Value of Dynamic 18F-FDG PET/CT in Predicting the Success of Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer: A Prospective Study.

Objectives: This prospective study was planned to compare the predictive value of dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in locally advanced breast cancer patients (LABC) receiving neoadjuvant chemotherapy (NAC). Methods: Twenty seven patients with LABC [median age: 47, (26-66)] underwent a dynamic 18F-FDG PET study at baseline, and after 2-3 cycles of (NAC) were included (interim). Maximum standardized uptake value (SUVmax) values and SUV ratios for the 2nd, 5th, 10th, and 30th minutes and dynamic curve slope (SL) values and SL ratios were measured using 18F-FDG dynamic data. In addition, the values of SUVmean (2minSUVmean), SULpeak (2minSULpeak), metabolic volume (2minVol), and total lesion glycolysis (2minTLG) were measured for the first 2 min. Percent changes between baseline and interim studies were calculated and compared with the pathological results as the pathological complete response (PCR) or the pathological non-complete response (non-PCR). Receiver operating characteristic curves were obtained to calculate the area under the curve to predict PCR. Optimal threshold values were calculated to discriminate between PCR and non-PCR groups. Results: Baseline study SUV 30 (p=0.044), SUV 30/2 (p=0.041), SUV 30/5 (p=0.049), SUV 30/10 (p=0.021), SL 30/2 (p=0.029) and SL 30/5 (p=0.027) values were statistically significant different between PCR and non-PCR groups. The percentage changes of 2minVol between PCR and non-PCR groups were statistically significant. For the threshold value of -67.6% change in 2minVol, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.2%, 77.8%, 63.6%, 93.3%, and 80.7%, respectively (area under the curve: 0.826, p=0.009). Conclusion: Semiquantitative parameters for dynamic 18F-FDG PET can predict PCR. % changes in 2minVol can identify non-responding patients better than other parameters.

Diuretic Renal Scintigraphy in Adults: Practical Aspects and Reporting.

Diuretic renal scintigraphy (DRS) is used worldwide for evaluation of kidney functions, diagnosis of pelvic or ureteric obstruction and documentation of the effectiveness of surgical interventions. Although it is a basic imaging procedure of nuclear medicine, there is a wide range of variability in acquisition procedures. Nuclear medicine physicians have the opportunity to modify DRS imaging protocols according to specific clinical problem or question. This plasticity requires readers experience. Interpretation of dynamic images and the quantitative parameters entails knowledge of physiology and pathophysiology of kidneys and collective system. Standardization of patient preparation, imaging protocols and reporting not only would increase the readers' confidence but also would increase the reliability of DRS.

Imaging in Renal Transplants: An Update.

Renal transplantation has become the best treatment for the patients with chronic renal insufficiency. The surgical procedures, immunosuppressive regiments and patient follow-up have evolved especially in the last 10 years. However, the diagnosis for renal transplantation dysfunction remained the same in these years. Serum creatinine levels and estimated glomerular filtration rate calculated by serum creatinine based equations are used in routine patient follow-up. Pelvic ultrasonography and color Doppler ultrasonography are used as a first-line imaging method. Assessment of allograft functions both qualitatively and quantitatively are possible using nuclear medicine procedures. Surgical complications, acute tubular necrosis, subacute and/or acute rejection, infections, toxicity due to immunosuppressive medications, complications relating the collecting system, chronic rejection are the main causes for renal function impairment. The imaging procedures can diagnose the worsening of renal transplant function; however, they still lack the ability to differentiate types of rejection as histopathology or differentiate rejection from other causes of allograft dysfunction. The transplant biopsy gives detailed diagnosis for allograft dysfunction, guide the treatment and therefore it is the preferred diagnostic choice in recent years. On recent years, literature on radionuclide imaging is focused on perfusion analysis for the early diagnosis of renal transplant dysfunction and prognostic use of perfusion parameters, and then this article will focus on these studies and their outcome.

Comparison of clinical and PET-derived prognostic factors in patients with non-Hodgkin lymphoma: a special emphasis on bone marrow involvement.

OBJECTIVE: In patients with non-Hodgkin lymphoma (NHL), we investigated F FDG PET/computed tomography (CT) parameters, clinical findings, laboratory parameters, and bone marrow involvement (BMI) status for predictive methods in progression-free survival (PFS) and overall survival (OS), and whether F FDG PET/CT could take the place of bone marrow biopsy (BMB). METHODS: The performance of F FDG PET/CT (BMPET) was evaluated. The prognostic value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), stage, international prognostic index (IPI) score, IPI risk, lactate dehydrogenase (LDH), B2 microglobulin, Ki67 proliferation index, and the presence of BMI was evaluated for OS and PFS. Kaplan-Meier curves were drawn for each designated cutoff value, and 5-year PFS and 7-year OS were evaluated using log-rank analysis. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BMPET and BMB to identify BMI were 69, 100, 86.1, 80, 100%, and 81.6, 100, 92.5, 89, 100%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of BMPET in patients with Ki67- proliferation index >25% were all 100%. BMPET, IPI risk, MTV, and LDH were found to be independent prognostic predictors for PFS, whereas BMPET, SUVmax, and MTV for OS. Five-year PFS analysis estimated as follows: BMPET (+) = 22%, BMPET (-) = 80%, LDH ≤ 437 (U/L) = 86%, LDH > 437 (U/L) = 51%, MTV ≤ 56 (cm) = 87%, MTV > 56 (cm) = 49%, low IPI risk = 87%, intermediate IPI risk = 69%, high IPI risk = 25%. Seven-year OS analysis was found as: SUVmax ≤ 17.6 = 80%, SUVmax > 17.6 = 48%, MTV ≤ 56 (cm) = 84.4%, MTV > 56 (cm) = 45.8%, BMPET (-) = 72.5%, BMPET (+) = 42%. CONCLUSION: In the Ki-67 proliferation index > 25% group, F FDG PET/CT was able to differentiate BMI independently from NHL subgroups. We recommend using this method with large patient groups. MTV and BMPET were independent prognostic indicators for OS and PFS and may help to determine high-risk patients.

Peri- and Postsurgical Evaluations of Renal Transplant.

Renal transplantation is the best treatment of choice for patient with chronic renal insufficiency because it provides better quality of life and longer survival. Survival rates for grafts and patients have improved over the recent decades because of significant evolution of surgical techniques and immunosuppressive treatment. However, renal transplantation is still associated with several complications, which may result in poor outcome. Cause of allograft dysfunction, which occurs in the early or late post-transplantation period, should be recognized immediately, so that it can be managed correctly. Surgical complications are rare and include renal artery stenosis, vascular thrombosis, hematoma, ureteral obstruction, urinary leak, hematoma, lymphocele, and perinephric fluid collections. Parenchymal complications, which are histopathologically categorized according to Banff classification, include antibody-mediated rejection, T-cell mediated rejection, interstitial fibrosis and tubular atrophy, calcineurin inhibitors, acute tubular injury, and others. Detection of changes in the allograft function is an important task in the appropriate management of complications. Although first-line imaging tool in the recognition of complications is ultrasonography, radionuclide imaging is a modality capable of assessing graft function qualitatively and quantitatively. Sequential renal scintigraphy is of particular importance in the differential diagnosis of complications, which need prompt and accurate management. Renal scintigraphy within 24-48 hours of transplantation surgery is recommended to serve as a baseline for comparison when functional impairment develops. In addition, studies have shown that early renal scintigraphy has a predictive value for the short-term and long-term graft outcomes. This article focuses in the main complications after renal transplantation, their imaging findings, and the role of renal scintigraphy.

Nuclear medicine training and practice in Turkey.

Nuclear medicine applications in Turkey started in the early 1950s, grew as an independent medical discipline and finally were recognized by the Ministry of Health in 1973. Later on, the professional organization of nuclear medicine physicians and other related professionals including radiopharmacists and technologists under the Turkish Society of Nuclear Medicine were established in 1975. Recently after completing more than a half century in Turkey, nuclear medicine has proved to be a strong and evolving medical field with more than 600 physicians serving for the changing needs of clinical practice throughout these years. This article describes past and present facts in this field and attempts to provide insights into the future which hopefully will be brighter than before.

A gamma-distribution convolution model of 99mTc-MIBI thyroid time-activity curves.

BACKGROUND: The convolution approach to thyroid time-activity curve (TAC) data fitting with a gamma distribution convolution (GDC) TAC model following bolus intravenous injection is presented and applied to 99mTc-MIBI data. The GDC model is a convolution of two gamma distribution functions that simultaneously models the distribution and washout kinetics of the radiotracer. The GDC model was fitted to thyroid region of interest (ROI) TAC data from 1 min per frame 99mTc-MIBI image series for 90 min; GDC models were generated for three patients having left and right thyroid lobe and total thyroid ROIs, and were contrasted with washout-only models, i.e., less complete models. GDC model accuracy was tested using 10 Monte Carlo simulations for each clinical ROI. RESULTS: The nine clinical GDC models, obtained from least counting error of counting, exhibited corrected (for 6 parameters) fit errors ranging from 0.998% to 1.82%. The range of all thyroid mean residence times (MRTs) was 212 to 699 min, which from noise injected simulations of each case had an average coefficient of variation of 0.7% and a not statistically significant accuracy error of 0.5% (p = 0.5, 2-sample paired t test). The slowest MRT value (699 min) was from a single thyroid lobe with a tissue diagnosed parathyroid adenoma also seen on scanning as retained marker. The two total thyroid ROIs without substantial pathology had MRT values of 278 and 350 min overlapping a published 99mTc-MIBI thyroid MRT value. One combined value and four unrelated washout-only models were tested and exhibited R-squared values for MRT with the GDC, i.e., a more complete concentration model, ranging from 0.0183 to 0.9395. CONCLUSIONS: The GDC models had a small enough TAC noise-image misregistration (0.8%) that they have a plausible use as simulations of thyroid activity for querying performance of other models such as washout models, for altered ROI size, noise, administered dose, and image framing rates. Indeed, of the four washout-only models tested, no single model approached the apparent accuracy of the GDC model using only 90 min of data. Ninety minutes is a long gamma-camera acquisition time for a patient, but a short a time for most kinetic models. Consequently, the results should be regarded as preliminary.

Renal Function Assessment During Peptide Receptor Radionuclide Therapy.

Theranostics labeled with Y-90 or Lu-177 are highly efficient therapeutic approaches for the systemic treatment of various cancers including neuroendocrine tumors and prostate cancer. Peptide receptor radionuclide therapy (PRRT) has been used for many years for metastatic or inoperable neuroendocrine tumors. However, renal and hematopoietic toxicities are the major limitations for this therapeutic approach. Kidneys have been considered as the "critical organ" because of the predominant glomerular filtration, tubular reabsorption by the proximal tubules, and interstitial retention of the tracers. Severe nephrotoxity, which has been classified as grade 4-5 based on the "Common Terminology Criteria on Adverse Events," was reported in the range from 0%-14%. There are several risk factors for renal toxicity; patient-related risk factors include older age, preexisting renal disease, hypertension, diabetes mellitus, previous nephrotoxic chemotherapy, metastatic lesions close to renal parenchyma, and single kidney. There are also treatment-related issues, such as choice of radionuclide, cumulative radiation dose to kidneys, renal radiation dose per cycle, activity administered, number of cycles, and time interval between cycles. In the literature, nephrotoxicity caused by PRRT was documented using different criteria and renal function tests, from serum creatinine level to more accurate and sophisticated methods. Generally, serum creatinine level was used as a measure of kidney function. Glomerular filtration rate (GFR) estimation based on serum creatinine was preferred by several authors. Most commonly used formulas for estimation of GFR are "Modifications of Diet in Renal Disease" (MDRD) equation and "Cockcroft-Gault" formulas. However, more precise methods than creatinine or creatinine clearance are recommended to assess renal function, such as GFR measurements using Tc-99m-diethylenetriaminepentaacetic acid (DTPA), Cr-51-ethylenediaminetetraacetic acid (EDTA), or measurement of Tc-99m-MAG3 clearance, particularly in patients with preexisting risk factors for long-term nephrotoxicity. Proximal tubular reabsorption and interstitial retention of tracers result in excessive renal irradiation. Coinfusion of positively charged amino acids, such as l-lysine and l-arginine, is recommended to decrease the renal retention of the tracers by inhibiting the proximal tubular reabsorption. Furthermore, nephrotoxicity may be reduced by dose fractionation. Patient-specific dosimetric studies showed that renal biological effective dose of <0Gy was safe for patients without any risk factors. A renal threshold value <28Gy was recommended for patients with risk factors. Despite kidney protection, renal function impairment can occur after PRRT, especially in patients with risk factors and high single or cumulative renal absorbed dose. Therefore, patient-specific dosimetry may be helpful in minimizing the renal absorbed dose while maximizing the tumor dose. In addition, close and accurate renal function monitoring using more precise methods, rather than plasma creatinine levels, is essential to diagnose the early renal functional changes and to follow-up the renal function during the treatment.

SPECT-PET in Epilepsy and Clinical Approach in Evaluation.

In epilepsy, a detailed history, blood chemistry, routine electroencephalography, and brain MRI are important for the diagnosis of seizure type or epilepsy syndrome for the decision of appropriate drug treatment. Although antiepileptic drugs are mostly successful for controlling epileptic seizures, 20%-30% patients are resistant to medical treatment and continue to have seizures. In this intractable patient group, surgical resection is the primarily preferred treatment option. This particular group of patients should be referred to the epilepsy center for detailed investigation and further treatment. When the results of electroencephalography, MRI, and clinical status are discordant or there is no structural lesion on MRI, ictal-periictal SPECT, and interictal PET play key roles for lateralization or localization of epileptic region and guidance for the subsequent subdural electrode placement in intractable epilepsy. SPECT and PET show the functional status of the brain. SPECT and PET play important roles in the evaluation of epilepsy sydromes in childhood by showing abnormal brain regions. Most of the experience has been gained with (18)FDG-PET, in this respect. (11)C-flumazenil-PET usually deliniates the seizure focus more smaller than (18)FDG-PET and is sensitive in identifying medial temporal sclerosis. (11)C-alpha-methyl-l-tryptophan is helpful in the differentiation of epileptogenic and nonepileptogenic regions in children especially in tuberous sclerosis and multifocal cortical dysplasia for the evaluation of surgery. Finally, when there is concordance among these detailed investigations, resective surgery or palliative procedures can be discussed individually.

Evaluation of thyroid diseases and differentiated thyroid cancer in acromegalic patients.

Thyroid diseases are frequently seen in patients with acromegaly. The aim of this study is to evaluate thyroid diseases and thyroid cancer in acromegalic patients followed in a single institution. The data of 92 acromegalic (43 male, 49 female) patients followed over 12 years were retrieved retrospectively from the hospital recordings. All available data for gender, age, body weight and height, duration of acromegaly, age at diagnosis of acromegaly, treatment methods for acromegaly and history of thyroid disease, serum GH, IGF-1, thyroid function tests, thyroid ultrasonography (US), thyroid scintigraphy and thyroid fine needle aspiration biopsy (FNAB) results were recorded for the patients. The mean age of the patients was 43.9 ± 10.8 years and the mean disease duration was 12 ± 6.9 years. Thyroid US was performed in 64 patients who had nodular or diffuse goiter on palpation during the post-treatment follow-up and nodules were found in 44 (47.8 %) patients. Final diagnosis in 64 patients with thyroid US results and thyroid function tests including 26 patients with FNAB were as follows: 31 (48.4 %) benign multinodular goiter (MNG), 6 (9.4 %) simple nodular goiter, 1 (1.6 %) toxic MNG, 1 (1.6 %) Hurthle cell adenoma, and 5 (7.8 %) differentiated thyroid cancer. In addition, 9 (14.1 %) patients had diffuse goiter. One of the patients with diffuse goiter had amiodarone induced thyrotoxicosis. Eleven (17.1 %) patients had normal thyroid US and no other thyroid disease. Patients with nodules had longer disease duration than patients without nodules (14.2 ± 6.6 vs. 9.4 ± 3.4 years, p = 0.043). Thyroid volume was positively correlated with post-treatment GH and post-treatment IGF-1 levels (r = 0.309, p = 0.041 and r = 0.423, p = 0.004), respectively. We found that 7.8 % of our acromegalic patients with thyroid US results were diagnosed with thyroid cancer. Therefore, acromegalic patients must be considered as a high risk group for the development of thyroid cancer and must be closely followed for thyroid nodules and tumors.

The relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 and glutathione S transferase Pi polymorphisms.

The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients' cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.

Correlations between histopathologic and scintigraphic parameters of salivary glands in patients with Sjögren's syndrome.

The aim of this study is to evaluate the diagnostic value of quantifying salivary gland scintigraphy in correlation to the labial biopsy findings of Sjögren's syndrome (SS). Thirty patients suspected of having SS referred to our clinic for salivary gland scintigraphy were included to this study. All patients underwent salivary gland biopsy as well. The severity of histopathologic changes was graded according to the Chisholm and Mason scoring system. Dynamic scintigraphy was performed and region of interests (ROI) were drawn. Time activity curves for salivary glands were generated. Count rates of maximum, minimum activity after lemon juice stimuli, and last minute activities of parotid and submandibular glands were obtained. On the basis of this ROI counts, excretion fraction (EF%) was calculated for all salivary glands. The mean EF% for normal parotid gland and pathologic parotid gland was 54.5 ± 13.9 and 45.8 ± 18.42, respectively, while it was 46.7 ± 11.7 for the normal submandibular gland and 29.3 ± 18.8 for the pathologic submandibular gland. With progression in histopathologic grades from 0 to 4, the EF decreased in all salivary glands. Decreased EF in the salivary glands is correlated with the SS, and salivary gland scintigraphy is a sensitive and valid method for evaluation of the function of the salivary glands.

Guidance document for structured reporting of diuresis renography.

This Guidance Document for structured reporting of diuresis renography in adults was developed by the International Scientific Committee of Radionuclides in Nephro-urology (ISCORN; http://www.iscorn.org). ISCORN chose diuresis renography for its first structured report Guidance Document because suspected obstruction is the most common reason for referral, most radionuclide renal studies are conducted at institutions that perform fewer than 3 studies per week, and a large percentage of studies are interpreted by physicians with limited training in nuclear medicine. Ten panelists were asked to categorize specific reporting elements as essential, recommended, optional (without sufficient data to support a higher ranking), and unnecessary (does not contribute to scan interpretation or quality assurance). The final document was developed through an iterative series of comments and questionnaires with a majority vote required to place an element in a specific category. The Guidance Document recommends a reporting structure organized into indications, clinical history, study procedure, findings and impression and specifies the elements considered essential or recommended in each category. The Guidance Document is not intended to be restrictive but, rather, to provide a basic structure and rationale so that the diuresis renography report will: (1) communicate the results to the referring physician in a clear and concise manner designed to optimize patient care; (2) contain the essential elements required to evaluate and interpret the study; (3) clearly document the technical components of the study necessary for accountability, quality assurance and reimbursement; and (4) encourage clinical research by facilitating better comparison and extrapolation of results between institutions.

Amyloid goiter and hypopituitarism in a patient with systemic amyloidosis.

Systemic amyloidosis may infiltrate the thyroid or other endocrine glands but rarely causes endocrine dysfunction. We describe a 45 years old female patient with diffusely enlarged goiter and hypopituitarism secondary to amyloid infiltration of the thyroid gland and possibly pituitary gland, respectively. She was on chronic haemodialysis for 3 years due to systemic amyloidosis. While she was being prepared for thyroidectomy, adrenal failure developed. Her anterior pituitary hormone levels were low and magnetic resonance imaging of the hypophysis showed low signal intensity in right part of the adenohypophysis. She improved with corticosteroid replacement therapy and underwent subtotal thyroidectomy without any complication. Histopathologically, amyloid deposition was demonstrated in the thyroid gland. To our knowledge, this is the first case with amyloid goiter and hypopituitarism secondary to systemic amyloidosis. Amyloid infiltration should be considered in a systemic amyloidosis patient presenting with rapidly enlarged thyroid gland and signs of hypopituitarism.

Evaluation of SISCOM in routine regional cerebral blood flow alterations after clozapine, in schizophrenia.

Subtraction ictal single photon emission tomography (SPET) co-registered to magnetic resonance imaging (SISCOM) is an ictal-interictal brain perfusion SPET subtraction method, developed for evaluation of brain perfusion changes applied for the identification of epileptic foci. The aim of this study was to test whether regional cerebral blood flow (rCBF) alterations due to clozapine in schizophrenic patients could also be detected with SISCOM. We have studied the brain perfusion SPET data obtained both before (pre-SPET) and 8 weeks after (post-SPET) clozapine treatment, in 20 patients with schizophrenia. These data were used for SISCOM processing. In order to identify any alterations in the perfusion pattern using SISCOM, pre- and post-SPET data were subtracted from each other. Activation maps were created and merged on either pre- or post-SPET images. Visual interpretation of brain perfusion SPET studies were performed and compared with SISCOM findings. We found that final SISCOM images and visual evaluation of pre- and post-SPET studies were well concordant in 17/20 patients. Discordance was observed in 3 patients. In 1 of these 3 patients alterations observed with SISCOM were confirmed as subtle changes on visual re-evaluation of the images. In the remaining 2 of these 3 patients, SISCOM did not confirm the changes observed by visual analysis. Additionally, SISCOM depicted perfusion alteration in occipital cortex in 5 patients. In conclusion, the algorithm of SISCOM seemed to be useful and complementary to visual evaluation, to assess rCBF changes due to clopazine in outpatient schizophrenic patients who had treatment refractoriness or intolerance of previous antipsychotics and to provide additional information when both pre- and post-SPET data were subtracted from each other.

The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: relationship with treatment response.

The purpose of this study was to investigate the effect of clozapine on regional cerebral blood flow (rCBF) and its relationship with response to treatment. In addition, we aimed to study the influence of clozapine on proton magnetic resonance spectroscopy ((1)H-MRS) findings in the dorsolateral prefrontal cortex (DLPFC) in a subgroup of patients. Psychopathology, neurocognitive functioning, and SPECT imaging of 22 patients were assessed at the baseline and 8 weeks after the initiation of clozapine treatment. In 10 of these patients intermediate-echo (TE: 135 ms) single-voxel (1)H-MRS was also performed at the baseline and after 8 weeks. Clozapine treatment increased the right frontal (superior and medial)/caudate perfusion ratio in the whole group, while it increased bilateral frontal (superior and medial)/caudate perfusion ratios in treatment responders. In addition, percentage changes in left and right frontal (superior and medial)/caudate perfusion ratios compared to the baseline were higher in treatment responders than in non-responders. The improvement in attention was related to the increase in percentage change in the right frontal (superior and medial)/caudate perfusion ratio, while the improvement in verbal fluency was related to the increase in percentage changes in both right and left frontal (superior and medial)/caudate perfusion ratios and to right frontal (superior and medial)/thalamus perfusion. Baseline frontal (superior and medial)/thalamus perfusion could explain 32% of the variability of percentage improvements in psychopathology. (1)H-MRS showed that the baseline PANSS general psychopathology score was inversely correlated with the baseline NAA/Cre ratio. An increased NAA/Cre ratio in DLPFC after 8 weeks of clozapine treatment was also revealed by (1)H-MRS. Our SPECT imaging results suggest the presence of an imbalance in fronto-striato-thalamic circuitry that changes with clozapine, especially in the responders, while (1)H-MRS results indicate a supportive effect of clozapine on neuronal integrity.

Impact of renin-angiotensin system polymorphisms on renal haemodynamic responsiveness to acute angiotensin-converting enzyme inhibition in type 2 diabetes mellitus.

INTRODUCTION: The aim of this study was to document the impact of renin-angiotensin system (RAS) polymorphisms on renal haemodynamics and renal hormones in type 2 diabetes mellitus. MATERIALS AND METHODS: Fifty-nine adult patients were studied. Renal haemodynamics were evaluated using 99mTc-MAG3 clearance (MAG3( Cle)) using Bubeck's method and captopril renogram. RAS hormones and angiotensin-converting enzyme (ACE) levels were measured before and after captopril.ACE, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms were analysed. RESULTS: Post-captopril MAG3(Cle) values were significantly lower in patients with microalbuminuria compared to nonproteinuric patients. Statistically significant negative correlation was found between clearance percentage change values and HbA(1c) levels (r: -0.42, p=0.009). MAG3(Cle) was relatively lower following captopril administration in DD patients, while a relative increment was observed in I allele carriers (p=0.02).TheAC-CC group had significantly higher mean post-captopril clearance value compared to the AA genotype (480.9+/-56.1 ml/min/1.73 m(2) vs. 428.4+/-74.8 ml/min/1.73 m(2), p=0.022). CONCLUSIONS: Our data indicate that the heterogeneity of patients' response to ACE inhibition is, at least partly, genetically determined, and the genetic polymorphisms in RAS might predict the acute responsiveness to ACE inhibitors.