Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC).

Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.

Noctilisin, a Venom Glycopeptide of Sirex noctilio (Hymenoptera: Siricidae), Causes Needle Wilt and Defense Gene Responses in Pines.

During oviposition, female Sirex noctilio (F.) (Siricidae) woodwasps inject their conifer hosts with a venom gland secretion. The secretion induces a variety of host physiological changes that facilitate subsequent lethal infection by a symbiotic fungus. A heat-stable factor that can migrate from the site of oviposition in the trunk through the xylem to needles in the crown of attacked pines was purified by size-fractionation and reversed-phase-high-performance liquid chromatography using activity assays based on defense gene induction as well as the needle wilt response in pine shoot explants. An 11-amino acid, posttranslationally modified peptide (SEGPROGTKRP) encoded by the most abundant transcript recovered from S. noctilio venom gland tissue comprised the backbone of the 1,850 Da active factor. Posttranslational modifications included hydroxylation of a Pro residue at position 6 as well as O-glycosylation of Ser and Thr residues at positions 1 and 8, respectively. The O-linked sugars were identical α-linked N-acetylgalactosamine residues modified at the C6 position by addition of phosphoethanolamine. In contrast to the native peptide, a synthetic version of the hydroxylated peptide backbone lacking the glycosyl side chains failed to induce pine defense genes or cause needle wilt in excised shoots. This peptide, hereafter called noctilisin, is related to the O-glycosylated short-chain proline-rich antimicrobial peptides exemplified by drosocin. The noctilisin structure contains motifs which may explain how it avoids detection by pine defense systems.

Access and surgical approach to the isolated intranasal basal cell carcinoma.

Primary intranasal basal cell carcinoma (BCC) is a rare tumour that presents a therapeutic challenge. Here we present two cases illustrating the lateral alarotomy to gain access to an isolated BCC involving only the intranasal lining. Successful intranasal access was achieved in both cases using the alarotomy technique. We also review other methods of repair for the isolated intranasal lining defect. The presentation of intranasal BCC purely as an isolated entity without cutaneous involvement is rare, and our surgical approach via alarotomy allows optimum visibility for tumour resection.

Systemic treatment of locally advanced nonmetastatic cutaneous squamous cell carcinoma: a review of the literature.

BACKGROUND: There is a small subset of locally advanced nonmetastatic cutaneous squamous cell carcinoma (cSCC) for which local therapy is not curative or feasible, making systemic therapy a possible treatment option. OBJECTIVES: To calculate overall response rates (ORR), median time to response (TTR) and median duration of response (DOR) of locally advanced nonmetastatic cSCC to systemic therapy [targeted agents, biological response modifiers (BRM) and chemotherapy]. PATIENTS AND METHODS: Medline and PubMed were searched for reports of nonmetastatic locally advanced cSCC treated with systemic therapy from 1970 to 2011. No limits were placed on study design. ORR, TTR and DOR were calculated for systemic therapy overall and for each treatment category. RESULTS: Twenty-eight observational studies yielded 119 patients for analysis. The ORR for systemic therapy was 72% (TTR 9 weeks, DOR 42 weeks). Targeted therapy and BRM achieved ORR of 100% (TTR 12 weeks, DOR 20 weeks) and 86% (TTR 10 weeks, DOR 20 weeks), respectively, and oral chemotherapy, intravenous chemotherapy and intra-arterial chemotherapy achieved ORR of 20% (TTR 10 weeks, DOR 24 weeks), 68% (TTR 3 weeks, DOR 44 weeks) and 100% (TTR 15 weeks, DOR 112 weeks), respectively. A limitation of this study was that no controlled data were identified and sample sizes were small. CONCLUSIONS: Systemic treatment leads to objective responses in locally advanced cutaneous SCC that are not amenable to local cure.

Melanoma in solid organ transplant recipients.

This manuscript outlines estimated risk and clinical course of pretransplant MM, donor-transmitted MM and de novo MM posttransplantation and includes an analysis of risk factors for metastasis, data from clinical studies and current and proposed management. MM in situ and thin melanoma (<1 mm) in the transplant population has similar recurrence and survival estimates to those in the general population. A minimum wait time of 2 years prior to transplantation is suggested for MM with a Breslow depth <1 mm and no clinical evidence of metastasis. More advanced MM may adopt a more aggressive course in transplant recipients. Sentinel lymph node biopsy may be of additional prognostic benefit. Revision of immunosuppression in the management of de novo melanoma in collaboration with the transplant team should be considered. Larger studies utilizing uniform staging criteria or at minimum Breslow depth, are required to assess true risk and outcome of MM in the immunosuppressed transplant population. Emphasis remains on patient education and regular screening to provide early detection of MM.

The l2 minor capsid protein of low-risk human papillomavirus type 11 interacts with host nuclear import receptors and viral DNA.

Analysis of the interactions of low-risk human papillomavirus type 11 (HPV11) L2 with karyopherin beta (Kap beta) nuclear import receptors revealed that L2 interacted with Kap beta 1, Kap beta 2, and Kap beta 3 and formed a complex with the Kap alpha 2 beta 1 heterodimer. HPV11 L2 contains two nuclear localization signals (NLSs)-in the N terminus and the C terminus-that could mediate its nuclear import via a classical pathway. Each NLS was functional in vivo, and deletion of both of them abolished L2 nuclear localization. Both NLSs interacted with the viral DNA. Thus, HPV11 L2 can interact with several karyopherins and the viral DNA and may enter the nucleus via multiple pathways.

Nuclear import strategies of high-risk HPV18 L2 minor capsid protein.

We have investigated the nuclear import strategies of high-risk HPV18 L2 minor capsid protein. HPV18 L2 interacts with Kap alpha2 adapter, and Kap beta2 and Kap beta3 nuclear import receptors. Moreover, binding of RanGTP to either Kap beta2 or Kap beta3 inhibits their interaction with L2, suggesting that these Kap beta/L2 complexes are import competent. Mapping studies show that HPV18 L2 contains two NLSs: in the N-terminus (nNLS) and in the C-terminus (cNLS), both of which can independently mediate nuclear import. Both nNLS and cNLS form a complex with Kap alpha2beta1 heterodimer and mediate nuclear import via a classical pathway. The nNLS is also essential for the interaction of HPV18 L2 with Kap beta2 and Kap beta3. Interestingly, both nNLS and cNLS interact with the viral DNA and this DNA binding occurs without nucleotide sequence specificity. Together, the data suggest that HPV18 L2 can interact via its NLSs with several Kaps and the viral DNA and may enter the nucleus via multiple import pathways mediated by Kap alpha2beta1 heterodimers, Kap beta2 and Kap beta3.

HIV-associated changes in adaptive, emotional, and behavioral functioning in children and adolescents with hemophilia: results from the Hemophilia Growth and Development Study.

OBJECTIVE: To assess changes in adaptive, emotional, and behavioral functioning over four years in children and adolescents with hemophilia and with or without HIV infection and to evaluate the relationship of these changes to immune status. METHODS: Participants were 277 HIV-seropositive and 126 HIV-seronegative boys with hemophilia. Participants with HIV infection were divided into three groups based on trajectory of immune functioning (CD4+ cell counts) over the course of the study. Caregivers completed the Vineland Adaptive Behavior Scales and Pediatric Behavior Scale (PBS). RESULTS: Results showed declining Vineland Communication scores for participants with consistently poor immune functioning. These participants also started with more PBS Attention Deficit and Deviation symptoms, which then decreased more sharply than for other groups. Low CD4+ counts were consistently associated with more Health and Depression-Anxiety symptoms on the PBS. However, with few exceptions, group means remained within normal limits. CONCLUSIONS: According to their caregivers, boys with hemophilia and HIV infection showed considerable resilience with regard to adaptive behavior and emotional and behavioral problems. However, over time changes occurred in these areas that appear to be related to immune functioning.

Attention in HIV-infected children: results from the Hemophilia Growth and Development Study.

Attentional functioning was examined in three groups of 7- to 19-year-old male participants with hemophilia: (1) HIV seronegative controls (HIV-, N = 66), (2) HIV seropositive participants with CD4+ lymphocyte counts greater than or equal to 200 (HIV+ CD4+ > or = 200, N = 79), and (3) severely immune suppressed HIV seropositive participants (HIV+ CD4+ < 200, N = 28). Two measures sensitive to attention deficits were used: the Continuous Performance Test (CPT) and the Span of Apprehension (Span). On the CPT, there was a decrement in attention in both HIV+ groups, as indexed by an increase in false alarm rate from Block 1 to Block 3, that was not present in the HIV- group. The longer the HIV+ children were required to sustain attention to the CPT, the more they responded to the incorrect stimulus. This effect decreased as age increased. Span percent correct and latency to correct were associated with the presence of a premorbid history of intracerebral hemorrhage, but were not sensitive to HIV status or degree of immune suppression in the HIV+ children, suggesting morbidity related to hemophilia. The remaining CPT and Span variables--hit rate, sensitivity, latency, percent correct, and latency to correct--showed the expected associations with age, but none showed conclusive associations with HIV status or immune suppression in the HIV+ participants.

Declining immune function in children and adolescents with hemophilia and HIV infection: effects on neuropsychological performance. Hemophilia Growth and Development Study.

OBJECTIVE: To determine whether declines in immune functioning are associated with changes in neuropsychological performance in children and adolescents with hemophilia who are infected with the human immunodeficiency virus (HIV). METHODS: Participants were 333 males with hemophilia, ages 6-19 years at entry. A baseline and four annual neuropsychological evaluations were given. A longitudinal growth curves analysis of data was performed to detect changes associated with declining immune function. The cohort was stratified into four groups: (1) HIV- (n = 126); (2) HIV+, average of first two and last two CD4 counts > or = 200, (n = 106; High CD4 group); (3) HIV+, average first two counts > or = 200, average last two counts < 200 (n = 41; CD4 Drop group); and (4) HIV+, average first two and last two counts < 200 (n = 60; Low CD4 group). RESULTS: There were significant differences among the four groups over time in nonverbal intelligence, perceptual/performance skills, nonverbal memory, academic achievement, and language. The Low CD4 group consistently showed the greatest decrement in performance. On measures showing a practice effect for repeated measurements, the Low CD4 group participants' scores remained stable over time, suggesting opposing effects of practice and HIV-related declines. Lowered academic performance relative to IQ was found in all groups. CONCLUSIONS: Declines in neuropsychological functioning are directly related to declines in immune functioning in HIV+ children, adolescents, and young adults with hemophilia. Hemophilia itself may be a risk factor for academic underachievement.

The LGM Vena-Tech caval filter: results of a multicenter study.

Caval filters have proved essential to the progress being made in the prevention of recurrent pulmonary embolism. A prospective multicenter study was conducted to evaluate the efficacy and possible complications relating to the LGM Vena-Tech percutaneous caval filter, which has been used in Europe since 1989. A total of 222 patients who had undergone LGM Vena-Tech filter placement between September 1989 and December 1991 were included in this study. Two hundred twenty caval filters were positioned via the percutaneous route: 154 of them via the jugular or subclavian vein and 66 via the femoral vein. Two filters could not be implanted. The in-hospital mortality rate was 1.7% (four patients), which included one patient who died of intraoperative recurrent pulmonary embolism. Mean follow-up was 15 months. Forty-one patients died during follow-up (actuarial survival 65.4% +/- 6% at 30 months). There were five cases of recurrent pulmonary embolism (cumulative freedom from pulmonary embolism 93.2% +/- 3.8% at 30 months). Ten patients had thrombosis of the inferior vena cava (actuarial caval patency 94% +/- 3.6% at 30 months). Eight filters (3.6%) migrated over distances that were less than the height of one vertebra. Shifting did not lead to any cases of thrombosis or recurrent pulmonary embolism. Ten filters tilted between 15 and 25 degrees in relation to the inferior vena cava axis. Recurrent pulmonary embolism never occurred concurrently with filter tilting. The LGM Vena-Tech caval filter ensures satisfactory prevention of pulmonary embolism with a low rate of complications. However, because its long-term fate is not known, its use should be restricted to cases in which heparin treatment has failed or is contraindicated.

Comparative evaluation of ceramic bracket base designs.

Since the initial introduction of ceramic brackets, base designs have been modified to reduce tooth damage during debonding. The purpose of this study was to compare shear and tensile bond strengths and fracture sites of four second-generation ceramic brackets: Allure IV (A) (GAC International, Inc., Central Islip, N.Y.), Ceramaflex (C) (TP Orthodontics, Inc., LaPorte, Ind.), Intrigue (I) (Lancer Orthodontics, Carlsbad, Calif.), Transcend 2000 (T) (Unitek Corp., Monrovia, Calif.), and a foil-mesh base stainless steel bracket, DynaBond II (D) (Unitek Corp., Monrovia, Calif.). Twenty brackets of each type were bonded to 100 mandibular bovine incisor teeth with Concise bonding adhesive. The samples were thermocycled for 24 hours and the brackets were debonded with an Instron universal testing machine (Instron Corp., Canton, Mass.). A modified Transcend debonding instrument was used for tensile debonding, whereas a chisel was used for shear debonding. An analysis of variance was performed with a 0.05 level of confidence. Mean shear strengths (kg/cm2) necessary to debond were 174.0 (A), 71.0 (C), 189.0 (I), 228.0 (T), and 160.0 (D). Mean tensile strengths (kg/cm2) were 27.0 (A), 26.7 (C), 51.3 (I), 56.5 (T), and 48.6 (D). Fracture sites examined with a light microscope showed no enamel damage with any of the ceramic brackets. Intrigue was the only bracket to fracture and had 30% bracket fracture in the tensile mode and 20% bracket fracture in the shear mode. The percentage of fractures at the adhesive-bracket base interface for shear and tensile modes, respectively, were 80, 100 (A); 100, 90 (C); 10, 60 (I); 60, 90 (T); and 90, 80 (D).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemophilia growth and development study: baseline neurodevelopmental findings.

Reported baseline findings from the neurological assessment component of the Hemophilia Growth and Development Study (HGDS). HIV-positive (HIV+; n = 207) and HIV-negative (HIV-; n = 126) young males with hemophilia ages 6 to 18 years, were enrolled in a prospective study of their growth and development. At baseline, HIV+ and HIV- subjects were not significantly different in test performance. The number of subjects exhibiting below-average performance in three or more areas assessed was about 25% overall. For both groups, mean test scores were within the average range. Academic and adaptive skills were lower than expected based on mean IQ scores, and more behavioral/emotional problems than expected were reported by parents. Absolute CD4 cell counts per mm3 were not related to neuropsychological performance at baseline. Results suggest that the subjects with HIV were relatively free of HIV-related neuropsychological impairment at baseline and that observed differences from a general population reflect effects of hemophilia as a chronic illness.

Multiple aneurysms in a seven-year-old child.

Arterial aneurysms, rarely encountered in childhood, pose difficult etiologic and therapeutic problems. We report the case of a seven-year-old Algerian girl with aortoiliac, visceral, and limb aneurysms revealed by a tumefaction in the left popliteal fossa. Aortic rupture subsequently occurred. The aneurysms were resected with subsequent prosthetic or vein graft replacement. Three years later, clinical and functional results of the grafts were satisfactory. Possible etiologies include inflammatory arteritis, dysplasia, or idiopathic primary aneurysms.