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Journal Article 2013; 34(4): 287-293 PubMed PMID: 23803871 Citation  Keywords:  Adult, Antidepressive Agents:therapeutic use, Cross-Over Studies, Depressive Disorder, Major:drug therapy, Double-Blind Method, Female, Hallucinogens:therapeutic use, Humans, Infusions, Intravenous, Ketamine:therapeutic use, Male, Middle Aged, Receptors, .   

OBJECTIVES: Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder.

METHODS: In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients.

RESULTS: Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point.

CONCLUSION: The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects....

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Case Reports 2013; 34(4): 273-274 PubMed PMID: 23803870 Citation  Keywords:  Diagnosis, Differential, Female, Humans, Middle Aged, Neoplasm Recurrence, Local:diagnostic imaging, Neuroendocrine Tumors:diagnostic imaging, Organometallic Compounds, Pancreatic Neoplasms:diagnostic imaging, Positron-Emission Tomography, Radiopharmaceut.   

: 56-year old woman was operated of a pancreatic NET in May 2011. Abdominal pain had led to imaging and consecutively the finding of cholecystolithiasis and the tumor. The gall bladder, left hemi-pancreas, regional lymph nodes and the (unintentional injured) spleen were resected. At routine control examination in October 2012 CT presented three contract enhancing intra-abdominal lesions with a diameter of 2-3.5 cm. Consecutively 68Ga-DOTA-NOC PET-CT showed high tracer uptake (SUV 10-12) at these lesions. Therefore a relapse of the neuro-endocrine tumor was suspected. After reoperation in December 2012 histology did not reveal any sign of neuroendocrine tumor but identified spleen tissue most probably caused by splenosis accidentally seeded at the first operation. Physiologically the spleen is highly avid at 68Ga-DOTATOC PET, but splenosis presents with less standard uptake value. In our case the described lesions presented with an SUV quite comparable to that of neuroendocrine tumor tissue....

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Journal Article 2013; 34(4): 309-313 PubMed PMID: 23803869 Citation  Keywords:  Electrophoresis, Polyacrylamide Gel:instrumentation, Female, Humans, Hyperlipoproteinemias:diagnosis, Lipoprotein(a):analysis, Lipoproteins:analysis, Male, Middle Aged, Nephelometry and Turbidimetry,.   

OBJECTIVE: Identification of lipoprotein subfractions in lipoprotein profile by Lipoprint LDL system, where a lipoprotein(a), an independent risk factor for the development of cardiovascular disease, migrates with. The concentration of lipoprotein(a) in serum over 0.3 g/l increases the risk of athero-thrombosis and a brain stroke. The persons with increased levels of lipoprotein(a) and contemporarily increased cholesterol level in serum, are at increased risk of the inception of cardiovascular or cerebrovascular event even 3-times.

PATIENTS AND METHODS: In a general group of subjects with increased serum concentration of lipoprotein(a) a lipoprotein profile analysis was performed. The general group of subjects was divided into two groups: subgroup with the lipoprotein(a) concentration in the range between 0.3-0.8 g/l and a subgroup with the lipoprotein(a) concentration over 0.8 g/l, to learn if the lipoprotein(a) particles of different serum concentration and different size do not migrate in different positions of the lipoprotein spectrum. For the analysis of serum lipoproteins an innovated electrophoresis method on polyacrylamide gel (PAG) - Lipoprint LDL system USA, was used. Lipids: a total cholesterol and triglycerides in serum were analysed by an enzymatic method CHOD PAP (Roche Diagnostics, FRG), lipoprotein(a) was analysed by an immuno-nephelometric method (Roche Diagnostics, FRG).

RESULTS: In the Lipoprint LDL system using a polyacrylamide gel (PAG) for the lipoprotein separation, lipoprotein(a) migrates in the position IDL2-IDL3. In the band of IDL2 a high Lp(a) values can be identified, when the increment of IDL2 subfraction is over the value of 0.015 g/l, i.e. 15 mg/dl (reference range for IDL2) and when the increment of IDL3 subfraction is over the value of 25 mg/dl, i.e. 0.025 g/l (reference range for IDL3).

CONCLUSIONS: A clear contribution of new method is: identification of the lipoprotein subpopulations where the lipoprotein(a) migrates with different migration position for the mild increased lipoprotein(a) concentration and high lipoprotein(a) concentration in serum was not confirmed....

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Journal Article 2013; 34(4): 322-328 PubMed PMID: 23803867 Citation  Keywords:  Adult, Antipsychotic Agents:therapeutic use, Benzodiazepines:therapeutic use, Humans, Insulin:blood, Male, Middle Aged, Risperidone:therapeutic use, Schizophrenia:blood, Schizophrenic Psychology, Severity of Illness Index, Treatment Outcome, Young Adult,.   

OBJECTIVE: Recent studies have suggested that higher insulin levels are associated with better psychopathology profiles in cross-sectional samples of patients with schizophrenia. This study examines whether drug-induced fasting insulin changes between third and eight week of treatment are related to clinical improvement in non-diabetic patients receiving the atypical neuroleptics: risperidone or olanzapine.

METHODS: non-diabetic men with a diagnosis of schizophrenia according to the DSM-IV diagnostic classification were recruited from psychiatric inpatient units. Following a drug-free period, neuroleptic treatment was initiated (risperidone n=36, olanzapine n=35) and doses were adjusted to achieve maximal clinical efficacy. All patients were hospitalized throughout the study. Initial and final evaluations of serum insulin levels and psychopathology (assessed with the Positive and Negative Syndrome Scale, PANSS), were carried out at weeks 3 and 8 after the onset of treatment, respectively.

RESULTS: There were no differences between and within the risperidone and olanzapine groups in changes of serum insulin level between the third and eighth week of treatment. In the olanzapine group, Pearson correlation analysis revealed a significant negative correlation between changes in fasting serum insulin levels and the PANSS-Total, Positive and General Psychopathology subscale scores. Only improvement in the PANSS-Negative Symptom subscale score was not correlated with insulin level change between the third and eighth week of treatment. In the risperidone group, correlations between PANSS subscales scores and the corresponding serum insulin levels change were positive, albeit statistically non-significant. In both groups the improvement in PANSS-Total scores was not correlated with changes in BMI.

CONCLUSION: Olanzapine-related changes in endogenous fasting insulin levels were correlated with clinical improvement in acutely ill non-diabetic schizophrenic patients. Because the interesting linkage between insulin and positive and negative symptoms could be an epiphenomenon, randomized studies are needed to further explore the role of insulin in therapeutic responses in patients with schizophrenia....

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Journal Article 2013; 34(3): 241-248 PubMed PMID: 23685424 Citation  Keywords:  Adult, Chemoradiotherapy:adverse effects, Cotinine:urine, Dose-Response Relationship, Radiation, Female, Glucocorticoids:administration & dosage, Graves Ophthalmopathy:metabolism, Humans, Male, Middle Aged, Nicotine:pharmacokinetics, Nicotinic Agonists:ph.   

OBJECTIVES: Radioiodine therapy (RIT) is frequently used as the definitive treatment in patients with Graves' hyperthyroidism when remission is not achieved with anti-thyroid drugs (ATDs). In this observational study, we intended to examine whether the use of high doses of radioiodine (RAI) [22 mCi (814 MBq)] with prophylaxis of oral glucocorticoids (oGCS) does not exacerbate Graves ophthalmopathy (GO) in smokers and non-smokers, especially regards to the urine level cotinine and ocular changes before and after RIT.

PATIENTS AND METHODS: The studied group consisted of 26 smokers, aged 28-61 years and 25 non-smoker patients, aged 21-54 years, respectively. The patients were enrolled to RAI after one-year of ineffective ATDs treatment. Criterion for inclusion in the study were patients with mild GO with hyperthyroidism at diagnosis based on the severity (NOSPECTS) and activity (CAS) scale. All the patients were subjected to RIT with oGCS prophylaxis and evaluated prospectively during a one-year follow-up. The ophthalmological examination was performed at various stages of RIT: initial pre-radioiodine administration, at the time of treatment 6, and 12 months after RAI. The present study is unique, because the urine cotinine measurement was employed to detect nicotine exposure, also in regard to smoking intensity.

RESULTS: In smokers, the values of serum TPO-Abs were statistically significant in the second and six month (p<0.05) and in the second and after one year (p<0.005). The TSHR-Abs concentration was significantly higher in smokers (p<0.05), rising from 22.9±1.2 IU/L before therapy to 29.6±5.3 IU/L - 2 months, 32.6±8.6 IU/L - 6 months, and slightly decreased 28.9±10.6 IU/L - 12 months. These observed changes were statistically different between groups at baseline (p<0.05) and after one-year of follow-up (p<0.005). Mean urine cotinine were considerably higher in smokers comparing to non smokers in each point of observation [903.4±770.0 and 5.2±1.7 ng/mL at baseline (p<0.001), 412.8±277.3 and 3.0±0.6 ng/mL after 2 months (p<0.001), 452.0±245 and 6.6±3.6 after 6 months (p<0.001), 379.4±236.8 and 1.0±1.2 after one year (p<0.001)]. The CAS values in the smoking group before RIT increased statistically from 2.8±0.2 points at baseline to 4.3±0.3 after 6 months, and 4.0±0.5 (12 months), while in the non-smoking patients it was 1.4±0.2, 2.8±0.3 and 2.2±0.2, respectively. The level of urine cotinine correlated positively with CAS and TSHR-Ab in the smoking group (r=0.41; p<0.05) at baseline and during follow-up (2 months: r=0.46; p<0.001, 6 months: r=0.47, p<0.005; 12 months: r=0.46; p<0.005). In the NOSPECS classification, the symptoms changed from mild to moderate, mostly in smoking patients.

CONCLUSIONS: 1) ablative RIT dose with prophylactic oral prednisone is a safe treatment in both smokers and non-smokers with mild GO; 2) The post hoc analysis showed that urinary level of cotinine can be very helpful in the assessment of exacerbation of ophthalmological clinical symptoms before and after RIT particularly in smokers....

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Clinical Trial 2013; 34(3): 217-221 PubMed PMID: 23685420 Citation  Keywords:  Adult, Aged, Ambulatory Surgical Procedures:methods, Anesthesia, General:methods, Anesthesia, Spinal:methods, Consciousness Monitors, Female, Hemorrhoids:surgery, Humans, Male, Middle Aged, Operative Time, Pain, Postoperative:prevention & control, Patient.   

OBJECTIVES: The gradual advancement of one-day surgery and conjoint ambulatory anaesthesia results from possibilities to execute mini-invasive surgeries. Such surgeries offer great benefits to the patient due to faster reconvalescence and less pain as well as faster return to normal life. The HAL-RAR method for haemorrhoid surgery, introduced as early as in 1995 by Dr. Morigan in Japan.

DESIGN AND SETTING: The goal of our study including 137 patients was research of effects of the spinal and general anaesthesia while monitoring the Bispectral Index (BIS) during the surgery. We focused mainly on the need of postoperative analgesia and possibility to discharge patient to home care after the surgery with the above mentioned type of anaesthesia. BIS helped us to monitor the sufficiency of anaesthesia and anaesthetics dosage regulation that was reflected in earlier awakening and faster reconvalescence, as well as saving anaesthetics.

RESULTS: The length of surgery was not affected by the particular type of anaesthetic procedures (25.7 minutes for the general anaesthesia and 30.2 minutes for the spinal anaesthesia). The need for postoperative analgesia was necessary for the period of 240.0 minutes after the completion of surgery for the general anaesthesia and 313.0 minutes for the spinal anaesthesia after the administration of anaesthetics intrathecally.

CONCLUSIONS: BIS is a processed EEG parameter measuring the hypnotic effect of hypnotics and sedatives in brain. BIS helps to reduce the use of anaesthetics during anaesthesia. Our results are promising and we continue in the study, monitoring also other possible parameters....

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Journal Article 2013; 34(3): 207-211 PubMed PMID: 23685418 Citation  Keywords:  Adult, Cohort Studies, Female, Follow-Up Studies, Galactorrhea:diagnosis, Humans, Hyperprolactinemia:diagnosis, Middle Aged, Pituitary Gland, Anterior:physiology, Pituitary Neoplasms:diagnosis, Pregnancy, Pregnancy Outcome, Prolactin:blood, Prolactinoma:d.   

OBJECTIVES: To determine the frequency of macroprolactinemia in a cohort of hyperprolactinemic women, describing 1) the association of macroprolactinemia with clinical variables and morphological changes in the pituitary gland and 2) clinical status and prolactin levels after 10 years of follow-up.

DESIGN: Blood samples were obtained from 32 patients for hormonal assessment. Treatment with cabergoline or bromocriptine was interrupted 3 months before the determination of serum prolactin and macroprolactin. Macroprolactin was measured using the polyethylene glycol (PEG) precipitation method. Computed tomography was performed in all patients.

RESULTS: The frequency of macroprolactinemia was 28.1%. In 19 patients prolactin remained elevated (persistent hyperprolactinemia). In 13, prolactin returned to normal (former hyperprolactinemia). Nine patients with PEG recovery between 40 and 50%, and the only two macroprolactinemic patients with previous hyperprolactinemia were excluded from the analysis of clinical outcomes. Only one of seven macroprolactinemic patients had an abnormal pituitary image (empty sella). None had galactorrhea.

MAIN FINDINGS: Classic symptoms of hyperprolactinemia and abnormal imaging findings are not common in patients in whom macroprolactin is the predominant form of PRL.

CONCLUSIONS: Women with hyperprolactinemia, especially if asymptomatic, should be routinely screened for macroprolactinemia. Macroprolactinemia remains stable in the long term....

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Case Reports 2013; 34(3): 173-176 PubMed PMID: 23685414 Citation  Keywords:  Amino Acid Substitution:genetics, Chromosomes, Human, X, Female, Humans, Insulin Receptor Substrate Proteins:genetics, Middle Aged, Schizophrenia, Paranoid:genetics, Signal Transduction:genetics,.   

: This report deals with a female patient with schizophrenia who was found to have a mutation in the insulin receptor substrate-4 gene that is located on chromosome Xq22.3. Since this mutation is expected to change amino acid coding from histidine to tyrosine and cause an altered insulin receptor substrate-4 protein, and the insulin receptor substrate-4 protein may be involved in neuronal growth and function in the brain, it is possible that it is this insulin receptor substrate-4 gene mutation that underlies this patient's schizophrenia development....

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