The value of ultrasonography in detecting early arthropathic changes and contribution to the clinical approach in patients of hemophilia.

PURPOSE\AIM: Hemophilia affects the blood clotting process, is a genetic disease characterized by recurrent bleeding. The hemophilia early arthropathy detection with ultrasound (HEAD-US) procedure and scoring method were designed for the detection of early changes in affected joints of patients. In this article, it was aimed to detect early arthropathic changes in the joints of hemophilia patients with the HEAD US scoring system and to investigate its clinical contribution. It was aimed to investigate the effectiveness of HEAD-US scoring in showing early joint damage in subclinical hemophilia cases and its contribution to treatment. METHODS: The present study included 50 hemophilia patients who were admitted to Departments of Pediatric and Adult Hematology for routine follow-up. During routine follow-up controls, patients were scored by physical examination and HJHS 2.1 and by ultrasonography and HEAD US. Statistical tests were used to analyze joint health status and the results of US examination in the patient group. RESULTS: A total of 294 joints (elbow n = 100, knee n = 94, ankle n = 100) were evaluated by ultrasonography. The mean HJHS and HEAD-US scores of the patients were 14.94 ± 15.18 and 15.6 ± 12.6, respectively. CONCLUSIONS: HEAD-US is accepted to be more sensitive than HJHS in detecting early signs of arthropathy. Detection of early abnormalities by ultrasonography will enable the development of individualized treatment protocols and to the prevention of arthropathy development.

Coating of PLA-nanoparticles with cyclic, arginine-rich cell penetrating peptides enables oral delivery of liraglutide.

Until today, the oral delivery of peptide drugs is hampered due to their instability in the gastrointestinal tract and low mucosal penetration. To overcome these hurdles, PLA (polylactide acid)-nanoparticles were coated with a cyclic, polyarginine-rich, cell penetrating peptide (cyclic R9-CPP). These surface-modified nanoparticles showed a size and polydispersity index comparable to standard PLA-nanoparticles. The zeta potential showed a significant increase indicating successful CPP-coupling to the surface of the nanoparticles. Cryo-EM micrographs confirmed the appropriate size and morphology of the modified nanoparticles. A high encapsulation efficiency of liraglutide could be achieved. In vitro tests using Caco-2 cells showed high viability indicating the tolerability of this novel formulation. A strongly enhanced mucosal binding and penetration was demonstrated by a Caco-2 binding and uptake assay. In Wistar rats, the novel nanoparticles showed a substantial, 4.5-fold increase in the oral bioavailability of liraglutide revealing great potential for the oral delivery of peptide drugs.

Idiopathic acute massive pulmonary embolism in childhood.

Acute pulmonary embolism (PE) is an uncommon clinical condition in childhood. We hereby present a case report of a 10-year-old child who presented to the emergency department with an acute massive PE. He was transferred by ambulance to our emergency department for dyspnea and perioral cyanosis. His parents denied any previous history of illness or familial disease. Arterial blood gas analysis, electrocardiography, and clinical symptoms and signs collectively raised a suspicion of a probable PE. A contrast-enhanced pulmonary computed tomography scan revealed a massive thrombus in the distal part of the right pulmonary artery with no contrast passage into upper, middle, and lower lobar arteries. Upon ascertaining, the diagnosis of PE, intravenous saline infusion, 3 L/min oxygen through nasal route, and subcutaneous enoxaparin 0.4 cc was administered promptly. As our hospital lacked a pediatric intensive care unit and a further need for administration of pharmacological thrombolysis was anticipated, we transferred the patient to a tertiary care center. PE should always be kept in mind as a differential diagnosis in emergency departments even in pediatric patients.

Prevalence of several herpesviruses and human papillomavirus in acute apical abscesses.

AIM: To investigate and compare the radiographic size of acute apical abscess lesions for the presence of Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6) and human papillomaviruses (HPV) DNA by means of the real-time polymerase chain reaction (PCR) method. METHODOLOGY: According to the radiographic size of acute apical abscess lesions, 11 lesions were categorized as large (≥5 mm) and 10 lesions as small (<5 mm). DNA extracts from purulent exudate aspirates of 21 cases of acute apical abscess and 10 control samples were evaluated for the presence of viral loads using real-time PCR methods following the kit protocols recommended by the manufacturers. Statistical analysis was performed using chi-squared test with Yates's correction and Fisher's exact test. RESULTS: HCMV DNA was detected in 27% of large and in 10% of small abscess lesions. EBV was identified in 18% of large and in 10% of small abscess lesions. HPV and HHV-6 DNA were found in 9% of large abscess lesions. None of the small abscess lesions contained HPV or HHV-6 DNA. Viral coinfections were found in two samples as the pair of HCMV/EBV and HCMV/HHV-6 from large abscess lesions. No significant associations were found between any of the target viruses and size of periapical lesions. As for the healthy pulps used as noninflamed controls, no control specimens contained viral DNA. CONCLUSIONS: HCMV was the most frequent herpesvirus amongst the target viruses in samples from both large and small apical abscess lesions. In large lesions, EBV and HHV-6 tended to occur in coinfection with HCMV. Additional studies are required to elucidate the role of herpesviruses in the pathogenesis of periapical abscess.

Temporomandibular disorders in patients with rheumatoid arthritis: A clinical study.

OBJECTIVES: The aim of this study is to evaluate the prevalence and type of temporomandibular disorders (TMD) in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Fifty-four patients having RA treatment at Cukurova University in Rheumatology Clinic were enrolled to the study. Demographic and rheumatologic data were recorded. The patients were examined in Dental Faculty by using Research Diagnostic Criteria/TMD (RDC/TMD) axis I and answered RDC/TMD axis II Biobehavioral Questionnaire. Data were evaluated according instructions for scoring and assessment of RDC/TMD. Mann-Whitney test was performed to compare continuous variables between two groups and Kruskal-Wallis test was performed to compare continuous variables for more than two groups. RESULTS: Although their activity situations were 55.6% active and 44.4% inactive, the distribution of treatment modality was 31.5% for anti-tumor necrosis factor-α (TNF-α) and 68.5% for disease-modifying antirheumatic drugs (DMARD). The distribution of temporomandibular joint (TMJ) involvement was; 9.3% with no involvement, 7.4% with joint involvement, 64.8% with muscular involvement, 18.5% with both muscular and joint involvement. Rheumatologic functional scores were (0) 3.7%, (1) 50%, (2) 38.9%, (3) 7.4%. Patients' chronic pain was graded from 0 to 4 and the distribution was 3.7%, 24.1%, 20.4%, 31.5% and 20.4%, respectively. The mean duration of RA for anti-TNF-α (11.47 ± 7.67) was significantly higher compared with DMARD (7.09 ± 5.21) P = 0.040. CONCLUSION: There was a high prevalence of TMD in RA patients, and muscular involvement was the highest among the TMJ involvements. Thus, this study supports TMJ examination should be encouraged in the rheumatology settings.

Endoscopically operated 15 ventral skull-base dermoid and epidermoid cysts: Outcomes of a case series and technical note.

BACKGROUND: Epidermoid and dermoid tumors in the sellar region are rare. These cystic lesions are a surgical challenge, as the thin capsule adheres firmly to nearby structures. A case series of 15 patients is presented. METHODS: The patients were operated on in our clinic between April 2009 and November 2021. The endoscopic transnasal approach (ETA) was used. Lesions were located in the ventral skull base. In addition, the literature was reviewed to compare clinical features and outcomes of ventral skull-base epidermoid/dermoid tumors operated on via ETA. RESULTS: In our series, removal of cystic contents and tumor capsule (gross total resection: GTR) was achieved in 3 patients (20%). GTR was not possible for the others, because of adhesions to vital structures. Near total resection (NTR) was achieved in 11 patients (73.4%), and subtotal resection (STR) in 1 (6.6%). At a mean follow-up of 55±26.27 months, there were no cases of recurrence requiring surgery. CONCLUSION: Our series demonstrates that ETA is suitable for resection of epidermoid and dermoid cysts in the ventral skull base. GTR cannot always be the absolute clinical aim, because of inherent risks. In patients with expected long-term survival, the aggressiveness of surgery should be weighed on an individual risk/benefit basis.

Susac Syndrome: Clinical characteristics, diagnostic findings and treatment in 19 cases.

Susac's Syndrome (SS), which was first described in 1979, is a rare and presumably autoimmune disorder characterized by encephalopathy, hearing loss, and visual disturbance resulting from branch retinal artery occlusion (BRAO). This study reports 19 SS patients' clinical characteristics, MRI features, CSF analysis, treatment strategies and outcomes. At initial presentation, only three of 19 patients demonstrated the complete clinical triad. Clinic presentation varied from isolated hemiparesis to the full triad (encephalopathy, hearing loss and visual disturbances). Corpus callosum (CC) involvement was noted in the MRI of 18 patients (97%) and BRAO was detected in 17 (95%) patients. All patients were treated with intravenous methylprednisolone after the initial assessment. This case series is presented to emphasize the differences in clinical presentation of SS and the importance of MRI and FFA in diagnosis.

A late-onset Epstein-Barr virus-related lymphoma completely remitted in a child with renal allograft.

Lymphomas are frequently encountered malignancies following renal transplantations. A 17-year-old boy was found to have lymphoma 1.5 years after a the first cadaveric transplantation performed due to reflux nephropathy. Polyclonal anti-thymocyte globulin (induction) with prednisolone (PRD), azathioprine (AZT), and tacrolimus (Tac) regimen had been given after the transplantation. A hypoechoic mass (25 mm) was detected in the upper pole of the allograft by renal Doppler ultrasound performed due to graft dysfunction with a high basal serum creatinine (Cr) (2.2 mg/dL). The renal biopsy revealed a large B-cell lymphoma with CD20 staining in the medulla. The serum displayed a positive Epstein-Barr virus (EBV), immunoglobulin (Ig)G, negative IgM with negative DNA-polymerase chain reaction. However, the biopsy was positive for EBV-LMA. The viral status at the time of transplant was unknown. After withdrawing AZT and Tac therapies, a chemoimmunotherapeutic regimen consisting of PRD, cyclophosphamide, and anti-CD20 monoclonal antibody was administered twice. The patient excreted the necrosed tumor particles over a 2-month interval with hydronephrotic colic attacks. The basal Cr improved at 6 months (to 1.4 mg/dL). A low dose of Tac (0.5 mg/d) was added to PRD. The patient has remained in complete remission for 2.5 years with a well-functioning renal allograft. Although this case was a late-onset lymphoma, the patient displayed a picture like excreting stones from the allograft and remitted completely. This case illustrates that localization of a tumor may play a more important role than the elapsed time from transplant in the diagnosis in EBV-related posttransplant lymphoproliferative disease.

Up- and down-regulation of granulocyte/macrophage-colony stimulating factor activity in murine skin increase susceptibility to skin carcinogenesis by independent mechanisms.

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in tumorigenesis is complex. On the one hand, GM-CSF can promote tumor cell growth, survival, and even metastasis. On the other hand, it can stimulate tumor cell rejection. In skin, it is early expressed after topic application of tumor-promoting agents and therefore may be responsible for changes that correlate with skin tumor promotion (e.g., epidermal hyperproliferation and inflammation). To analyze GM-CSF function in skin tumorigenesis, we generated transgenic mice epidermally overexpressing either GM-CSF or a GM-CSF antagonist. Both types of transgenic mice exhibited significantly increased numbers of benign tumors in a two-step skin carcinogenesis experiment using 7',12'-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-CSF displayed a significantly elevated carcinoma burden following a single-step carcinogenesis protocol consisting of tumor initiation only. Therefore, endogenous promotion is responsible for elevated tumor development in GM-CSF-overexpressing mice. In antagonist transgenic animals, an increased tumorigenicity of modified B16 tumor cells after cutaneous transplantation as compared with nontransgenic or GM-CSF transgenic mice was observed. Thus, the antitumor activity leading to the repression of tumor cell growth in control mice is GM-CSF dependent and is compromised in mice expressing the antagonist. We suggest that both, up-regulation and down-regulation of GM-CSF activity in skin, increase the incidence and growth of tumors via two independent mechanisms: endogenous tumor promotion in the case of increased GM-CSF activity and compromised tumor cell rejection in the case of decreased GM-CSF activity.

Age and gender related changes in bronchial tree: a morphometric study with multidedector CT.

OBJECTIVE: The aims of this study are the identification of differences in the diameter, length, area and branching angles of the trachea and bronchi with gender and age, and the identification of trachea types by using MDCT images. PATIENTS AND METHODS: The thoracic MDCT images of 253 patients (0-74 years old, 142 male and 111 female) were evaluated. Tracheal diameter, tracheal cross-sectional area, diameter and length of bronchi, and several angles of the bronchial tree [e.g. subcarinal angles (SCA), interbronchial angles (IBA)] were measured. RESULTS: Average anteroposterior and transverse diameter of the trachea in adult patients were measured as 15.8 ± 2.9 mm and 17.5 ± 3.7 mm respectively. Average tracheal cross-sectional areas in adult patients were calculated as 160.7 ± 41.3 mm² in females and as 275.7 ± 57.3 mm² in males. Four types of trachea were identified as circular (68% in adults, 73% in children), oval (13%, 15%), rectangular (11%, 5%) and horseshoe shaped (8%, 7%). The average right and left SCA were calculated as 34.5º ± 8.1º and 38.1º ± 8.9º respectively. The average right and left IBA were calculated as 32.4º ± 7.7º and 35.2º ± 8.1º respectively. CONCLUSIONS: The findings of this study may be helpful during bronchoscopy and tube and stent application procedures. MDCT seems to be a convenient technique for the evaluation of the bronchial tree.

The designer cytokine hyper-IL-6 mediates growth inhibition and GM-CSF-dependent rejection of B16 melanoma cells.

The low immunogenic B16 melanoma cell line was transfected with a mammalian expression vector containing the complementary DNA for a sIL-6R/IL-6 fusion protein, termed Hyper-IL-6 (H-IL-6), which was shown to have biological activities at 100-1000-fold lower concentrations than IL-6 in combination with sIL-6R. The secreted p84 glycoprotein was detected in the supernatant of transfected cells and was fully active on BAF3/gp130 cells, which respond to IL-6/sIL-6R but not to IL-6 alone. Administration of recombinant H-IL-6 to C57BL/6 mice resulted in a prolonged acute phase protein gene expression indicating long systemic persistence of the fusion protein. Transfected B16 cells (B16/H-IL6 cells) showed morphological alterations in combination with a dramatic growth inhibition in vitro. Subcutaneous injection in C57BL/6 mice resulted in an almost complete rejection of B16/H-IL6 cells. This effect was partially abolished in FVB/BL/6 mice transgenic for a GM-CSF receptor antagonist, indicating a GM-CSF-dependent rejection of H-IL-6 transfected B16 cells. These results demonstrate that the anti-tumor effect of cytokines like IL-6 which are secreted by transfected melanoma cells at least in part depends on GM-CSF activity.

The status of iron absorption in older patients with iron deficiency anemia.

OBJECTIVE: The aim of this study is to evaluate the iron absorption status by using the oral iron absorption test (OIAT) in older patients with iron deficiency anemia (IDA) in comparison with younger patients. PATIENTS AND METHODS: This is a cross-sectional study including 100 patients with iron deficiency anemia. Patients were divided in two groups; group 1 who is 65 and older and group 2 who is younger than 65. OIAT in which a fasting serum iron level is compared with a second serum iron level obtained three hours following oral ingestion of iron sulfate was performed. An increase in serum iron of at least 100 mcg/dL indicates that oral iron absorption is adequate. The Independent-Samples t-test was used to show the statistical difference between the means of two groups. RESULTS: There were 100 patients in the study; 69 of them have completed the study. The means of the oral iron absorption test results of the groups was compared with an independent t-test, which showed that the mean of group 1 was lower than group 2 and this was statistically significant (p = 0.001). The mean of OIAT results was 86.1 and 163.5 in group 1 and 2 respectively. CONCLUSIONS: In our knowledge, the present study is among the first that shows the status of iron absorption objectively by using OIAT in older patients. Our study shows iron absorption is decreased in older patients with IDA in comparison with younger patients. In the light of this finding; OIAT should be offered before initiating treatment in older patients when IDA is diagnosed and intravenous iron treatment should be considered more on the base of results.

Intrarenal Doppler findings of upstream renal artery stenosis: a preliminary report.

To diagnose 60% or greater diameter-reducing stenosis of the renal artery (RAS), color Doppler imaging (CDI) and angiography were performed on 44 hypertensive and 16 normotensive cases. In this prospective, double-blind study we evaluated the related intrarenal waveform changes. In both the right and left kidneys of normotensive cases, at the level of interlobar arteries, the results indicated a symmetric finding in peak systolic/end diastolic velocities (S/D), pulsatility index (PI) and resistive index (RI) ratios. The results in the stenotic kidneys among the hypertensive group indicated that index values were significantly lower in the stenotic kidneys than those of the contralateral kidneys, the kidneys of control and nonstenotic hypertensive cases. To quantify this observation we suggest "perfusion indexes," which require more studies on a greater number of hypertensive cases. It was concluded that measuring the index values of intrarenal arterial waveforms is easier and more accessible in diagnosing RAS than obtaining those of the main renal artery.

Case report: computed tomography findings in lipoid proteinosis: report of two cases.

Lipoid proteinosis (Urbach-Wiethe disease (Urbach, E and Wiethe, C, Lipoidosis cutis mucosae, Virchows Arch. Patholog. Anat., 273, 285-319 (1929)) is a rare generalized disease with autosomal recessive inheritance. It most often involves the skin and mucosal membranes of the aerodigestive tract; but also involves the central nervous system, lung, lymph nodes and striated muscles. We present the computed tomography findings in the cranium and larynx of two siblings with lipoid proteinosis.

Smoking and Behçet's disease.

It has recently been claimed that some of the symptoms in patients with Behçet's disease (BD) can be activated after the patient has stopped smoking. In this study we investigated the effect of smoking on the symptoms of Behçet's disease. Fifty asymptomatic current smokers (CS) who promised to stop smoking (group 1) and 60 current non-smokers (NS) (group 2) (21 of them ex-smokers) with BD were examined at the beginning and a week later for the presence of symptoms of BD. Forty-seven of the 50 CS completed the study. Oral aphthous ulcers were observed in 31 (65.9%) of them at the end of the study period. Besides oral aphthous lesions, genital ulcers were detected in two and erythema nodosum in two other patients. Only 15 (25%) group 2 patients developed oral aphthous ulcers during the study period. The difference between the frequencies of oral aphthous lesions in these groups was significant (p=0.0002). We concluded that cessation of cigarette smoking can activate the mucocutaneous symptoms, especially oral aphthous lesions, in patients with BD.

Is "zero-hour" biopsy of the transplanted kidney risky?

"Zero-hour" renal allograft biopsy provides valuable diagnostic information for comparison to subsequent kidney material. However, the invasive nature of the biopsy procedure tends to limit its widespread use in many centers. We undertook this retrospective study to examine the rate and clinical importance of complications in our series of patients routinely undergoing zero-hour biopsies performed between 1994 and 2001. Two hundred thirty-six zero-hour biopsies included only one sample performed with a 14G needle from lower posterior part of kidney by using a manual tru-cut technique. Doppler ultrasonography was performed after first 5 days. An average of 34 +/- 19 glomeruli were obtained in the biopsies. The biopsy specimens were adequate for diagnosis in 77% of the procedures. Ten (4%) patients experienced complications of intraparenchymal arteriovenous fistula (n = 4), which regressed spontaneously; perirenal hematoma (n = 4); intraparenchymal hematoma (n = 2); and a minimal perirenal collection (n = 41). We conclude that zero-hour biopsy is a safe diagnostic method. The rate of complications is low, as well as generally mild and self-limiting.

Intima media thickness as a predictor of atherosclerosis in renal transplantation.

It has been reported that an increase in carotid artery intima-media thickness (IMT), a sign of early atherosclerosis, has a predictive value for future cardiovascular (CV) events. There are limited data about IMT measurements in renal transplant patients who display a high rate of CV mortality. In this study carotid artery IMT was measured by high resolution B-mode ultrasonography in 102 randomly selected RT patients to assess the relationship between IMT and CV disease and risk factors. A positive correlation was found between IMT and age, triglyceride level, and hematocrit. IMT was significantly higher among patients who were diabetic (0.68 +/- 0.27 vs 0.50 +/- 0.2) or had CV disease (0.88 +/- 0.28 vs 0.53 +/- 0.21). An increased IMT was associated with a longer duration of ESRD, higher lipid level, lower serum albumin, and presence of previous CMV disease. CV disease was more frequent among patients with increased IMT. Considering its relation to CV risk factors, it is concluded that the measurement of carotid artery IMT is an easy, reliable and non-invasive method to be used to assess atherosclerotic disease in renal transplant patients.

Comparison of tacrolimus and cyclosporin in renal transplantation by the protocol biopsies.

Acute and chronic lesion scores on renal allograft protocol biopsies may predict long-term graft function. The aim of this study was to compare the effects of tacrolimus (Tac) and cyclosporine microemulsion (CsA) based immunosuppressive protocols using protocol biopsies from well-functioning renal allografts. 35 consecutive renal transplant patients were randomized to Tac (n: 17) versus CsA (n: 18) treatment arms. Patient age and sex, donor type and age, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Treatment protocol consisted of prednisolone, azathioprine and Tac or CsA. Biopsies performed on the third, sixth and twelfth months were blindly evaluated by the same pathologist. The incidences of acute rejection (AR) episodes among CsA vs Tac groups were 33% vs 29%, respectively (NS). The Creatinine level was lower in Tac than CsA, although it was not significant (Table). Subclinical AR and subclinical chronic allograft nephropathy were detected on protocol biopsies in 3 (2 CsA, 1 Tac) and 12 (7 CsA, 5 Tac) patients, respectively. Acute lesion score at the third month PBx was significantly lower in the Tac group (p < 0.05). Chronic lesion scores in all biopsies were lower in the Tac group, although not significantly. The protocol biopsy findings suggest that graft injury may be less pronounced among the Tac group.

Renal vascular resistance in progressive systemic sclerosis: evaluation with duplex Doppler ultrasound.

The study was planned to evaluate renal vascular resistance by means of duplex Doppler ultrasonography in patients with progressive systemic sclerosis (PSS) with or without signs of renal involvement. Twenty-two female patients with PSS (mean age 38.5 +/- 17.3 years) and 20 age-matched (mean age 36.7 +/- 7.2 years) female healthy controls participated to the study. Doppler indices of renal vascular resistance--resistive index (RI), pulsative index (PI), and systolic-to-diastolic flow velocities ratio (S/D ratio)--were determined on main renal artery and interlobar artery. RI, PI and S/D ratio were found to be increased in PSS patients with signs of renal involvement as compared to those without renal manifestations and healthy controls (p<0.0001 for all groups). Doppler indices of renal vascular resistance were closely related to the duration of the disease, age, and plasma renin activity. Doppler ultrasound is a useful and informative technique in the monitoring of PSS patients with renal involvement.