High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency.

Pituitary hormone deficiency occurs in ∼1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated individuals with hypopituitarism that were predicted to affect a minor isoform, POU1F1 beta, which can act as a transcriptional repressor. These variants retain repressor activity, but they shift splicing to favor the expression of the beta isoform, resulting in dominant-negative loss of function. Using a high-throughput splicing reporter assay, we tested 1,070 single-nucleotide variants in POU1F1. We identified 96 splice-disruptive variants, including 14 synonymous variants. In separate cohorts, we found two additional synonymous variants nominated by this screen that co-segregate with hypopituitarism. This study underlines the importance of evaluating the impact of variants on splicing and provides a catalog for interpretation of variants of unknown significance in POU1F1.

Analysis of select esthetic nasal parameters in virtually planned orthognathic patients.

PURPOSE: Bony changes after orthognathic surgery are always followed by changes of the overlying soft tissues. Therefore, morphologic changes of the nose may be expected after procedures involving the maxilla. The purpose of this study was to evaluate the changes in the nasal region due to orthognathic surgery using computed tomography (CT) images of virtually planned patients. METHODS: 35 patients who underwent Le Fort I osteotomy, with or without bilateral sagittal split osteotomy, were included. 3D measurements on preoperative and postoperative images were performed and analyzed. RESULTS: The results revealed that aesthetically acceptable results can be achieved by orthognathic surgery alone. CONCLUSIONS: According to the results of this study, it can be concluded that it is best to reserve decisions on rhinoplasty to the post-orthognathic period.

Cytomegalovirus reactivation in ulcerative colitis patients: Early indicators.

Background: The association of. c: ytomegalovirus (CMV) infection with ulcerative colitis (UC) still remains a controversial topic for the clinicians. Aim: In this study, we aimed to elucidate the CMV infection related parameters in the exacerbation of UC. Material and Methods: In this study, 812 UC patients who have admitted to our institution between June 2008 and November 2020 were analyzed retrospectively. CMV infection was diagnosed by the detection of CMV DNA with polymerase chain reaction (PCR) in tissue biopsies with presence of clinical colitis symptoms. CMV negative UC patient group was defined as UC activation group with negative PCR results. Result: A total of 153 patients met the inclusion criteria during the study period, with a median age of 41.8 years. CMV PCR positivity had been detected in tissue biopsy in 43 (28.1%) UC patients. CMV-positive patients had a statistically significant higher frequency of steroid resistance, treatment with azathioprine, longer disease duration, longer remission, and hospitalization day. The mean C-reactive protein (CRP) level, platelet to lymphocyte ratio (PLR) were higher, and mean albumin level was lower in CMV positive patients, with statistically significance. Also, colectomy and anti-tumor necrosis factor-α (TNF-α) therapy were more frequent in CMV-reactivated group in long-term follow-up. In a multivariable model, steroid resistance, treatment with azathioprine, long disease duration, low albumin value was independently associated with colonic CMV infection. Conclusion: Steroid resistance, treatment with azathioprine, long disease duration, low albumin levels were significant risk factors for CMV colitis, among patients with UC activation.

Intrusion of a Liquid Droplet into a Powder under Gravity.

Intrusion of a liquid droplet into a hexagonal close-packed array of spheres under gravity is investigated using analytical methods and volume-of-fluid simulations. Four regimes of ultimate fluid behavior are identified: (A) no liquid imbibition into the bed, (B) trapping of liquid high in the bed, (C) liquid descending to the bottom of the bed, and (D) liquid spreading around the surface of all particles. These regimes are mapped based on the contact angle and Bond number of the system. Many aspects of the dynamics and ultimate liquid behavior are captured using a simplified model of a mass of liquid moving under gravity in a vertical capillary of undulating cross-sectional area. This simplified model is used to form momentum transport equations with four forms of nondimensional time, which are shown to collapse the simulation data with different fluid parameters in different regimes.

Genome-wide association study and meta-analysis of intraocular pressure.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10(-8)). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.

Xiphoid syndrome: an uncommon occupational disorder.

We report a case of a 45-year-old man, complaining of swelling and pain in his epigastric region for the last 3 years. According to his medical history, he had undergone various investigations and treatments for gastro-oesophageal reflux, without relief. He had had a history of chronic repeated microtraumas to his sternum during 9 years of working as a carpenter, as a result of placing wood against his anterior chest wall and pushing the former into a plank cutting machine. On examination, a tender swelling was palpable as an immobile, hard mass showing minimal protrusion under the skin on the xiphoid process. He was diagnosed as having xiphoid syndrome. We prescribed anti-inflammatory medication and advised him to avoid pressure on his anterior chest wall, especially on the sternum, while cutting wood. At follow-up, the symptoms were relieved. Xiphoid syndrome may be seen in people performing hard physical work who incur sustained pressure or friction on their anterior chest wall. The case emphasizes the importance of the occupational history as well as clinical and radiological investigation of unusual conditions as mentioned above.

The use of HbA1c as an aid in the diagnosis of gestational diabetes mellitus.

The ability of HbA1c was evaluated in the diagnosis of gestational diabetes mellitus (GDM) and for the implications of its use in clinical practice. A total of 339 pregnant women with an estimated gestational age of 24-28 weeks were evaluated for GDM using an oral glucose tolerance test (OGTT) based on International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. A ROC curve was drawn to determine the sensitivity and specificity of HbA1c in detecting GDM. An HbA1c cut-off value of ≥ 5.2% had sensitivity of 64.15% and specificity of 67.48% in diagnosing GDM, and a positive predictive value of 26.77%. Using two cut-offs in the 'rule-in and rule-out' algorithm, 94.4% of the GDM cases would have been detected but 33% (43 of the 130) women would had been misclassified. HbA1c is not suitable to use alone for the diagnosis of GDM and is not useful in decreasing the need for OGT testing.

Bilateral sagittal split ramus osteotomy using a conventional osteotome-hammer and a magnetic mallet device: an in vitro comparison.

OBJECTIVE: The conventional chisel osteotome technique (CCOT) and the magnetic mallet osteotome technique (MMOT) with a newly manufactured custom osteotome tip for the magnetic mallet device (MMD) were compared to determine whether magneto-dynamic osteotomies are as reliable for orthognathic surgery as the conventional method. MATERIALS AND METHODS: A custom osteotome tip compatible with a magnetic mallet device was manufactured. Thirty-two fresh 1-year-old sheep hemi-mandibles were chosen for osteotomy procedures to achieve the most human-like results. Sagittal split ramus osteotomies were performed, and lingual fracture pattern (LFP), basis split pattern (BSS), duration of sagittal split osteotomy, and alveolar inferior nerve injury were investigated macroscopically. RESULTS: Six of the defined fracture schemes were observed out of the 27 lingual split patterns. After LFP and BSS evaluation, the unfavorable fracture counts for MMOT and CCOT are 3 and 4, respectively. The macroscopic nerve damage assessment for both groups is 2 for MMOT and 1 for CCOT. Although the average durations are similar in both groups, the difference between MMOT samples is closer. None above showed a significant difference. CONCLUSIONS: MMOT was evaluated as a reliable alternative to CCOT in bilateral sagittal split ramus osteotomy based on the lingual and basis split patterns, duration, and nerve damage findings.

Evaluation of inter-maxillary fixation techniques for multi-piece Le Fort I osteotomies using finite element analysis.

OBJECTIVE: A strong postoperative occlusal relationship is essential for the long-term stability of the jaw relations post orthognathic surgery. In multi-piece Le Fort I osteotomy, obtaining a satisfactory inter-maxillary fixation (IMF) of the mobilized segments in the correct position and according to the preoperative plan is difficult. Herein, we aimed to evaluate three different IMF techniques (tooth-supported, bone-supported, or hybrid IMF) using finite element analysis (FEA) of the occlusal surfaces of four models: three multi-piece (lateral incisor-canine, central incisor-central incisor, and canine-first premolar) and a single one-piece Le Fort I osteotomy scenario. MATERIALS AND METHODS: Three different IMF techniques were applied separately to three different multi-piece models and a single one-piece Le Fort I model designed using related software. Simulation brought the lower and upper jaw models to the planned occlusion. Each model's occlusal force was applied to determine their distributions under 100 N, 300 N, and 800 N loads. Forces on the maxilla and mandible during fixation, the effect of these forces on the force distribution in the occlusion, and the accumulated stresses in these regions were determined with Algor Fempro and Rhinoceros software to determine the ideal fixation method. Data obtained were interpreted and evaluated according to the advantages and disadvantages of the actual surgical scenario. RESULTS: In all four models studied, the hybrid IMF technique was found to be the ideal IMF technique, followed by the teeth- and bone-supported IMF techniques. CONCLUSIONS: FEA allows the manipulation of single parameters, which clinical methods cannot obtain, thereby allowing each to be examined separately. Further clinical trials are required to validate these findings.

Efficacy of a modified sequential therapy including bismuth subcitrate as first-line therapy to eradicate Helicobacter pylori in a Turkish population.

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are not satisfactory. Sequential therapy is an alternative method to overcome this problem. OBJECTIVES: The aim of this study was to assess efficacy of a modified sequential therapy with the addition of a bismuth preparation, as first-line treatment in the eradication of H. pylori infection. MATERIALS AND METHODS: One hundred and forty-two H. pylori-positive patients were included in the study. Patients were given a 14-day sequential therapy program consisting of pantoprazole, 40 mg (b.i.d. for 14 days); colloidal bismuth subcitrate, 300 mg 4 (two tablets before breakfast and dinner, for 14 days); amoxicillin, 1 g (b.i.d.for the first 7 days); tetracycline, 500 mg (q.i.d. for the second 7 days); and metronidazole, 500 mg (t.i.d. for the second 7 days). Eradication was tested by urea breath test (UBT) 6 weeks after completion of treatment. RESULTS: Of the 142 patients included, 131 completed the study. "Per-protocol" and "intention-to-treat" analyses revealed high eradication rates in this group (92.0-95% CI, 87.2-96.8%, and 81.0-95% CI, 74.5-87.4%, respectively). There was no relation to sex and age with this modified sequential therapy. Compliance was satisfactory (11 patients - four women and seven men were unavailable for follow-up), and side effects were minimal (six patients had to stop treatment - metronidazole-related facial swelling and numbness on the face and hands in two patients; tetracycline-related fever and epigastric pain and nausea and vomiting in two patients; and amoxicillin-related diarrhea and vaginal discharge in two patients). These side effects were reversible and resolved after the cessation of the related medication. CONCLUSIONS: This 14-day modified sequential treatment, including bismuth, achieves a significantly high eradication rates in patients with H. pylori infection, with five satisfactory patient compliance and minor side effects.

Plasma ghrelin levels in patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an auto-inflammatory disorder characterized by febrile attacks. Increased acute-phase reactants are characteristic during febrile attacks. Ghrelin is a natural G-protein that decreases secretion of pro-inflammatory cytokines and acts as anti-inflammatory agent. The aim of this study was to investigate whether there is any change in ghrelin levels and whether increases in ghrelin levels can be used as a marker in these patients. SUBJECTS AND METHODS: Thirty-seven male patients and 30 healthy men as a control group were included in the study. Blood samples were obtained for ghrelin measurements both before the attacks (pre-attack period; ghrelin 1 group) and during the attacks (ghrelin 2 group). Samples were kept at -80°C until the analysis was conducted and plasma ghrelin levels were measured using an immune-sorbent assay method. RESULTS: Mean ghrelin levels measured during the attacks were significantly higher (11.01 ± 4.78 pg/ml) as compared to pre-attack levels (5.78 ± 2.17 pg/ml; p < 0.001). Similarly, mean ghrelin levels measured in FMF patients during an attack were significantly different from that of the control group (6.57 ± 4.13 pg/ml; p < 0.001). CONCLUSIONS: In this study, high ghrelin levels were measured during attacks in FMF patients. This finding is in line with previous results regarding the fact that inflammatory response arising during an FMF attack is an acute inflammatory event. Our findings suggest that ghrelin levels measured during FMF attacks could be used as a biochemical indicator for the FMF attack in FMF patients and that it could be used for support of the diagnosis of the disease.

Genome-wide association study in a rat model of temperament identifies multiple loci for exploratory locomotion and anxiety-like traits.

Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability to these disorders. To model these heritable tendencies, we selectively bred rats for high and low exploration in a novel environment [bred High Responders (bHR) vs. Low Responders (bLR)]. To identify genes underlying the response to selection, we phenotyped and genotyped 538 rats from an F2 cross between bHR and bLR. Several behavioral traits show high heritability, including the selection trait: exploratory locomotion (EL) in a novel environment. There were significant phenotypic and genetic correlations between tests that capture facets of EL and anxiety. There were also correlations with Pavlovian conditioned approach (PavCA) behavior despite the lower heritability of that trait. Ten significant and conditionally independent loci for six behavioral traits were identified. Five of the six traits reflect different facets of EL that were captured by three behavioral tests. Distance traveled measures from the open field and the elevated plus maze map onto different loci, thus may represent different aspects of novelty-induced locomotor activity. The sixth behavioral trait, number of fecal boli, is the only anxiety-related trait mapping to a significant locus on chromosome 18 within which the Pik3c3 gene is located. There were no significant loci for PavCA. We identified a missense variant in the Plekhf1 gene on the chromosome 1:95 Mb QTL and Fancf and Gas2 as potential candidate genes that may drive the chromosome 1:107 Mb QTL for EL traits. The identification of a locomotor activity-related QTL on chromosome 7 encompassing the Pkhd1l1 and Trhr genes is consistent with our previous finding of these genes being differentially expressed in the hippocampus of bHR vs. bLR rats. The strong heritability coupled with identification of several loci associated with exploratory locomotion and emotionality provide compelling support for this selectively bred rat model in discovering relatively large effect causal variants tied to elements of internalizing and externalizing behaviors inherent to psychiatric and substance use disorders.

Modified high-level Le Fort I advancement without malar augmentation: assessment of effect on midfacial aesthetics.

The 'beauty arch', an aesthetic feature of the midface, is a double-S-shaped curve that extends downward from the lateral canthus. This retrospective study evaluated whether modified high Le Fort I advancement (combined with impaction or down-grafting) without malar augmentation can approximate a patient's 'ideal' beauty arch (IBA). Pre- and postoperative profile (natural head position) photographs for 36 patients with midfacial hypoplasia were aligned digitally. For each individual, standardized methods were used to identify landmarks and draw the preoperative real beauty arch (RBA), postoperative RBA, and IBA. Distances from a defined landmark to each arch were measured and means were compared. The mean advancement range was 4.2 ± 2.2 mm, and the mean pre- and postoperative RBA distances were significantly different (138.7 ± 24.1 vs 145.0 ± 25.8 pixels, respectively; P = 0.0001). In the impaction and down-grafting subgroups, there was no significant correlation between amount of maxillary movement and the difference between pre- and postoperative RBA distances (P > 0.05 for both). The postoperative RBA was satisfactorily close to the IBA in 35 cases (97.2%); one patient required later augmentation. The findings suggest that modified high Le Fort I advancement surgery without malar augmentation provides satisfactory malar projection for most patients with maxillary hypoplasia.

The origin of SARS-CoV-2 in Istanbul: Sequencing findings from the epicenter of the pandemic in Turkey.

OBJECTIVE: Turkey is one of the latest countries that COVID-19 disease was reported, with the first case on March 11, 2020, and since then, Istanbul became the epicenter of the pandemic in Turkey. Here, we reveal sequences of the virus isolated from three different patients with various clinical presentations. METHODS: Nasopharyngeal swab specimens of the patients were tested positive for the COVID-19 by qRT-PCR. Viral RNA extraction was performed from the same swab samples. Amplicon based libraries were prepared and sequenced using the Illumina NextSeq platform. Raw sequencing data were processed for variant calling and generating near-complete genome sequences. All three genomes were evaluated and compared with other worldwide isolates. RESULTS: The patients showed various clinics (an asymptomatic patient, patient with mild disease, and with severe pulmonary infiltration). Amplicon-based next-generation sequencing approach successfully applied to generate near-complete genomes with an average depth of 2.616. All three viral genomes carried the D614G variant (G clade according to GISAID classification) with implications for the origin of a spread first through China to Europe then to Istanbul. CONCLUSION: Here, we report the viral genomes circulating in Istanbul for the first time. Further sequencing of the virus isolates may enable us to understand variations in disease presentation and association with viral factors if there is any. In addition, the sequencing of more viral genomes will delineate the spread of disease and will guide and ease the necessary measures taken to stem the spread of the novel coronavirus.

Comparison of computed tomography histogram analysis and chemical-shift magnetic resonance imaging for adrenal mass characterization.

BACKGROUND: Computed tomography (CT) histogram analysis and chemical-shift magnetic resonance imaging (MRI) are currently used modalities for adrenal mass characterization. However, it is not yet clear which modality can be regarded as most sensitive in terms of adrenal mass characterization. PURPOSE: To prospectively compare CT histogram analysis and chemical-shift MRI in the characterization of adrenal masses. MATERIAL AND METHODS: Between May 2007 and November 2008, 93 patients (45 males, 48 females; mean age 56.7 years, range 22-85 years) with 109 adrenal masses prospectively underwent both unenhanced CT and chemical-shift MRI examinations. These masses consisted of 67 adenomas and 42 metastases. Histogram analysis was applied with a circular region of interest (ROI) that recorded mean attenuation, total number of pixels, number of negative pixels, and the percentage of negative pixels on unenhanced CT images for each adrenal mass. In the CT histogram analysis, a 10% negative pixel threshold for unenhanced CT was calculated. In chemical-shift MRI, signal intensity drop between in-phase and opposed-phase images was quantitatively calculated so that adrenal-to-spleen chemical-shift ratios and adrenal signal intensity indexes were determined for each of the adrenal masses. A mass was regarded as an adenoma if it contained more than 10% negative pixels by CT histogram analysis, showed an adrenal-to-spleen chemical-shift ratio of less than 0.71, and had an adrenal signal intensity index of more than 16.5% by chemical-shift MRI. The results were compared to reveal which method was most sensitive in the diagnosis of adrenal masses and whether or not a correlation exists between these two modalities. Final diagnoses were based on imaging follow-up of minimum 6 months, biopsy, surgery, and adrenal washout study. RESULTS: On unenhanced CT examinations, all of the 67 adenomas and 21 out of 42 metastases exhibited negative pixels. None of the metastases showed more than 10% negative pixels on CT histogram analysis. An increase in the percentage of negative pixels correlated well with a decrease in the mean CT attenuation. CT histogram analysis using a 10% negative pixel threshold gave a 91% sensitivity and 100% specificity for the diagnosis of an adenoma. On chemical-shift MRI, for an adrenal-to-spleen chemical-shift ratio of less than 0.71, a 97% sensitivity and 100% specificity were achieved, while a 97% sensitivity and 93% specificity were obtained for an adrenal signal intensity index of more than 16.5% for adenoma diagnosis. CONCLUSION: CT histogram analysis method using a 10% negative pixel threshold on unenhanced CT had a good sensitivity and perfect specificity for the differentiation of adrenal adenomas from non-adenomas. In spite of the good results obtained with the CT histogram analysis method, chemical-shift MRI using adrenal-to-spleen chemical-shift ratio and adrenal signal intensity index formulas had a higher sensitivity and could help in the characterization of adrenal masses appearing indeterminate by CT histogram analysis.

Comparison of three different second-line quadruple therapies including bismuth subcitrate in Turkish patients with non-ulcer dyspepsia who failed to eradicate Helicobacter pylori with a 14-day standard first-line therapy.

BACKGROUND AND AIM: Many studies have reported poor results with standard first-line treatment for Helicobacter pylori. Second-line regimens that may overcome bacterial resistance can minimize side-effects and optimize compliance. The aim of this study was to evaluate the efficacy of proton pump inhibitor (PPI) and bismuth subcitrate-based quadruple therapy, after failure of a PPI plus clarithromycin and amoxicillin as first-line therapy. METHODS: Patients who failed to eradicate the infection after initial therapy were randomly separated into three groups. The first group received lansoprazole, bismuth subcitrate, metronidazole and amoxicillin (LBMA); in the second group metronidazole was replaced by tetracycline (LBTA); and the third group was given metronidazole and tetracycline in addition to same doses of lansoprazole and bismuth subcitrate (LBMT). RESULTS: In the LBMA group, the eradication rate was 74.7% and was significantly related to sex, with no relationship to age. In the LBTA group the eradication rate was 81.5% with similar rates in males and females. No relation to sex or age was observed. In the LBMT group the eradication rate was 82.1% with no difference between women and men and it was not related to age, either. Eradication rates in study groups were similar (P > 0.05). CONCLUSION: A-14-day regimen of lansoprazole, bismuth subcitrate and antibiotic pairs, tetracycline-amoxicillin and tetracycline-metronidazole, is an effective quadruple therapy after one failed course of standard triple therapy. The evaluation of tolerability of and compliance with quadruple therapy needs further studies.

Effect of Helicobacter pylori infection and eradication therapy on interleukin-6 levels in patients with Familial Mediterranean Fever.

It is being questioned if Helicobacter pylori infection, which causes a chronic inflammatory response, can increase the frequency and severity of attacks in patients with Familial Mediterranean Fever (FMF) and if the impact of inflammatory response can be diminished by eradication of the infection. To evaluate if there is difference in interleukin (IL)-6 levels of H. pylori-positive and -negative patients both before and during FMF attacks; if there is a change in IL-6 levels following successful eradication treatment; and if MEFV gene mutations have an effect on IL-6 levels. IL-6 levels were evaluated in 47 FMF patients before and during FMF attacks. Genetic testing to determine M694V, M694I, E148Q, V726V, M680I mutations was also performed in all patients. IL-6 levels were also determined after successful eradication of the infection in H. pylori-positive patients. IL-6 levels were compared in H. pylori-positive and -negative patients, and before and after eradication treatment in patients who cleared the infection. Number of patients in tested mutation groups was not enough to compare IL-6 levels in these groups. Thirty-four patients (73.9%) were H. pylori-positive. Before FMF attack there was no statistically significant difference in IL-6 levels of H. pylori-positive and -negative groups. IL-6 levels were significantly higher in both groups during the attacks than before the attacks (p < 0.05). There was a statistically significant decline in IL-6 levels both before and during FMF attacks, following eradication therapy in patients who cleared the infection (p < 0.05). In patients with homozygous M694V mutation, IL-6 levels before and during the FMF attacks were not significantly different in H. pylori-positive and -negative groups, despite a much lower level found in H. pylori-negative group (p > 0.05). Comparisons were not performed in other mutation groups because of small number of patients in each group. C-reactive protein (CRP) and fibrinogen levels were not significantly different between the groups (p > 0.05). We believe that the observation of IL-6 levels are lower both before and during FMF attacks both in H. pylori-negative patients and in patients who cleared the infection after eradication therapy is very important in the determination of the role of eradication of H. pylori on decreasing the frequency and severity of FMF attacks. As for today, the correlation between H. pylori infection and FMF seems unlikely; however, studies evaluating the interaction of cytokines in both diseases and their relations and roles will be needed to reach better conclusions.

Urinary glycosaminoglycan levels as a marker of renal amyloidosis in patients with familial Mediterranean fever.

INTRODUCTION AND AIM: Familial Mediterranean Fever (FMF) is an autosomal recessive disease with a defect in the pyrine gene and is manifested with short attacks of inflammatory serositis, fever, and erysipelas-like skin lesions. Secondary amyloidosis is the most serious complication of the disease, in which extracellular deposits of amyloid (an amorphous and eosinophilic protein) are seen in tissues. Glycosaminoglycans are mucopolysaccharide molecules that take place in amyloid deposits with fibrillar links to amyloid. They form glycoproteins by linking to proteins, and their free forms are excreted in the urine in the form of polysaccharides. The aims of this study were to evaluate if the urinary levels of glycosaminoglycans have a predictive value in the diagnosis of amyloidosis secondary to FMF and if these levels are affected by treatment with colchicine. MATERIALS AND METHODS: The study included 55 volunteer patients (age range: 18-36 years) with FMF (15 with amyloidosis) of the same socio-economic circumstances without other concomitant inflammatory, malignant, or chronic diseases, along with 20 healthy subjects as control. Urinary glycosaminoglycan levels were determined twice, once when the patients were on medication and once after they have stopped treatment for two weeks. RESULTS: Initial mean urinary GAG levels were significantly lower in amyloidosis patients. Mean urinary GAG levels determined two weeks after the cessation of colchicine was also significantly lower than controls in both amyloidosis and non-amyloidosis FMF patients. Likewise, in patients with a disease duration longer than ten years, urinary GAG levels were also lower than those with a disease duration of less than three years. CONCLUSION: Urinary GAG level can have a predictive value for amyloidosis in patients with FMF, and it can also be used as a non-invasive marker for screening the effects of colchicine on fibrillogenesis as well as for the follow-up of the patients.