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.

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.

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.

[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.

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.

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.

Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome.

BACKGROUND: About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion. AIMS: To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam. METHODS: A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7α-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4. RESULTS: Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat. CONCLUSIONS: Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

Validating biomarkers of treatable mechanisms in irritable bowel syndrome.

BACKGROUND: A valid biomarker is 'an indicator of normal biologic or pathogenic processes, or pharmacological responses to a therapeutic intervention'. There is no validated biomarker for irritable bowel syndrome (IBS). The aim of the study was to assess ability of three quantitative traits to identify treatable processes to discriminate between IBS-diarrhea (IBS-D) patients, IBS-constipation (IBS-C) patients and healthy volunteers (HV). METHODS: In 30 HV, 30 IBS-C patients and 64 IBS-D patients, we characterized bowel symptoms and quantitated pathophysiological mechanisms: bile acid (BA) synthesis (serum C4 and FGF19), fecal BA and fat, colonic transit (CT), and intestinal permeability (IP). We used multiple logistic regression and receiver-operating characteristic (ROCAUC ) to appraise three factors (fecal BA, CT, and IP) individually and in combination to identify discriminant targets for treatment in IBS. KEY RESULTS: There were significant associations between the three subgroups and symptoms reflecting bowel function and the quantitative traits. There were significant associations between fecal BA and CT at 48 h (r = 0.43; p < 0.001) and between fecal BA and IP (r = 0.23; p = 0.015). Individually, fecal BA and CT48 (but not IP) were significant independent predictors for distinguishing HV from IBS. In combination, they discriminated HV from IBS-D patients (ROCAUC 0.70), HV from IBS-C patients (ROCAUC 0.73), and IBS-C patients from IBS-D patients (ROCAUC 0.86). Colonic transit and fecal BA excretion together discriminate between healthy volunteers and IBS-C patients or IBS-D patients, or between the IBS subgroups with 75-90% specificity at 60% sensitivity. CONCLUSIONS & INFERENCES: Colonic transit and fecal BA individually and together constitute useful biomarkers to identify treatable mechanisms in IBS and to differentiate subgroups of IBS.

[Palliative care for newborns: practices in a level-III unit during a 5-year period]. / Soins palliatifs en néonatologie : analyse et évolution des pratiques sur 5ans dans un centre de niveau 3.

UNLABELLED: The "Patients' rights and end-of-life care" act known as "Leonetti's Law" promulgated in 2005 has promoted the use of palliative care to avoid unreasonable obstinacy when life-sustaining treatment appears disproportionate. Very little is known about this new practice for newborns in French neonatal units. AIMS: To describe and evaluate the practice of palliative care in the newborn (mode of entry, characteristics, and modalities) and its evolution over time. PATIENTS AND METHODS: Ambispective observational study conducted in a level III neonatal center. We included all newborns presenting conditions for which palliative care was introduced. Quantitative and qualitative analyses of routinely collected data, recorded from medical and nursing charts. We compared the recorded data between periods P1 (2006-2007) and P2 (2008-2010) using the Chi(2) test to assess changes over time. RESULTS: A total of 93 newborns benefited from palliative care during the study period. The main medical conditions motivating palliative care initiation in the newborns were severe complications of prematurity (36/93, 39%), anoxic-ischemic encephalopathy (19/93, 20.5%), severe malformations (8/93, 8.5%), severe congenital heart disease (8/93, 8.5%), and other various etiologies (22/93, 23.5%). Both the number of newborns in palliative care/total number of births and the number of deaths after palliative care/total number of neonatal deaths remained stable. In case of prenatal diagnosis (n=31), there was an increase in the number of "palliative care from birth projects" (13/22 in P2 vs. 1/9 in P1, P=0.02). Collective meetings during the decision process were significantly more frequently reported in the infants' charts in P2 (48/59 in P2 vs. 18/34 in P1, P<0.01). Withdrawing and withholding life-sustaining treatment and limiting procedures of care and/or procedures of surveillance/monitoring were more frequent in P2 as compared to P1, respectively 12/34 vs. 37/59 (P=0.02) and 14/34 vs. 39/59 (P=0.03). A titration of level III analgesics treatment was high in both periods and remained stable. However, a trend toward an increase of systematic pain evaluation over time was observed (81.6% in P2 vs. 64.5% in P1; P=0.085). CONCLUSION: A significant number of newborns affected by various pathologies undergo neonatal palliative care. Despite their recent introduction in neonatal medicine, palliative care practices have changed significantly. These practices are mostly in compliance with the "patients' rights and end-of-life care" act promulgated in France in 2005.

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.

[Does the nasopharyngeal samples virological analysis reflect the lower respiratory tract infection in children population? A PCR multiplex study]. / L'analyse virologique des aspirations nasopharyngées reflète-t-elle l'infection respiratoire basse chez l'enfant ? Étude en PCR multiplex.

Respiratory tract infections are frequent in young children and are related to viruses in most cases. Multiplex Polymerase chain reaction (PCR) based techniques are valuable tools for describing the spectrum of such viruses. The goal of this study was to assess the correlation of virus detection in samples obtained by nasopharyngeal aspiration and by bronchoalveolar lavage. Both samples were taken at the same time in 30 children with lower respiratory tract infection, and were analyzed by multiplex virus PCR (xTAG™ RVP). A strong correlation has been found (P = 0.0002) and the most frequently isolated virus was the entero-rhinovirus spp. These results strengthen the opinion that viruses colonize both the upper and lower respiratory tract. Nasopharyngeal samples should be sufficient to the diagnosis of lower respiratory tract viral infection in immuno-competent children.

Extrusion-induced changes to the chemical profile and viscosity generating properties of citrus fiber.

Each of 8 variants in extrusion conditions was applied to a commercially available citrus fiber. Extrusion under conditions where the specific mechanical energy (SME) exceeded 400 kJ·kg(-1) was able to solubilize up to 30% of the fibers. Where the SME was ∼200 kJ·kg(-1) the degree of fiber solubilization was between 8 and 12%. All extruded fibers showed a loss of water-retaining capacity compared to the reference fiber, and this was attributed to the disruption of the integrated cell wall structure during the extrusion process. Nevertheless, within the 8 extruded variants there was a wide range of viscosity generating capacity which depended on the level of SME to which the fibers were subjected. The SME also had a pronounced effect on the nature of the solubilized fibers in terms of both their monosaccharide composition and their molecular weight profile. Both pectic and hemicellulosic polysaccharides were solubilized. It is concluded that extrusion has promise as a physical process for manipulating both the technological functionality and the health promoting properties of dietary fibers.

On the cause of controlling affinity to small molecules of imprinted polymeric membranes prepared by noncovalent approach: a computational and experimental investigation.

Imprinting technique applied to membrane preparation via phase inversion methods yields membranes with enhanced affinity toward target molecules. In the imprinted membranes prepared by noncovalent approach hydrogen bond and electrostatic interactions can play a crucial role in determining the performance of these membranes. In this work, quantum mechanical calculations and experiments were performed to understand the physical-chemical causes of the affinity increase in imprinted polymeric membranes to 4,4'-methylendianiline (MDA), dissolved in an organic solvent. An ad hoc synthesized copolymer of acrylonitrile and acrylic acid was used to prepare the membranes. The calculated binding energies show that the hydrogen bonds and electrostatic interactions among polymeric chains are comparable to the strength of the same interactions occurring between polymer and MDA. Using this result and correlated experimental data, this work concluded that one of the causes responsible for the increased affinity of the imprinted membranes is the augmented availability of free carboxylic groups in the nanocavities of the membranes. However, along with this reason, the membrane pore sizes must evermore be taken into account. The knowledge acquired in this study helps us to better understand the mechanisms of molecular recognition and hence to optimize the design of new imprinted membranes.

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.

[Tracheomalacia (TM) or bronchomalacia (BM) in children: conservative or invasive therapy]. / Trachéobronchomalacie de l'enfant : de l'abstention à l'interventionnel.

Tracheomalacia (TM) or bronchomalacia (BM) refers to softness or weakness of the trachea or the bronchi. Its management is not evidenced-based. Conservative therapy is preferred in milder cases, since the outcome is usually favourable within the first 2 years of life. The clinical utility of non-specific treatments (anti-inflammatory agents, bronchodilators, antibiotics, physiotherapy) has not been proven by clinical trials. Treatment of symptomatic cases should be discussed on an individual basis. Airway surgery should be avoided, and non-invasive ventilation may be proposed as a temporary measure. In case of very severe cases, aortopexy, trachostomy or stent placement are the preferred treatments. Regular respiratory monitoring until remission is mandatory.

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).