Comparative immunohistochemical analysis of inflammatory cytokines in distinct subtypes of Sweet syndrome.

Background: A dysregulated immune response has been implicated in Sweet syndrome (SS) pathogenesis; however, cytokine profiles across different conditions associated with SS - including adult-onset immunodeficiency (AOID) due to anti-interferon (IFN)-γ autoantibodies - remain unknown. Objective: To investigate alterations in inflammatory cytokines in skin lesions of distinct subtypes of SS. Methods: Skin biopsies were collected from 42 AOID- and 52 non-AOID-associated SS patients and 18 healthy controls. The comparative immunohistochemical study was conducted using monoclonal antibodies against interleukin (IL)-1ß, IL-6, IL-17, IFN-γ, and tumor necrosis factor-α on paraffin-embedded sections. The quantitative percentage positivity and intensity were calculated using computer-based image analysis. Results: The results showed stronger and more diffuse dermal immunoreactivity for IFN-γ and IL-17 in the AOID-associated (p < 0.001 and p < 0.001, respectively) and non-AOID-associated SS (p < 0.001 and p < 0.001, respectively) groups. However, no significant differences in the levels of these two cytokines were observed between the AOID- and non-AOID-associated SS groups. Increased expression of IFN-γ together with IL-17 was also noted in almost all subtypes among non-AOID-associated SS. Conclusions: These results demonstrate that IFN-γ and IL-17 are implicated in immunopathology of all SS subtypes, including AOID-associated SS, despite the presence of anti-IFN-γ autoantibodies.

Treatment modalities of ALK-positive relapsed/refractory inflammatory myofibroblastic tumor of the brain and lungs in 7-year-old girl: case-based reviews.

PURPOSE: Inflammatory myofibroblastic tumor (IMT) belongs to mesenchymal neoplasm of intermediate malignancy in WHO classification. Primary CNS disease or CNS metastases (CNS-IMT) occur in minority. We describe a case of relapsed/refractory IMT of lungs with multiple brain metastases in young child who achieved long-term complete response after alectinib. This systematic review also summarizes treatment modalities and outcome of children and adolescent with CNS-IMT. METHODS: PRISMA 2020 guideline was applied to select an article from PubMed, Scopus, and Cochrane databases without time limits. This review focused on children and adolescent 0-24 years of age with CNS-IMT or inflammatory pseudotumor (CNS-IPT). The clinical characteristics and treatment outcome were explored. RESULTS: A total of 51 patients in 49 publications were identified. Median age of patients with CNS-IMT/IPT was 15-year-old and 60.8% were male. The most common location of tumor was cerebral cortex (54.9%). Complete resection of CNS-IMT/IPT was performed in 27 cases with 100% complete response and 18.5% recurrence. Nearly half of patients who received partial resection without adjuvant therapy experienced progressive disease, while the contrast group totally achieved partial response. Overall responses in 7 patients treating with ALK inhibitors were 57.1% durable complete response and 42.9% transient partial response. CONCLUSION: First-line treatment of CNS-IMT/IPT is complete resection. Patients who received partial tumor removal might have benefit from adjuvant therapy. ALK inhibitors reveal a promising result in unresectable CNS-IMT/IPT. Our case has shown a success in treating relapsed and refractory CNS-IMT as well as the primary site using 2nd-generation ALK inhibitor.

Double Motor Nerve Transfer for All Finger Flexion in Cervical Spinal Cord Injury: An Anatomical Study and a Clinical Report.

PURPOSE: To explore the feasibility of restoring all finger flexion after a cervical spinal cord injury. METHODS: Double nerve transfer was conducted in 22 cadaver upper extremities. Donor nerves were the brachialis branch of the musculocutaneous nerve and the extensor carpi radialis brevis (ECRB) branches of the radial nerve. Recipient nerves were the anterior interosseous nerve (AIN) and the flexor digitorum profundus (FDP) branch of ulnar nerve (ulnar-FDP). Nerve transfers were evaluated on 3 parameters: surgical feasibility, donor-to-recipient axon count ratio, and distance from the coaptation site to the muscle entry of recipient nerve. A complete C6 spinal cord injury reconstruction was accomplished in a patient using a double nerve transfer of ECRB to ulnar-FDP and brachialis to AIN. RESULTS: In the cadaver study, nerve transfers from ECRB to AIN, brachialis to AIN, and ECRB to ulnar-FDP were all feasible. The transfer from the brachialis to ulnar-FDP was not possible. Mean myelinated axon counts of AIN, brachialis, ulnar-FDP, and ECRB were 2,903 ± 1049, 1,497 ± 606, 753 ± 364, and 567 ± 175, respectively. The donor-to-recipient axon count ratios of ECRB to AIN, brachialis to AIN, and ECRB to ulnar-FDP were 0.24 ± 0.15, 0.55 ± 0.38, and 0.98 ± 0.60, respectively. The distance from coaptation of the ECRB to the ulnar-FDP muscle entry was shorter than for the other nerve transfers (54 ± 14.29 mm). At 18 months, there was restoration of flexion in all fingers and functional improvement from double nerve transfer of the brachialis to the AIN and the ECRB to the ulnar-FDP. CONCLUSIONS: Restoration of all finger flexion may be feasible by the ECRB to ulnar-FDP and brachialis to AIN double nerve transfer. CLINICAL RELEVANCE: Double nerve transfer can be used in C6-C7 spinal cord injury and patients with lower arm-type brachial plexus injury who have no finger flexion but have good brachialis and ECRB.

Intracranial fetus-in-fetu with numerous fully developed organs.

Fetus in fetu (FIF) is an extremely rare anomaly featuring a monozygotic, diamniotic, parasitic twin, enclosed within its host twin. It is characterized by the presence of vertebrae and well-developed organs in a fetiform mass. Only 18 cases of intracranial FIF have been published. Of them, only five cases were prenatally detected. This study prenatally demonstrated triplet FIFs at 31 weeks within amniotic-like sac in the fetal skull, consisting of multiple well-defined organs. The FIF attached to the host twin via body stalk containing a single main feeding artery and vein, representing umbilical vessels. Surgical removal was performed at the age of two months. Pathological examination showed the triplet FIF, consisting of numerous well-developed organs (musculocutaneous-skeletal, nervous, respiratory, gastrointestinal systems etc.), with soft tissue/skin coverings, but no vertebral body was seen. Molecular genetic analysis revealed identical genetic mapping among the three FIFs and the host. This case provides strong evidence against Willis's hypothesis but supports Spencer's theory of abnormal twinning.

Clinical Course, Outcomes and Complications of Thai Pediatric Pure Type versus Mixed Type Lupus Membranous Nephritis.

Background: Due to the relative infrequency of lupus membranous nephritis (LMN) compared to other types of lupus nephritis (LN) in pediatric patients, the current literature on pediatric LMN is limited. The knowledge regarding clinical manifestations, outcomes and infectious complications are mainly based on studies in the adult population. Similar to disease expression in SLE, the renal manifestations of LMN are affected by environmental factors and vary among racial and ethnic groups. Objective: To describing clinical features, common infectious complications, and outcomes of pediatric-onset LMN in Thailand and the correlation between pure and mixed types of LMN classified by renal pathology. Material and Method: This was a retrospective analysis of 40 patients with LMN as seen in the Pediatric Nephrology Clinic, Maharaj Nakorn Chiang Mai from January, 2003 to December, 2012. Patients were categorized into pure and mixed types of LMN the comparisons of the clinical course, results of treatment and infectious complications between the two types had been analyzed and recorded data for 2 years. Results: Kidney biopsy was performed. Of the 40 patients with LMN, 50% were diagnosed as mixed-type LMN. The clinical symptoms presented including rash, hypertension, edema, serositis and arthritis were found at 57.7%, 45%, 40%, 25% and 25% respectively. All of the patients were treated with an immunosuppressive drug such as: Cyclophosphamide, Azathioprine, Cyclosporine or Mycophenolate mofetil, together with systemic steroids. During the two years follow up, every patient had normal GFR. Twenty nine patients (72.5%) had renal remission in proteinuria with complete remission in 7 patients (17.5%) and partial remission in 22 patients (55%). An average time from the onset to remission was 12 months. GFR and proteinuria were not significant difference between the two groups after treatment. The infections found in patients who received cyclophosphamide include herpes infection, salmonellosis, lung abscess, nocardiosis, giardia intestinalis and cerebral cysticercosis. Furthermore, steroid side effect was avascular necrosis of the hip joint. Conclusion: The mixed-type LMN patients had a higher blood pressure, higher BUN and positive LE cell than those of the pure-type LMN patients. Hypertension at initial presentation can be a predictor of proliferative lesion in renal pathology. However, a proliferative lesion accompanied with LMN does not affect renal outcomes. With similar renal outcomes, the immunosuppressive with low adverse effects may be considered as a preferable treatment.

The Correlation of Muscle Biopsy Scores with the Clinical Variables in Idiopathic Inflammatory Myopathies.

OBJECTIVES: To compare the muscle pathology findings among subgroups of idiopathic inflammatory myopathies (IIM) patients, and to determine the correlations of muscle biopsy scores with muscle power and creatine kinase (CK). METHODS: The medical records of IIM patients consisting of the demographic data, clinical parameters and laboratory conducted were retrospectively reviewed. Their initial muscle biopsies were reviewed, and four domains were scored: inflammation, vascular, muscle, and connective tissue. RESULTS: Ninety-five IIM patients (28 patients with idiopathic polymyositis (PM) 9 idiopathic dermatomyositis (DM), 5 DM associated with malignancy, and 53 PM/DM associated with connective tissue disease) with median (IQR: Q1, Q3) disease duration of 1.2 (0.5, 3.1) months were included. No significant differences in initial muscle pathology findings and muscle pathology score among the subgroups were found. Muscle degeneration and endomysial fibrosis scores were negatively correlated with muscle power (r=-0.23 and-0.24, respectively, p<0.05) and positively correlated with CK (r=0.27 and 0.39, respectively, p<0.01). No significant correlation was detected either inflammation or vasculitis scores with muscle power and CK levels. CONCLUSION: In this study, muscle biopsy cannot be used to differentiate among subgroups of IIM patients. In addition, we found only modest correlation of muscle biopsy scores with muscle power and CK. Further study is necessary to confirm our findings.

Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRß expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain.

Epstein-Barr virus-associated smooth muscle tumor of the tonsil.

Smooth muscle tumors of the tonsil are rare. Recently, the occurrence of Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) has been increasingly recognized in immunocompromised patients, mainly post-transplantation and AIDS patients. The clinicopathologic features of EBV-SMT are different from conventional smooth muscle tumors. To the best of our knowledge, EBV-SMT involving the tonsil in an AIDS patient has not been reported. A 27-year-old man presented with a 2.2cm right tonsillar mass six months after AIDS diagnosis. The tumor was composed of a cellular proliferation of oval to spindle-shaped cells with mitotic count up to 10 in 10 high-power fields. The diagnosis of EBV-SMT was confirmed by in situ hybridization for EBV-encoded RNA (EBER) transcripts. Synchronous lesions were also detected in the liver and peritoneum by an abdominal computed tomographic scan. EBV-SMT should be included in the differential diagnoses of a mesenchymal tumor in immunocompromised patients, and in the differential diagnoses of a smooth muscle tumor occurring in uncommon sites including the tonsil.

Effect of Kaempferia parviflora Wall. ex. Baker on sexual activity of male rats and its toxicity.

Kaempferia parviflora Wall. Ex. Baker (Krachaidum) has long been used among Thai men for sexual enhancement. The aim of this study was to determine the effect of K. parviflora ethanolic extract on the sexual behavior of male rats and its toxicity. The experiment was divided into three groups of rats given K. parviflora extract at doses of 60, 120, and 240 mg/kg BW for 60 days, whilst a control group received distilled water at 1 ml/day per oral. The results showed that all groups of male rats had significantly higher courtship behavior during the first 10-minute period of observation than in the 2nd and 3rd 10-minute periods, except those receiving the highest dose of K. parviflora. They revealed the same amount of courtship behavior throughout a whole 30-minute period, which was significantly lower than the control group. There was no significant difference between treated and control groups in other sexual behaviors; mount frequency (MF), intromission frequency (IF), mount latency (ML), or intromission latency (IL). Toxicological study revealed no significant difference of hemoglobin, WBC or differential cell count. All dosages had no effect on kidney and liver function, according to the normal values of blood urea nitrogen (BUN), creatinine (Crea), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Nevertheless, the histopathological study showed a morphological change in the liver. It was concluded that K. parviflora extract at 240 mg/kg BW reduced the time in the first 10 mintues of rat courtship behavior and the use of high and chronic doses of K. parviflora in humans should be considered inadvisable.