Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia

Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.     

Alpha-methyl-l-tryptophan positron emission tomography in epilepsy with cortical developmental malformations

Preliminary studies suggest that alpha[(11)C]methyl-l-tryptophan positron emission tomography can detect the epileptic focus within malformations of cortical development. We determined the sensitivity and specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying epileptic focus in children with intractable, neocortical epilepsy with and without malformations of cortical development. Seventy-three epileptic children were classified into lesional and nonlesional groups, and compared regarding focal increased alpha-[(11)C]methyl-l-tryptophan uptake. The sensitivity and specificity of focal increased alpha-[(11)C]methyl-l-tryptophan uptake, using intracranial electroencephalogram localization of seizure onset as the standard, were compared between lesional and nonlesional groups. The specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography for detecting seizure onset lobe was equally high in lesional (97%) and nonlesional groups (100%), whereas sensitivity was higher in the lesional than the nonlesional group (47% versus 29%; P = 0.047). The incidence of alpha-[(11)C]methyl-l-tryptophan uptake abnormality was higher in the lesional than the nonlesional group (P < 0.01). Alpha-[(11)C]methyl-l-tryptophan positron emission tomography localized and visualized epileptogenic regions in 25% of patients with nonlocalizing magnetic resonance imaging. Although overall sensitivity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying neocortical epileptic focus is modest, specificity is extremely high. When an alpha-[(11)C]methyl-l-tryptophan focus is detected, it likely represents the epileptogenic region to be resected.     

Elucidation of the anatomy of a satiety network: Focus on connectivity of the parabrachial nucleus in the adult rat

We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c‐Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well‐known feeding‐related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding‐activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding‐activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding‐activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding‐activated neuronal groups, suggesting that short‐loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803–2827, 2016. © 2016 Wiley Periodicals, Inc.     

Effect of perinatal stress on the biogenic amine neurotransmitter level of the adult rat's brain

The amount of biogenic amines (dopamine and serotonin) and their metabolites (DOPAC, HVA, 5-HIAA, and 5-HTOL) in five regions of the brain (frontal cortex, hypothalamus, hippocampus, striatum, and brainstem) was studied in the male and female offspring of control and perinatally (48 h before birth or 48 h after birth) food and water deprived dams, when they were three months old, by using HPLC-EC determination. The increase of amine or metabolite level was dominant (19 values increased and 10 decreased related to control). Before-birth stress caused increase in 9 case and only 2 decreased, while in the case of after-birth stress 10 increased and 8 decreased. However, though there is no possibility to decide an exact tendency of direction, the after-birth stress (transmitted by milk) has more expressed effect. Striatum and brainstem were the most touched regions. There was a gender dependence with the dominance of males, except striatum. Blood plasma nociceptin level was also studied and there was a significant elevation in males after pre- and postnatal deprivation, while in females only after postnatal deprivation. The importance of the results in correlation with other stress effects is discussed.     

Beta lactoglobulin homologue placental protein 14 (PP14) in serum of patients with trophoblastic disease and non-trophoblastic gynecologic malignancy

Summary Serum levels of beta lactoglobulin homologue placental protein 14 (PP14) were measured by a sensitive radioimmunoassay in various trophoblastic diseases and non-trophoblastic gynecologic malignancies. While trace amounts of protein were detected in sera of non-pregnant subjects (22.3±13.7 g/l), during first half of normal pregnancy a dramatic rise of serum-PP14 levels was demonstrable with a peak-value at 7th–10th week of gestation, followed by a decline thereafter. Serial determinations of PP14 have been performed in 31 patients with trophoblastic tumour (20 hydatidiform moles, 4 invasive moles and 7 choriocarcinomas). In patients with hydatidiform moles and invasive moles (273.5±106.5g/l and 162.2±109.6g/l) respective values before therapy were much exceeding the nonpregnant controls. After therapy there was a rapid decline of the serum-PP14 levels within two weeks. In patients with choriocarcinoma the PP14 values were moderately elevated (66.4±25.7g/l), and declined following the remission of disease. In 32 gynecological tumours (21 carcinomas of the cervix, 4 endometrial carcinomas, 5 ovarian carcinomas, 2 carcinomas of the vulva) the pretreatment levels were not different to normal controls.     

Serum levels of placenta-specific tissue protein 12 (PP12) in pregnancies complicated by pre-eclampsia, diabetes or twins

PP12 is one of the recently discovered soluble tissue antigens of the placenta. During normal pregnancy maternal serum PP12 levels rise during the first 18 weeks reaching a mean peak value of 139.9 +/- 40.26 micrograms/l; after that there is a fall to a mean value of 111.9 +/- 42.39 micrograms/l between 28 and 40 weeks. Significantly higher mean serum PP12 levels were found in the third trimester in two high risk pregnancy groups (281.09 +/- 117.08 micrograms/l in pre-eclamptic toxaemia and 203.71 +/- 73.77 micrograms/l in diabetes) while serum PP12 levels remained normal (114.94 +/- 58.06 micrograms/l) in twin pregnancy. The increase of serum PP12 concentration in toxaemia and in diabetes may be of considerable diagnostic significance.     

Comparison of 150 simultaneous bilateral and 300 unilateral percutaneous nephrolithotomies

PURPOSE: To compare the results, complications, efficiency, and safety of simultaneous bilateral percutaneous nephrolithotomy (SBPN) and unilateral percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We compared the results and complications of 150 SBPNs with those of 300 unilateral PCNLs. All the procedures were performed by one surgeon which provides relatively constant parameters. The success rates, preoperative and postoperative laboratory results, and complications were compared on the basis of stone size and the number of nephrostomy tracks. RESULTS: There were no significant differences between the results and complications of SBPN and PCNL. The SBPN itself did not cause more blood loss than unilateral PCNL. In both groups, the blood loss was in direct proportion to the size of the stones and the number of nephrostomy tracks. After SBPN, kidney function improved >20% in 12.2% of the patients and worsened for more than 3 days in only 4%. Temporary worsening of kidney function occurred in the unilateral procedure group as well (8%), mostly in cases of solitary kidneys or bilateral stones. The SBPN was not more hazardous than unilateral PCNL (complication rate 11.3% v 14.3%, respectively). In both groups, most of the complications were in proportion to the size and difficulties of the stones. CONCLUSION: Simultaneous bilateral percutaneous nephrolithotomy is a safe and advantageous procedure that is not more hazardous than the separate PCNL in cases of bilateral large stone burdens. To our knowledge, these are the largest reported series of these procedures and the only comparative analysis of SBPN and PCNL.     

Positron emission tomography in presurgical localization of epileptic foci

The success of cortical resection for intractable epilepsy of neocortical origin is highly dependent on the accurate presurgical delineation of the regions responsible for generating seizures. In addition to EEG and structural imaging studies, functional neuroimaging such as positron emission tomography (PET) can assist lateralization and localization of epileptogenic cortical areas. In the presented studies, objectively delineated focal PET abnormalities have been analyzed in patients (mostly children) with intractable epilepsy, using two different tracers: 2-deoxy-2-[18F]fluoro-D-glucose (FDG), that measures regional brain glucose metabolism, and [11C]flumazenil (FMZ), that binds to GABAA receptors. The PET abnormalities were correlated with scalp and intracranial EEG findings, structural brain abnormalities, as well as surgical outcome data. In patients with extratemporal foci and no lesion on MRI, FMZ PET was more sensitive than FDG PET for identification of the seizure onset zone defined by intracranial EEG monitoring. In contrast, seizures commonly originated from the border of hypometabolic cortex detected by FDG PET suggesting that such areas are most likely epileptogenic, and should be addressed if subdural EEG is applied to delineate epileptic cortex. In patients with cortical lesions, perilesional cortex with decreased FMZ binding was significantly smaller than corresponding areas of glucose hypometabolism, and correlated well with spiking cortex. Extent of perilesional hypometabolism, on the other hand, showed a correlation with the life-time number of seizures suggesting a seizure-related progression of brain dysfunction. FMZ PET proved to be also very sensitive for detection of dual pathology (coexistence of an epileptogenic cortical lesion and hippocampal sclerosis). This has a major clinical importance since resection of both the cortical lesion and the atrophic hippocampus is required to achieve optimal surgical results. Finally, the author demonstrated that in patients with neocortical epilepsy, FDG PET abnormalities correctly regionalize the epileptogenic area, but their size is not related to the extent of epileptogenic tissue to be removed. In contrast, complete resection of cortex with decreased FMZ binding predicts good surgical outcome suggesting that application of FMZ PET can improve surgical results in selected patients with intractable epilepsy of neocortical origin.     

The role of scintigraphy in the diagnosis of mandibular bone changes

Investigating the scintigraphic images of jaws may have a diagnostic value of bone alterations of dental origin. Anterior view of whole body bone scintigraphy revealed hot spot on jaws of 61% (279) of patients. Twenty-six patients (mean age 58.3 year) from all of those who had increased tracer uptake (ITU) in the maxillo-mandibular region were called back for dental examination. 279 out of 459 (61%) patients had ITU in the maxillo-mandibular region. Dental examination revealed the dental origin of ITU in all cases. In case of periapical pathosis tracer uptake showed 28.79% increase compared to the contralateral side. In marginal periodontitis 23.82% ITU was found. In case of loading due to prosthesis 13.06% ITU was observed. The mean DMF-T value was 26.36 +/- 4.52 (D = 4.12, M = 20.8, F = 1.44). The prosthetic index was 0.42 on the mandible. The above mentioned data mean very low oral health conditions of the patients included in this examination. The results show that bone scintigraphy is a valuable procedure in detecting tooth related jaw lesions. Bone scintigraphy provides very useful data on oral health of these patients. Enrolling of these patients into regular dental care is inevitable.