European Council of Legal Medicine (ECLM) on-site inspection forms for forensic pathology, anthropology, odontology, genetics, entomology and toxicology for forensic and medico-legal scene and corpse investigation: the Parma form.

Further to a previous publication by the European Council of Legal Medicine (ECLM) concerning on-site forensic and medico-legal scene and corpse investigation, this publication provides guidance for forensic medical specialists, pathologists and, where present, coroners' activity at a scene of death inspection and to harmonize the procedures for a correct search, detection, collection, sampling and storage of all elements which may be useful as evidence, and ensure documentation of all these steps. This ECLM's inspection form provides a checklist to be used on-site for the investigation of a corpse present at a crime or suspicious death scene. It permits the collection of all relevant data not only for the pathologist, but also for forensic anthropologists, odontologists, geneticists, entomologists and toxicologists, thus supporting a collaborative work approach. Detailed instructions for the completion of forms are provided.

Quantitation of circulating wild-type alpha-1-antitrypsin in heterozygous carriers of the S and Z deficiency alleles.

BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency disease results from mutations in the A1AT gene. Controversy exists in regards to treatment of heterozygous carriers of the S and Z deficiency alleles. Quantitation of allelic expression has not been possible with standard laboratory methods. Here we show that the recently described method for liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of A1AT tryptic peptides can differentiate between mutated (S and Z) and wild-type (non-S and non-Z) proteins allowing for quantitation of circulating allelic expression in heterozygous patients. METHODS: Serum (244 M/M, 61 M/Z, and 63 M/S) was combined with isotopically labeled peptide standards, digested with trypsin, and quantitated by LC-MS/MS. Total and allele-specific A1AT quantitation was performed by comparison of peptide peak height ratios to a standard curve for each peptide. Linear regression was used to compare results and central 95(th) percentile intervals were calculated using parametric analysis. RESULTS: Quantitation of circulating wild-type A1AT based on the proteotypic and allelic (non-S and non-Z) peptides was validated in M/M patients. Proteotypic peptide concentrations correlated linearly with quantitation by non-Z and non-S peptides [slopes (Spearman correlation coefficient) of 1.09 (0.89) and 0.98 (0.80), respectively]. Allele-specific quantitation showed significant differences in wild-type protein expression in M/Z and M/S patients. Although average total A1AT concentration was lower for M/Z patients, the percentage of wild-type protein in M/Z patients was significantly higher at 82 % (55- > 95 %) compared to 63 % (43-83 %) for M/S heterozygotes. In a cohort of M/Z patients with sufficient total A1AT (≥80 mg/dL), half had insufficient wild-type protein that could have clinical implications for pulmonary dysfunction. CONCLUSIONS: For the first time, a method to quantitate A1AT allele protein expression is described. Given the wide range of circulating wild-type protein observed in heterozygous patients, this method has the potential to reveal correlations between allele concentration and development and/or severity of clinical symptoms.

GLYOXALASE I A111E, PARAOXONASE 1 Q192R AND L55M POLYMORPHISMS IN ITALIAN PATIENTS WITH SPORADIC CEREBRAL CAVERNOUS MALFORMATIONS: A PILOT STUDY.

It is already known that the conditions of increased oxidative stress are associated to a greater susceptibility to vascular malformations including cerebral cavernous malformations (CCMs). These are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1(Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Polymorphisms in the genes encoding for enzymes involved in the antioxidant systems such as glyoxalase I (GLO I) and paraoxonase I (PON I) could influence individual susceptibility to the vascular malformations. A single nucleotide polymorphism was identified in the exon 4 of GLO 1 gene that causes an amino acid substitution of Ala for Glu (Ala111Glu). Two common polymorphisms have been described in the coding region of PON1, which lead to glutamine → arginine substitution at 192 (Q192R) and a leucine → methionine substitution at 55 (L55M). The polymorphisms were characterized in 59 patients without mutations in the CCM genes versus 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that the frequency of patients carrying the GLO1 A/E genotype among the case group (56%) was four-fold higher than among the controls (14.1%). In the cohort of CCM patients, an increase in the frequency of PON192 Q/R genotype was observed (39% in the CCM group versus 3.7% in the healthy controls). Similarly, an increase was observed in the proportion of individuals with the genotype R/R in the disease group (5%) in respect to the normal healthy cohort (0.5%). Finally, the frequency of the PON55 heterozygotes L/M genotype was 29% in patients with CCMs and 4% in the healthy controls. The same trend was observed in PON55 homozygous M/M genotype frequency (CCMs 20% vs controls 10%). The present study aimed to investigate the possible association of GLO1 A111E, PON1 Q192R and L55M polymorphisms with the risk of CCMs. We found that individuals with the GLO1 A /E genotype, PON192/QR-RR genotypes and PON55/LM-MM genotypes had a significantly higher risk of CCMs compared with the other genotypes. However, because CCM is a heterogeneous disease, other additional factors might be involved in the initiation and progression of CCM disease.

Improved TV-CS Approaches for Inverse Scattering Problem.

Total Variation and Compressive Sensing (TV-CS) techniques represent a very attractive approach to inverse scattering problems. In fact, if the unknown is piecewise constant and so has a sparse gradient, TV-CS approaches allow us to achieve optimal reconstructions, reducing considerably the number of measurements and enforcing the sparsity on the gradient of the sought unknowns. In this paper, we introduce two different techniques based on TV-CS that exploit in a different manner the concept of gradient in order to improve the solution of the inverse scattering problems obtained by TV-CS approach. Numerical examples are addressed to show the effectiveness of the method.

Comparison of cutaneous termic response to a standardised warm up in trained and untrained individuals.

AIM: Warm up prior to exercise induces an increased production of metabolic heat, which triggers the thermoregulatory system to initiate heat loss mechanisms. Variations in cutaneous tissue temperature have been already reported in trained subjects, by means of high resolution thermal imaging. Purpose of this paper was to quantitatively evaluate, by means of infrared thermography, the differences in the cutaneous temperature among trained and untrained subjects. METHODS: Forty male volunteers performed a standard warm up exercise on a stationary cycle, divided in three steps: 1) 0-5 minutes at 100 Watt; 2) 5-10 minutes at 130 Watt; and 3) 10-15 minutes at 160 Watt. Thermal images from thorax and upper limbs were collected during the exercise. Heart rate was also measured. RESULTS: In comparison to baseline, trained subjects exhibited a significant temperature reduction in the third step (trunk, P<0.01; upper limbs, P<0.009), while no difference was observed in untrained subjects. In the comparison between groups, a statistically significant difference was observed in both regions of interest, in the second (trunk, P<0.01; upper limbs, P<0.02), and in the third step (trunk, P<0.0002; upper limbs, P<0.0008). During the whole exercise, heart rate increased progressively in all participants, but more markedly in untrained subjects. CONCLUSION: Cutaneous thermoregulatory response differs among trained and untrained participants. Infrared thermal imaging is useful in detecting these differences, providing additional data to the physiological evaluation of subjects performing sport activities.

Activity and phenotype of natural killer cells in peptide transporter (TAP)-deficient patients (type I bare lymphocyte syndrome).

In this paper we describe the function and phenotype of natural killer (NK) lymphocytes from HLA class I-deficient patients. These cells are, as has been previously reported, unable to lyse HLA class I- K562 cells, but are able to perform antibody-dependent cellular cytotoxicity (ADCC), although with lower efficiency as compared to NK cells from normal individuals. Transporter associated to antigen processing (TAP)- NK cells proliferate when cultured in the presence of lymphoblastoid B cells (B-LCs) and interleukin 2 and develop a spectrum of cytotoxicity similar to that of activated normal NK cells. Importantly, activation of the TAP- NK cells induces strong cytotoxicity to autologous B-LCs. Analysis of the phenotype of circulating TAP- NK lymphocytes showed them to display a normal diverse repertoire of HLA class I-specific NK receptors. These receptors were expressed at normal levels, apart from the CD94-NKG2A complex, which appeared to be overexpressed. This latter finding could reflect an adaptation to the low expression of HLA class I molecules. Finally, functional analyses indicated that the inhibitory receptors in TAP- individuals can transduce inhibitory signals. Our results suggest that in vivo, the NK cells of TAP- patients could participate in immune defense, at least through ADCC, but upon activation, may be involved in autoimmune processes.

Functional infrared imaging of paroxysmal ischemic events in patients with Raynaud's phenomenon.

The use of thermal infrared (IR) imaging together with the study of the thermal recovery from a controlled cold challenge has been proposed in the diagnosis and follow-up of therapeutic response of Raynaud's Phenomenon (RP) and Systemic Sclerosis (SSc). The controlled cold challenge test usually performed during IR investigations may induce a RP in patients with the latter condition. In our Institution we routinely perform capillaroscopy and thermal IR to follow-up SSc patients. In this paper, we describe the thermal recovery patterns shown by two SSc patients (a 40 year-old male with diffuse variant of SSc and a 71 year-old female with a limited variant of SSc) who presented ischemic and paroxysmal RP attack while recovering from the routine controlled cold challenge test. During RP attack, the cutaneous temperature of some fingers continued to decrease for some minutes even after the cessation of the cold stress. To the best of our knowledge, to date, no literature report has documented the thermal behaviour of SSc patients' fingers which occasionally present ischemic and paroxysmal response. Triggering of ischemic RP attack appears to not rely only on morphological and structural finger impairment, but also upon other aspects, like the emotional attitude of the subject and the possible discomfort experienced with the proceeding of the functional cold stress test.

Homozygous human TAP peptide transporter mutation in HLA class I deficiency.

Human lymphocyte antigen (HLA) class I proteins of the major histocompatibility complex are largely dependent for expression on small peptides supplied to them by transporter associated with antigen processing (TAP) protein. An inherited human deficiency in the TAP transporter was identified in two siblings suffering from recurrent respiratory bacterial infections. The expression on the cell surface of class I proteins was very low, whereas that of CD1a was normal, and the cytotoxicity of natural killer cells was affected. In addition, CD8+ alpha beta T cells were present in low but significant numbers and were cytotoxic in the most severely affected sibling, who also showed an increase in CD4+CD8+ T cells and gamma delta T cells.

A multicenter open-label experience on the response of psoriasis to Adalimumab and effect of dose escalation in non-responders: the Aphrodite project.

There is much evidence to show the efficacy of adalimumab, a human monoclonal antibody targeting tumour necrosis factor-alpha, in the treatment of plaque psoriasis. In this open-label experience, 147 high-need patients suffering from plaque psoriasis, with a mean Psoriasis Area and Severity Index (PASI) of 18.8, and concomitant psoriatic arthritis (PsA) received subcutaneous injections of 40 mg of adalimumab every other week (EOW). This was actually the dosage regimen recommended for PsA, as the drug had not then been approved for psoriasis at the time of the patients enrolment. At week 12, an improvement of at least 50 percent of the PASI (PASI-50) was observed in 111 (77 percent) patients. Continuation of treatment in responders with adalimumab 40 mg EOW led to a sustained response, with the PASI-50 achieved by 97 percent of patients in the as-treated analysis at week 24 (PASI-75 in 82 percent and PASI-90 in 45 percent out of 109 patients who received EOW injections up to week 24). Thirty subjects who failed to attain the PASI-50 response at week 12 were treated with adalimumab 40 mg every week for a further 12 weeks. At week 24, 80 percent of these patients obtained a PASI-50 response after dose escalation. Tolerability was good in the majority of patients. Only two patients discontinued treatment because of an adverse event (repeated flu-like episodes and a pleuropericarditis of unknown origin, respectively).

Hierarchically structured phase separated biopolymer hydrogels create tailorable delayed burst release during gastrointestinal digestion.

The on demand delivery of novel peptide actives, traditional pharmaceuticals, nutrients and/or vitamins is a ever present challenge due to the digestive and metabolic degradation of the active and the delivery vehicle. Biodegradable biopolymer hydrogels have long held promise as candidates for creating tailored release profiles due to the ability to control gel porosity. The present study describes the creation of novel hierarchical biopolymer hydrogels for the controlled release of lipids/lipophilic actives pharmaceutical ingredients (APIs), and mathematically describes the mechanisms that affect the timing of release. The creation of phase separated protein/polysaccharide core (6.6 wt% gelatin, 40 wt% Oil in water emulsion) shell structures (7 g/L xanthan with 70-140 g/L ß-lactoglobulin) altered enzyme mass transport processes. This core shell structure enabled the creation of a tailorable burst release of API during gastrointestinal digestion where there is a delay in the onset of release, without affecting the kinetics of release. The timing of the delay could be readily programmed (with release of between 60 and 240 min) by controlling either the thickness or protein concentration (between 70 g/L and 140 g/L ß-lactoglobulin) of the outer mixed biopolymer hydrogel shell (7 g/L xanthan with 70-140 g/L ß-lactoglobulin). Enzyme diffusion measurements demonstrated that surface erosion was the main degradation mechanism. A kinetic model was created to describe the delayed burst release behaviour of APIs encapsulated within the core, and successfully predicted the influence of shell thickness and shell protein density on the timing of gastro-intestinal release (in vitro). Our work highlights the creation of a novel family of core-shell hydrogel oral dosage forms capable of programmable delivery of lipids/lipophilic APIs. These findings could have considerable implications for the delivery of peptides, poorly soluble drugs, or the programmed delivery of lipids within the gastrointestinal tract.

Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to visceral leishmaniasis data in Brazil.

Visceral leishmaniasis (VL) is a parasitic disease that is endemic in more than 80 countries, and leads to high fatality rates when left untreated. We investigate the relationship of VL cases in dogs and human cases, specifically for evidence of VL in dogs leading to excess cases in humans. We use surveillance data for dogs and humans for the years 2007-2011 to conduct both spatial and spatio-temporal analyses. Several models are evaluated incorporating varying levels of dependency between dog and human data. Models including dog data show marginal improvement over models without; however, for a subset of spatial units with ample data, models provide concordant risk classification for dogs and humans at high rates (∼70%). Limited reported dog case surveillance data may contribute to the results suggesting little explanatory value in the dog data, as excess human risk was only explained by dog risk in 5% of regions in the spatial analysis.

Comparison of thermal infrared and laser doppler imaging in the assessment of cutaneous tissue perfusion in scleroderma patients and healthy controls.

In this study we propose a non-invasive method to calculate blood flow by means of thermal infrared imaging and bio-heat transfer modeling. The method is able to provide high time-resolution series of cutaneous blood flow images with the same spatial resolution of the thermal images. The method was tested against a standard laser Doppler imaging system, which to date is considered the gold standard for non-invasive assessment of cutaneous blood flow, on both healthy subjects and patients suffering from systemic sclerosis (SSc; a pathological condition with microvessel endothelium injury). Twenty healthy subjects and twenty SSc patients simultaneously underwent laser Doppler and thermal imaging of the dorsum of the hand. A linear correlation between perfusion values obtained with the two methods was found for the healthy control group (R = 0.85, Pearson Product Moment Correlation). A significant correlation was not observed for the SSc patient group. The results of this study suggest that combined laser Doppler, thermal imaging and bio-heat transfer modeling could effectively discriminate between healthy vs. impaired conditions of the cutaneous tissue thermal properties and cutaneous vasculature. Such method, in addition to providing a potential effective imaging-based tool for a variety of biomedical and clinical applications ranging from diagnostics to treatment follow-up, may help the understanding of the morphological and functional impairment secondary to the disease. The thermal imaging-based method provided faster and better time-resolved imaging of cutaneous perfusion than standard laser Doppler techniques as the thermal cameras can provide up to 100 complete 524 x 524 pixel images per second, thus allowing real time monitoring of tissue perfusion rates.

Influence of body mass index, comorbidities and prior systemic therapies on the response of psoriasis to adalimumab: an exploratory analysis from the APHRODITE data.

Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor (TNF)-alpha, which is effective for the treatment of psoriasis and psoriatic arthritis (PsA). The aim of this study is to determine whether the response of psoriasis to adalimumab treatment might be influenced by certain particular factors, such as body mass index (BMI), history of biologic therapy, blood hypertension and metabolic comorbidities. For this reason, an exploratory analysis was conducted on 144 patients with psoriasis and concomitant PsA treated with adalimumab 40 mg every other week, evaluating the influence of such factors on the Psoriasis Area and Severity Index (PASI) response rate at week 12. Our preliminary results suggest that the response rate at week 12, in terms of both PASI-50 and PASI-75, appeared to be independent of the presence of hypertension and/or metabolic comorbidities. The PASI-50 response was observed more frequently in patients with BMI less than 30 as compared to obese patients (79% vs 58%, p = 0.02). Previous use of anti-TNF biologics did not appear to affect per se the rate of responders, although it was associated with a lower PASI-75 rate among responders.

Low influenza vaccination coverage in asthmatic children in France in 2006-7.

In France, annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Since 1988, each year from September to December, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-7 influenza vaccination coverage rate (VCR) in 433 asthmatic children aged 6 to 17 years (mean age: 9.5 years; male: 61%) who consulted a paediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza VCR was 15.7% for the 2006-7 season (13.9% for the 2005-6 season and 10.9% for the 2004-5 season). General practitioners vaccinated 72.1% of the children. "Lack of information" (42%) was the most frequently reported reason for non-vaccination. Vouchers (received by 39.6% of the children) significantly increased the VCR (31% versus 5.9%; p<0.001). In France, in 2006-7, the influenza VCR in asthmatic children was far below the national public health objective (at least 75% for the year 2008). Concerted action is needed to improve the influenza VCR in asthmatic children.

[Influenza vaccination coverage in asthmatic children in France in 2006-2007]. / Couverture vaccinale contre la grippe chez les enfants asthmatiques en France en 2006-2007.

In France, an annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Each year, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-2007 influenza vaccination coverage rate in 433 asthmatic children aged six to 17 years (mean age: 9.5 years; male: 61%) who consulted a pediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza vaccination coverage rate was 15.7% for the 2006-2007 season (13.9% for the 2005-2006 season and 10.9% for the 2004-2005 season). General practitioners vaccinated 72.1% of the children. Lack of information (42%) was the most frequently reported reason for non-vaccination. Free vouchers (received by 39.6% of the children) significantly increased the vaccination coverage rate (31% versus 5.9%; p < 0.001). In France, in 2006-2007, the influenza vaccination coverage rate in asthmatic children was far below the national public health objective to achieve for the year 2008 (at least 75%). Concerted action is needed to improve the influenza vaccination coverage rate in asthmatic children.

[Bilateral vocal cords paralysis in newborn]. / Paralysies bilatérales des cordes vocales chez le nouveau-né.

OBJECTIVE: This study aims at analyzing medical and surgical management as well as long-term follow-up of newborn (n=8) suffering from bilateral vocal cord paralysis. METHODS: This retrospective study reports information regarding pregnancy and birth history, family history, initial and delayed clinical features, treatment and follow-up of these infants. The following laryngeal procedures have been performed: Laser cordectomy (n=3), arytenoidopexy by external approach (n=2), botulinum toxin injection alone or associated with surgical treatments (n=6), enlargement laryngoplasty (n=1), endolaryngeal prostheses insertion (n=2). RESULTS: Any spontaneous recovery has been noticed. Four patients experiencing swallowing disorders required a gastrostomy in proportion to neurologic diseases and association of anomalies. Electromyograms performed were unremarkable. Botulinum toxin injected alone in laryngeal adductor muscles was not effective. The best results were observed when both arytenoidopexy and botulinum toxin injection were carried out. Bilateral cordectomies have been disappointing because of persistent vocal cord adduction. CONCLUSION: The low probability of spontaneous recovery and the drawbacks of tracheotomy encourage us to perform vocal cords adduction procedures as soon as possible.

Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea.

BACKGROUND: The serum biomarkers, elevated 7αC4 (C4) and decreased FGF19, have been proposed as screening tests for bile acid diarrhoea. AIM: To analyse prevalence, specificity and reproducibility of fasting C4 and FGF19 in identifying bile acid diarrhoea in patients with irritable bowel syndrome with predominant diarrhoea or functional diarrhoea (summarised as IBS-D). METHODS: We prospectively studied fasting serum C4 and FGF19 in 101 IBS-D patients; we reviewed data from 37 of the 101 patients with prior fasting serum C4 and FGF19 and from 30 of the 101 patients with prior faecal bile acids per 48 hours. We compared results with normal values (C4 ≥52.5 ng/mL [n=184], FGF-19 ≤61.7 pg/mL [n=50]). We used Spearman correlation and Bland-Altman plots to appraise reproducibility. RESULTS: Among the 101 patients, there was a negative correlation between serum C4 and FGF19 (Rs=-.342, P=.0005). Bile acid diarrhoea was diagnosed in 10 patients based on elevated serum C4 levels (mean 23.5±23.1 [SD] ng/mL) and 21 patients based on decreased FGF19 levels (121.6±84.2 pg/mL). With replicate tests in patients with stable IBS-D, 78% of C4 and 70% of FGF19 measurements remained concordant, with 3% and 11% respectively consistently positive for bile acid diarrhoea in the 101 patients. Compared to 48 hours faecal bile acids, specificity for C4 and FGF19 was 83% and 78%, respectively. Bland-Altman plots demonstrated greater reliability of C4 than FGF19. CONCLUSIONS: Among 101 patents with IBS-D, fasting FGF19 and C4 levels had good specificity and negative predictive value, suggesting utility as screening tests to exclude bile acid diarrhoea.

[Glomerulo-tubular balance in diabetes mellitus: molecular evidence and clinical consequences]. / Bilancio glomerulo-tubulare nel diabete mellito: evidenze molecolari e conseguenze cliniche.

Diabetes mellitus is fast becoming a world epidemic. About one-third of individuals with diabetes, after 10 yrs, develop diabetic nephropathy, the first cause of end-stage kidney disease. The evolution of diabetic nephropathy can be considered in three stages: glomerular hyperfiltration, microalbuminuria (30-300 mg/24 hr) and proteinuria (>300 mg/24 hr). This study was designed to investigate the tubular basis of glomerular hyperfiltration in early diabetes mellitus. Diabetes was inducted in rats with i.p. streptozotocin (65 mg/kg bw) for 6 days. At the end of the treatment, the glomerular filtration rate (GFR), measured by inulin clearance, had substantially increased in diabetic rats compared with controls. Quantitative polymerase chain reaction (PCR) and Western blot analysis reveal that in diabetic rats compared with controls, mRNA and protein abundance was higher for type 3 sodium/hydrogen exchanger (NHE3) in proximal tubule and ascending limbs of Henle's loop, and higher for bumetanide-sensitive sodium-potassium-2 chloride cotransporter (NKCC2) in ascending limbs of Henle's loop. Western blot analysis confirmed the PCR results. Finally, the abundance of á -ENaC protein was unchanged in diabetic rats compared to controls. These results show that the primary sodium reabsorption increase in proximal tubule reduces salt concentrations at the macula densa. This elicits a tubuloglomerular feedback-dependent increase in single nephron GFR.

[Congenital lacrimonasal duct cyst: Do not forget this radiological and clinical entity]. / Kyste lacrymonasal congénital: une entité radioclinique à ne pas méconnaître.

Although obstruction of the lacrimonasal duct is a fairly common finding in newborns, development of a dacryocystocele (nasolacrimal duct cyst) is uncommon and is caused by stenosis in the proximal and distal area of the nasolacrimal duct leading to a cystic dilatation. Its diagnosis remains difficult for the pediatrician, the ENT specialist, the ophthalmologist, and the radiologist. The study of six cases of dacryocystocele and the review of the literature led the authors to describe the clinical and radiological features of this uncommon entity. The symptomatology includes nasal obstruction and, when bilateral, significant respiratory distress in the newborn (obligate nose-breather) and dilatation of the lacrimal duct with blue cystic swelling inferior to the medial canthus or with an inflammatory aspect of the lacrimal duct in case of infection. A careful endoscopic examination of the nasal cavities and CT or MRI imaging reveals a cystic tumor, which arises in the inferior meatus, inferolateral to the inferior turbinate, and can partly or completely obstruct the endonasal space, uni- or bilaterally. CT and MRI are equally sensitive in detecting dacryocystocele and are also useful for differential diagnosis for other cystic or tumoral nasal lesions such as meningoencephalocele, dermoid cyst, and glioma. To avoid the risk of potential complications (respiratory distress or even sudden infant death, infectious ophthalmologic complications), this radiological and clinical entity should not be forgotten. Endoscopic marsupialization leads to immediate and definitive healing recovery.

Mitochondrial haplotype diversity in the tortoise species Testudo graeca from North Africa and the Middle East.

BACKGROUND: To help conservation programs of the endangered spur-thighed tortoise and to gain better insight into its systematics, genetic variation and evolution in the tortoise species Testudo graeca (Testudines: Testudinidae) was investigated by sequence analysis of a 394-nucleotide fragment of the mitochondrial 12S rRNA gene for 158 tortoise specimens belonging to the subspecies Testudo graeca graeca, Testudo graeca ibera, Testudo graeca terrestris, and a newly recognized subspecies Testudo graeca whitei. A 411-nucleotide fragment of the mitochondrial D-loop was additionally sequenced for a subset of 22 T. graeca, chosen because of their 12S gene haplotype and/or geographical origin. RESULTS: Haplotype networks generated by maximum-likelihood and neighbor-joining analyses of both the separate and the combined sequence data sets suggested the existence of two main clades of Testudo graeca, comprising Testudo graeca from northern Africa and Testudo graeca from the Turkey and the Middle East, respectively. CONCLUSION: Mitochondrial DNA haplotyping suggests that the tortoise subspecies of T. g. graeca and T. g. ibera are genetically distinct, with a calculated divergence time in the early or middle Pleistocene. Other proposed subspecies could not clearly be recognized based upon their mt haplotypes and phylogenetic position, and were either part of the T. g. graeca or of the T. g. ibera clade, suggesting that genetic evidence for the existence of most of the 15 proposed subspecies of T. graeca is weak.