Band 5, Heft 3

Statins are widely used and well tolerated cholesterol-lowering drugs, and when used for therapy purposes reduce morbidity and mortality from coronary heart disease. Simvastatin is one of nine known statins, specific inhibitors of hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting step of cholesterol biosynthesis, and is believed to reduce plasma cholesterol levels by decreasing the activity of this enzyme. Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Although statins are generally safe, minor and severe adverse reactions are well known complications of statin use. Adverse events associated with simvastatin therapy are uncommon, but potentially serious. In this review some details about statins including their adverse effects in humans and animals, the effects of simvastatin on various intracellular and mitochondrial processes, and molecular mechanisms underlying simvastatin cytotoxicity are discussed.

Syngeneic transplantation of murine aorta segments with advanced atherosclerotic lesions in defined recipients is a valuable model for regression studies. To date, this model has not been used to study the regression of initial atherosclerotic lesions. The aim of this study was to evaluate a microsurgical technique of syngeneic heterotopic transplantation of the thoracic aorta of young apolipoprotein E-deficient (ApoE-/-) mice to the abdominal aorta of wild-type recipients. Stereological quantification methods were tested in order to assess changes in structure and volume of the aortic wall including the involvement of immune cells in changes of the atherosclerotic lesions. The animals were euthanised one month after surgery and histological analysis including stereological quantification of changes in both the grafts and adjacent aorta segments was performed. The overall survival rate of the recipients was 62.5%. No regression of initial atherosclerotic lesion was achieved and neointima formation and elastin degradation prevailed in all transplanted specimens. The volume of the arteriosclerotic lesions was higher (p<0.001) and elastin length density was lower (p<0.001) in transplanted ApoE-/- samples as compared to adjacent segments. In transplanted grafts, T- and B-lymphocytes, macrophages and neutrophilic granulocytes formed non-random clusters within the vessel wall and they were colocalised with the sutures. The reproducibility of the promising regression model was derogated in young mice by the striking dependence of the results upon the operation technique. Stereological assessment has proven to be accurate, correct and reproducible; it has provided us with robust quantitative estimates, which can be achieved with a reasonable effort.

Scombroid fish or histamine food poisoning is an illness typically associated with fish consumption, rarely encountered and reported in Europe. Symptoms develop quickly and resemble an allergic reaction. This paper reports three cases of severe scombroid poisoning in previously healthy patients, which presented diffuse macular erythema, hypotension, palpitations, and abnormal electrocardiogram (ECG). All patients required intensive care, with a complete resolution of symptoms and ECG changes within 24 hours. This is the first Romanian report of scombroid poisoning, emphasizing that medical personnel should be aware of this condition, because symptoms and ECG changes often lead to confusion with other diseases.

Signal averaged electrocardiogram (SAECG) is considered an important noninvasive indicator identifying patients at risk for ventricular arrhythmias. The aim of this study was to improve noninvasive prediction of CAD by integrating SAECG with the result of exercise tests in diabetic patients. Diabetic patients with stable angina pectoris underwent exercise testing and SAECG. Then a diagnostic score was derived that combined results of exercise testing and SAECG. A diagnostic score (0 to 2 points) was calculated by assigning 1 point for a positive exercise test result and 1 point for a positive SAECG. One hundred and seventy patients were included in the study. In patients with a score of 0, the likelihood of CAD is 18% whereas the likelihood of CAD is 95% in patients with a score of 2. Triple vessel CAD is present in 54%, 7% and only 1.5% of patients with score 2, 1 and 0 respectively. Therefore, patients with score 2 have a poor prognosis compared with score 1 or 0. A diagnostic score combining exercise testing and SAECG can distinguish patients with CAD from those without CAD with high accuracy in diabetic patients.

Direct current cardioversion, which produces electrical energy, is highly effective for the termination of cardiac arrhythmia and sometimes is indicated in patients with coronary artery stents due to arrhythmias. Only a few reports have been published describing the potential adverse interactions between foreign bodies and electrical cardioversion. The aim of this animal study was to investigate the acute effect of repeated external defibrillation on coronary artery tissue and adjacent myocardium at the implantation site of coronary stents. Custom-made stainless steel stents were implanted in the coronary arteries of 7 dogs. Rapid ventricular pacing was performed to induce ventricular fibrillation. Defibrillation was achieved [5 J/kg; n=2 and 8 J/kg; n=3]. In 2 animals, coronary stent was implanted but defibrillation was not performed [control group]. The animal’s heart were excised and sent for microscopic examination. The light and electron micrographs of heart muscles showed no histological and ultrastructural changes in defibrillated and control dogs. It is concluded that nickel coating provides good resistance to heat in coronary stents and repeated defibrillation does not cause histopathological changes typical of thermal injury at the implantation site of coronary stent.

Anemia is an indisputable finding in patients scheduled for coronary artery bypass graft (CABG) that can occur any time preoperatively. In presence of severe coronary artery disease, anemia can dramatically affect surgical outcomes. Therefore, we conducted this study to determine the effect of low preoperative hemoglobin (Hgb) on postoperative outcome in patients who underwent coronary artery bypass graft (CABG). In all, 4432 patients who had undergone isolated CABG at Tehran Heart Center over the 2-year period from March 2006 to February 2008 were studied. All medical records of the aforementioned patients were derived from our hospital surgery data bank. After adjustment for confounders, the association of different preoperative levels of Hgb with risk of cardiac, pulmonary, infectious, and ischemic complications, and also with prolonged ventilation and resource utilization, were assessed in a multivariable model. After adjustment for confounders that may affect mortality and morbidities, we found that cardiac, infectious, ischemic, and pulmonary complications, as well as postoperative mortality, were significantly higher in anemic patients compared to those with normal Hgb levels. In addition, total ventilation time, total intensive care unit hour stay (ICU), hospital length of stay (HLOS), and postsurgery length of stay (PLOS) were significantly longer in anemic patients. We concluded that isolated CABG patients with preoperative anemia have significantly higher mortality and morbidity, and use more health care resources. Preoperative anemia is an independent variable for increased resource utilization, morbidity, and mortality.

We report the case of a 52-year-old woman who presented with a several-year history of palpitation (exacerbated by emotional stress and physical activity) and recent development of atypical chest pain. An investigation was undertaken to diagnose the patient’s problem and to recommend the best possible therapy. Transthoracic echocardiography and a computerized axial tomography scan showed evidence of complete absence of the pericardium, which is a rare congenital heart defect.

De novo translocation interrupting the transcription unit of SATB2 gene has been associated with cleft palate only (CPO). We tested for the presence of the copy number of SATB2 gene in a sample of 92 patients with CPO using a quantitative real-time PCR approach. In one patient (1%, 95% CI = 0.2%–6%), a 19 Mb de novo deletion encompassing the SATB2 gene was detected. These results suggest that SATB2 gene deletions do not play an important role in the etiology of cleft palate.

The A3243G mutation in the mitochondrial tRNALeu (UUR) gene is one of the most common causes of mitochondrial DNA related disorders. Originally it was described in MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic acidosis, Stroke-like episodes), later it had been found to be associated with various phenotypes. In our study the mutation frequency of the A3243G mtDNA mutation was investigated in patients with maternal sensoneural hearing loss, stroke-like episodes, ataxia and myopathy with undetermined etiology. We screened 631 Hungarian patients in North-East, South-West and Central Hungary between 1999 and 2008 for this mutation. The mtDNA analysis was performed from blood and/or muscle tissue. The A3243G substitution was present in 6 patients in heteroplasmic form. The segregation analysis detected 8 further cases. The frequency of the A3243G mutation was 2.22% in the investigated patients. The A3243G mutation frequency in Hungary does not differ significantly from other countries using similar patient selection criteria, however in Finland a higher mutation rate was found. In studies investigated the mutation frequency of this mutation in diabetes mellitus similarly wide variety was detected as well. We conclude that the study design has a huge impact on the result of the genetic epidemiological investigation analyzing the mutation frequency of the A3243G mutation due to the broad clinical phenotype and the different mutation load in different tissues.

Cardiovascular complications, including stroke, may be attributed the highest rate of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of our study was to evaluate the prevalence of CKD in patients with symptomatic ischaemic cerebrovascular disease and to establish of whether CKD may define a particular risk pattern of cerebral vessels modifications in this category of patients. The prevalence of CKD was evaluated in 590 consecutive patients with symptomatic ischaemic cerebrovascular disease admitted to a department of neurology. The types of stroke, the vascular territories, the vascular modifications and the haemodynamic changes (resistance index- RI) found by neurosonology (extracranial and transcranial Doppler ultrasound) were analysed in relation to classic and non-classic cerebrovascular risk factors, as well as to stages of CKD (defined by estimated glomerular filtration rate-eGFR-MDRD4 formula-K/DOQI 2002). The prevalence of CKD in the studied patients was 70.84%. Atherosclerosis in a diffuse pattern was detected in 79.7% of CKD patients, while carotid artery stenoses were found in 10% of cases, occlusions- 5.3%, stenoses + occlusions-1.2%, and multiple stenoses- 3.8% of cases. The RI evaluated in the internal carotid arteries correlated with fibrinogen(P<0.0001) and GFR(P<0.0001), while IR in the middle cerebral arteries correlated with fibrinogen(P<0.05), C-reactive protein(P<0.0001), and GFR(P<0.0001). There is a strong relation between symptomatic cerebrovascular disease and CKD, a fact demonstrated by the increased prevalence of CKD in these patients and by the severity of the cerebral vessels lesions.

The aim of the present study was to characterize the pattern of adverse drug reactions (ADRs) reported in a university teaching hospital in south-east Serbia. The study was conducted based on ADRs reported during a six-month period to the ADR reporting unit of the university clinical center. Evaluation of data was done for various parameters, such as patient demographics, drug and reaction characteristics, and outcome of reactions. Assessment was also done for causality, severity and predisposing factors. During the 6-month study period, 44 ADRs were reported, with an overall incidence of 0.33%. No significant difference was seen in the overall incidence of ADRs observed in males and females. Incidence of ADRs among elderly (43.2%) and older (25%) adults was significantly higher than in other age groups. Type A reactions (66.7%) accounted for majority of the reports. The most commonly affected organ system was the renal system, (22.7%) with hyperkalemia as the only reported reaction. ACE inhibitors (48.6%) were the drug class most commonly involved, where fosinopril (25.7%) was the individual drug most frequently reported. Additional treatment was pursued for management of ADRs in majority (52.3%) of the reports. In 52.3 % of the reports, the patient had recovered from the reaction by the time of evaluation. Upon causality assessment, the majority of the reports were rated as probable (43.2%). Mild and moderate reactions accounted for 43.2% and 54.6%, respectively. In 36.3% of the reports, the reaction was considered to be preventable. The most common predisposing factors were polypharmacy and multiple disease state. The pattern of ADRs reported in our hospital is comparable to the results of studies conducted in hospital set up elsewhere. Our evaluations revealed opportunities for intervention to ensure safer drug use.

Melanosis coli is a brown to black discoloration of the colon mucosa usually associated with long-term ingestion of laxatives. However, melanosis coli can be found in patients with no history of laxative use. Regular use of herbal remedies could be the major source of anthranoid laxatives in such patients. We designed a prospective case series study to identify the clinical characteristics and etiology of melanosis coli in affected patients. This study took place in Ankara, Turkey, between 08/2005 and 11/2006. Patients with endoscopic diagnosis of melanosis coli were interviewed for demographical data and use of herbal remedies. A total of 380 colonoscopies were performed during this period. Melanosis coli was diagnosed endoscopically in 12 patients (3.17%), 11 of whom were found to have characteristic pigment-laden macrophages in histopathological examination. Herbal remedies were the main etiological factor in the development of melanosis coli in 10 out of 11 patients. Diffuse involvement was found in 2 patients who had a history of long-term use. In 8 patients, melanosis coli was located in the left side of the colon. Although melanosis coli is a harmless discoloration of colonic mucosa resulting from complementary or alternative medicine, we believe that this association with herbals was overlooked or not inquired in patients. Therefore, it should be emphasized that “natural” or “alternative” is not equal to “safe”.

Bezoars are collections of indigestible materials found in the gastrointestinal tract. Rapunzel syndrome is a rare complication of a gastric trichobezoar in which the mass of hair extends through the pylorus into the small bowel and can even reach the colon. A 12-year-old girl with severe pain and a feeling of “fullness” in the upper abdomen was admitted to Pediatric Surgery. Two days before admission, the patient presented with vague abdominal pain, vomiting with a little blood, and black stool. On physical examination she was pale and listless with patchy alopecia. Abdominal examination showed a mobile, palpable mass in the epigastrium. The initial hematocrit was 7,1%, and the erythrocyte count was 1,12×1012 cells per liter. Abdominal ultrasound and computed tomographic (CT) examinations confirmed the presence of a tumor-like formation in stomach. A giant bezoar with ulceration on the back wall of the stomach was verified by upper gastrointestinal endoscopy. Endoscopic extraction was not possible because of the size of the bezoar. Gastrotomy was performed to remove the bezoar that occupied most of the stomach, with a long tail that extended deeply into the duodenum (Rapunzel syndrome). The bezoar, 35 by 10 cm in diameter, was black and consisted of hair and synthetic fibers. Prompt diagnosis and treatment of trichobezoars are important to avoid a possible fatal outcome.

The recto-anal region is innervated by extrinsic and intrinsic nerves and a number of neuropeptides including substance P (SP) have been suggested to participate in the regulation of intestinal movements. We examined the age-related changes in the distribution of SP-immunoreactive nerve structures in the distal part of the rat large intestine. Using immunohistochemistry, the presence of SP was studied in fresh tissues from Wistar rats at different ages taken at three sampling sites, the distal rectum, anal canal and internal anal sphincter. In the 15-day old rats the myenteric plexus of the distal rectum and anal canal was well outlined by numerous SP-immunoreactive varicose nerve fibres encircling immunonegative perikarya. In the circular muscle layer, nerve fibres and small nerve bundles ran parallel to the muscle cells, while in the longitudinal muscle layer, only occasional nerve fibres were seen. At the level of the internal anal sphincter, no myenteric ganglia were present. Here, thin varicose fibers ran parallel to the smooth muscle cells. In the 3-month old rats, a larger number of intensely staining SP-immunoreactive nerve fibres were found and in the circular muscle layer, thicker nerve strands were observed. In the 26-month old rats, the density and staining intensity of SP-immunopositive nerve fibres in the myenteric plexus was lower than in the 3-month-old rats. Similar changes in the SP-immunostained fibres in the internal anal sphincter were observed. Degenerative alterations in SP-containing fibres during aging appear to play a role in ano-rectal motility and sphincter control.

The interaction between cancer cells and platelets has been known for a long time. Although platelet indices have been also investigated in several clinical settings, it has not been exactly demonstrated in cancer patients. We investigated platelet indices in colorectal cancer patients and compared with healthy subjects. Two hundred and twenty-one colorectal cancer patients and 110 healthy subjects were enrolled into the retrospective study. Data were obtained from computerized medical records of our hospital. Medical record review was performed for all patients regarding thrombocyte indices. Platelet count (325.000/mm3 ± 265.000/mm3 vs 267.000/mm3 ± 67.000/mm3; p=0.025; respectively) and plateletcrit (Pct) (0.25% ± 0.10 vs 0.21 ± 0.05; p<0.001; respectively) were increased in patients compared with healthy subjects while mean platelet volume (MPV) and platelet distribution width (PDW) were similar. The platelet indices were not related to existence of metastasis or acute abdomen. Platelet count and Pct, but not MPV and PDW, are elevated in colorectal cancer patients. Future studies that investigate platelet morphology, function, and putative role of platelets in tumorigenesis and metatasis should be established.

Hypothyroidism in pregnancy is associated with serious maternal and fetal risk. Rarely, it is manifested by life-threatening cardiac complications, such as gross pericardial effusion and tamponade. We present a case of successfully treated gross pericardial effusion and tamponade in a 22-week pregnant woman with hypothyroidism. The patient was treated by pericardial drainage with further treatment of hypothyroidism with levothyroxine. During the follow-up pregnancy was uncomplicated without recurrence of pericardial effusion and successful delivery of full-term baby. We conclude that careful monitoring of thyroid functional tests and proper management should be performed in pregnant women with hypothyroidism to prevent cardiac complications of the disease, like pericardial effusion and tamponade.

Pseudocyesis or delusion of pregnancy is a rare psychopathological syndrome described in humans and higher mammals. We describe and discuss two cases of this rare syndrome in a 46-year perimenopausal and a 59-year old postmenopausal woman. Gynecologic, ultrasound examination, and biochemistry testing (β-HCG) confirm the diagnosis of nonexistent clinical and biochemical pregnancy. These examinations have the potential to confirm abdominal tumors, while psychiatric examinations generally reveal the psychic basis of the disease; which should be treated through team approach by both the psychiatrist and gynecologist. Additionally, special reference should be given to long-term psychiatric follow-up and management of the current mental stress and emotional problems by a combination of antipsychotics and psychotherapy, depending on each individual clinical picture.

It was the aim of this study to assess fluoride retained in saliva after use of fluoride-containing tablet DENTTABS® compared to toothpaste containing amine fluoride. Four subjects (2 normal saliva secretors, 1 slow secretor, and 1 fast secretor) participated in this crossover study comparing DENTTABS® and ELMEX®. After baseline sample collection, calibrated study personnel brushed the subjects’ teeth with the assigned product for 3 minutes. Saliva samples were taken at baseline (T0), immediately after brushing (T1) and then 10 (T2), 25 (T3) and 85 (T4) minutes post-brushing. The amount of saliva collected was measured, and the fluoride content was analysed. All 4 subjects repeated all study cycles 5 times. Statistical analysis was done using the Mann-Whitney-U test and Spearman correlation. The fluoride retention was significantly higher after brushing with DENTTABS® at T1 and T2. There was a correlation between individual salivary flow rate and the F- content. Flow rate in g/min ranged from 1.1 to 3.8 at T1 and from 0.2 to 1.1 at T4 with much higher F- retention in slow secreting cycles. The saliva fluoride clearance kinetics of two equal amounts of fluoride-containing oral hygiene products demonstrate higher retention for DENTTABS®.

Elevated pulse wave velocity (PWV) reflects increased arterial stiffness. Several studies have investigated PWV in peritoneal dialysis (PD) patients, but direct comparisons with healthy controls were not done. The potential influence of peritoneal transport characteristics on arterial stiffness in PD patients was suggested in recent studies. The aims of this study were to compare PWV in PD patients and healthy volunteers, and to investigate factors associated with increased PWV. The carotid-femoral PWV was measured in 28 PD patients and 28 healthy controls, matched for age and gender. A peritoneal equilibration test (PET) was performed in all PD patients. Based on the PET, patients were classified as: high transporters (H) (n=8), high-average (HA) (n=12), low-average (LA) (n=6), and low transporters (L) (n=2). Six of the PD patients were diabetic. PWV was significantly higher in the PD patients than in the controls (9,9±2,4 vs. 8,0±0,9; p=0,0004). In the PD group, PWV was higher in H/HA than in L/LA patients (10,4 ± 2,5 vs. 8,6 ± 1,0; p=0,008), but all the diabetic patients were in the H/HA group. PWV was significantly higher in diabetic than in non-diabetic PD patients (12,8 ± 2,0 vs. 9,1 ± 1,7; p=0,004). In the PD patients, significant positive correlations were found between PWV and: age, pulse pressure, Kt/V, and duration of PD therapy. In conclusion, the carotid-femoral PWV is elevated in peritoneal dialysis patients. Increased PWV in PD patients is associated with age, diabetic status, and longer duration of PD therapy, but not with this type of peritoneal transport.

The aim of this study was to assess the relationship between lifestyle characteristics and the probability of metabolic syndrome in the Lithuanian middle-aged population of Kaunas city. Study sample was comprised of 1403 individuals aged 35–64 years. Metabolic syndrome was defined by International Diabetes Federation definition. Lifestyle habits were evaluated using frequency questionnaires. The prevalence of metabolic syndrome was identified in 29.7% of men and 35.1% of women. In men only alcohol intake increased the risk of metabolic syndrome: wine intake daily or several times a week increased the risk of metabolic syndrome in men aged 35–49 years by 3.8-fold whereas intake of spirits once a week or more often increased the risk of metabolic syndrome in men aged 50–64 years by 2.8-fold. In women aged 50–64 years beer intake daily or several times a week (OR=11.9; p=0.015) and some unhealthy nutrition habits — intake of cakes 4 times a week or more often (OR=5.49; p=0.005) and slather spread butter on bread (OR=2.09; p=0.028) increased the odds of metabolic syndrome. Our findings indicated that frequent intake of wine and spirits increased the risk of metabolic syndrome in men; frequent intake of beer, cakes, slather spread butter on bread and low education level increased the risk of metabolic syndrome in women.

Primary aldosteronism (PA) has long been considered a rare disease, but a higher prevalence was suggested recently. The aim of this study was to evaluate the prevalence of PA in a group of Bulgarian hypertensive patients, including patients with adrenal incidentalomas (AI). The aldosterone to renin ratio (ARR)>750 was used as a positive screening test and the Captopril test was performed to confirm the diagnosis. Adrenal CT scan was used to differentiate between the main subtypes of PA- aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). The diagnosis of APA was retrospectively confirmed after surgery. After excluding other forms of endocrine hypertension, except PA, we investigated a total of 472 consecutive hypertensive patients, among them 96 patients with AI. Final diagnosis of PA was reached in 38 patients (8.05%) in the entire hypertensive population and in 12 patients (12.5%) among hypertensive patients with AI. In the group of PA, 15 patients (39.5%) were diagnosed with APA and 23 patients (60.5%) had an IHA. Among all patients with PA 21 (55.3 %) presented with hypokalemia. Our findings of a relatively high prevalence of PA support an early diagnosis of this potentially curable disease, especially in hypertensive patients with AI.