Fingermark age determinations: Legal considerations, review of the literature and practical propositions.

The question of the age of fingermarks is often raised in investigations and trials when suspects admit that they have left their fingermarks at a crime scene but allege that the contact occurred at a different time than the crime and for legal reasons. In the first part of this review article, examples from American appellate court cases will be used to demonstrate that there is a lack of consensus among American courts regarding the admissibility and weight of testimony from expert witnesses who provide opinions about the age of fingermarks. Of course, these issues are not only encountered in America but have also been reported elsewhere, for example in Europe. The disparity in the way fingermark dating cases were managed in these examples is probably due to the fact that no methodology has been validated and accepted by the forensic science community so far. The second part of this review article summarizes the studies reported on fingermark dating in the literature and highlights the fact that most proposed methodologies still suffer from limitations preventing their use in practice. Nevertheless, several approaches based on the evolution of aging parameters detected in fingermark residue over time appear to show promise for the fingermark dating field. Based on these approaches, the definition of a formal methodological framework for fingermark dating cases is proposed in order to produce relevant temporal information. This framework identifies which type of information could and should be obtained about fingermark aging and what developments are still required to scientifically address dating issues.

Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy.

BACKGROUND: Sentinel lymph-node (LN) biopsy (SLNB) is a valuable tool to assess the regional LN status in Merkel cell carcinoma (MCC). However, its prognostic value is still debated. This study was undertaken to assess SLNB usefulness for MCC management and to determine the impact of SLNB status on disease-free survival (DFS) and overall survival (OS) by comparing SLNB-positive versus -negative patients according to demographic, clinical and treatment characteristics. PATIENTS AND METHODS: In this retrospective, multicenter observational study, SLNB was proposed to all patients referred for clinically N0 MCC. Treatment schedule consisted of wide-margin surgical resection of primary MCC followed by adjuvant radiation therapy (aRT) to the primary site and, for SLNB-positive patients, radical LN dissection followed by regional aRT. Univariate and multivariate analyses determined factors associated with DFS and OS. RESULTS: Among 87 patients with successful SLNB, 21 (24.1%) were SLNB-positive. Median follow-up for the entire series was 39 months; respective 3-year DFS and OS rates were 73% and 81.4%, respectively. Univariate analysis (all patients) identified SLNB-negativity as being associated with prolonged OS (P = 0.013) and aRT (all sites considered) was associated with longer DFS (P = 0.004) and OS (P = 0.018). Multivariate analysis (all patients) retained SLNB status and aRT (all sites considered) as being associated with improved DFS (P = 0.014 and 0.0008) and OS (P = 0.0020 and 0.0019). Moreover, for SLNB-negative patients, tumor-bed irradiation was also significantly associated with prolonged DFS (P = 0.006) and OS (P = 0.014). CONCLUSIONS: The present study demonstrates that SLNB-negativity is a strong predictor of longer DFS and OS in stage I and II MCC patients. The similar benefit for aRT on tumor bed observed in this study has to be confirmed by a prospective study. The results advocate for SLNB being considered to all MCC patients.

The reporting of clinical signs in laboratory animals: FELASA Working Group Report.

Observing and reporting clinical signs in laboratory animals is necessary for many reasons: the assessment of animal welfare, compliance with the principle of refinement (e.g. humane endpoints), regulatory compliance (e.g. reporting severity) and, importantly, as a scientific outcome, e.g. in animal models of disease or safety studies. Developments in the reporting of clinical signs will enhance the scientific value gained from animal experiments and further address the ethical cost. This paper discusses systematic approaches to the observation and reporting of clinical signs in animals (to be) used for research. Glossaries from public and corporate institutions have been consulted and a reference glossary has been set up, providing terminology to be tailored for institutional or project-specific use. The clinical examination of animals must be carried out by competent and specifically trained staff in a systematic way and repeated at adequate intervals and clinical observations must be registered effectively to allow this information to be used. The development of institutional or project-specific glossaries and the use of handwritten records or automated databases are discussed in detail. Among the users are animal care staff, veterinarians and researchers who will need to agree on a given set of clinical signs to be monitored routinely or as a scientific read-out and to train for the proper application. The paper introduces a long list of clinical signs with scientific terminology, descriptions and explanations as a reference glossary to be published and maintained online as a living document supported by the authors as an editorial committee.

[Impact of nutrition management in patients with head and neck cancers treated with irradiation: is the nutritional intervention useful?]. / Intérêt de la prise en charge nutritionnelle des patients traités par irradiation des voies aérodigestives supérieures: la consultation diététique est-elle utile?

AIMS: The head and neck tumors are most often associated with a precarious nutritional status. Radiotherapy increases the risk of denutrition because of its secondary effects on the secretory and sensorial mucous membranes. The purpose of our retrospectively study was to evaluate the interest of a precocious and regular nutritional therapy on the ability to maintain the nutritional status of the patient during the radiotherapy. PATIENTS AND METHODS: The fifty-two patients included in the survey have been classified retrospectively in two different groups based on their observance to the nutritional therapy: group 1 "good observance", group 2 "bad observance". RESULTS: The 31 patients of group 1 have lost an average of 1.9 kg by the end of the irradiation, whereas the 21 patients of group 2 have lost an average of 6.1 kg (p<0.001). The almost stability in weight of patients in group 1 was linked to a lower frequency of breaks in the radiotherapy (6 vs 33% p=0.03) and in a decrease in grade of inflammatory mucous membranes (10% of grade 3 in group 1 vs 52% in group 2, p=0.006). The quantity of calories ingested in form of nutritional supplements was greater in group 1 and consequently enabled patients to stabilized their weight (1200 calories in group 1 versus 850 calories in group 2, p<0.005). CONCLUSIONS: The given nutritional advice and the prescription of adapted nutritional supplements consequently allowed limiting efficiently the weight lost during the irradiation and the grade of mucositis. The systematization of a precocious nutritional therapy for patients irradiated for head and neck tumors seems absolutely essential.

Swiss DVI at the tsunami disaster: expect the unexpected.

The conclusions reached while considering various aspects of the implemented strategy in the identification procedures in the wake of the tsunami disaster of December 26, 2004 are outlined. The lessons to be learned are discussed.

[Detection of the sentinal node by lymphoscintigraphy in squamous-cell carcinoma of the oral cavity: a prospective study of 31 patients]. / Détection du ganglion sentinelle par lymphoscintigraphie dans les cancers epidermoïdes de la cavité buccale: étude prospective de 31 patients.

INTRODUCTION: This study aimed at evaluating the relevance of sentinel node detection by lymphoscintigraphy in patients diagnosed with squamous-cell carcinoma of the oral cavity in the absence of neck adenopathy. PATIENTS AND METHODS: A prospective study was carried out in 31 patients diagnosed with T1 to T3 squamous-cell carcinoma of the oral cavity without any clinically detectable neck adenopathy. A lymphoscintigraphy was performed the day before surgery. All patients underwent sentinel lymph node biopsy guided by a gamma-ray detecting probe and modified neck dissection. Pathologic evaluation of the sentinel lymph node included, in addition to the standard protocol, immunohistochemical analysis and thin sections of E stained preparations. RESULTS: In 3 patients, the lymphoscintigraphy failed to detect any sentinel lymph node. In the remaining group of 28 patients, 20 patients showed a negative sentinel node concordant with a histologically negative neck dissection. In 5 patients, a positive lymph node was found although the rest of the neck dissection was negative. In 3 patients, sentinel lymph node was found to be negative but other neck nodes were positive. The overall sensitivity of lymphoscintigraphy in our study was 62%. DISCUSSION: Surprisingly, the results of our study do not support the clinical usefulness of sentinel lymph node detection as a reliable and accurate staging method in patients with oral squamous cell carcinoma. We observed that lymphoscintigraphy was not a reliable method for detecting micrometastases in patients diagnosed with a squamous-cell carcinoma of the oral cavity without clinical evidence of neck matastases.

[Two cases of malignant tumors of the face after hematopoietic stem cell transplantation]. / Deux cas de tumeurs malignes de la face après allogreffe de cellules souches hématopoïétiques.

INTRODUCTION: Malignant solid tumors are a complication of hematopoietic stem cell transplantation (HSCT). OBSERVATION: Two patients underwent HSCT for acute leukemia. Chronic graft-versus-host disease (GVHD) developed. At 5 years one patient developed squamous cell carcinoma of the tongue and the other mucoepidermoid carcinoma of the parotid gland. DISCUSSION: Several factors are involved in the development of secondary malignant tumors after HSCT. Pre- and post-graft immunosuppressive treatment inhibits the defence system and cell repair and can trigger chronic GVHD with chronic inflammation of the epithelial tissue leading to accelerated cell turn over and a risk of genetic anomalies favoring penetration of viral particles. Squamous cell carcinoma of the oral cavity after HSCT presents the same clinical, histological and prognostic features as in the non-grafted patient. These patients require prolonged surveillance. Improved grafting and ant-HPV vaccination techniques may reduce the risk of cancer after HSCT.

[Vascularized osseous flaps for mandibular reconstruction after osteoradionecrosis]. / Reconstruction mandibulaire par lambeau osseux vascularisé après ostéoradionécrose.

INTRODUCTION: The reconstruction of mandibular continuity destroyed by osteoradionecrosis can be a difficult task. The aim of this study was to evaluate the reliability and contribution of vascular osseous flaps for mandibular reconstruction after osteoradionecrosis. MATERIAL AND METHOD: A retrospective study of patients undergoing mandibular reconstruction after osteoradionecrosis between 1989 and 2002 was performed. Twenty-five mandibular reconstructions were performed in 23 patients: 16 fibular free flaps, 5 osteomuscular serrato-costal free flaps, 1 osteocutaneous external brachial free flap, 1 medial femoral condylar free flap and 2 armed pectoralis major pediculed flaps. RESULTS: We observed two major complications (8%): loss of one fibular flap and one medial femoral condylar free flap. We observed 42% minor complications. Overall quality of life was constantly enhanced. DISCUSSION: Fibular flap is definitely a good method for immediate or secondary mandibular reconstruction. A serratocostal flap must be considered as an alternative flap when the fibular flap is unavailable.

Genetic modifications of the adeno-associated virus type 2 capsid reduce the affinity and the neutralizing effects of human serum antibodies.

The high prevalence of human serum antibodies against adeno-associated virus type 2 (AAV) vectors represents a potential limitation for in vivo applications. Consequently, the development of AAV vectors able to escape antibody binding and neutralization is of importance. To identify capsid domains which contain major immunogenic epitopes, six AAV capsid mutants carrying peptide insertions in surface exposed loop regions (I-261, I-381, I-447, I-534, I-573, I-587) were analyzed. Two of these mutants, I-534 and I-573, showed an up to 70% reduced affinity for AAV antibodies as compared to wild-type AAV in the majority of serum samples. In addition, AAV mutant I-587 but not wild-type AAV efficiently transduced cells despite the presence of neutralizing antisera. Taken together, the results show that major neutralizing effects of human AAV antisera might be overcome by the use of AAV capsid mutants.

[Cutaneous angiosarcoma of the head: three cases]. / Angiosarcomes cutanés céphaliques: à propos de trois cas.

Cutaneous angiosarcoma of the head is an uncommon finding. We report three cases, two women with a scalp localization and a man with a facial (frontal) localization. Recurrence was observed in one woman after surgery; this patient was given palliative treatment due to her poor health condition. The other women experienced three recurrences. After the last surgery, latissmus dorsi free flap graft, she has been disease free. The man was treated with surgery and radiotherapy. Regional lymph node metastasis appeared 5 years after the initial treatment. He is now disease free after surgery and cervical radiotherapy. Wide surgery and careful long-term follow-up are essential. The latissimus dorsi free flap can provide successful cure.

Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells.

Gene therapy vectors based on adeno-associated virus-2 (AAV2) offer considerable promise for human gene therapy. Applications for AAV vectors are limited to tissues efficiently transduced by the vector due to its natural tropism, which is predominantly skeletal muscle, neurons, and hepatocytes. Tropism modification to elevate efficiency and/or selectivity to individual cell types would enhance the scope of AAV for disease therapies. The vascular endothelium is implicitly important in cardiovascular diseases and cancer, but is relatively poorly transduced by AAV vectors. We therefore genetically incorporated the peptide SIGYPLP, which targets endothelial cells (EC), into position I-587 of AAV capsids. SIGYPLP-modified AAV (AAVsig) showed enhanced transduction of human EC compared with AAV with a wild-type capsid (AAVwt), a phenotype independent of heparan sulphate proteoglycan (HSPG) binding. In contrast, AAVsig did not enhance transduction of primary human vascular smooth muscle cells or human hepatocytes, principal targets for AAV vectors in local or systemic gene delivery applications, respectively. Furthermore, infection of EC in the presence of bafilomycin A(2) indicated that intracellular trafficking of AAV particles was altered by targeting AAV by means of SIGYPLP. AAV vectors with enhanced tropism for EC will be useful for diverse gene therapeutics targeted at the vasculature.

[Complications of orthognathic surgery. Apropos of a series of 84 patients]. / Complications de la chirurgie orthognathique. A propos d'une série de 84 patients.

BACKGROUND: Patients demand satisfactory functional and esthetic results from orthognatic surgery. The aim of this study as to assess adverse outcomes after orthognatic surgery. PATIENTS AND METHODS: We retrospectively reviewed 84 patients who underwent maxillary (22.6%), mandibular (29.8%) or bimaxillary (38.1%) osteotomy in 1997. We re-examined 76 of these patients at a mean 21 months follow-up. Data were recorded for the preoperative, early postoperative, secondary postoperative and late postoperative periods. RESULTS: Infectious complications occurred in 2% of the cases of maxillary surgery. For mandibular surgery there were 10.5% infectious complications including 83% that resolved spontaneously, 3.5% neurological complications and 1.7% temporomandibular joint complications. DISCUSSION: Maxillary osteotomy has proven reliable. Major adverse outcome is infrequent but serious. Adverse outcomes in mandibular surgery are more common but less problematic.

[Primary osseous leiomyosarcoma of the jaw. Apropos of a case]. / Léiomyosarcome osseux primitif des maxillaires. A propos d'un cas.

Primary leiomyosarcoma of bone is a malignant smooth muscle tumour uncommonly found in the jaws. We report a case of primary leiomyosarcoma of the mandible in a 31-year-old man treated with wide resection and radiotherapy then secondary reconstruction with a fibula free flap. No recurrence or distant metastasis has developed four years after the initial surgery. We review the literature on primary leiomyosarcoma of the jaws.

Monoclonal antibodies against the adeno-associated virus type 2 (AAV-2) capsid: epitope mapping and identification of capsid domains involved in AAV-2-cell interaction and neutralization of AAV-2 infection.

The previously characterized monoclonal antibodies (MAbs) A1, A69, B1, and A20 are directed against assembled or nonassembled adeno-associated virus type 2 (AAV-2) capsid proteins (A. Wistuba, A. Kern, S. Weger, D. Grimm, and J. A. Kleinschmidt, J. Virol. 71:1341-1352, 1997). Here we describe the linear epitopes of A1, A69, and B1 which reside in VP1, VP2, and VP3, respectively, using gene fragment phage display library, peptide scan, and peptide competition experiments. In addition, MAbs A20, C24-B, C37-B, and D3 directed against conformational epitopes on AAV-2 capsids were characterized. Epitope sequences on the capsid surface were identified by enzyme-linked immunoabsorbent assay using AAV-2 mutants and AAV serotypes, peptide scan, and peptide competition experiments. A20 neutralizes infection following receptor attachment by binding an epitope formed during AAV-2 capsid assembly. The newly isolated antibodies C24-B and C37-B inhibit AAV-2 binding to cells, probably by recognizing a loop region involved in binding of AAV-2 to the cellular receptor. In contrast, binding of D3 to a loop near the predicted threefold spike does not neutralize AAV-2 infection. The identified antigenic regions on the AAV-2 capsid surface are discussed with respect to their possible roles in different steps of the viral life cycle.

A statistical study of air bubbles on athletic shoesoles.

Comparisons of a shoemark with a shoesole (and standards) sometimes lead to associations based on air bubbles (among other manufacturing or acquired characteristics). Today, the assessment of the evidential value of air bubbles coincidences relies largely upon the examiner's experience and/or follows sometimes a verification based on the examination of a small number of analogous pairs collected for the case at hand. Statistical data related to the occurrence and characteristics of air bubbles on shoesoles in an attempt to model the potential variability have been gathered. Seventy-one pairs of shoes with the same design, brand, model and size were obtained. Right and left soles were photographed. An image-processing algorithm was developed to allow the systematic acquisition of data such as: (1) the number of air bubbles on the sole and around given structural elements; (2) the measure of air bubbles characteristics such as their surface and position. These data allow a discussion of the assessment of the probability of finding on shoesoles (same design, brand, model and size) a certain number of air bubbles on a surface with the same positions and morphology.

Intracellular distribution of mammalian protein kinase A catalytic subunit altered by conserved Asn2 deamidation.

The catalytic (C) subunit of protein kinase A functions both in the cytoplasm and the nucleus. A major charge variant representing about one third of the enzyme in striated muscle results from deamidation in vivo of the Asn2 residue at the conserved NH(2)-terminal sequence myrGly-Asn-Ala (Jedrzejewski, P.T., A. Girod, A. Tholey, N. König, S. Thullner, V. Kinzel, and D. Bossemeyer. 1998. Protein Sci. 7:457-469). Because of the increase of electronegativity by generation of Asp2, it is reminiscent of a myristoyl-electrostatic switch. To compare the intracellular distribution of the enzymes, both forms of porcine or bovine heart enzyme were microinjected into the cytoplasm of mouse NIH 3T3 cells after conjugation with fluorescein, rhodamine, or in unlabeled form. The nuclear/cytoplasmic fluorescence ratio (N/C) was analyzed in the presence of cAMP (in the case of unlabeled enzyme by antibodies). Under all circumstances, the N/C ratio obtained with the encoded Asn2 form was significantly higher than that with the deamidated, Asp2 form; i.e., the Asn2 form reached a larger nuclear concentration than the Asp2 form. Comparable data were obtained with a human cell line. The differential intracellular distribution of both enzyme forms is also reflected by functional data. It correlates with the degree of phosphorylation of the key serine in CREB family transcription factors in the nucleus. Microinjection of myristoylated recombinant bovine Calpha and the Asn2 deletion mutant of it yielded N/C ratios in the same range as encoded native enzymes. Thus, Asn2 seems to serve as a potential site for modulating electronegativity. The data indicate that the NH(2)-terminal domain of the PKA C-subunit contributes to the intracellular distribution of free enzyme, which can be altered by site-specific in vivo deamidation. The model character for other signaling proteins starting with myrGly-Asn is discussed.

The p24 family member p23 is required for early embryonic development.

The p24 family of type I integral-membrane proteins, which are localised in the endoplasmic reticulum (ER), the intermediate compartment and the Golgi apparatus, are thought to function as receptors for cargo exit from the ER and in transport vesicle formation. Members of the p24 family have been found in a molecular complex and are enriched in COPI-coated vesicles, which are involved in membrane traffic between the ER and Golgi complex. Although expressed abundantly, simultaneous deletion of several family members does not appear to affect cell viability and protein secretion in yeast. In order to gain more insights into the physiological roles of different p24 proteins, we generated mice deficient in the expression of one family member, p23 (also called 24delta1, see for alternative nomenclature). In contrast to yeast genetics, in mice disruption of both p23 alleles resulted in early embryonic lethality. Inactivation of one allele led not only to reduced levels of p23 itself but also to reduced levels of other family members. The reduction in steady-state protein levels also induced structural changes in the Golgi apparatus, such as the formation of dilated saccules. The generation of mice deficient in p23 expression has revealed an essential and non-redundant role for p23 in the earliest stages of mammalian development. It has also provided genetic evidence for the participation of p24 family members in oligomeric complexes and indicates a structural role for these proteins in maintaining the integrity of the early secretory pathway.

Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita.

Mutations in the DKC1 gene are responsible for causing the bone marrow failure syndrome, dyskeratosis congenita (DKC; OMIM 305000). The majority of mutations identified to date are missense mutations and are clustered in exons 3, 4 and 11. It is predicted that the corresponding protein dyskerin is a nucleolar phosphoprotein which functions in both pseudo-uridylation and cleavage of precursor rRNA. Dyskerin contains multiple putative nuclear localization signals (NLSs) at the N-terminus (KKHKKKKERKS) and C-terminus [KRKR(X)(17)KKEKKKSKKDKKAK(X)(17)-KKKKKKKKAKEVELVSE]. By fusing dyskerin with the enhanced green fluorescent protein (EGFP) and by following a time course of expression in mammalian cell lines, we showed that full-length dyskerin initially localizes to the nucleoplasm and subsequently accumulates in the nucleoli. A co-localization to the coiled bodies was observed in some cells where dyskerin-EGFP had translocated to the nucleoli. Analysis of a series of mutant constructs indicated that whereas the most C-terminal lysine-rich clusters [KKEKKKS-KKDKKAK(X)(17)KKKKKKKKAKEVELVSE] influence the rate of nucleoplasmic and nucleolar accumulation, the KRKR sequence is primarily responsible for the nuclear import. Nucleolar localization was maintained when either the N- or C-terminal motifs were mutated, but not when all NLSs were removed. We conclude that the intranuclear localization of dyskerin is accomplished by the synergistic effect of a number of NLSs and that the nucleolar localization signals are contained within the NLSs. Further, examination of dyskerin-EGFP fusions mimicking mutations detected in patients indicated that the intracellular mislocalization of dyskerin is unlikely to cause DKC.