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PubMed1995

Risperidone in the treatment of affective illness and obsessive-compulsive disorder.

BACKGROUND: Risperidone is a new-generation atypical antipsychotic agent with potent dopaminergic and serotonergic antagonist activity. Compared with traditional dopamine-blocking neuroleptics, risperidone is more effective in treating negative symptoms of schizophrenia and may be less likely to cause extrapyramidal symptoms or tardive dyskinesia. Although risperidone is marketed for the treatment of schizophrenia, its novel psychopharmacologic effects and potentially mild side effect profile suggest the possibility of other therapeutic applications. An open prospective study was undertaken to determine whether risperidone might diminish psychosis, severe agitation, or rapid cycling in patients having acute and chronic primary affective illnesses (bipolar and major depressive disorder) and to document response characteristics and side effects. Additionally, a small number of patients with refractory obsessive-compulsive disorder (OCD) without comorbid tic or delusional disorders were given open trials of risperidone added to their medication. METHOD: Outpatients who fulfilled DSM-IV criteria for bipolar I, bipolar II, or major depressive disorder and suffered from psychosis or agitation associated with their illness (N = 20) and those who had treatment-refractory DSM-IV OCD (N = 5) were started on open trials of risperidone at daily doses of 1 to 1.5 mg. Doses were adjusted upwards to a maximum of 6 mg depending on clinical response. RESULTS: Seventeen (85%) of 20 patients (13 bipolar, 4 major depressive disorder) showed complete or partial improvement after treatment with risperidone doses ranging from 1 to 6 mg/day (mean = 3.5 mg). Beneficial effects included decreases in agitation, psychosis, sleep disturbance, and rapid cycling. Four patients (20%) discontinued risperidone because of intolerable side effects. Five patients with refractory OCD also showed significant symptomatic improvement after the addition of risperidone. CONCLUSION: The findings suggest that (1) risperidone may be useful in the acute/p.r.n. and chronic treatment of psychosis, agitation, and cycling accompanying affective illness, and (2) risperidone may be useful in augmenting pharmacologic response in OCD.

Adult↗
PubMed2004

Case report: severe infraocclusion ankylosis occurring in siblings.

AIM: This was to report a rare case of strong familiar tendency of ankylosis of maxillary second primary molars. CASE REPORT: Three Caucasian children, male twins of 8.5 years and a sister of 10 years, were diagnosed as having severely infraccluded maxillary second primary molars with underlying second premolars. In all three cases, the early extraction of the infraoccluded molars and an active treatment with cervical extraoral traction allowed the physiologic eruption of second premolars. Follow-up showed that normal vertical relationship and bone height had been obtained. CONCLUSION: Early diagnosis, as well as appropriate treatment and careful follow-up are very important in the presence of severe infraocclusion, when the marginal ridge of affected primary teeth is at or below gingival level.

Child↗
PubMed1980

Alteration of erythrocyte phosphate transport in primary depressive disorders.

Plasma and erythrocyte phosphate levels, concentrations of red cell organic phosphate ester fractions (acid labile and acid resistant phosphate pools) and intracellular ATP content were determined in 16 patients with bipolar depression, in 14 subjects with unipolar depression as a group of primary affective disorders, in 15 patients suffering from neurotic depression and in 45 healthy controls. Simultaneous in vitro measurements were carried out to detect the exchange rates of inorganic phosphate between the extracellular phosphate pool and the different intracellular phosphate fractions, by use of 32P and applying tracer kinetic analysis. Plasma and red cell inorganic phosphate levels, passive phosphate transport and transfer of inorganic phosphate into the membrane ATP pool were significantly lowered in the primary depressive group as compared to the biochemical values observed in the neurotic group and in the healthy controls. The results suggest an alteration in anion transport across the red cell membrane in primary depressive disorders.

Adenosine Triphosphate↗
PubMed1990

Association between family history of affective disorder and the depressive syndrome of Alzheimer's disease.

For each of 41 index patients with probable Alzheimer's disease and a first episode of major depression and 71 nondepressed Alzheimer's disease patients, two first-degree relatives were interviewed by a rater blind to presence or absence of depression in the proband. The depressed patients had significantly more first- and second-degree relatives with depression than did control subjects. The lifetime risk for major depression, adjusted for differences in age distribution, was significantly greater in first-degree relatives of index patients, suggesting that depression in Alzheimer's disease is genetically related to primary affective disorder. Alzheimer's disease may be useful for studying aspects of depressive pathophysiology.

Age Factors↗
PubMedDate not supplied

Limbic-striatal interactions in reward-related processes.

Stimuli with formerly motivationally neutral properties gain incentive properties from their predictive association with primary reinforcement, and are termed conditioned reinforcers. Infusions of the indirect dopamine (DA) agonist d-amphetamine into the ventral striatum selectively enhanced responding for a light that was positively correlated with water. These selective stimulatory effects were blocked by 6-OHDA lesions of the ventral, but not dorsal striatum, and resembled those produced by DA itself when infused into the ventral striatum. However, the choice of the lever producing the conditioned reinforcer was not affected by ventral striatal DA depletion. This choice was, however, attenuated by excitotoxic lesions of the basolateral nucleus of the amygdala, suggesting an interaction between this structure and DA-dependent processes of the ventral striatum in the processes by which reward-related stimuli come to affect action. Parallel findings were obtained using a second order schedule of sexual reinforcement. Other observations indicated that the amygdala lesion did not impair the discriminative property of the reward-related stimuli, or affect primary motivation. Experiments using explicit conditional visuo-spatial discrimination tasks suggest that similar discriminative properties are preserved following DA depletion from the ventral, but not the dorsal, striatum. These results possibly represent a dissociation between stimulus-response (or habit) and stimulus-reward associative mechanisms, modulated respectively by the dorsal and ventral striatum.

Animals↗
PubMed2002

Chemotherapeutic agents sensitize osteogenic sarcoma cells, but not normal human bone cells, to Apo2L/TRAIL-induced apoptosis.

Apo2L/TRAIL is a member of the tumor necrosis factor (TNF) family of cytokines that induces death of cancer cells but not normal cells. Its potent apoptotic activity is mediated through its cell surface death domain-containing receptors, DR4 and DR5. Apo2L/TRAIL interacts also with 3 "decoy" receptors that do not induce apoptosis, DcR1, DcR2, which lack functional death domains, and osteoprotegerin (OPG). The aim of our study was to investigate the cytotoxic activity of Apo2L/TRAIL on established osteogenic sarcoma cell lines (BTK-143, HOS, MG-63, SJSA-1, G-292 and SAOS2) and in primary cultures of normal human bone (NHB) cells. When used alone, Apo2L/TRAIL at 100 ng/ml for 24 hr induced greater than 80% cell death in only 1 (BTK-143) of the 6 osteogenic sarcoma cell lines. In contrast, Apo2L/TRAIL-resistant cells were susceptible to Apo2L/TRAIL-mediated apoptosis in the presence of the anticancer drugs, Doxorubicin (DOX), Cisplatin (CDDP) and Etoposide (ETP) but not Methotrexate (MTX) or Cyclophosphamide (CPM). Importantly, neither Apo2L/TRAIL alone nor in combination with any of these drugs affected primary normal human bone cells under equivalent conditions. Apo2L/TRAIL-induced apoptosis, and its augmentation by chemotherapy in the resistant cell lines was mediated through caspase-8 and caspase-3 activation. Furthermore, Apo2L/TRAIL-induced apoptosis and its augmentation by chemotherapy was effectively inhibited by caspase-8 zIETD-fmk and caspase-3 zDEVD-fmk protease inhibitors and by the pan-caspase inhibitor zVAD-fmk. The pattern of basal Apo2L/TRAIL receptor mRNA expression, or expression of the intracellular caspase inhibitor FLICE-inhibitory protein, FLIP, could not be readily correlated with resistance or sensitivity to Apo2L/TRAIL-induced apoptosis. However, the augmentation of Apo2L/TRAIL effects by chemotherapy was associated with drug-induced up-regulation of death receptors DR4 and DR5 mRNA and protein. No obvious correlation was seen between the expression of OPG mRNA or protein and susceptibility of cells to Apo2L/TRAIL-induced apoptosis. Stable over-expression of a dominant negative form of the Fas-associated death domain protein (FADD) in the Apo2L/TRAIL-sensitive BTK-143 cells completely inhibited Apo2L/TRAIL-induced cell death. Our results indicate that chemotherapy and Apo2L/TRAIL act synergistically to kill cancer cells but not normal bone-derived osteoblast-like cells, which has implications for future therapy of osteosarcoma.

Apoptosis Regulatory Proteins↗
PubMed2006

Differential effects of plasma membrane electric excitation on H+ fluxes and photosynthesis in characean cells.

Cells of characean algae exposed to illumination arrange plasma-membrane H(+) fluxes and photosynthesis in coordinated spatial patterns (bands). This study reveals that H(+) transport and photosynthesis patterns in these excitable cells are affected not only by light conditions but also by electric excitation of the plasma membrane. It is shown that generation of action potential (AP) temporally eliminates alkaline bands, suppresses O(2) evolution, and differentially affects primary reactions of photosystem II (PSII) in different cell regions. The quantum yield of PSII electron transport decreased after AP in the alkaline but not in acidic cell regions. The effects of electric excitation on fluorescence and the PSII electron flow were most pronounced at light-limiting conditions. Evidence was obtained that the shift in chlorophyll fluorescence after AP is due to the increase in DeltapH at thylakoid membranes. It is concluded that the AP-triggered pathways affecting ion transport and photosynthetic energy conversion are linked but not identical.

Action Potentials↗
PubMed1992

Ultrastructural characterization of substance-P-immunoreactive synaptic terminals in the cat's normal and rhizotomized trigeminal subnucleus caudalis.

Deafferenting injuries often cause transient or permanent physiological alterations within the central projection field of affected primary afferent fibers. Aberrant sensory perceptions, dysesthesias, and hyperalgesias represent the clinical sequelae of such injuries; however, the results of experimental deafferentations have been subject to a variety of interpretations (Rodin and Kruger, 1984b). Neurochemical studies show an increased sensitivity of partially deafferented neurons to substance P (SP). Our previous studies (Hoffmann et al., 1991) documented, primarily at the light-microscopic level, a moderate transient loss of SP-immunoreactive (SPIR) boutons in the trigeminal subnucleus caudalis (Vc)--a loss that seemed to preferentially affect the slightly larger, possibly complex boutons with multiple contacts. However, despite the elimination of the trigeminal input, the larger boutons reappeared. In the present study, therefore, we examined Vc using electron-microscopic immunocytochemistry, in order to document these changes over time and to clarify the structure and relationships of this population of boutons. SPIR boutons occurred in lamina I and II degrees of the substantia gelatinosa of Vc, ranged in size from 1 to 5 microns in diameter, and displayed mixed populations of clear and dense-core vesicles. Most formed single or multiple axodendritic junctions, but a significant number engaged in axoaxonic contacts with both SPIR-labeled and unlabeled terminals. A small number appeared to be the central element of a typical glomerulus, particularly in lamina II degrees. Three to seven days following an ipsilateral retrogasserian rhizotomy, synaptic degeneration was evident in the substantia gelatinosa and often involved glomerular terminals. However, most of these were SPIR-negative and occurred primarily in lamina II degrees. Those SPIR boutons that displayed degenerative features often made single or multiple axodendritic contacts, and in some instances were scalloped. By 30 days, most remaining SPIR boutons were small, with a lower incidence of contacts; however, some of these were axoaxonic. In addition, many SPIR terminals were only very lightly stained--a feature not encountered to such an extent in the contralateral Vc. At 45 days, complex SPIR boutons were again evident in the field, and some showed densely packed vesicles. An increased incidence of clusters of two to four SPIR axoaxonic contacts was also observed. Finally, almost all SPIR boutons encountered at this stage were intensely stained. It is suggested that these alterations represent a compensatory neuroplastic response on the part of overlapping cervical and cranial primary afferents to the partial deafferentation resulting from the interruption of the trigeminal root.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed2000

Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo.

The secreted MIA protein is strongly expressed by advanced primary and metastatic melanomas but not in normal melanocytes. Previous studies have shown that MIA serum levels correlate with clinical tumour progression in melanoma patients. To provide direct evidence that MIA plays a role in metastasis of malignant melanomas, A-mel 3 hamster melanoma cells were transfected with sense- and antisense rhMIA cDNA and analysed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MIA in A-mel 3 cells significantly increased their metastatic potential without affecting primary tumour growth, cell proliferation or apoptosis rate in hamsters, compared with control or antisense transfected cells. Additionally, MIA overexpressing transfectants showed a higher rate of both tumour cell invasion and extravasation. Cells transfected with MIA antisense generally exerted an opposite response. The above changes in function attributed to the expression of MIA may underlie the contribution of MIA to the malignant phenotype.

Animals↗
PubMed2001

Light therapy for seasonal affective disorder in primary care: randomised controlled trial.

BACKGROUND: Studies of light therapy have not been conducted previously in primary care. AIMS: To evaluate light therapy in primary care. METHOD: Fifty-seven participants with seasonal affective disorder were randomly allocated to 4 weeks of bright white or dim red light. Baseline expectations for treatment were assessed. Outcome was assessed with the Structured Interview Guide for the Hamilton Depression Scale, Seasonal Affective Disorder Version. RESULTS: Both groups showed decreases in symptom scores of more than 40%. There were no differences in proportions of responders in either group, regardless of the remission criteria applied, with around 60% (74% white light, 57% red light) meeting broad criteria for response and 31% (30% white light, 33% red light) meeting strict criteria. There were no differences in treatment expectations. CONCLUSIONS: Primary care patients with seasonal affective disorder improve after light therapy, but bright white light is not associated with greater improvements.

Adolescent↗
PubMed2005

Assessing recovery in middle cerebral artery stroke using functional MRI.

PRIMARY OBJECTIVE: To understand the temporal evolution of brain reorganization during recovery from stroke. RESEARCH DESIGN: A patient who suffered left middle cerebral artery stroke 9 months earlier was studied on three occasions, approximately 1 month apart. METHODS AND PROCEDURES: Brain activation was studied using functional Magnetic Resonance Imaging (fMRI). During each session, the patient performed a finger-to-thumb opposition task, which involved one bimanual and two unimanual conditions. Each condition consisted of overt movement of fingers and imagery of the same task. RESULTS: With recovery, greater recruitment was observed of the affected primary motor cortex (M1) and a decrease in activation of the unaffected M1 and supplementary motor area. In addition, the widespread activation of brain areas seen during the initial session changed to a more focused pattern of activation as the patient recovered. Imagery tasks resulted in similar brain activity as overt execution pointing to imagery as a potential tool for rehabilitation.

Aged↗
PubMed2003

Primary rabbit epithelial cells exposed to adrenal, gonadal, and pituitary hormones in culture.

Various studies have investigated the effects of Monkey Kidney Epithelial cells to various agents but there are few studies that are looking at other species to determine the effects these agents may have. Studying other species and their effects may provide valuable information on the differences that are seen between humans and information as to why treatment works for some and not for others. The specific objective of this study was to investigate the effects of cortisol (C), testosterone (T), dehydroepiandrosterone (DHEA), estradiol (E), and Growth Hormone (G) individually and in combination on the proliferation and viability of Primary Rabbit Kidney epithelial cells in culture. In phase I: a total of 30 tubes plated with PRKEC were divided into six equal groups. In-groups 1-5, tubes were treated with physiological doses of hormones individually i.e., C, T, DHEA, E, and G respectively. Data obtained suggests that: (1) PRKEC treated with T for 24, 48, 72, and 96 hours displayed a significant increase in catalase, LDH, as well as MDA, (2) PRKEC treated with DHEA for 48 hours displayed a reduction in cell proliferation (70%) and an increase in MDA, LDH, and catalase. The hormones studied affect Primary Rabbit Kidney Epithelial cell growth, function, and viability, however the data suggests that further study needs to be conducted to determine the full impact of steroids and growth agents on Kidney Epithelial cells.

Adrenal Cortex Hormones↗
PubMed2005

Endoluminal angioplasty of the popliteal artery. Review of 54 consecutive patients.

AIM: To determine the results of endoluminal angioplasty for occlusive or stenotic lesions of the popliteal artery. METHODS: Retrospective study of symptomatic patients having popliteal occlusive lesions treated by endoluminal balloon angioplasty. All patients underwent systematic preoperative and postoperative color duplex scan and preoperative angiography. The principal endpoints were primary and primary assisted patency. RESULTS: Fifty-four percutaneous endoluminal angioplasties of the popliteal artery, including six procedures with stents, were performed in 50 patients. In all cases, the superficial femoral artery was patent and without significant stenosis. Primary patency for the entire cohort was 57.4+/-6.7% at 1 and 2 years. Primary assisted patency was 86.3+/-4.8% at 1 year, and 79.1+/-5.9% at 2 years. The results of angioplasty appeared to be better in patients with intermittent claudication when compared to patients with critical limb ischaemia, (p=0.0006). Angioplasty of single occlusive lesions had a better prognosis than that of multiple occlusive lesions (p=0.01). Results of angioplasty were better at the below-knee and median popliteal artery than at the femoro-popliteal junction or in the above-knee popliteal artery (p=0.03). Tibial run-off and isolated popliteal stenosis versus isolated popliteal thrombosis did not seem to affect primary patency rate. CONCLUSION: Results of angioplasty of the popliteal artery are acceptable for claudicants, especially those with TASC-A lesions and those with lesions in the distal two thirds of the popliteal artery.

Aged↗
PubMed1991

Human neutrophil responses to pathogenic Escherichia coli are receptor-specific and selectively augmented by recombinant human tumor necrosis factor-alpha.

The effect of recombinant human tumor necrosis factor-alpha (rhTNF alpha) on neutrophil (PMNL) response to uropathogenic Escherichia coli was assessed. A strain expressing mannose-sensitive adhesins (type 1 fimbriae) stimulated significant primary granule, secondary granule, and leukotriene B4 (LTB4) release. The same strain grown to suppress fimbrial expression and three non-type 1-fimbriated strains stimulated only background low-level PMNL activation. The binding of the type 1-fimbriated strain to PMNL was inhibitable by D-mannose and concanavalin A, while that of non-type 1-fimbriated strains was not but was inhibited by antibodies to the PMNL complement receptors 1 and 3. TNF alpha (10(-9) M) synergistically augmented the non-type 1-fimbriated E. coli-stimulated LTB4 release and additively increased secondary granule release without affecting primary granule release. In contrast, none of the responses to the type 1-fimbriated strain were augmented by TNF alpha. In the absence of mannose-sensitive adhesins, the activation of PMNL by E. coli may involve both complement receptors 1 and 3 and be augmented by TNF alpha.

Bacterial Adhesion↗
PubMed1978

Deranged anterior pituitary responsiveness to hypothalamic hormones in depressed patients.

Abnormal anterior pituitary (AP) responsiveness to acute administration of thyrotropin-releasing hormone (TRH) and luteinizing hormone-follicle stimulating hormone-releasing hormone (LH-RH) was investigated in 14 patients (two men and 12 women) suffering from primary affective disorders. In ten, TRH, 500 microgram given intravenously, induced a rise in plasma growth hormone (GH) level, while in eight patients it induced a rise in plasma levels of FSH or LH or both. When LH-RH, 150 microgram was administered intravenously to ten patients, it induced a rise in plasma GH level in one patient and increased plasma prolactin level in three patients. Collectively, in only three of 14 patients was conventional AP responsiveness to hypothalamic neurohormones present. These findings demonstrate the existence of a profound derangement of AP responsiveness to hypothalamic neurohormones in depressed patients and suggest that a primary alteration in the physiologic links between the central nervous system and the AP may be at the origin of the neuroendocrine disturbance.

Adult↗
PubMed2003

Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.

Aged↗
PubMed2006

Detection of compound mode of action by computational integration of whole-genome measurements and genetic perturbations.

BACKGROUND: A key problem of drug development is to decide which compounds to evaluate further in expensive clinical trials (Phase I- III). This decision is primarily based on the primary targets and mechanisms of action of the chemical compounds under consideration. Whole-genome expression measurements have shown to be useful for this process but current approaches suffer from requiring either a large number of mutant experiments or a detailed understanding of the regulatory networks. RESULTS: We have designed an algorithm, CutTree that when applied to whole-genome expression datasets identifies the primary affected genes (PAGs) of a chemical compound by separating them from downstream, indirectly affected genes. Unlike previous methods requiring whole-genome deletion libraries or a complete map of gene network architecture, CutTree identifies PAGs from a limited set of experimental perturbations without requiring any prior information about the underlying pathways. The principle for CutTree is to iteratively filter out PAGs from other recurrently active genes (RAGs) that are not PAGs. The in silico validation predicted that CutTree should be able to identify 3-4 out of 5 known PAGs (approximately 70%). In accordance, when we applied CutTree to whole-genome expression profiles from 17 genetic perturbations in the presence of galactose in Yeast, CutTree identified four out of five known primary galactose targets (80%). Using an exhaustive search strategy to detect these PAGs would not have been feasible (>1012 combinations). CONCLUSION: In combination with genetic perturbation techniques like short interfering RNA (siRNA) followed by whole-genome expression measurements, CutTree sets the stage for compound target identification in less well-characterized but more disease-relevant mammalian cell systems.

Algorithms↗
PubMedDate not supplied

[The dependence of estradiol and progesterone reception in the endometrium on its histological structure in women with the syndrome of luteal phase failure].

A study of the level of the sex steroid receptors in the endometrium of women with the syndrome of insufficiency of the luteal phase of the cycle (ILP-syndrome) has shown that disorders of receptor processes affect, first of all, progesterone receptors. An increase in a degree of a delay of endometrial development was accompanied by a rise of the level of progesterone in the endometrium which depended on the estradiol-progesterone ratio in the circulation, detectable on the 20th day of the menstrual cycle. The ILP-syndrome is characterized by the sufficient induction of progesterone receptors at the end of the proliferative--the beginning of the luteal phase of the cycle and by their insufficient inhibition with a low level of progesterone in the middle of the luteal phase. Insufficient synthesis of receptors as a result of sharp hypoestrogenemia is less frequent. The primary affection of the receptor apparatus as a cause of the ILP-syndrome against a normal hormonal background in the examinees was undetectable.

Adult↗