IS THERE A RELATIONSHIP BETWEEN TUBEROUS SCLEROSIS COMPLEX AND INSULINOMA?

Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disease characterized by multiple hamartomas in multiple organs. However, there is limited evidence about neuroendocrine tumors (NETs) in patients with TSC, and routine screening of NETs is not recommended in the guidelines. Insulinomas are also an extremely rare disease. According to our knowledge, we presented the 10th TSC patient diagnosed with insulinoma in the literature. Thirty-two years old male patient diagnosed with TSC at the age of 27 due to typical skin findings, renal angiomyolipoma, history of infantile seizures, and cranial involvement was referred to our clinic. The main symptoms of the patient were palpitations, diaphoresis, confusion, and symptoms were improved after consuming sugary foods. Seventy-two hours fasting test was performed, and a low glucose level at 41 mg/dl, a high insülin level at 21.65 µIU/mL, and a high C-peptide level at 7.04 ng/mL were found at the 8th hour. In addition, a 12x7 mm lesion in the pancreatic tail was detected in abdominal imaging. Ga-68 PET-CT (gallium-68 positron emission tomography-computed tomography) detected an increased uptake of Ga-68 in the pancreatic tail. The patient underwent distal pancreatectomy, and pathological evaluation was consistent with an insulinoma. The patient's symptoms improved postoperatively. Since in nearly all TSC cases, as in our case, neuropsychiatric abnormalities, such as epilepsy, are one of the main disease manifestations, and these symptoms may be confused with the clinical manifestations of hypoglycemia in insulinoma. Therefore, patients with newly developed neurological symptoms and behavioral defects should be evaluated in terms of insulinoma.

Development and Optimization of Self-emulsifying Drug Delivery Systems (SEDDS) for Enhanced Dissolution and Permeability of Rosuvastatin.

Rosuvastatin calcium is commonly used statin for treatment of dyslipidemia. It has low bioavailability. The aim of this study was to develop new rosuvastatin calcium self-emulsifying drug delivery systems (SEDDS) as an alternative formulation and to evaluate the permeability of rosuvastatin calcium SEDDS by using Caco-2 cells. Rosuvastatin calcium SEDDSs were developed by using pseudo ternary phase diagram and characterized by using heating cooling cycle, robustness to dilution, stability and in vitro drug release and permeability. The permeability studies of rosuvastatin calcium SEDDS (Papp (A→B) for F1-RS=1.492×10-5±0.413×10-5 and Papp (A→B) for F2-RS=1.254×10-5±0.19×10-5) across Caco-2 cells showed that permeability value from apical to basolateral was higher than permeability value of commercial formulation (Papp (A→B) =7.13×10-5±0.668×10-5). In conclusion, SEDDS as a drug carrier may be used as an effective and alternative hyperlipidemia therapy for oral delivery of rosuvastatin calcium.

Factors Affecting the Selection of Patients on Waiting List: A Single Center Study.

INTRODUCTION: There is an increasing gap between organ supply and demand for cadaveric transplantation in our country. Our aim was to evaluate factors affecting selection of patients on waiting list at our hospital. METHOD: Patients who have been waiting on list and who were transplanted were compared in order to find factors, which affected the selection of patients. Non-parametric Mann-Whitney U test was used for comparison and cox regression analysis was used to find the risk factors that decrease the probability of transplantation in this retrospective case-control study. RESULTS: Patients in the transplanted group were significantly younger, had relatively lower body mass index than the awaiting group. Cardiovascular diseases were more in the awaiting group than the transplanted group. There was no patient with diabetes in transplanted group, despite fifteen diabetic patients were in the awaiting group. Selected patients had lower immunologic risk with regard to peak panel reactive antibody levels. No significant difference was found for gender, hypertension, hyperlipidemia, viral serology, time spent on dialysis and on waiting list between two groups. With cox regression analysis female gender, older age, diabetes mellitus, high body mass index, positive hepatitis B serology and high levels of peak class 1-2 peak panel reactive antibody positivity were found as risk factors that decrease the probability of transplantation. CONCLUSION: A tendency for selection of low risk patients was found with this study. Time and energy consuming complications and short allograft survival after transplantation in high risk patients and the scarcity of cadaveric pool in our country may contribute to this tendency.

A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome.

Denys-Drash syndrome (DDS) is a rare disorder characterized by glomerulopathy, genital abnormalities and predisposition to Wilms' tumor. It is associated with constitutional Wilms'tumor suppressor 1 (WT1) gene mutations, in which the majority being missense mutations in the zinc-finger region. Here, we present a newborn with DDS, associated with a novel heterozygous missense mutation, p.Asp396His, on exon 9 of WT1.

Evaluation of efficacy and safety of mycophenolate sodium in patients with de novo and maintenance renal transplantation: results of a multicenter, prospective, observational study.

OBJECTIVE: This study evaluates the effect of enteric-coated mycophenolate sodium (EC-MPS) on patient and graft survivals, the incidence of rejection episodes, and graft function among de novo and maintenance renal transplant recipients. PATIENTS AND METHODS: This open label, multicenter, prospective, post-marketing observational study of 470 renal transplantation patients at 23 centers in Turkey includes 331 de novo patients whose mean age was 29.6 ± 13.2 years and 139 maintenance patients of 34.0 ± 13.0 years. The latter subjects had EC-MPS substituted for mycophenolate mofetil or added to the immunosuppressive therapy. Patients were followed for 12 months to evaluate graft function and treatment failure. RESULTS: The most common primary disease requiring transplantation was glomerulonephritis (24.3%). De novo and maintenance groups were similar in terms of overall rejection rates and acute rejection incidence whereas chronic rejection was evident only among the latter cohort (P < 0.001). Time to an acute rejection episode was significantly longer among maintenance rather than de novo patients (220.8 versus 18.7 months; P = 0.015). Overall, 12 and 36 month survival rates were 91.6 ± 1.3% and 86.9% ± 0.3% among subjects experiencing acute rejection versus 99.7 ± 0.2% and 50.3% for those displaying chronic rejection. Among maintenance group no deterioration of renal function was observed after conversion from mycophenolate mofetil to EC-MPS. The incidences of leukopenia, new-onset anemia, or liver dysfunction were similar between de novo and maintenance patients. Gastrointestinal discomfort was more prevalent among the maintenance group, reaching a significant level at the fourth visit (P < 0.05). EC-MPS dose reduction was required in only 16.7% of patients at visit, it was more frequent among the de novo group (17.9 versus 13.8%). CONCLUSION: EC-MPS was an effective adjunctive therapy for de novo as well as maintenance renal transplant recipients in the Turkish population due to a relatively low incidence of dose reductions necessitated by adverse events as well as with an increased likelihood of long-term graft survival.

Electrolyte free water clearance could be an early sign of renal dysfunction in renal transplant patients.

Data on free water excretion capacity of renal transplant recipients are scant. The aim of this study was to evaluate the ability of electrolyte free water clearance (E-CH(2)O) by the allograft in renal transplant patients and the effects of various immunosuppressive drugs. Renal transplant recipients with good graft function (creatinine < 1.5 mg/dL) as well as controls were divided into five groups according to their immunosuppressive regimen: group I, azathioprine (n = 15); group II, cyclosporine (n = 28); group III, tacrolimus (n = 28); group IV healthy controls (n = 20); and group V renal transplant donors (n = 16). Following a 12-hour fast, we administered oral water loading (20 mL/kg) with urine collection for 3 hours. We calculated creatinine clearance for 3 hours and E-CH(2)O. No matter which immunosuppressive drug, the E-CH(2)O of recipients (groups I, II, and III) was lower than that of donors or healthy controls. The creatinine clearance of the cyclosporine arm was significantly lower than all of the other groups. Decreased E-CH(2)O in renal transplant patients might be due to diminished water input to the loop of Henle related to subclinical allograft insufficiency as a result of posttransplantation pathology and/or immunosuppressive drug therapy or the transport of water into the extrarenal interstitium as a result of vascular endothelial dysfunction due to the pretransplant uremic milleu.

Perineal hernia because of retroflexion of the urinary bladder in a rottweiler bitch during pregnancy.

A young pregnant rottweiler bitch was presented with a large mass of tissue protruding through the vulvar lips. Foetal death was diagnosed on ultrasonography, and ovariohysterectomy was performed, at which time the bladder was observed to be dislocated caudally into the pelvic cavity under the vagina. The bladder was manually repositioned during surgery. One week later, the bitch was healthy with no evidence of dysuria, stranguria or urinary incontinence. Two months later, the owner reported that the bitch was clinically normal with no recurrence of the retroflexion. To the authors' knowledge, this is the first reported case of retroflexion of the urinary bladder during pregnancy.

Treatment of renal transplant recipients with low bone mineral density: a randomized prospective trial of alendronate, alfacalcidol, and alendronate combined with alfacalcidol.

We sought to compare the treatment modalities of alendronate, alfacalcidol, and alendronate combined with alfacalcidol in renal transplant recipients with low bone mineral density. Sixty-four kidney graft recipients (22 women, 42 men) were recruited to this study. Of these 64 patients, 9 served as the control group with T scores more than -1. The remaining 55 patients randomly assigned to treatment had T scores less than -1 and were assigned to 3 groups: group 1 received alfacalcidol (0.5 microg/d); group 2, alendronate (10 mg/d); and group 3, alendronate (10 mg/d) + alfacalcidol (0.5 microg/d per os). Twenty-five patients were allocated to alfacalcidol, 13 patients to alendronate, and 17 patients to alendronate + alfacalcidol treatment. Bone mineral densities of the lumbar spine and femoral neck were measured before and 12 months after treatment. The groups were compared for risk factors of osteoporosis, biochemistry, and bone mineral density. Kruskal-Wallis, one-way ANOVA, and Student t tests were used. With the alendronate + alfacalcidol group, bone mineral density at the lumbar spine significantly increased by 7.9% (P = .006) with a significant improvement in T score (P = .003). Bone mineral density at the femoral neck significantly increased by 8% in the alendronate + alfacalcidol group (P = .01) with a significant improvement in T score (P = .02). The use of a combination of alendronate and alfacalcidol seemed to be safe and more effective than the separate use of the 2 agents to improve bone mass in renal transplant recipients.

Development of a rational antibiotic usage course for dentists.

AIM: The aims of this report are to describe the development process of this rational antibiotic usage course and to evaluate the short-term efficiency of the course in terms of the level of improvement in knowledge and feedbacks of the participants. MATERIALS AND METHODS: A needs assessment survey was carried out on the curriculum development process in order to determine the patterns of drug usage and level of knowledge on antibiotics of potential participants. A total of 162 dentists from two dental hospitals in Izmir were interviewed using standard questionnaires. The course content and educational strategies were determined according to the needs assessment results. Fifty-eight dentists applied to the first three courses conducted between 2002 and 2004. Pre/post-test design was performed for level of improvement in knowledge and a questionnaire form, scored by Likert Scale with 5 point, was used for participants' feedback. RESULTS: The mean score, which was 9.74 +/- 2.71 in pre-test, increased to 18.16 +/- 1.58 in post-test and the difference was significant (t = -28.805; P = 0.000). The knowledge and approach of the trainers was appreciated most of all. Participants enjoyed the course very much, and reported a high level of satisfaction regarding the content, trainers, educational techniques and teaching material. The suggestions for future courses included increasing the course length (21.2%). Results from the needs assessment survey revealed that the study population over-used antibiotics, relied on incorrect sources of information, was unaware of the results of irrational antibiotic usage and did not check sufficiently with patients before prescribing. CONCLUSIONS: These findings supported the need for regular courses in the application of antibiotics in dental practice and continuous refreshment of knowledge.

Pregnancy-associated plasma protein-A: evaluation of a new biomarker in renal transplant patients.

OBJECTIVE: Trophoblasts produce high concentrations of pregnancy-associated plasma protein-A (PAPP-A) during pregnancy. PAPP-A has been described as a new inflammatory marker and an independent risk factor for posttransplant cardiovascular risk. This study evaluated the clinical significance of PAPP-A in renal transplant patients. METHODS: The study included 78 adult renal transplant patients (56 men and 22 women) and 37 control subjects (27 men and 10 women). We determined serum PAPP-A, urea, creatinine, uric acid, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, 24-hour proteinuria, and C-reactive protein (CRP) levels. RESULTS: The PAPP-A level was significantly higher among renal transplant patients [median (interquartile range), 10.5 (6.4 to 15.4) mU/L] than the control group [3.9 (3.1 to 5.2) mU/L; P<.001]. There were significant positive correlations between serum PAPP-A levels and urea (r=.547, P=.001), creatinine (r=.497, P=.001), uric acid (r=.452, P=.001), and CRP values (r=.387, P=.001). The drugs used for immunosuppression in transplant patients (cyclosporine, tacrolimus, and others) did not significantly affect serum PAPP-A levels (P>.05). CONCLUSION: We concluded that PAPP-A level was elevated in renal transplant patients and that high levels of PAPP-A might be a prognostic marker owing to their close association with high serum levels of urea, creatinine, uric acid, and CRP.

Theophylline granule formulation prepared by the wet granulation method: comparison of in vitro dissolution profiles and estimation of in vivo plasma concentrations.

The primary and secondary objectives of this study were to develop and evaluate the predictability of in vitro-in vivo correlation models for theophylline sustained release (SR) granules. Theophylline SR granules meeting the USP Drug Release Test criteria were prepared using ethyl cellulose (EC) and/or stearyl alcohol (SA) and the wet granulation method. In vitro dissolution studies of granule formulation were performed, and a commercial dosage form was prepared using USP XXIII apparatus II at pH 4.5. Differences and similarities between in vitro dissolution curves were compared using both model-dependent (t-test) and -independent (f1, f2 test) statistical techniques, and it was shown that the three dissolution profiles i.e model-dependent, model-independent, and methods based on ANOVA were very similar. The in vivo performance of the commercial dosage form was tested by oral route using male rabbits and in vitro-in vivo correlations were established. This study indicates that the dosage forms with similar in vitro dissolution profiles may have a similar in vivo performance, and that this performance could be estimated using appropriate correlation equations.

Cellulitis as a manifestation of miliary tuberculosis in a renal transplant recipient.

Cutaneous involvement is an unusual presentation of tuberculosis (TB) and is rarely reported in renal transplant recipients. We describe a 37-year-old renal transplant recipient with disseminated Mycobacterium tuberculosis infection that presented as cellulitis. The organism was isolated from tissue and blood cultures. The patient was treated with quadruple anti-TB therapy for 12 months. Anti-TB therapy led to a complete resolution of TB lesions. We also provide a review of the literature on cutaneous TB in renal transplant recipients. Skin TB in renal transplant recipients usually occurs with nontuberculous mycobacteria. The spectrum of the skin lesions can be quite different and can mimic bacterial infections. Mycobacteriosis should always be included in the differential diagnosis of a skin lesion in renal transplant recipients.

Osteoporosis after renal transplantation.

This study was performed to determine risk factors associated with osteoporosis that develops after renal transplantation. Sixty-five kidney graft recipients were included in this study. They were divided into four groups according to the time since transplantation: Group 1 (< 1 year; n = 26), group 2 (1-3 years; n = 16), group 3 (3-5 years; n = 12) and group 4 (> 5 years; n = 11). These groups were matched according to probable risk factors for osteoporosis, findings of serum biochemistry, biochemical markers of bone turnover and measurements of bone mineral density. One way ANOVA test and Kruskal-Wallis test were used for statistical analysis. Osteoporosis was found in 22 recipients (33.8%). There were significant differences in recipient age, cumulative steroid dose, and episodes of acute rejection between the four groups. Increasing age, cumulative steroid dose and episodes of acute rejection were found to be risk factors for osteoporosis in our study.

Amyloid goitre in familial Mediterranean fever: report on three patients and review of the literature.

Familial Mediterranean fever (FMF) is a hereditary disease, the most threatening complication of which is systemic amyloidosis. The thyroid gland may be asymptomatically involved in most patients with systemic amyloidosis secondary to FMF. However, clinically detectable thyroid goitre is quite rare, and until now only nine cases of thyroid goitre secondary to amyloid deposition in FMF have been reported. Of 1,100 FMF patients regularly followed up at our centre, thyroid goitre due to the accumulation of amyloid substance could be detected in only three (0.27%). In this report, we summarise the clinical and laboratory features of these patients. All three patients were euthyroid. Total thyroidectomy was performed for compressive symptoms in one patient and for aesthetic purposes in the other two. In countries with a high prevalence of FMF, such as Turkey, secondary amyloidosis of the thyroid gland should be borne in mind in long-standing FMF patients.

Diffuse diabetic glomerulosclerosis in a patient with impaired glucose tolerance: report on a patient who later develops diabetes mellitus.

Diabetic glomerulosclerosis might be seen in diabetics but its presence in patients with impaired glucose tolerance is quite rare. A 31-year-old woman who was admitted to our department was diagnosed with hypertension, nephrotic syndrome and impaired glucose tolerance. Her renal biopsy was compatible with diabetic glomerulosclerosis. She developed overt diabetes mellitus (DM) after one year of impaired glucose tolerance. Hypertension might have accelerated the progression of diabetic nephropathy.

The antinociceptive effect of moclobemide on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy.

The aim of our study was to investigate the antinociceptive activity of moclobemide on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy. The neuropathy was produced by ligation of the sciatic nerve and nociceptive thresholds were determined 15-21 days after surgery by a modification of the Randall-Sellito method. Group 1 (n= 10) received 0.2 ml peroral (p.o.) saline, Group 2 (n= 10) 5 mg x kg(-1), Group 3 (n= 10) 10 mg x kg(-1) and Group 4 (n= 10) 20 mg x kg(-1) p.o. moclobemide. Nociceptive pressure thresholds were then measured every 20 minutes after drug administration. Analysis of variance, Tukey's test and a paired Student's t-test were employed for statistical analysis. The perorally administered moclobemide (5, 10 and 20 mg x kg(-1)) produced an antinociceptive effect on both lesioned and non-lesioned hind paws ( P< 0.05). However, the analgesic effect on the lesioned paw was significantly more potent than the non-lesioned paw. The peak value ( p) remained constant while the maximal increment between the control threshold and the peak value ( I(max)) was significantly more pronounced for the lesioned paw ( P< 0.001). The results of this study may suggest that moclobemide can be a therapeutic alternative to treat some clinical symptoms in peripheral neuropathic conditions.

Fever of unknown origin in uremic patients: a controlled prospective study.

Twenty-nine uremic patients with fever of unknown origin (FUO) admitted to our clinic between 1994 and 1998 were evaluated prospectively. A group of 50 consecutive non-uremic patients with FUO followed up during the same period was used for comparison. The causes of FUO found in the uremic and non-uremic groups, respectively were as follows: infectious diseases, 69 vs. 44% (p = 0.03); collagen vascular diseases, 6.9 vs. 6%; neoplasms, 3.4 vs. 26%; miscellaneous causes, 3.4 vs. 16%; and undiagnosed, 17.2 vs. 8%. Tuberculosis was the most common cause of FUO in both groups. The spectrum of underlying conditions for FUO in our uremic patients differed from that in the non-uremic patients and the uremic patients had a very high propensity for infectious diseases, especially tuberculosis.

Mycobacterium tuberculosis infections after renal transplantation.

The incidence of tuberculosis was found to be 5.8% (16/274) in 274 kidney graft recipients in our centre between 1986 and 1998. The kidney recipients were evaluated retrospectively. A total of 51 recipients received isoniazid prophylaxis for 6 months. The prevalence of tuberculosis was found similar (6% vs. 8.8%, p = 0.15) between recipients with prophylaxis and no prophylaxis. Eight patients were recipients of cadaveric donor kidneys and 8 were recipients of living donor kidneys. Lungs were the most frequently affected site, as in the normal population. M. tuberculosis grew in 7 patients. In 5 patients, M. tuberculosis was also detected on direct microscopy and polymerase chain reaction. In 4 patients, diagnosis was made on clinical grounds and later confirmed by positive response to therapy. In 8 patients, invasive procedures were performed for diagnosis. Five patients had miliary tuberculosis at the time of diagnosis. In 3 patients dissemination occurred during follow-up. Nine patients responded to anti-tuberculous therapy while still preserving their graft function, 1 patient rejected the graft while under treatment and returned to haemodialysis. Five patients (31%) died. Since the risk of dissemination of tuberculosis is high in these patients, anti-tuberculous therapy should be started whenever clinical findings suggestive of tuberculosis are present, even in the absence of any microbiological and/or histological evidence.

Effect of arachidonic acid on specific binding of [3H]naloxone to opioid receptors.

The effects of arachidonic acid (AA) on binding of [3H]naloxone to the agonist and antagonist configurations of opioid receptors were investigated in rat brain. Equilibrium binding parameters of the agonist and antagonist configurations of the receptors were evaluated from homologue displacement data in the presence or absence of AA. Addition of AA at a concentration of 0.6 mM (1.5 mumole/mg of protein) reduced by 22% and 53% the maximal number of binding sites (Bmax) respectively in the absence or presence of 100 mM NaCl. Binding affinity (KD) was not altered significantly (P < 0.05) either in the presence or absence of 100 mM NaCl and AA. We conclude that AA mediated reduction in [3H]naloxone specific binding was chiefly due to a decrease in the number of binding sites.