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Biomedical subjects

Daniel Berg

Publications and source records attributed to Daniel Berg.

9 recordsLinked to original sources

Mutations in DNA polymerase eta are not detected in squamous cell carcinoma of the skin.

The major etiological agent in skin cancer is exposure to UV-irradiation and the concomitant DNA damage. UV-induced DNA lesions, such as thymine dimers, block DNA synthesis by the major DNA polymerases and inhibit the progression of DNA replication. Bypass of thymine dimers and related lesions is dependent on the translesion polymerase DNA polymerase eta (Poleta). In the inherited disorder, xeroderma pigmentosum variant (XPV), inactivation of Poleta results in extreme sensitivity to UV light and a marked increase in the incidence of skin cancer. Here, we tested the hypothesis that somatic mutations and/or polymorphisms in the POLH gene that encodes Poleta are associated with the induction of UV-dependent skin cancers. We sequenced the exonic regions of the Poleta open reading frame in DNA from 17 paired samples of squamous cell skin carcinoma and adjacent histologically normal tissue. We analyzed approximately 120,000 nucleotides and detected no mutations in POLH in the tumors. However, we identified 6 different single-nucleotide polymorphisms, 3 of them previously undocumented, which were present in both the tumor and paired normal tissue. We conclude that neither mutations nor polymorphisms in the coding regions of POLH are required for the generation of human skin squamous cell carcinoma.

Adult↗

Decreased expression of angiogenic factors in placentas with chorioamnionitis after preterm birth.

Chorioamnionitis and funisitis are associated with neonatal morbidity and mortality. We hypothesized that chorioamnionitis may stress fetal endothelium, activate proinflammatory gene transcription. and affect angiogenic homeostasis in fetal capillaries. Placentas from preterm infants were stained for heat-shock protein 70, nuclear factor-kappaB, hypoxia-inducible factor-1alpha, and vascular endothelial growth factor (VEGF). VEGF receptors (VEGF-R) 1 and 2 as well as the receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE-2), which is involved in vascular remodeling, were quantified. Immunohistochemistry was analyzed by counting positive capillaries in placental terminal villi. Staining intensity was quantified by a three-step semiquantitative scale. The samples were divided into three matched groups according to histology: chorioamnionitis with funisitis ("funisitis"), chorioamnionitis without funisitis ("chorioamnionitis"), and control group with no inflammation. In tissues from the funisitis or chorioamnionitis group, heat-shock protein 70 expression was increased over the control group. More nuclear factor-kappaB-positive nuclei of endothelial cells in capillaries were counted in the funisitis and chorioamnionitis groups. Expression of VEGF and VEGF-R1 and -R2 were reduced in cases of funisitis or chorioamnionitis in comparison with controls. Hypoxia-inducible factor-1alpha expression tended to be slightly lower in the funisitis and chorioamnionitis groups but did not reach statistical significance. We speculate that cellular stress and changes in angiogenic homeostasis induced by proinflammatory activation of fetal endothelium in chorioamnionitis may not be limited to the placenta but may also involve other fetal organs.

Angiogenesis Inducing Agents↗

Activation of umbilical cord endothelial cells and fetal inflammatory response in preterm infants with chorioamnionitis and funisitis.

Chorioamnionitis and funisitis are associated with preterm labor and postnatal morbidity. Activation of endothelium resulting in up-regulation of adhesion molecules seems to be a key mechanism in development of organ damage. We investigated whether chorioamnionitis with or without funisitis in preterm infants induced expression and shedding of adhesion molecules in the umbilical cord and resulted in increased concentrations of E-selectin, intercellular adhesion molecule (ICAM)-1, IL-1beta, IL-6, and IL-8 in the cord blood. Data were obtained by using immunohistochemistry and ELISA. Thirty-two preterm infants were divided into three groups according to histology: chorioamnionitis with funisitis, chorioamnionitis without funisitis, and controls without signs of inflammation. ICAM-1 expression on arterial endothelium was higher with funisitis compared with chorioamnionitis alone or with the control group. Similar results for ICAM-1 expression were found in venous endothelium, vascular walls, Wharton's jelly, and amnion epithelium. Endothelial E-selectin and vascular cell adhesion molecule (VCAM)-1 expression was only induced significantly with funisitis. Serum-concentrations of soluble ICAM-1 were higher with funisitis compared with chorioamnionitis alone or control group. Similarly, concentrations of soluble E-selectin, IL-1beta, IL-6, and IL-8 were increased exclusively with funisitis. In conclusion, only chorioamnionitis with funisitis was associated with systemic inflammation and endothelial activation with up-regulation and shedding of umbilical cord adhesion molecules. We speculate that this activation of endothelium may not be limited to the umbilical cord but may also involve other organs resulting in neonatal morbidity. This underlines the importance of funisitis as a risk factor for adverse outcome.

Cell Adhesion↗

Teaching and evaluation of surgical skills in dermatology: results of a survey.

OBJECTIVES: To assess how the surgical skills of residents are taught and evaluated within dermatology residency programs in the United States; to assess which surgical techniques training directors and residents consider important for residents to perform or at least understand by the end of residency training. METHODS: A 126-question survey was sent to all 106 of the US dermatology residency programs accredited by the Accreditation Council for Graduate Medical Education. Contact was initially made via e-mail. Surveys were addressed to the program director, surgical training director, and chief resident of each program. A follow-up survey was mailed to nonresponders. RESULTS: Ninety-five surveys were returned representing 71 (67%) of 106 programs. Eighty-nine percent of programs (n=63) reported having a formal curriculum in dermatologic surgery. Among programs represented, 97% (n=69) taught surgical skills in the procedure room, 84% (n=57) used pigs' feet, and fewer than 10% (n=6) used human cadavers. Ninety-four percent of programs (n=61) scheduled surgical lectures; two thirds (n=41) formally assigned surgical reading, and over half (n=36) used Web-based lectures to teach skills. To assess training, most programs (86%; n=50) used subjective global evaluation at the end of a surgery rotation. Fewer than 30% (n=15) discussed specific objectives prior to the rotation. Only about 25% of programs (n=17) reported the use of written or oral examinations to assess resident surgery skills. Traditional biopsy and simple surgical procedures were reported as most important to know and perform. Interest by both faculty members and residents in more advanced surgical techniques was more limited and variable. Cosmetic surgery techniques were most likely to be viewed as unimportant. CONCLUSIONS: Most dermatology programs teach surgical skills by traditional apprenticeship methods supplemented by work in pigs' feet laboratory classes and regularly scheduled lectures. Skill assessment is mainly done through subjective means. Almost all respondents thought that basic biopsy and excisional skills were essential for residents to know and perform. More complex surgical techniques and the use of lasers were considered less important. Cosmetic techniques were those most frequently viewed as unimportant.

Animals↗

Management of lentigo maligna and lentigo maligna melanoma with staged excision: a 5-year follow-up.

OBJECTIVE: To assess the long-term cure rate for treatment of lentigo maligna (LM) and lentigo maligna melanoma (LMM) by means of a staged, margin-controlled, vertical-edged excision with rush permanent specimens and a radial sectioning technique. DESIGN: Retrospective follow-up study. SETTING: University-affiliated and private-practice dermatologic surgery clinics. PATIENTS: Fifty-nine patients treated for 55 LMs and 7 LMMs between January 1, 1990, and December 31, 2001. INTERVENTIONS: The technique included vertical excision with initial 2- to 3-mm margins examined by rush permanent sections (prepared and read within 24 hours). Further excision took place as guided by histologic findings. Data on patient and lesion characteristics were obtained via a medical chart review. Patients were then contacted and examined for local recurrence. Biopsies were performed on all patients with possible recurrence on clinical examination. MAIN OUTCOME MEASURES: Local recurrence of LM or LMM. RESULTS: After a mean follow-up of 57 months (median, 54 months; 293.8 person-years), 95% of patients were free of recurrence. Three patients had local recurrence and no patients had evidence of metastasis. Two of the 3 local recurrences were of previously excised LM, and 1 was of an LMM. Half (32) of all lesions required 2 or more stages. One required more than 4 stages. The average margin of excision was 0.55 cm. Three of the 58 lesions read as LM on biopsy were found to have invasive disease (LMM) at the time of definitive excision. CONCLUSIONS: The technique described herein for the treatment of LM and LMM provides a long-term disease-free survival of 95%. The cure rate is greater than that reported for standard excision and is similar to that for other margin-control techniques. To our knowledge, this is the largest reported study and has the longest follow-up for this excision method for LM and LMM.

Adult↗

Specialty clinics for the dermatologic care of solid-organ transplant recipients.

BACKGROUND: Solid-organ transplant recipients constitute a complex patient population that experiences numerous and aggressive skin cancers. Proactive, comprehensive, ongoing, and effective dermatologic care of these patients is a necessity. OBJECTIVE: The objective of this study was to emphasize the need for organized dermatologic care for transplant recipients and to collect and present various proactive paradigms established in and designed for different practice settings to manage organ transplant recipients at high risk for skin cancer. METHODS: Information about practice setting, patient demographics, and the care model used was obtained through questionnaires sent to a selection of 12 physicians known to care for transplant recipients in various practice settings. RESULTS: All 12 physicians completed the questionnaire. The organized dermatologic care of transplant recipients occurs in three basic clinic settings: multidisciplinary transplant clinics, designated dermatology transplant subspecialty clinics, and integration of transplant recipient care within existing dermatology clinics. CONCLUSIONS: Various practice settings offer both advantages and disadvantages in providing preventive and therapeutic care of organ transplant recipients at risk for skin cancer. Regardless of the clinic design used, an organized and firmly established clinic model to allow proactive and ongoing care for these patients is important for education, prevention, and early intervention.

Dermatology↗

Two-handed next generation suturing simulator.

A realistic two-handed surgical suturing simulation would have a broad impact on the way doctors are trained in the field of surgery. Current state-of-the-art in suturing simulators do not accurately represent realistic suturing conditions, leaving many necessary components, i.e. two-handed interaction, skin undermining, skin repositioning etc., out of the model completely. The goal of this research is to develop a next generation immersive suturing simulator that uses an integrated two-handed tension based haptic device for tactile feedback, a hi-fidelity finite element model for more accurate skin, tissue and needle modeling and stereoscopic vision for depth-of-field.

Computer Simulation↗

Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management.

In the United States more than 100,000 people are living with solid organ transplants. The intense immunosuppressive regimens necessary for prolonged survival of allografts significantly increase the rates of both internal and cutaneous malignancies in recipients of solid organ transplants. Skin cancer is the most common cancer in patients after transplantation. Because of the early onset and high tumor burden in transplant recipients, dermatologists have significant challenges in managing the treatment of these patients. This article describes the epidemiology and clinical presentation of skin cancer during posttransplantation immunosuppression, discusses pathogenic cofactors, and reviews the optimal management for mild and severe skin cancer in transplant recipients.

Basal Cell Carcinoma↗