Secukinumab and acitretin as a combination therapy for three clinical forms of severe psoriasis in multi‐drug refractory patients: A case series of high efficacy and safety profile

Secukinumab, the first monoclonal antibody that inhibits interleukin‐17A, has been shown to have rapid and long‐lasting efficacy in the treatment of moderate‐to‐severe psoriasis. However, there are still difficult‐to‐treat cases in which even dose‐escalation fails to provide a clinical response. In such cases, combining secukinumab with a conventional systemic agent may be a rational approach. Although methotrexate is most commonly preferred, acitretin may also be considered a good alternative, with its lower hepatotoxic potential. Data are limited regarding the use of combination therapy of secukinumab and acitretin for psoriasis. We herein present three patients with chronic plaque, generalized pustular and erythrodermic psoriasis, respectively, accompanied by multiple comorbidities, in whom skin clearance could not be achieved with several conventional and biologic therapies (including escalated dose regimens of secukinumab in two patients). Alternatively, we used a combination of secukinumab with low‐dose acitretin, which resulted in a complete or almost complete skin clearance in all patients, with no adverse events or increased toxicity. Based on our real‐life clinical experience with those patients, acitretin seems an effective and safe option to be used in combination with secukinumab. Even in patients who are refractory to multiple drugs including escalated doses of secukinumab, the addition of low‐dose acitretin may be helpful in achieving treatment goals, decreasing the need for switching to another biologic therapy.     

A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue

The syndrome of McCune-Albright syndrome (MAS) is clasically defined as a triad presentation with the findings of polyostotic fibrous dysplasia, café-au-lait spots, and sexual precocity. However, not all patients present with complete symptoms. A 52-year-old man was diagnosed as having a variant of McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, acromegaly due to pituitary tumor and subclinical hyperthyroidism due to toxic multinodular goiter. Sexual precocity and café-au-lait spots were not noted. Acromegaly was confirmed by laboratory examination (IGF-1, glucose suppression test and TRH stimulation test). Long acting somatostatin analogue was used as treatment. Although the pituitary tumor could not be removed due to technical problems, mass lesions on the cranium were removed subtotally. Histopathological evaluation demonstrated that the lesion complied with fibrous dysplasia. Genomic DNAs were isolated from the craniofacial bones and peripheral leucocytes of the patient. After amplifying the related regions, Gs alpha (Gs alpha) gene was analysed by automatic DNA sequence analysis. An activating mutation of the Gs alpha gene (Arg 201 Cys) was found in the genomic DNA isolated from the bone tissue of the patient, but not in the genomic DNA isolated from the blood. We described a case of MAS associated with Gs alpha mutation in the bone tissue, presenting with polyostotic fibrous dysplasia, subclinical hyperthyroidism and acromegaly.     

Association of macroscopic gut inflammation with disease activity, functional status and quality of life in ankylosing spondylitis

The aim of this cross-sectional study was to evaluate the frequency of intestinal inflammation and its association with disease activity, functional status and quality of life in patients with ankylosing spondylitis (AS). A total of 25 patients with AS had undergone ileocolonoscopy and concomitant histological study. Clinical and demographical parameters, BASDAI, BASFI, and SF-36 scores were compared between patients with and without macroscopic gut inflammation (MGI). Colonoscopic study revealed MGI in 9 patients and macroscopically normal gut mucosa in 16 patients. On histological examination, of 25 patients 20 had gut inflammation, mostly in ileum. BASDAI score was higher (P < 0.05), SF-36 pain and physical scores, and chest expansion measurement were lower (P = 0.00, P = 0.01, P = 0.01), duration of morning stiffness was longer (P = 0.01) in patients with MGI. Serum C-reactive protein, erytrocyte sedimentation rate levels were similar between groups (P > 0.05). There is high prevalence of histological gut inflammation in AS patients. More active disease should suggest gut inflammation in AS patients.     

Relation between intracranial volume and the surface area of the foramen magnum

Several investigators have estimated the intracranial volume (ICV) in the past which indirectly reflects the brain volume. Most of these studies have been made on the dry skulls using linear dimensions, packing methods or occasionally radiological methods. It is also reported that the etiology of cerebellar tonsillar herniation is closely related to the size of the foramen magnum (FM). In the present study the ICVs have been estimated in 28 dry skulls using filling water method and the surface area of FMs were measured planimetry method. The estimated mean ICV was 1,311 +/- 133 cm. Surface area of FM was 760 +/- 144 mm. Antero-posterior and lateral direct roentgenograms of the skulls were also taken and the width, height and length (WHL) of the skull were measured by means of the cephalometry on radiograms. The relationship between the ICV, WHL and surface area of FM were analyzed statistically. The ICV, WHL and surface area of FM was correlated well (r = 0.271, P < 0.005; r = 0.265, P < 0.005, respectively) and a regression formula was proposed. Our results showed that skulls with larger ICV and WHL have larger FM surface area. We also suggested a regression formula that could be used to predict the surface area of FM regarding to the ICV and WHL values. In the next step, we took roentgenograms of skulls and obtain ICV measuring the width, length and height of skulls by means of cephalometry and investigate the relation between the findings of cephalometry and surface area of FM. The cephalometry could apply on living subjects and, thereby, our findings could provide some data to evaluate the etiology of Arnold Chiari malformation and achondroplasia for living subjects.     

Synthesis and Biological Evaluation of Novel Bromophenol Derivatives as Carbonic Anhydrase Inhibitors

Here, we provide an alternative synthesis of the natural bromophenol 3,4‐dibromo‐5‐(2,3‐dibromo‐4,5‐dihydroxybenzyl)‐6‐(ethoxymethyl)benzene‐1,2‐diol ( 3 ) and the first synthesis of (4,5‐dihydroxy‐2‐methylphenyl)(3,4‐dihydroxyphenyl)methanone ( 18 ) and its brominated derivatives 19 – 21 . The compounds were characterized and tested against the two most studied members of the pH regulatory enzyme family, carbonic anhydrase (CA). The inhibitory potencies of the novel compounds and two natural bromophenols 2 , 3 were analyzed at the human isoforms hCA I and hCA II as targets and the K_I values were calculated. The K_I values of the novel compounds were measured in the range of 13.7–32.7 µM for the hCA I isozyme and 0.65–1.26 µM for the hCA II isozyme. The structurally related compound 14 was also tested in order to understand the structure–activity relationship, and the clinically used sulfonamide acetazolamide (AZA) was tested for comparison reasons. All of the compounds exhibited competitive inhibition with 4‐nitrophenylacetate as substrate. The compounds showed strong inhibitory activity against hCA I, being more effective as compared to the clinically used AZA (K_I: 36.2 µM), but rather less activity against hCA II.     

Relationship between Structural and Functional Assessment of the Visual System in Mildly Disabled Relapsing-Remitting Multiple Sclerosis Patients

Studies that explored the anterior visual pathway in the patients with multiple sclerosis (MS) have demonstrated contradictory results about the correlation between structural and functional status of optic nerve and retina. We aimed to investigate the functional and structural findings in our cohort of mildly disabled relapsing-remitting MS patients. A total of 134 eyes (80 eyes of the patients with MS and 54 eyes of the control group) were investigated. Eyes of MS patients were divided into two groups—as eyes with history of optic neuritis (ON group) and without history of optic neuritis (NON group). Ophthalmological investigation including visual evoked potentials, standard automated perimetry, and optical coherence tomography were performed for all participants. Retinal and macular thicknesses were significantly decreased in ON and NON groups compared with controls. Also, visual evoked potential latencies and visual field loss were worse in the both MS groups compared with control group. We did not find any correlation between visual evoked potentials and retinal or macular thickness values but visual field parameters were correlated between retinal and macular layer loss in the NON group. According to our results and some previous studies, although both functional and structural changes were detected in patients with MS, functional status markers do not always show parallelism (or synchrony) with structural changes, especially in eyes with history of optic neuritis.     

Volumetric evaluation of the relations among the cerebrum,cerebellum and brain stem in young subjects: a combination of stereology and magnetic resonance imaging

The Cavalieri estimator using a point grid is used to estimate the volume of three-dimensional structures based on two-dimensional slices of the object. The size of the components of intracranial neural structures should have proportional relations among them. The volume fraction approach of stereological methods provides information about volumetric relations of the components of structures. The purpose of our study is to estimate the volume and volume fraction data related to the cerebrum, cerebellum and brain stem. In this study, volume of the total brain, cerebrum, cerebellum and brain stem were estimated in 24 young Turkish volunteers (12 males and 12 females) who are free of any neurological symptoms and signs. The volume and volume fraction of the total brain, cerebrum, cerebellum and brain stem were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods. The mean (+/-SD) total brain, cerebrum and cerebellum volumes were 1,202.05 +/- 103.51, 1,143.65 +/- 106.25 cm(3) in males and females, 1,060.0 +/- 94.6, 1,008.9 +/- 104.3 cm(3 )in males and females, 117.75 +/- 10.7, 111.83 +/- 8.0 cm(3) in males and females, respectively. The mean brain stem volumes were 24.3 +/- 2.89, 22.9 +/- 4.49 cm(3) in males and females, respectively. Our results revealed that female subjects have less cerebral, cerebellar and brain stem volumes compared to males, although there was no statistically significant difference between genders (P > 0.05). The volume ratio of the cerebrum to total brain volume (TBV), cerebellum to TBV and brain stem to TBV were 88.16 and 88.13% in males and females, 9.8 and 9.8% in males and females, 2.03 and 2.03% in males and females, respectively. The volume ratio of the cerebellum to cerebrum, brain stem to cerebrum and brain stem to cerebellum were 11.12 and 11.16% in males and females, 2.30 and 2.31% in males and females, 20.7 and 20.6% in males and females, respectively. The difference between the genders was not statistically significant (P > 0.05). Our results revealed that the volumetric composition of the cerebrum, cerebellum and brain stem does not show sexual dimorphism.     

Combined transbronchial needle aspiration and PET/CT for mediastinal staging of lung cancer

In this study, we aimed to evaluate the performance of transbronchial needle aspiration (TBNA) combined with positron emission tomography/computed tomography (PET/CT) for the staging of lung cancer. Twenty-five patients having lymphadenopathies greater than 1 cm on thorax CT and maximum standardized uptake value (SUVmax) ≥ 2.5 on PET/CT were included in this prospective study performed between March 2006 and March 2008. Forty-three lymphnode stations were sampled by using TBNA. Surgical histology, as confirmed by mediastinoscopy, was accepted as the "gold standard". The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of combined TBNA and PET/CT for correct lymph node staging were 67%, 100%, 100%, 76% and 84%; respectively. The initial clinical staging was downstaged after TBNA in 13/19 (69%) patients with adequate TBNA samples, whereas staging was correct in 17/19 (89%) patients assessed by combined TBNA and PET/CT. Staging was completed by TBNA, without mediastinoscopy, in 6/25 (24%) patients. Among the clinical factors that were assessed, only the PET SUVmax was associated with positive TBNA results [odds ratio (OR) 1.27, 95% CI 1.004-1.61, p= 0.046]. A PET SUVmax ≥ 5 was eleven times more likely in patients with positive TBNA results [OR 10.68, 95% CI 1.91-59.62, p< 0.01]. In conclusion, the combination of TBNA with PET/CT increased the sensitivity of TBNA. Combined TBNA and PET/CT may also allow adequate mediastinal staging of lung cancer in most patients with enlarged lymph nodes, and reduce the need for mediastinoscopy. The SUVmax cut off point for a positive TBNA result was ≥ 5.     

Temperament and character personality profile in relation to suicide attempts in patients with schizophrenia

Introduction

Schizophrenia is associated with a significant risk of suicide, and suicide still remains one of the main causes of death in schizophrenic patients. Beside classic risk factors for suicidality, temperament and character traits have been researched and considered as risk factors for suicidal behavior in recent years.

Method

Subjects were 94 patients with schizophrenia who were under treatment. All patients were in a stable phase of the illness. Patients with lifetime suicide attempt (n = 46) and without suicidal attempt (n = 48) were compared with each other in terms of temperament and character traits by using the Temperament and Character Inventory.

Results

Harm avoidance and persistence scores were higher in suicidal schizophrenic patients compared with nonsuicidal schizophrenic patients. The scores of self-directedness and cooperativeness were lower in suicidal schizophrenic patients compared with nonsuicidal schizophrenic patients. These 4 variables remained significant predictors of lifetime suicidal attempts in a logistic regression model.

Conclusion

To the best of our knowledge, the present study is the first that specifically compares schizophrenic patients with and without suicidal behavior by the Cloninger temperament and character model. Our data indicate that schizophrenic patients will show a greater risk for suicide according to certain personality configurations. However, to establish causal relationships between personality and suicidality in schizophrenia, longitudinal studies are warranted within a multifactorial interactive framework of biologic and clinical variables.