Early intervention service needs of mothers with a child diagnosed with autism spectrum disorder in Turkey: A qualitative study.

BACKGROUND: Early intervention services play a crucial role in the prevention and management of Autism Spectrum Disorder (ASD). With the increasing prevalence of ASD, understanding the specific needs of mothers and their children is essential for the development of effective interventions and support systems. METHODS: This interview study examines the early intervention service needs of Turkish mothers with children aged 2-6 who have been diagnosed with ASD. Semi-structured in-depth interviews were conducted with nine mothers. Thematic analysis was carried out following the guidance and six steps procedures described by Braun and Clarke. FINDINGS: The study's findings reveal six distinct themes that encompass the needs expressed by the participating mothers: 1) psychological support needs, 2) social support needs, 3) financial support needs, 4) strengthening the family, 5) government-based enhancement, and 6) the need for social awareness. DISCUSSION: The findings underscore the significance of comprehensive early intervention services tailored to address the needs of mothers. The stressors associated with the impact of ASD on families are highlighted, aligning with Guralnick's framework. The findings emphasize the need for holistic intervention programs and stress the importance of collaborative relationships among parents, educators, and service providers. APPLICATION TO PRACTICE: The practical implications of this study benefit healthcare professionals, policymakers, educators, and stakeholders. The emphasis lies in aligning interventions with the ASD needs of both mothers and children, ultimately aiding in the development of effective policies and the enhancement of the quality of care for individuals with ASD in Turkey.

Stellate ganglion blockade with percutaneous bupivacaine injection followed with surgical denervation in the management of electrical storm.

Electrical storm is a life-threatening medical emergency that requires immediate diagnosis and treatment. It can remain a clinical challenge despite anti-arrhythmic drugs and catheter ablation therapies. Autonomic modulation techniques have gained increased recognition in the treatment of refractory electrical storm cases. In our case, we present a patient with recurrent ventricular tachycardia/fibrillation episodes one week after a myocardial infarction. Patient's arrhythmia was refractory to antiarrhythmic drugs and hemodynamical status was unstable, thus catheter ablation under temporary mechanical circulatory support was the initial strategy. Ventricular fibrillation episodes relapsed 48 h after catheter ablation and we proceeded with autonomic modulation treatment options. Bilateral stellate ganglion blockade was performed under ultrasound guidance using bupivacaine. Sinus bradycardia was present and no ventricular arrhythmias were detected on post-procedure ECG. Stellate ganglion blockade was complemented with video-assisted thoracoscopic cardiac sympathetic denervation. After the last procedure, patient remained on sinus rhythm, was hemodynamically stable and extubated successfully.

Breast Reduction Using the Superomedial Pedicle- and Septal Perforator-Based Technique: Our Clinical Experience.

BACKGROUND: Adequate tissue removal must be performed for symptom relief following reduction mammoplasty. However, this is not always possible in patients with gigantomastia because the pedicle is planned wider and the breast cannot be sufficiently reduced to prevent compromising the blood supply to the pedicle. To maximize blood circulation to the nipple-areola complex in our patients, the pedicle was planned to include the internal thoracic artery branches coming from both the second and third interspaces and the intercostal artery branches coming from the fourth and fifth intercostal spaces. METHODS: A total of 185 patients underwent reduction mammoplasty with the superomedial pedicle- and septal perforator-based technique. The mean weight of excised tissue was 928.77 g from the right breast and 899.92 g from the left, whereas the mean distance of nipple-areola transfer was 11.52 cm on the right breast and 11.27 cm on the left. RESULTS: Complications developed in 11 patients (5.94%): hematoma occurred in three patients, partial loss of areola and fat necrosis in five patients, and wound dehiscence in three patients. CONCLUSIONS: The pedicle included vessels of both superomedial and septum origin without any disruption in circulation. Consequently, the blood supply of the nipple-areola complex was preserved. Furthermore, in cases where the pedicle was long, intercostal perforators were identified and the pedicle was narrowed thoroughly; thus, the breast was reduced to the desired volume while minimizing the risk of complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of the morphological characteristic and sex differences of sternum by multi-detector computed tomography.

BACKGROUND: Sternum is one of the skeleton parts which have frequently congenital anomalies and variations are commonly used by researchers in determining sex. We evaluated the morphological characteristics and sex-related changes of the sternum in adult individuals using multidetector computed tomography in our study. MATERIALS AND METHODS: Two hundred adults (103 female and 97 male) aged between 18 and 87 years were evaluated. Utilising the morphological characteristics of the sternum based on the multislice images; length, width and the thickness of manubrium, length, width and the thickness of corpus sterni, total length of sternum, sternal angle, sternal index (SI), length of the xiphoid process, the thickness of xiphoid process, the number of indents of xiphoid process were measured and a total of 20 parameters were evaluated by adding age, height and weight to these variables. RESULTS: The mean length of the manubrium, the length of corpus sterni, the length of total sternum, SI, sternal angle were found in females 46.7 ± 5.1, 86.6 ± 9.7, 133.1 ± 1.1, 54.47 ± 10.0 and 163.75 ± 5.79; in males 51.2 ± 6,102.4 ± 13.3, 154.1 ± 13.1, 50.11 ± 10.02 and 162.21 ± 6.17, respectively. We found that Hyrtl's Law and SI did not provide adequate accuracy for sex determination in our patients. It has been detected that the length of the manubrium alone is not helpful for individual samples. Total length of the sternum was found to be more reliable than the length of the manubrium and the length of corpus sterni. We determined sternal cleft and sternal foramen as 0.5% and 3.5%, respectively. CONCLUSIONS: We suggest that the morphometric standards cannot be universally applied and can demonstrate individual differences. The standard rules must be implemented for every population.

The LDL/HDL ratio and atherosclerosis in ankylosing spondylitis.

OBJECTIVES: In ankylosing spondylitis (AS) patients, cardiac and vascular involvement may manifest as atherosclerosis and coronary artery disease. Systemic inflammation, oxidative stress, increased low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol constitute a significant risk for atherosclerosis. This study investigated the relationship between carotid intima-media thickness (CIMT), LDL/HDL ratio, total oxidant status (TOS; an indicator of oxidative stress) and ischemic modified albumin (IMA; an ischemic marker in AS patients). PATIENTS AND METHODS: Sixty AS patients were diagnosed using the Modified New York Criteria; 54 age- and gender-matched participants were included as controls. CIMT, LDL/HDL ratio, TOS and IMA were measured using the most appropriate methods. RESULTS: IMA was higher in AS patients compared to controls (p < 0.0001). TOS was also increased in AS patients (p = 0.005); as was CIMT (p < 0.0001). The LDL/HDL ratio was also greater in AS patients compared to controls (p = 0.047). A positive correlation was found between CIMT and LDL/HDL ratio among AS patients. CONCLUSION: Elevated CIMT, IMA and TOS levels suggest an increased risk of atherosclerotic heart disease in AS patients. The LDL/HDL ratio was higher in AS patients compared to controls, and there was a correlation between LDL/HDL ratio and CIMT, albeit statistically weak. Therefore, the LDL/HDL ratio is not a reliable marker to predict atherosclerotic heart disease in AS patients.

Atherogenic index of plasma may be strong predictor of subclinical atherosclerosis in patients with Behçet disease.

OBJECTIVES: Behcet's disease (BD) is a systemic vasculitis characterized by cardiovascular complications. Early diagnosis of these complications can reduce morbidity and mortality. Carotid artery intima-media thickness (cIMT) and the logarithmic value of triglyceride to high density lipoprotein ratio (atherogenic index of plasma, AIP) are good markers of atherosclerosis. The purpose of this study was to investigate whether AIP is a predictive marker of subclinical atherosclerosis in BD patients. PATIENTS AND METHODS: A total of 84 BD patients (60 male, 24 female) and 84 healthy control individuals (58 male, 26 female) were included in this study. cIMT measurements were made, and AIP values were calculated. RESULTS: cIMT (p < 0.001) and AIP (p < 0.001) values of the BD patients were higher than those of the control group. A strong independent relationship was found between the AIP value and cIMT (ß = 0.232, p = 0.018). In the subgroup analysis, the cIMT and AIP values of male BD patients were higher than those of female BD patients. CONCLUSION: Increased AIP and cIMT values can be a good marker for subclinical atherosclerosis in BD patients, especially in male BD patients.

Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a progressive chronic inflammatory disease mainly characterized by axial skeleton and sacroiliac joint involvement. We aimed to investigate the relation between neutrophil-to-lymphocyte ratio (NLR) and disease severity of AS and to explore its availability in clinical practice. METHODS: A total of 102 AS patients and 60 individuals who were age- and gender-compatible with the control group were included into the study. Patients were divided into 2 groups according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores. Patients with BASDAI scores < 4 were considered to be having mild disease activity, whereas those with scores ≥ 4 were considered to be displaying severe disease activity. Hemogram test during the diagnosis, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and other laboratory values of the control group were recorded. RESULTS: NLR was observed to be higher in AS patients compared to the controls (2.47 ± 1.33 and 1.72 ± 0.47; respectively; p<0.0001). NLR was observed to be significantly higher in severe AS disease activity compared to the mild AS disease activity (2.72 ± 1.41, 2.20 ± 1.19; respectively; p = 0.001). NLR had statistical significant differences between mild disease activity compared to the controls (2.20 ± 1.19 and 1.72 ± 0.47, respectively; p = 0.263). There was a positive correlation between NLR and BASDAI (r = 0.193, p = 0.041). The performance of NLR evaluating the disease severity by Roc analysis had sensitivity of 69%, specificity of 54% (cut-off value 1.91), and AUC of 0.652 (95% Cl, 0.549-0.755) (p = 0.006). CONCLUSIONS: NLR may be a simple and inexpensive marker to indicate disease activity in patients with AS in daily clinical practice (Tab. 3, Fig. 3, Ref. 25).

2-step lignin-first catalytic fractionation with bifunctional Pd/ß-zeolite catalyst in a flow-through reactor.

This work demonstrates an additive and hydrogen-free 2-step lignin-first fractionation in flow-through. First, solvolytic delignification renders lignin liquors with its native chemical structure largely intact; and second, ß-zeolite catalytic depolymerization of these liquors leads to similar monomer yields as the corresponding 1-step fractionation process. Higher delignification temperatures lead to slightly lower ß-O-4 content in the solvated lignin, but does not affect significantly the monomer yield, so a higher temperature was overall preferred as it promotes faster delignification. Deposition of Pd on ß-zeolite resulted in a bifunctional hydrogenation/dehydration catalyst, tested during the catalytic depolymerization of solvated lignin with and without hydrogen addition. Pd/ß-zeolite displays synergistic effects (compared to the Pd/γ-Al2O3 and ß-zeolite tested individually and as a mixed bed), resulting in higher monomer yield. This is likely caused by increased acidity and the proximity between the metallic and acid active sites. Furthermore, different ß-zeolite with varying SAR and textural properties were studied to shed light onto the effect of acidity and porosity in the stabilization of lignin monomers. While some of the catalysts showed stable performance, characterization of the spent catalyst reveals Al leaching (causing acidity loss and changes in textural properties), and some degree of coking and Pd sintering.

Cystatin C in serum as an early marker of renal involvement in Familial Mediterranean Fever patients.

BACKGROUND: The major renal involvement in Familial Mediterranean Fever (FMF) is the occurrence of amyloidosis that primarily affects the kidneys manifested by proteinuria and ending in death from renal failure. AIM: This study aims to investigate whether serum cystatin (cys-C) levels could be used as an early marker of renal involvement in FMF patients. PATIENTS AND METHODS: Forty-six patients with FMF during the attack period (AP), and 41 patients with FMF during attack-free periods (AFP), and 11 patients with FMF associated amyloidosis, and 38 healthy controls were enrolled in the study. We determined cys-C levels in the serum of FMF patients and healthy controls. RESULTS: Serum cys-C levels were significantly increased in patients with FMF and secondary amyloidosis, and serum cys-C is a more accurate and efficient marker for detecting renal involvement than estimated glomerular filtration rate (e-GFR) in patients with FMF. CONCLUSIONS: We propose a cutoff level of the serum cys-C of 876.5 pg/mL for screening renal involvement in patients with FMF, and amyloidosis should be strongly suspected when the serum cys-C reaches 1565.5 pg/mL.

Serum 17-OH progesterone and free testosterone levels in women patients with Familial Mediterranean Fever: a pivotal study.

BACKGROUND: Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by short lived, febrile serosae inflammatory attacks. FMF has various effects in multiple systems and organs. AIM: In the present study, our aim was to evaluate adrenal steroidogenesis in female FMF patients. PATIENTS AND METHODS: There were 71 women in the study including 41 women with FMF and 30 women as healthy control group (HC group). Of 41 FMF patients, twenty were evaluated in attack period (AP-FMF group) whereas 21 of them were evaluated in attack-free period (AFP-FMF group). In all subjects; serum free testosterone, 17-OHP levels as hormones, IL-1 beta, TNF-alpha, IL-6, IL-18 as proinflammatory cytokines, CRP, fibrinogen, white blood cell (WBC) counts, and erythrocyte sedimentation rate (ESR) as acute phase reactants were measured in samples of venous blood taken in the morning before breakfast. RESULTS: Serum 17-OHP levels in AP-FMF group and AFP-FMF group were higher than in HC group (p < 0.001). A positive correlation was detected between serum levels of 17-OHP and IL-1 beta in FMF patients (p = 0.006; r = 0.486). There was no difference between FMF patients and HC group in terms of free testosterone levels (p > 0.05). CONCLUSIONS: Our results showed an increase in 17-OHP levels in FMF patients. These results may indicate that, regardless to the attack period adrenal steroidogenesis could be affected negatively in FMF patients.

The value of NT-pro-brain natriuretic peptide and left ventricular ejection fraction for prediction of premature ventricular complexes burden.

OBJECTIVE: We aimed to investigate the relation of NT-pro BNP level and left ventricular ejection fraction with premature ventricular complex burden. PATIENTS AND METHODS: A total of 94 patients with PVC burden > 5% (age 45.9+12.9 years, 53 males, 41 females) were included in the study. The primary outcome was PVC burden % and main prognostic factors were LVEF% and NT-Pro BNP level. Gender, age, DM, HTN, presence of symptoms, symptom duration and heart rate were used as adjustment predictor variables. We created four different linear multivariable models to compare performance measures of prognostic factors: Model-1 has gender, age, DM, HTN, symptoms and heart rate, while LVEF has been added in addition to model-1 in model-2. Model-3 included NT-Pro-BNP alongside model-1 variables, while model-4 included both LVEF and NT-Pro-BNP variables in addition to model-1 variables. Accordingly, we compare the performance (R2, likelihood ratio X2) of models. RESULTS: The median PVC burden was 18% (IQR; 11-27). When model-1 consisting of gender, age, DM, HTN, presence of symptoms, symptomS duration and heart rate and model-2 consisting of LVEF in addition to variables of model-1 were compared, it was observed that both LRX2 and R2 values improved (likelihood ratio test p-value=0.013). Model-1 compared with model-3 which consisting of NT-pro BNP in addition to variables of model-1, and it was observed that both LRX2 and R2 values improved (likelihood ratio test p-value=0.008). However, when compared to model-1, the most significant improvement was observed in both LRX2 and R2 values in model-4 consisting of model-1 plus NT-Pro-BNP and LVEF (likelihood ratio test p-value <0.001). CONCLUSIONS: We determined that NT-pro-BNP levels and LVEF could predict PVC burden in patients. Higher levels of NT-pro-BNP and lower LVEF values were associated with increased PVC burden.

Molecular cloning of the OMP19 gene from Brucella melitensis strain H38 and its antigenicity compared to that of commercial OMP19.

Brucellosis is a worldwide zoonosis, that can still be classified as endemic despite its ancient origins which causes economic losses and public health problems. Although effectively controlled by vaccination in animals, there is currently no vaccine for use in humans. Outer Membrane Proteins (OMP) that play an active immunogenic and protective role in the Brucellae family. OMP19 is present in all Brucella species as a surface antigen and is a potent immunogen responsible for Brucellosis intracellular infection. For this reason, the study was aimed to be used safely as a potential recombinant vaccine candidate against all Brucella infections, especially in humans and pregnant animals. This study evaluated a Brucella lipoprotein antigen, i.e. 19 kilodalton (kDa) outer membrane protein (OMP19), which was amplified and cloned into the pETSUMO vector system. The immunogenic power of the purified recombinant OMP19 antigen against brucellosis was compared with that of OMP19 (Raybiotech Inc, USA) in a mouse model and the obtained rOMP19 antigen was found to be similar to the commercially available recombinant protein.

Basal blood concentrations of some orexigenic and anorexigenic hormones in obese and nonobese individuals according to blood groups.

OBJECTIVE: Obesity is a serious public health problem associated with excessive food intake. Regulation of food intake in highly organized organisms is under the control of a large number of orexigenic and anorexigenic molecules. Therefore, the main purpose of this study has been to determine the relationship between obesity and some of the circulating orexigenic and anorexigenic peptides that have a role in appetite control and to determine whether the concentrations of these molecules differ according to blood groups. PATIENTS AND METHODS: The study included 400 individuals of whom 100 were obese women, 100 obese men, 100 healthy men and 100 healthy women. Obese women and men were divided into 4 groups, according to their blood groups. In the control group, healthy women and healthy men were similarly divided into 4 blood groups. Each blood group within the groups, therefore, had 25 participants. RESULTS: When leptin, nesfatin-1, obestatin and neuropeptide-Y, ghrelin and galanin levels of the control group and obese participants were compared, regardless of blood groups, leptin, nesfatin-1, obestatin and neuropeptide-Y were significantly higher, whereas only the ghrelin levels were significantly lower in obese patients. When the amounts of these hormones were measured according to gender, the situation was similar. When leptin, nesfatin-1, obestatin and neuropeptide-Y values of the control and obese participants' blood groups were compared with each other; these hormones were high in all blood groups; however, leptin levels in A blood group, nesfatin-1 levels in AB and O blood group, obestatin levels in AB blood group, neuropeptide-Y levels in A, B, AB blood groups were significantly higher. When the ghrelin levels of the blood groups in the control group and obese participants were compared, it was only significantly lower in the AB blood group. The ghrelin levels in the other blood groups of the obese individuals were again low, but not significantly so. When the distribution of hormones according to gender was evaluated, a situation parallel to the above results was recorded. CONCLUSIONS: Leptin, nesfatin-1, obestatin and neuropeptide-Y and galanin levels of obese individuals were significantly higher than the control values, whereas the ghrelin values were significantly lower regardless of blood groups. Also, these hormones in blood partly varied with ABO blood groups. These different concentrations of hormones in ABO blood groups might be related with stimulation or suppression of appetite in human. However, further studies in other ethnic groups are needed to confirm these results.

Granulomatous amebic encephalitis: an under-recognized cause of infectious mortality after hematopoietic stem cell transplantation.

Granulomatous amebic encephalitis (GAE) is a rare, nearly always fatal form of encephalitis that occurs mostly in the setting of immune compromise or chronic disease. The prevalence and clinical characteristics of this Acanthamoeba infection in hematopoietic stem cell transplant (HSCT) recipients are not well described. We present an HSCT patient in whom the diagnosis of GAE was made at autopsy. A systematic review of previously reported cases is provided to highlight the clinical presentation and early diagnostic features of GAE in HSCT recipients. Amebic infection usually initially involves the skin or lungs over a period of months, and becomes rapidly fatal once it crosses the blood-brain barrier. GAE is usually discovered postmortem owing to lack of awareness of this deadly infection and delay in diagnosis. Subacute presentation of multiple recurrent panniculitis-like subcutaneous nodules associated with eosinophilia and a history of chronic rhinitis or sinusitis warrant investigation for a possible amebic infection. Prolonged corticosteroid use and a recent exposure to unhygienic water are potential risk factors for GAE. Successful outcomes may be achieved with early intensive treatment using a combination of effective drugs.

The role of psychological factors and serum zinc, folate and vitamin B12 levels in the aetiology of trichodynia: a case-control study.

BACKGROUND: Cutaneous dysaesthesia syndromes are characterized by chronic cutaneous symptoms without objective findings, and their aetiologies are obscure. Trichodynia describes pain and a stinging sensation of the scalp related to diffuse alopecia. AIMS: To determine the prevalence rate of trichodynia in patients with diffuse alopecia; to assess the serum zinc, folate and vitamin B(12) levels; and to investigate the significance of psychological disorders in these patients. METHODS: The study comprised 91 patients with a diagnosis of diffuse hair loss and 74 healthy controls. Patients were questioned about the presence of trichodynia, and their serum zinc, folate and vitamin B(12) levels were assessed. They were also evaluated using the Beck Depression Inventory (BDI), the Beck Anxiety Inventory, and the Somatoform Dissociation Questionnaire (SDQ). RESULTS: The rates of androgenetic alopecia and telogen effluvium were 26.4% and 73.6%, respectively, Trichodynia was found in 30 patients (33%), and was more common in the telogen effluvium group than in the androgenetic alopecia group (P = 0.5). There was no significant difference between the patients with alopecia and controls for zinc, folate and vitamin B(12) levels, or for psychological test scores. However, the BDI and SDQ scores were significantly higher (P = 0.03 and P = 0.01, respectively) in patients with than those in without trichodynia. CONCLUSIONS: Trichodynia is a commonly encountered symptom in patients with diffuse alopecia, and depression and somatoform dissociation disorders may play an important role in its aetiology. Our data provide no evidence that serum levels of zinc, folate or vitamin B(12) are involved in the pathogenesis of trichodynia.

A prudent algorithm for hyperlipoproteinemia in renal transplant recipients.

BACKGROUND: Hyperlipidemia and particularly low-density lipoprotein cholesterol (LDL-C) have been proposed as independent risk factors predisposing to chronic allograft nephropathy. OBJECTIVE: The primary objective of this prospective randomized study was to evaluate the efficacy of the modified National Cholesterol Education Program (NCEP) Step I Diet to prevent posttransplantation hyperlipidemia. The secondary objective was to assess the impact of fluvastatin on the lipid profile of patients unresponsive to dietary measures. METHODS: The study population consisted of 143 consecutive patients who underwent transplantation between October 1998 and January 2005. Patients who failed to demonstrate total and LDL-C levels below the optimal values of 200 mg/dL and 130 mg/dL respectively, were recruited for fluvastatin treatment. The remaining patients who achieved and maintained the target lipid levels continued on the same dietary regimen. RESULTS: Baseline demographic characteristics were not different among the fluvastatin and modified Step I Diet groups. Mean total cholesterol (231.2 vs 187.3 mg/dL; P < .000), LDL-C (134.5 vs 99.2 mg/dL; P < .000), high-density lipoprotein cholesterol (HDL-C; 62.9 vs 55.7 mg/dL; P = .012), and triglyceride (170.3 vs 138.7 mg/dL; P = .011) levels following the dietary run-in period were significantly different between the patients assigned to fluvastatin treatment and those left on the diet, respectively. Fluvastatin achieved reductions ranging from 12% to 14% in the concentrations of total cholesterol (231.2 +/- 4.29 mg/dL to 202.7 +/- 3.89 mg/dL; P < .000) and LDL-C (134.5 +/- 3.53 mg/dL to 115.6 +/- 3.18 mg/dL; P < .000) among 91% of patients after 1 year of treatment. A substantial decrease in all lipoprotein concentrations occurred in 53 patients in the modified Step I Diet group with significant reductions in total cholesterol (187.3 +/- 4.98 mg/dL to 172.7 +/- 3.8 mg/dL; P < .000) and LDL-C (99.2 +/- 4.0 mg/dL to 96.2 +/- 3.44 mg/dL; P < .000). CONCLUSION: Initiation and education of the Step I Diet should be provided during hospitalization. The 3-month dietary run-in period was deemed sufficient to determine the effect of diet on lipid abnormalities. Reduction of lipoprotein levels by a 40-mg daily fluvastatin dose was sufficient, safe, and tolerable.

Late conversion from calcineurin inhibitor-based to sirolimus-based immunosuppression due to chronic toxicity: a prospective study with protocol biopsy amendment.

BACKGROUND: There is an emerging consensus on conversion from calcineurin inhibitor (CNI)-based regimens to proliferation signal inhibitor (PSI)-based protocols for the prevention of a progressive decline in graft function due to CNI toxicity. METHODS: Thirty-one primary renal transplant recipients within 17-48 years of age (mean, 32.2 +/- 1.6) were enrolled in this dual-center study. Eligible patients had a baseline (pre-engraftment) biopsy and completed at least 12 months of follow-up with deteriorating graft function indicative of chronic CNI toxicity with or without nonspecific interstitial fibrosis/tubular atrophy (IF/TA) on a biopsy specimen. A fast conversion protocol, being defined as a 50% initial reduction followed by complete withdrawal of CNI drug within 2 weeks of introducing rapamycin was performed in all patients. A sirolimus (SRL) loading dose was not prescribed; all subjects directly received maintenance (2-5 mg/d) doses of the drug. The primary endpoint of this study was assessement of renal function using cGFR and renal histology by protocol biopsy at 1 year after conversion. RESULTS: The mean follow-up after conversion was 21.6 months. The difference between cGFR before compared with cGFR after 12 months after conversion (40.8 +/- 2.36 mL/min vs 55.7 +/- 3.6 mL/min; P < .000) and at the last follow-up (40.8 +/- 2.36 mL/min vs 53.8 +/- 2.96 mL/min; P < .000) was significant. The mean IF/TA with glomerulosclerosis and chronic vasculopathy scores of biopsy specimens at baseline, during conversion, and at 12 months of the study were 2.25 +/- 0.3, 3.30 +/- 0.24, and 3.0 +/- 0.30, respectively. The change in scores was indicative of mild progression; however, the difference was not significant. IF/TA, glomerulosclerosis, and chronic vasculopathy scores improved in 8 (30%) subjects, remained unchanged in 11 (42%) and worsened in 7 (28%) after 1 year of SRL therapy. After conversion there was no patient or graft loss in this group. Moreover, SCr and GFR improved in 21 or 29 patients (72%), remained stable in 4 (14%), and decreased in 4 (14%) patients. The predictors of successful conversion in our study were GFR > or = 40.6 mL/min, SCr < or = 2.34 mg/dL, and histological allograft damage score < or =3. CONCLUSION: SRL-MPA/MMF-ST combination may be a good therapeutic strategy against chronic CNI toxicity, particularly for patients whose conversion biopsy specimens demonstrated mild IF/TA, glomerulosclerosis, and chronic vasculopathy scores (< or =3.1 +/- 0.3).

Assessment of Interleukin 2 Cytokine Expression Levels After Renal Transplantation.

AIM: End-stage renal disease is a disease in which the kidney is not able to perform its functions. Kidney transplantation is the most effective treatment and cost-effective modality of renal replacement therapy for patients with end-stage renal disease. However, the most important problem in end-stage renal disease patients is the unpredictability of immunologic response after transplants. In this study, it was aimed to investigate the possible association between the interleukin 2 (IL-2) expression level and an organ rejection or rejection episode. MATERIALS AND METHODS: Lymphocytes were isolated from peripheral blood obtained from 21 end-stage renal disease-diagnosed patients prior to transplant and at the sixth month after transplant. CD4+ T cells were separated from lymphocytes by the magnetic cell-sorting method. The purity of these cells were controlled by a flow cytometer. After total RNA isolation from CD4+ T cells, IL-2 was examined by the real-time polymerase chain reaction (RT-PCR) method. RESULTS: Among nonrejection patients (n = 18), the IL-2 expression level decreased in 12 patients in post-transplant time, and 3 of these were statistically significant (P < .05). The level was the same in 1 of 18 patients; it increased in 5 patients, and 1 of them was significant (P < .05). The IL-2 expression level also increased in 3 patients who had a rejection episode, and the increase was statistically significant in 2 samples (P < .05). CONCLUSION: When the patients were evaluated individually, it was observed that there might be a relationship between IL-2 expression levels in CD4+ T cells and rejection episodes. The clinical data of the patients, the immunosuppressive therapies, and post-transplant evaluation of cytokines should be considered together.

Efficacy and safety of enteric-coated mycophenolate sodium in de novo and maintenance renal transplant patients.

Enteric-coated mycophenolate sodium (ECMPS) has been developed as an alternative agent to mycophenolate mofetil (MMF), with the aim to provide reduction in gastrointestinal side effects. This open-label, single-arm, two-center prospective study sought to investigate the efficacy and safety of ECMPS used in combination with steroid and cyclosporine (CyA) in de novo and maintenance renal transplant patients with 12 months' follow-up. Twenty-one patients were recruited (mean age, 39 +/- 8 years) into the de novo group. Of these patients, 66% were male and 76.2% underwent living related kidney donation. The induction immunosuppression was ATG in 10 and basiliximab in 6 patients. At 12 months' posttransplantation, there was no graft or patient loss and two (10%) acute rejection episodes. None of the patients in this group discontinued the study medication due to drug-induced adverse events. One patient was excluded from the study because of recurrent oxalosis. Serum creatinine (SCr) levels at 3, 6, and 12 months after renal transplant were 1.30 +/- 0.3, 1.40 +/- 0.3, and 1.40 +/- 0.3 mg/dL, respectively. The maintenance group included 20 patients. Time posttransplantation (mean +/- SD) was 27 +/- 25 months. All patients in this group had been on maintenance azathioprine or MMF in combination with steroid and CyA. These patients were switched to ECMPS. They mean age was 36 +/- 8 years. Sixty-six percent of the patients were male and 57% received living donor kidneys. Acute rejection was nil, whereas two patients lost their grafts owing to chronic rejection in this group. Three patients were excluded from the study, one to discontinuation of the drug because of intractable diarrhea, the second to loss to follow-up, and the last case due to withdrawal of informed consent. Leukopenia was not observed in this group. The SCr levels prior to and at 3, 6, and 12 months after conversion to ECMPS were 1.80 +/- 1.0, 1.95 +/- 1.5, 1.50 +/- 0.8, and 1.60 +/- 0.8 mg/dL, respectively. This is the first phase IV study with ECMPS in the Turkish population. Renal function was preserved in both groups. Only 2.5% of patients were excluded because of side effects. Use of ECMPS in combination with prednisolone and CyA is an effective and safe therapeutic choice for both de novo and maintenance renal transplant patients.

Impact of calcineurin inhibitors on bone metabolism in primary kidney transplant patients.

OBJECTIVE: Posttransplant bone disease and bone metabolism markers were investigated in primary kidney transplant recipients receiving calcineurin inhibitor (CNI) based triple immunosuppression. We examined the safety profile and independent potential of CNIs on bone formation and bone resorption. The study also attempted to correct for modifiable and nonmodifiable factors that impact on posttransplantation bone metabolism, such as age, renal function, rejection, steroid dosage, and secondary hyperparathyroidism. MATERIALS AND METHODS: Serum alkaline phosphatase and osteocalcin were used as indices of bone formation and urinary deoxypyridinoline as a marker for bone resorption. Bone mineral density (BMD) data were assessed in all patients. Osteocalcin and deoxypyridinoline data were correlated with BMD scores to predict the clinical utility and sensitivity of these tests. Sixty-six patients among 300 kidney transplant recipients were enrolled as eligible candidates based upon more than 12 months' posttransplantation follow-up excellent graft function (GFR values >60 mL/min), and intact parathormone levels <100 pg/mL. RESULTS: Mean follow-up was 1395.3 +/- 179.3 days and 1488.9 +/- 225.1 days for cyclosporine (CsA) and FK506 groups, respectively. Mean values for alkaline phosphatase and osteocalcin were 108.8 +/- 6.0 versus 98.4 +/- 9.7 U/L and 10.1 +/- 1.2 versus 9.8 +/- 1.5 ng/mL for the CsA and FK506 groups, respectively. Both CsA and FK506 caused mild osteoblastic proliferation and matrix mineralization activity, as reflected by increased osteocalcin and alkaline phosphatase levels in 22.6% and 12.5% of patients, respectively. This bone formation activity was counterbalanced by a three-fold increase in urine deoxypyridinoline levels in both groups. Mean deoxypyridinoline levels were, respectively, 13.8 +/- 4.4 versus 11.3 +/- 2.1 nM/mMCr in the CsA and FK506 groups. Thirty-four (68%) patients in the CsA and 10 (62.5%) in the FK506 groups had elevated deoxypyridinoline levels. A strong correlation existed between deoxypyridinoline levels and BMD scores for the CsA group (P < .0001). Despite the presence of relatively greater elevations in deoxypyridinoline and BMD values among CsA-treated patients, there was no significant difference in terms of bone resorption potential of both groups. No correlation existed between iPTH values (<65 pg/mL or among 65 to 98.2 pg/mL) at any time versus osteocalcin, alkaline phosphatase, deoxypyridinoline, or BMD levels. The symptomatic bone disease and fracture rates were 0% in this series. CONCLUSION: Calcineurin inhibitor-based immunosuppression with low maintenance doses of glucocorticoids induces slight bone formation but relatively potent, clinically relevant bone resorption.