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Biomedical subjects

T Erbas

Publications and source records attributed to T Erbas.

At least 19 recordsLinked to original sources

Follow-up of pregnancy in acromegalic women: different presentations and outcomes.

Pregnancy in acromegaly is a rather rare event since the fertility is reduced in acromegalic women. Besides, metabolic complications of acromegaly are harmful to both mother and fetus. Little is known about the outcome of pregnancy in acromegalic women. Here, we report seven cases of pregnancy out of 48 acromegalic women followed for 16 years. At diagnosis, five patients had macroadenoma, one patient had microadenoma and the size of the tumor was not documented in one patient. In one patient, acromegaly was initially diagnosed during pregnancy at 29 weeks. When she was 33 weeks, she developed pituitary apoplexy and had an emergency transsphenoidal resection of her macroadenoma during which she also had a cesarian section and delivered a healthy baby girl. In the remaining six patients, pregnancy occurred 6 to 64.5 months after the adenoma resection. Three patients received radiotherapy before getting pregnant. In three patients, pregnancy occurred during bromocriptine treatment and the drug was withdrawn. In one patient, pregnancy occurred during chronic octreotide treatment and therapeutic abortion was performed. In another patient, therapeutic abortion was performed because of uncontrolled disease. In the remaining four patients, there were neither worsening of symptoms nor tumor growth. All four patients gave birth to full-term healthy infants. Out of our seven patients, two developed gestational diabetes mellitus which was controlled with diet. None of the patients had coronary artery disease, hypertension or dyslipidemia. These cases show that pregnancy might be uneventful in acromegalic women when the disease is controlled with prior surgery and radiotherapy.

Acromegaly↗

Lipoatrophy induced by subcutaneous administration of octreotide in the treatment of acromegaly.

Octreotide is the first somatostatin analogue to become available for clinical use in the treatment of acromegaly. To our knowledge, there are no reports describing lipoatrophy in patients treated with octreotide. Here, we report three patients who developed lipoatrophy after treatment with subcutaneous octreotide. Three patients (all women; 36, 43, and 50 years of age) with diagnosis of acromegaly due to pituitary macroadenoma who had undergone transsphenoidal surgery and radiotherapy received subcutaneos octreotide because of uncontrolled disease. The dose of octreotide was increased gradually in all patients. Lipoatrophy was noticed around the injection sites after about 6 years, 30 months, and 4 years of subcutaneous octreotide treatment in all patients. Thereafter, subcutaneous octreotide treatment was changed to intramuscular octreotide-LAR injection in all patients. In two of them, lipoatrophy around all injection sites did not regress after about 8 and 12 months of octreotide-LAR treatment, respectively. In the third patient, lipoatrophy around the injection sites regressed after 12 months of octreotide-LAR treatment. These cases highlight a potential for subcutaneous octreotide to induce lipoatrophy. The underlying mechanism is unknown but an immunological mechanism which is seen in lipoatrophy induced by insulin may be involved in the pathogenesis. Besides; simple trauma, personal susceptibility, mistakes in the administration of the drug, a problem in drug pH, or an idiosyncratic reaction of adipocytes to octreotide or additives in the drug may have caused lipoatrophy in our patients. Lipoatrophy in these cases was observed on long-term subcutaneous octreotide administration. Although intramuscular octreotide-LAR has largely replaced subcutaneous octreotide, we suggest close clinical follow-up for lipoatrophy in patients who are still on subcutaneous octreotide.

Acromegaly↗

Thermolabile methylenetetrahydrofolate reductase enzyme genotype is frequent in type 2 diabetic patients with normal fasting homocysteine levels.

OBJECTIVE: To investigate the plasma homocysteine concentrations with regard to nutritional, metabolic and genetic factors and to find out the frequency and impact of thermolabile methylenetetrahydrofolate reductase (T-MTHFR) polymorphism in patients with type 2 diabetes mellitus. DESIGN: A cross-sectional study. SUBJECTS: A total of 94 subjects with type 2 diabetes mellitus and 91 healthy age- and sex-matched nonsmoking volunteers were recruited. MAIN OUTCOME MEASURES: Age, sex, duration and complications of diabetes mellitus, metabolic variables, fasting plasma homocysteine levels, and presence of T-MTHFR polymorphism were evaluated for all participants. Presence of T-MTHFR polymorphism was analysed to define any possible role in diabetes progress, complications and metabolic milieu. RESULTS: Fasting homocysteine levels were similar in diabetic patients and controls. Prevalence of homozygous polymorphism of thermolabile MTHFR gene (TT) was encountered more frequently in patients with diabetes mellitus than the healthy controls (P = 0.004). Subgrouping of the patients with respect to MTHFR genotype revealed similar metabolic variables and frequency of chronic complications of diabetes mellitus in groups. Patients with TT genotype revealed longer diabetes duration when compared with the patients having heterozygous mutation of thermolabile MTHFR or normal homozygous MTHFR genotypes (P = 0.046). CONCLUSIONS: Type 2 diabetic patients have similar fasting plasma homocysteine levels with that of age- and sex-matched healthy people. There is no correlation between diabetic complications and this amino acid metabolite. On the contrary, thermolabile variant of MTHFR genotype is found to be more frequent in diabetic patients especially in those who have experienced a longer duration of disease.

Adult↗

Metabolic syndrome.

The metabolic syndrome is characterized by diabetes mellitus, obesity, hypertension, hyperlipidaemia and polycystic ovary syndrome. The lipid profiles of patient with metabolic syndrome is often characterized by the appearance of hypertrygliceridaemia and small, dense LDL-cholesterol, together with low HDL-cholesterol. Patients with these abnormalities are at an increased risk for premature coronary artery disease. Treatment is a multifactorial process and includes modification of lifestyle factors such as diet and physical activity, weight reduction, correction of dyslipidemia, meticulous blood pressure and glycemic control. The case of a 36-year-old woman who develops metabolic syndrome is discussed.

Adult↗

Small fiber neuropathy and neurovascular disturbances in diabetes mellitus.

Functional and organic abnormalities in small unmyelinated C fibers are the hallmark of type 2 diabetes. These may be silent clinically or present with burning feet, neurovascular abnormalities, wherein warm, cold, and heat pain thresholds are disturbed in association with impairment in skin blood flow and loss of PGP 9.5 immunostaining nerves in the skin. There is a dysfunctional phase preceding organic structural damage to the neurovascular unit. It coexists with elements of the metabolic syndrome, particularly insulin resistance (IR), elevated systolic blood pressure, and diabetic dyslipidemia i.e. dysfunction of the neurovascular unit may contribute to IR due to compromised blood flow with decreased delivery of fuels to their target tissues. If this proves to be the case, it will become important to re-focus energies on the defective neuropeptidergic regulation of blood flow as an approach to ameliorating diabetes. Because there is a functional phase that precedes structural damage, reversibility of the defect is achievable.

Animals↗

Methods for evaluation of peripheral neurovascular dysfunction.

Measurement of skin blood flow is a sensitive marker of C-fiber neurovascular dysfunction. It precedes development of abnormalities in diabetes mellitus, correlates with in vivo indices of the metabolic syndrome, and may be a "benchmark" for future studies on agents to improve microvascular dysfunction in diabetes mellitus. Skin blood flow can be measured under basal and stimulated conditions. There are different methods of evaluation. Iontophoresis and microdialysis are novel methods of drug delivery and the latter may be used as a means of extracting analytes in the skin. Theses methods are not invasive (iontophoresis) or minimally invasive (microdialysis). They can be performed repeatedly and safely in most patients. The use of microdialysis may be limited by sampling only water-soluble molecules. An alternative to microdialysis is iontophoresis, which works better with polar molecules. A combination of microdialysis and iontophoresis techniques can be useful in assessment of the pharmacokinetics of polar and nonpolar agents and the physiology and pathophysiology of the skin neurovascular system.

Diabetic Angiopathies↗

Dermal neurovascular dysfunction in type 2 diabetes.

OBJECTIVE: To review evidence for a relationship between dermal neurovascular dysfunction and other components of the metabolic syndrome of type 2 diabetes. RESEARCH DESIGN AND METHODS: We review and present data supporting concepts relating dermal neurovascular function to prediabetes and the metabolic syndrome. Skin blood flow can be easily measured by laser Doppler techniques. RESULTS: Heat and gravity have been shown to have specific neural, nitrergic, and independent mediators to regulate skin blood flow. We describe data showing that this new tool identifies dermal neurovascular dysfunction in the majority of type 2 diabetic patients. The defect in skin vasodilation is detectable before the development of diabetes and is partially correctable with insulin sensitizers. This defect is associated with C-fiber dysfunction (i.e., the dermal neurovascular unit) and coexists with variables of the insulin resistance syndrome. The defect most likely results from an imbalance among the endogenous vasodilator compound nitric oxide, the vasodilator neuropeptides substance P and calcitonin gene-related peptide, and the vasoconstrictors angiotensin II and endothelin. Hypertension per se increases skin vasodilation and does not impair the responses to gravity, which is opposite to that of diabetes, suggesting that the effects of diabetes override and counteract those of hypertension. CONCLUSIONS: These observations suggest that dermal neurovascular function is largely regulated by peripheral C-fiber neurons and that dysregulation may be a component of the metabolic syndrome associated with type 2 diabetes.

Diabetes Mellitus, Type 2↗

Platelet dysfunction in type 2 diabetes.

Insulin resistance is a uniform finding in type 2 diabetes, as are abnormalities in the microvascular and macrovascular circulations. These complications are associated with dysfunction of platelets and the neurovascular unit. Platelets are essential for hemostasis, and knowledge of their function is basic to understanding the pathophysiology of vascular disease in diabetes. Intact healthy vascular endothelium is central to the normal functioning of smooth muscle contractility as well as its normal interaction with platelets. What is not clear is the role of hyperglycemia in the functional and organic microvascular deficiencies and platelet hyperactivity in individuals with diabetes. The entire coagulation cascade is dysfunctional in diabetes. Increased levels of fibrinogen and plasminogen activator inhibitor 1 favor both thrombosis and defective dissolution of clots once formed. Platelets in type 2 diabetic individuals adhere to vascular endothelium and aggregate more readily than those in healthy people. Loss of sensitivity to the normal restraints exercised by prostacyclin (PGI(2)) and nitric oxide (NO) generated by the vascular endothelium presents as the major defect in platelet function. Insulin is a natural antagonist of platelet hyperactivity. It sensitizes the platelet to PGI(2) and enhances endothelial generation of PGI(2) and NO. Thus, the defects in insulin action in diabetes create a milieu of disordered platelet activity conducive to macrovascular and microvascular events.

Animals↗

Recognizing and treating diabetic autonomic neuropathy.

Diabetic autonomic neuropathy can cause heart disease, gastrointestinal symptoms, genitourinary disorders, and metabolic disease. Strict glycemic control can slow the onset of diabetic autonomic neuropathy and sometimes reverse it. Pharmacologic and nonpharmacologic therapies are available to treat symptoms.

Autonomic Nervous System Diseases↗

Plasma big-endothelin levels, cardiac autonomic neuropathy, and cardiac functions in patients with insulin-dependent diabetes mellitus.

BACKGROUND: The alteration of endothelin (ET) levels in diabetic patients with cardiac autonomic neuropathy (CAN) has not been studied extensively and its correlation with cardiac function parameters has not been discussed. HYPOTHESIS: The aim of the present study was to discuss the correlation between the degree of cardiac autonomic neuropathy, plasma big-ET levels, and cardiac functions in diabetic patients who were clinically free of cardiovascular disease. METHODS: Twenty subjects (32.1 +/- 7.8 years, 11 men, 9 women) with insulin-dependent diabetes mellitus (IDDM) were studied to evaluate the relationship between circulating big-endothelin (big-ET1) levels, CAN, and cardiac functions. The severity of CAN was scored according to Ewing's criteria. Cardiac functions were assessed using Doppler echocardiography. RESULTS: Left ventricular systolic function in the patient group was within normal limits and comparable with the values of the control group (n = 10). The mean E/A values of diabetics with CAN (1.15 +/- 0.33, p = 0.004) and without CAN (1.34 +/- 0.17) were significantly lower than those of controls (1.57 +/- 0.27). Diabetics with CAN had significantly higher big-ET1 values (81.1 +/- 94 pg/ml) compared with others (12.4 +/- 5.9 and 21.1 +/- 17.7 pg/ml, p = 0.04). Circulating big-ET1 levels showed a significant correlation with E/A values in the control group (p = 0.01, r = -0.7) and with peak A values (p = 0.003, r = 0.64) in diabetics. The CAN score correlated negatively with E/A values (p = 0.01, r = 0.54). CONCLUSIONS: High big-ET levels might have an important role in the pathogenesis or consequences of diastolic dysfunction in diabetics with CAN. Their role in cardiac autonomic neuropathy and diastolic dysfunction should be investigated further.

Adult↗

Effects of angiotensin-converting enzyme gene polymorphism on the left-ventricular function and mass in patients with acromegaly.

In this study we have investigated the contribution of the ACE genotype to the development of left-ventricular hypertrophy (LVH) and systolic and diastolic dysfunctions in acromegalic patients. The study group consisted of 30 acromegalic patients (21 women and 9 men, age: 37.9 +/- 10.8 years, disease duration: 9.0 +/- 6.9 years). The distribution of the DD, ID and II genotypes was 40.0 (n = 12), 46.6 (n = 14) and 13.3% (n = 4), respectively, being similar to frequencies observed in a healthy population. Plasma ACE levels were 55.0 +/- 12.0 (45-84), 28.7 +/- 15.7 (8-58) and 24.5 +/- 12.0 (16-33) U/I in patients with the DD, ID and II genotype, respectively. The mean serum ACE activity in the DD genotype was significantly higher than in the heterozygous group (p < 0.0001). Serum ACE activity showed a significant negative association with the mean growth hormone level (r = -0.52, p = 0.007). The LV early diastolic flow velocity/LV presystolic flow velocity (E/A) ratios were 1.2 +/- 0.4 for the DD genotype, 1.3 +/- 0.3 for the ID genotype and 0.7 +/- 0.1 for the II genotype. The E/A ratio was considerably lower in acromegalic patients with the II genotype compared to the other genotypes (p = 0.03). The LV mass index (LVMI) values were 131.5 +/- 4.2 g/m2 for the DD genotype, 141.7 +/- 50.3 g/m2 for the ID genotype and 159.6 +/- 48.2 g/m2 for the II genotype. However, there was no significant difference in LVMI among allelic groups. All other indices of systolic and diastolic function were not statistically different in the acromegalic patients. The present data fail to support a role of ACE gene polymorphism in determining LVH in acromegalic patients. However, the I allele may prove as a useful marker predicting the development of diastolic dysfunction in acromegalic patients.

Acromegaly↗

The effect of clozapine on glucose metabolism.

Although there have been several reports that clozapine precipitated hyperglycemia and diabetic ketoacidosis in some patients, the mechanism by which clozapine impairs glucose metabolism is not known. This study investigated the effect of clozapine on glucose metabolism in six schizophrenic patients while they were free of medication and receiving 200 mg/d and 450 mg/d of clozapine. Clozapine increased mean levels of blood glucose, insulin and C-peptide. It is possible, based on these findings, that the glucose intolerance was due to increased insulin resistance.

Adult↗

Safety and efficacy of [Lys(B28), Pro(B29)]-human insulin in patients with diabetes mellitus.

The primary objectives of this study were to assess the efficacy and safety of Lys(B28), Pro(B29) in the treatment of patients with diabetes mellitus and to compare Lys(B28), Pro(B29) to currently available regular insulin with respect to quality of life. This study was designed as an open-label, non-comparative one. The number of patients enrolled in the trial was 39. At Visit 1 (week 0), blood samples for fasting, 1- and 2-hour postprandial blood glucose, and HbA1c were taken. At Visit 2 (week 6) and Visit 3 (week 12), fasting, 1- and 2-hour postprandial blood glucose, and HbA1c levels were measured again. There was no significant change in HbA1c, fasting blood glucose and 1- and 2-hour postprandial blood glucose levels. The 1- and 2-hour postprandial blood glucose excursions decreased significantly from Visit 1 to Visit 3. There were no serious adverse events during the study. Half of the patients had less hypoglycemia with LysPro insulin, while 25% had an increase in episodes. Thirty percent of patients were more satisfied with LysPro insulin than with the short-acting insulin that they had previously used. In conclusion, LysPro therapy can be regarded as safe, since there were no unexpected adverse events and no changes in the usual physical parameters.

Adolescent↗

An unusual scintigraphic pattern of benign thyroid nodules. The "fish eye" sign.

The authors describe three cases of an unusual scintigraphic pattern of benign thyroid nodule with ultrasonographic appearance. A nodule of normal, increased and decreased Tc-99m pertechnetate concentration surrounded by a rim of cold area was noticed in three patients in whom fine-needle aspiration biopsies revealed benign follicular cells.

Adult↗

Neuroelectrophysiological evaluation of untreated hyperthyroid patients.

Hyperthyroidism is a common endocrinologic disorder affecting many organ systems. Musculoskeletal and neurological involvement present themselves as fatigue, muscle weakness and paralysis. Electromyography (EMG) is essential for differential diagnosis of muscle weakness. Well defined neuropathy and myopathy have been described in these patients. In the present study 17 hyperthyroid patients were evaluated with electrophysiological tests in addition to physical and neurological examinations and biochemical laboratory studies. Needle EMG, motor and sensory conduction velocities, median and tibial somatosensory evoked potentials (SEP) were studied. For assessment of the activity of disease clinical status, neurological symptom and disability scores and serum T3, T4 and TSH levels were examined. Statistical analysis of neuroelectrophysiological findings of the patient and the control groups yielded meaningful difference in the needle EMG, sensory conduction velocity and evoked potential findings. Abnormalities were observed in 80% of the proximal muscles besides polyphasic potentials that were seen in 20% of the extensor digitorum brevis muscle. Median, ulnar and sural nerve sensory action potential amplitudes were found to be lower than that of the control group. Sural sensory nerve conduction velocity of patients was decreased in 35.5%, prolongation of median SEP latencies and increase in the amplitudes were not however statistically significant. Prolongation of Tibial SEP N1, P2 latencies were seen in 47%, amplitudes of N1 were increased in 88.2%, P2 in 58.8%, N2 in 47%. The thyroid clinical status score was correlated with Tibial SEPs amplitude. These findings suggest the presence of an initial axonal type of mild polyneuropathy. As a conclusion electrophysiological studies can be useful in the diagnosis of asymptomatic polyneuropathy in hyperthyroid patients.

Adolescent↗

Short-term effects of somatostatin analogue (SMS 201-995) on left ventricular function in healthy persons: a scintigraphic study.

Since somatostatin has been reported to have a negative inotropic and chronotropic effect on atria and positive inotropic effect on ventricle, present study was designed to investigate the acute effects of somatostatin analogue SMS 201-995 infusion on the left ventricular function in healthy volunteers. After labeling the autologous red blood cells with 750-1000 MBq 99mTc-pertechnetate, ECG-gated radionuclide ventriculography was performed. Using Fourier analysis of the left ventricular time-activity curve, ejection fraction (EF), peak ejection rate (PER), peak filling rate (PFR), time to end-systole (TES) and normalized TES/T values were calculated. Study group consisted of 12 healthy volunteers. Somatostatin analogue SMS 201-995 infusion was given at a rate of 100 micrograms/h during 2h. Baseline, 1st, 2nd h and 4th h imagings were done using the same protocol. Simultaneously heart rate and blood pressure were recorded. The difference between parameters was tested using Kruskall-Wallis test. The mean heart rate, systolic and diastolic blood pressures and did not show any statistically significant change during the somatostatin analogue infusion and 2h later in comparison to baseline values. The mean PER and PFR had a slight decrease at the first hour of infusion, but the change was not significant. However, the significant correlation of PER values with heart rate, EF and TES observed at baseline study were disappeared during the infusion. These results indicate that somatostatin analogue infusion does not appear to change the left ventricular systolic and diastolic function in healthy persons significantly.

Adult↗

Scintigraphic evaluation of functional renal reserve using angiotensin-converting enzyme inhibition in patients with type II diabetes mellitus.

Acute effects of 20 mg oral enalapril (E), and angiotensin-converting enzyme inhibitor, on renal function and the renin-angiotensin-aldosterone system were investigated in 13 patients with type II diabetes mellitus (8 female, 5 male) and 10 hypertensive controls using a radionuclide method. Plasma glucose control was evaluated with fructosamine (F) determinations. After intravenous administration of 370 MBq 99mTc-DTPA, sequential images were recorded. Glomerular filtration rate (GFR), perfusion index (PI), time to maximum activity and reno index values of the kidneys were calculated. Two days later, renal scintigraphy was repeated after oral administration of E. Plasma levels of renin, angiotensin II and aldosterone were analyzed using RIA. Basal GFR values (mean: 92.6 ml/min) correlated with F (r = 0.364; p < 0.05). In the diabetic group, 5 patients had a decrease in GFR and an increase in PI after oral E. The mean percent change of GFR was 12 +/- 32 for patients and 20 +/- 12 for controls, respectively. Percent change of GFR had a slightly negative correlation with F values (r = -0.51; p < 0.05) and with PI (r = -0.65; p < 0.001). The patients with good metabolic control had an increase in GFR and a decrease in PI indicating an increase in renal blood flow and glomerular filtration. In patients with proteinuria and poorly controlled diabetes, in response to E-induced efferent arteriolar dilation, there is a decrease in GFR and an increase in PI which indicates a fall in filtration and renal blood flow. This glomerular hemodynamic pathology precedes morphological changes due to diabetes.

Adult↗

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.

Administration, Oral↗