Belkis Erbas

Comparison of Metoclopramide and Erythromycin in the Treatment of Diabetic Gastroparesis

OBJECTIVE To compare the effects of erythromycin and metoclopramide on gastric emptying and symptoms of gastroparesis in diabetic patients with delayed gastric emptying. RESEARCH DESIGN AND METHODS The study group consisted of 13 patients with symptoms of severe gastroparesis and delayed gastric emptying. Gastric emptying was evaluated using a radionuclide method, and gastrointestinal symptoms were scored. The patients were given either erythromycin (250 mg 3 times/day) or metoclopramide (10 mg 3 times/day) in random order for 3 wk, and after a washout period of 3 wk they were crossed-over to the other medication for another 3 wk. Parameters of gastric emptying were assessed before treatment and after both erythromycin and metoclopramide administration. RESULTS The half-time of gastric emptying in diabetic subjects was 110 (77–120) min before treatment. At 60 and 90 min, the median value of residual isotope activity was 66.5 (55–83.5) and 55% (43–74.3), respectively. The half-time decreased to 55 min (28.6–115) after 3 wk of treatment with erythromycin and percentages of meal retention in the stomach at 60 and 90 min were 49.9 (38.4–70) and 40.5% (29.7–60), respectively. After taking metoclopramide, the median value of half-time was 67 min (15–115) and percentages of meal retention at 60 and 90 min were 51 (34.5–93.9) and 42% (24–71.2), respectively. When compared with baseline values a significant difference in gastric emptying parameters was found after both erythromycin and metoclopramide. A significant improvement of the total score for gastrointestinal symptoms was observed with both drugs, but this improvement was more pronounced with erythromycin. CONCLUSIONS Erythromycin, a macrolide antibiotic and a motilin receptor agonist, appears to stimulate intestinal motility and seems to be an alternative agent for the treatment of gastroparesis caused by diabetic autonomic neuropathy.

Assessment of changes in regional cerebral blood flow in patients with major depression using the 99mTc-HMPAO single photon emission tomography method

Regional cerebral blood flow was investigated in 14 patients with major depression diagnosed according to the DSM-III-R criteria (six patients with single and eight patients with recurrent episodes) and in ten healthy volunteers. The mean ages of the patients and the controls were 33.5 ± 2.7 and 31.6 ± 2.6 years, respectively. The severity of the depression was assessed using the 17-item Hamilton Depression Scale (mean: 23.2 ± 1.5). None of the patients was under medication. After administration of 500 MBq technetium-99m hexamethylpropylene amine oxime, a single photon emission tomography study was performed and then transaxial, sagittal and coronal slices were obtained. For the semiquantitative analysis of the data, the ratios of the mean counts/pixel to the whole slice were calculated for 24 regions on three consecutive transaxial slices in the orbitomeatal plane. Additionally, left/right and frontal/occipital ratios were calculated. Both sides of the temporal region had a significantly decreased cerebral blood flow (CBF) when compared to the controls. The left/right ratio of the prefrontal region was also significantly lower in the patients than in the controls. The Hamilton score had a negative correlation with blood flow in the anterofrontal and left prefrontal regions. According to our results, regional CBF seems to be decreased in the left prefrontal and in both temporal regions in major depression. The severity of depression is correlated with the reduction in CBF in the regions of the anterofrontal and left prefrontal cortex.

Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: Importance of ace polymorphism

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affect renal prognosis in a number of diseases. We examined the influence of deletion (D) and insertion (I) polymorphism in the angiotensin I-converting enzyme (ACE) gene and the other polymorphic markers of RAS, and that of plasminogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropathy. Ninety-four children with third- or fourth-degree reflux were the subject of the study. They were stratified into two groups according to the technetium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consisted of 41 patients with no scar formation. In the second group (n = 53), there was significant scar formation in the refluxing units. ACE levels, ACE gene, angiotensin-1 receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and PAI-1 4G/5G polymorphisms were studied. In the second group with scarred kidneys, 18 patients had decreased renal function. The frequency of patients homozygous for the D allele was significantly greater in the second group with scar formation in the refluxing units compared with the first group of patients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence ofDD genotype and hypertension, decreased renal function, proteinuria, or sex of the patient. DDgenotype correlated with the serum ACE levels (P < 0.005). AT1and ATGpolymorphisms and PAI-1 polymorphism did not correlate with scar formation or any of the parameters. This study provides evidence that the DDgenotype of ACE may be a genetic susceptibility factor contributing to adverse renal prognosis in reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies.

Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy

Abstract:  The present study has been designed to determine melatonin levels in type 2 diabetic patients and test the relationship between the autonomic nervous system and melatonin dynamics. Thirty‐six type 2 diabetic patients and 13 age‐matched healthy subjects were recruited for the study. Circadian rhythm of melatonin secretion was assessed by measuring serum melatonin concentrations between 02:00–04:00 and 16:00–18:00 hr. Melatonin dynamics were re‐evaluated with respect to autonomic nervous system in diabetic patients with autonomic neuropathy who were diagnosed by the cardiovascular reflex tests, heart rate variability (HRV), and 24‐hr blood pressure monitoring. Nocturnal melatonin levels and the nocturnal melatonin surge were low in the diabetic group (P = 0.027 and 0.008 respectively). Patients with autonomic neuropathy revealed decreased melatonin levels both at night and during day when compared with healthy controls (P < 0.001 and 0.004 respectively) while the melatonin dynamics were similar to controls in patients without autonomic neuropathy. Nocturnal melatonin level was positively correlated with nocturnal high and low frequency components of HRV (P = 0.005 and 0.011 respectively) and systolic and diastolic blood pressures at night (P = 0.002 and 0.004 respectively) in patients with autonomic neuropathy. We found a negative correlation between nocturnal melatonin levels and the degree of systolic blood pressure decrease at night (r = −0.478, P = 0.045). As a conclusion this study has shown that circadian rhythm of melatonin secretion is blunted in type 2 diabetic patients and there is a complex relationship between various components of autonomic nervous system and melatonin secretion at night. Among the patients with autonomic neuropathy those with more preserved HRV and the systolic nondippers (<10% reduction in blood pressure during the night relative to daytime values) have more pronounced melatonin surge at night.

Regional cerebral blood flow and neuropsychological functioning in early and late onset alcoholism.

The aim of the study was to compare late and early onset alcoholism with regard to regional cerebral blood flow (rCBF) and neuropsychological functioning. Ten late onset and 13 early onset male alcoholics were included in the study, the criterion being the age of onset for alcohol abuse. Six healthy male volunteers were included as a control group. Regional measures of cortical cerebral blood flow were assessed using Tc-99m-HMPAO single photon emission computed tomography (SPECT) after a detoxification period. When compared with the control group, the early onset group showed reduced relative perfusion in the left superior frontal region, while relative perfusion in the late onset group was deficient in both right and left superior frontal regions. Both groups of alcoholic patients also displayed impairment in frontal lobe functions and non-verbal memory. The results of this study indicate that early onset alcoholism is associated with hypoperfusion in the left superior frontal region while the late onset subtype is characterized by uniformly hypoperfused left and right superior frontal regions. Additionally, both groups of alcoholic patients exhibit an almost identical pattern of neuropsychological abnormalities mainly related to frontal lobe functions and non-verbal memory. Collectively these findings support previous evidence suggesting a key role of frontal lobe pathology in understanding the neurobiology of alcoholism.

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.

Regional cerebral blood flow changes in chronic alcoholism using Tc-99m HMPAO SPECT. Comparison with CT parameters.

Twenty-eight patients were studied for regional cerebral blood flow changes as a result of chronic alcoholism. After the administration of 550 to 600 MBq Tc-99m HMPAO, tomographic slices were obtained using a SPECT camera. Eight regions per hemisphere were drawn on each transaxial section, and tracer redistribution was calculated for each region. Region-to-whole slice ratios were determined for each patient. Patients had significantly decreased frontal/whole slice (1 ± 0.02) ratios in comparison with a normal group (p< 0.01). Twenty-four out of 26 patients (85.7%) demonstrated abnormal rCBF. Eighteen out of 28 (64.3%) showed activity lower in the left hemisphere than in the right. Using CT parameters, 60% of the patients had either sulcal widening and/or ventricular enlargement. The frontal region and the left hemisphere were more affected by alcohol than other regions. More cerebral blood flow changes than morphologic changes were found caused by alcoholism.

Relationship between Endogenous Sex Hormone Levels, Lipoproteins and Coronary Atherosclerosis in Men Undergoing Coronary Angiography

This study was carried out in order to investigate the relationship between endogenous sex steroid hormones and coronary artery disease (CAD). Three hundred and thirty-seven men undergoing coronary angiography were enrolled in the study. Total testosterone, estradiol, free testosterone levels in men with CAD (n = 213) were compared to those of men without CAD (n = 124). No significant differences were found in the serum concentrations of estradiol, total and free testosterone and serum lipid profile between the two groups. Total and free testosterone were negatively (p < 0.05 to p < 0.001) and estradiol was positively (p < 0.05) correlated with age in both groups. Total cholesterol and low-density-lipoprotein levels were positively correlated with the level of free testosterone (r = 0.221, p < 0.01; r = 0.173, p < 0.05, respectively), and high-density-lipoprotein levels were negatively correlated with total testosterone in patients with CAD (r = –0.166, p < 0.05). The results of this study do not support the role of sex steroid hormones in CAD. However, the relationship between sex steroids and serum lipids needs further clarification.

Alterations in left ventricular function in patients with Behçet's disease using radionuclide ventriculography and Doppler echocardiography.

Behçets syndrome is a multisystem disease; however, cardiac involvement in this disorder has been relatively less recognized. Noninvasive imaging methods may reveal a cardiac disorder which has not manifested itself clinically. In this study, radionuclide ventriculography and Doppler echocardiography were performed in 24 patients with Behçets disease to assess the left ventricular systolic and diastolic function. Patients had neither known heart disease nor cardiac symptoms. Radionuclide ventriculography was performed using 99mTc-labeled red blood cells. Ejection fraction (EF), EF fraction in the first 100 ms (EFV), peak ejection rate, time to peak ejection, 1/3 EF, time to end systole, peak filling rate (PFR), time to peak filling and 1/3 filling fraction (1/3 FF) values were computed using Fourier analysis of the time activity curve of the left ventricle with 3 harmonics. Doppler echocardiography (DE) has described impairment of diastolic compliance using analysis of mitral flow. The mean EF (54.7 +/- 9%), EFV (11.6 +/- 3.6%), PFR (2.49 +/- 0.58 EDC/s) and 1/3 FF (33.64 +/- 14%) values were significantly lower in patients than those of the control group. Nine (37.5%) patients demonstrated an impairment of diastolic function and 3 (12.5%) had abnormal systolic function observed by the radionuclide method. DE showed abnormal ventricular compliance in 13.6% of patients. As a conclusion, noninvasive imaging methods such as radionuclide ventriculography and DE may be valuable to detect diastolic impairment as an early sign of cardiac involvement in Behçets disease.

Tc-99m HMPAO/SPECT determination of regional cerebral blood flow changes in schizophrenics.

Hypofrontality (hypometabolism and hypoperfusion) has been demonstrated in patients with schizophrenia by the use of several imaging methods, such as positron emission tomography (PET). In this study, Tc-99m hexamethylpropylene amineoxime (HMPAO) and SPECT were used to investigate regional blood flow changes in 20 schizophrenic patients (12 males and 8 females, aged 15—50 years) experiencing acoustic hallucinations. Tc-99m HMPAO (15-20 mCi) was injected intravenously, eight regions/hemisphere were drawn on transaxial sections, and tracer redistribution was calculated for each region. Frontal/occipital ratios (0.917 ± 0.045) and frontal/wholeslice ratios (0.984 ± 0.036) were determined for each patient. The patients had significantly lower frontal/occipital ratios (P < 0.0005) and lower frontal/wholeslice ratios (P < 0.01) in comparison to a normal group (11 cases).