low-risk, 46% in moderate-risk, and 29% in high-risk, respectively. CONCLUSION: Target vessel diameter <3.0 mm, lesion calcification, lesion length > 300 mm and no-BA run-off were associated with MALE after infrapopliteal angioplasty. Risk stratification based on these predictors allows estimation of future incidence of MALE in CLI with isolated infrapopliteal lesions.

Stromal expression of cathepsin K in squamous cell carcinoma.

BACKGROUND: Cathepsin K (CTSK), a cysteine protease with strong collagenolytic and elastolytic properties involved in extracellular matrix turnover, may be produced by neoplastic cells as well as stromal macrophages and fibroblasts. Its expression is suggested as associated with increased invasive and metastatic potential. OBJECTIVES: The aim of this study is to examine stromal expression of cathepsin K in skin tumors. METHODS: A series of 13 normal skin and 109 skin tumours, including 51 benign and 58 malignant epidermal tumours were tested for CTSK and Ki-67 expression by immunohistochemical analysis. RESULTS: Stromal CTSK expression and the tumoral Ki-67 labelling index were significantly higher in invasive squamous cell carcinoma (SCC) than in other epidermal tumours. CONCLUSION: Cathepsin K-positive stromal fibroblasts may play a crucial role in SCC progression by promoting extracellular matrix degradation, thereby facilitating SCC growth and invasion into surrounding tissue and vasculature. CTSK inhibitors may be a potential novel therapeutic option to decrease SCC progression.

Up-regulation of CC chemokine receptor 6 on tonsillar T cells and its induction by in vitro stimulation with alpha-streptococci in patients with pustulosis palmaris et plantaris.

Pustulosis palmaris et plantaris (PPP) is a tonsil-related disease; tonsillectomy is somewhat effective in treating the condition. However, the aetiological association between the tonsils and PPP has not yet been elucidated fully. Recently, some chemokines and chemokine receptors, including CC chemokine receptor (CCR) 4, CCR6 and CX chemokine receptor (CXCR) 3, have been reported to play important roles in the development of psoriasis, a disease related closely to PPP. In this study, we found that CCR6 expression on both tonsillar and peripheral blood T cells was up-regulated more intensively in PPP patients than in non-PPP patients (P < 0.001 for both), but CCR4 and CXCR3 expressions were not. In vitro stimulation with alpha-streptococcal antigen enhanced CCR6 expression significantly on tonsillar T cells in PPP patients (P < 0.05), but this was not observed in non-PPP patients. The chemotactic response of tonsillar T cells to the CCR6 ligand CC chemokine ligand (CCL) 20 was significantly higher in PPP patients than in non-PPP patients (P < 0.05). The percentage of CCR6-positive peripheral blood T cells decreased after tonsillectomy in PPP patients (P < 0.01); this decrease correlated with an improvement of skin lesions (P < 0.05, r = -0.63). The numbers of CCR6-positive cells and the expression of CCL20 were increased significantly in pathological lesions compared with non-pathological lesions in PPP skin (P < 0.01, P < 0.05 respectively). These results suggest that a novel immune response to alpha-streptococci may enhance CCR6 expression on T cells in tonsils and that CCR6-positive T cells may move to peripheral blood circulation, resulting in recruitment to target skin lesions expressing CCL20 in PPP patients. This may be one of the key roles in pathogenesis of the tonsil-related disease PPP.

Immunohistochemical analysis of the mammalian target of rapamycin signalling pathway in extramammary Paget's disease.

BACKGROUND: We have previously observed that persistent activation of the serine/threonine kinase, protein kinase B (AKT) is a frequent event in extramammary Paget's disease (EMPD). AKT promotes cell proliferation by its ability to coordinate mitogenic signalling with energy- and nutrient-sensing pathways that control protein synthesis through the atypical serine/threonine kinase, mammalian target of rapamycin (mTOR). CDK2, a member of the serine/threonine kinase family of cyclin-dependent kinases, is a key regulator of G(1)-S cell cycle progression, and has recently been shown to be one of the targets of AKT. The AKT-mTOR-p70 ribosomal protein S6 kinase (p70S6K) pathway has been described in some human malignancies, but not in EMPD. OBJECTIVE: To investigate the immunohistochemical staining of the AKT-mTOR-p70S6K pathway in EMPD and to evaluate the relationships among the components. METHODS: Samples of primary EMPD tissue were subjected to immunohistological staining with phosphorylated (p)-AKT, p-mTOR, p-4E-binding protein 1 (p-4EBP1), p-p70S6K/S6K1, p-ribosomal protein S6 (p-S6) and CDK2. Ten normal skin samples served as a control. RESULTS: Of the 32 EMPD tissue samples, 29, 27, 26, 29, 26 and 32 samples were positive for p-AKT, p-mTOR, p-4EBP1, p-p70S6K/S6K1, p-S6 and CDK2 staining, respectively. All these cell signalling molecules showed higher positivity in invasive EMPD than in EMPD in situ. There were significant correlations between p-AKT, p-mTOR, p-4EBP1, p-p70S6K/S6K1 and p-S6 and CDK2. CONCLUSIONS: The activation of the AKT-mTOR-p70S6K pathway may play an important role in the pathogenesis of EMPD. The high expression of the components of the pathway was highly correlated with CDK2 expression, suggesting that the AKT/mTOR pathway may induce the malignant transition through CDK2 in EMPD. The AKT-mTOR-p70S6K pathway might be a potential therapeutic target in EMPD.

Activation of the mammalian target of rapamycin signalling pathway in epidermal tumours and its correlation with cyclin-dependent kinase 2.

BACKGROUND: The enzyme mammalian target of rapamycin (mTOR) integrates many different cellular signals to control cell growth and proliferation, protein synthesis and breakdown, and other processes. Dysregulation of mTOR is implicated in a range of human diseases, including cancers and cardiovascular disorders. To date, there has been no report on the expression of protein kinase B (AKT)/mTOR cell signalling in epidermal tumours. OBJECTIVES: This study was designed to investigate the activation of the mTOR signalling pathway in epidermal tumours and to correlate this with cyclin-dependent kinase 2 (CDK2) expression. METHODS: Immunohistological staining was performed with phosphorylated (p-) AKT, p-mTOR, p-4E-binding protein 1 (p-4EBP1), p-ribosomal protein S6 (p-S6), p-p70 ribosomal protein S6 kinase 1 (p-p70S6K1) and CDK2 in 15 cases each of seborrhoeic keratosis, actinic keratosis, keratoacanthoma and Bowen's disease (BD), and 25 cases of squamous cell carcinoma (SCC). Fifteen normal skin (NS) samples served as control. RESULTS: Among 85 tumours, 40 (47%) were positive for p-AKT, 31 (36%) for p-mTOR, 44 (52%) for p-4EBP1, 38 (45%) for p-S6, and 39 (46%) for p-p70S6K1. CDK2 immunostaining was positive in all cases of SCC and BD, and in 67% of benign tumours. All of these markers were stained much more frequently in malignant tumours than in benign tumours or NS. p-AKT, p-mTOR, p-4EBP1, p-p70S6K1 and p-S6 each showed high correlation with CDK2. CONCLUSIONS: Constitutive activation of the AKT/mTOR pathway was frequent in epidermal tumours, especially in malignant tumours. Activation was highly correlated with CDK2 expression, suggesting that the AKT/mTOR pathway may induce the malignant transition through CDK2 in epidermal tumours.

Selective expansion of T cell receptor (TCR) V beta 6 in tonsillar and peripheral blood T cells and its induction by in vitro stimulation with Haemophilus parainfluenzae in patients with IgA nephropathy.

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a disease that often becomes worse during acute tonsillitis. Although many reports have shown that tonsillectomy is an effective treatment for IgAN patients, the immunological evidence has not yet been investigated fully. In this study, we compared the expression of T cell receptor (TCR) V beta families in tonsillar T cells of IgAN patients to those of non-IgAN patients. The reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analyses showed that the TCR V beta 6 was used more frequently in tonsillar T cells of IgAN patients than in those of non-IgAN patients (P < 0.01 each). Similarly, the proportions of TCR V beta 6-positive cells in peripheral blood T cells were significantly higher in IgAN patients than in non-IgAN patients (P < 0.05). After tonsillectomy, the proportions decreased in IgAN patients (P < 0.05), but did not in non-IgAN patients. Furthermore, in vitro stimulation with Haemophilus parainfluenzae antigen, which is reported to deposit in the glomerular mesangium of IgAN, enhanced expression of TCR V beta 6 in tonsillar T cells from both IgAN and non-IgAN patients. These results suggest that TCR V beta 6-positive tonsillar T cells might be activated by H. parainfluenzae, move into the kidney through blood circulation and induce glomerulonephritis.

Increased expression of an epidermal stem cell marker, cytokeratin 19, in cutaneous squamous cell carcinoma.

BACKGROUND: Cytokeratin 19 (CK19) has been considered to be a putative marker for epidermal stem cells in the hair follicle bulge. Cumulative reports have shown that epidermal stem cells play an important role in skin carcinogenesis. However, to date there has been no report on the clinical alteration of the stem cells in squamous cell carcinoma (SCC). OBJECTIVES: To investigate alteration of the stem cells and proliferating cells and to assess their relationship and potential contribution to SCC. METHODS: Thirty paraffin-embedded neoplastic skin lesions, consisting of 10 cases each of actinic keratosis (AK), Bowen disease (BD) and SCC, were examined immunohistologically for CK19 and Ki-67. RESULTS: Positive reactivity for CK19 was seen in 30% of AK, 50% of BD and 80% of SCC lesions. There was significantly higher expression levels of CK19 in SCC than in AK and BD (P < 0.05). In addition, BD lesions harboured a significantly higher number of CK19-positive cells than did AK lesions (P < 0.05). There were significant differences in Ki-67 labelling indices between AK and BD and between AK and SCC (P < 0.001), but not between BD and SCC (P > 0.05). Furthermore, a serial section comparison study showed that there was a minor population of cells co-expressing CK19 and Ki-67 in a subset of the tumour cells of SCC samples. The percentage of CK19+ cells significantly correlated with that of Ki67+ cells in all examined neoplastic skin lesions. CONCLUSIONS: These results suggest that CK19 expression may be associated with the retention of stem cell characteristics or a state that is uncommitted to terminal squamous differentiation.

Bone-peg grafting for osteochondritis dissecans of the humeral capitellum.

PURPOSE: To review the outcome of bone-peg grafting for osteochondritis dissecans (OCD) grade II lesions of the humeral capitellum. METHODS: Records of 10 male adolescent baseball players aged 10 to 15 (mean, 12.3) years who underwent bone-peg grafting for OCD grade II lesions of the humeral capitellum of the dominant arm were reviewed. The mean time from symptom onset to presentation was 11 (range, 1-36) months. The mean duration of conservative treatment was 5 (range, 1-25) months. The mean time from symptom onset to surgery was 17 (range, 3-39) months; it was >6 months in 6 patients. The mean size of the lesions was 13x14 mm. Patients were assessed for elbow pain, range of elbow and forearm motion, Timmerman- Andrews elbow score, return to sports activity level, and radiographic evidence of healing, osteoarthritic changes, and radial head hypertrophy. RESULTS: The mean follow-up period was 25 (range, 10-52) months. Postoperatively, elbow pain was absent in 6, mild in 2, and moderate in 2 patients. The mean range of elbow motion changed from 136º to 139° (p=0.80). The mean Timmerman-Andrews elbow score improved from 163 to 189 (p=0.014); it was excellent in 7, good in 2, and fair in one patient. The mean extent of lesion healing was 71% (range, 33-100%). Five patients achieved complete healing after a mean of 5.2 (range, 5-6) months and returned to sports at a competitive level. The other 5 achieved partial healing of 33 to 56% (mean, 41%) that occurred laterally but not medially. Two of them returned to sports at a competitive level: one changed the throwing side and another had radial head hypertrophy. The remaining 3 underwent arthroscopic debridement of the unhealed lesion at 5, 10, and 15 months. One patient developed secondary osteoarthritis and further underwent costal osteochondral autografting 10 months later. None of the 5 patients with partial healing versus 4 of the 5 patients with complete healing underwent surgery within 6 months of symptom onset. All 3 patients with a dot at the interface versus 2 of the 6 patients with a line at the interface between the fragment and the lesion on MRI had complete healing. CONCLUSION: Bone-peg grafting is a viable option for OCD grade II lesions of the humeral capitellum when performed within 6 months of symptom onset and when the interface between the fragment and the lesion appears as a dot (rather than a line) on MRI.

Wild-type p53 activates SAP expression in lymphoid cells.

SAP is an adaptor molecule with one SH2 domain and it is expressed in activated T and NK cells, where it is required for the appropriate signaling from the SLAM family of surface receptors. Deleted or mutated SAP genes that encode functionally defective protein are associated with the X-linked lymphoproliferative disease (XLP). This primary immunodeficiency is characterized by extreme sensitivity to Epstein-Barr virus (EBV) infection, dysgammaglobulinemia and a high rate of lymphoma development. The vigorous T- and B-cell proliferation that follows EBV infection and the high incidence of lymphomas (30%) in XLP patients might reflect functional defects in cell cycle and/ or apoptosis control. Our experiments show that SAP is a target of p53. In Burkitt lymphoma (BL) lines transfected with a temperatur-sensitive (ts) p53, SAP mRNA and protein expression was dependent on wild-type (wt) p53. Activation of endogenous wt p53 in BLs and lymphoblastoid cell lines led to the induction of SAP and this was inhibited by the specific p53 inhibitor pifithrin-alpha. Cell lines that carried mutant p53 did not express SAP under similar conditions. Moreover, we have shown binding of wt p53 to the promoter region of SAP by ChIP assay. Our results suggest that SAP contributes to the execution of some p53 functions.

Klinefelter's syndrome with prepenile scrotum.

Two cases of Klinefelter's syndrome with prepenile scrotum were presented. They underwent the operation for prepenile scrotum according to Glenn and Anderson's method. Thereafter urethroplasty was performed in each case. The decrease in response to testosterone in the target organ was noticed in 1 patient, suggesting that some androgen resistance in this case was attributable in part to anomaly of genitalia.