[Differential indication for psychotherapy in psychosis : Are there evidence-based criteria?] / Differenzialindikation für die Psychotherapie bei Psychosen : Gibt es empirisch begründbare Kriterien?

The major objective of this paper is to discuss the available evidence on the question as to which patients benefit most from psychotherapy in psychotic disorders and the question of which kind of psychotherapy. From a methodological perspective, this task can be seen as the question of moderators of treatment success. To answer this question, the status of efficacy research on psychotherapeutic interventions in schizophrenia is summarized in a first step. Secondly, studies comparing different active psychotherapeutic approaches are discussed. There are no studies available on routine psychotherapeutic care. However, there appears to be a rationale for recommending a combination of cognitive behavioural therapy (CBT) and family therapy. If patients prefer other approaches or if the treatment model does not suit the patient, other approaches should be offered. There is evidence for CBT that insight into psychosis, female gender, a higher level of education, and age >21 are indicators of a better course in CBT. Overall, the options for differential indications are highly limited and considerably more research is required.

Efficacy of aflibercept (EYLEA®) on inhibition of human VEGF in vitro.

INTRODUCTION: Pathological formation of blood vessels plays a key role in the growth and metastasis of tumors and also in several serious ophthalmological diseases such as wet age-related macular degeneration (AMD) or diabetic retinopathy. In AMD treatment, aflibercept (tradename EYLEA®) is used to deactivate the underlying pathological neovascularisation. Aflibercept is a recombinant fusion protein which binds to vascular endothelial growth factor (VEGF) receptors, thereby inhibiting VEGF pathway activation. VEGF is one of the most important angiogenesis factors. OBJECTIVE: This analysis investigates lasting efficacy of aflibercept in vitro for later application as therapeutic agent against macular degeneration (AMD). MATERIAL AND METHODS: VEGF-ELISA assays were performed to investigate binding affinities at different aflibercept concentrations. The impact of VEGF on the proliferation of human umbilical vein endothelial cells (HUVEC) was investigated using proliferation assays. Moreover, time-dependent kinetic studies were performed to analyze different aflibercept storage durations with regard to its inhibitory capabilities on human VEGF. RESULTS AND CONCLUSION: Our results reveal that aflibercept significantly lowers the amount of unbound VEGF as well as the proliferation rate of HUVEC. Moreover, in contrast to specifications given by the manufacturer, aflibercept retains its full inhibitory effect up to at least 120h after transference from the original vial into the injection syringe.

Cisto ósseo aneurismático em tecido mole em um cão - relato de caso / Aneurysmal bone cyst in soft tissue in a dog - Case Report

Este trabalho descreve o diagnóstico e o tratamento instituído para um cão com um raro cisto ósseo aneurismático originado em tecido mole. O paciente foi apresentado para atendimento no Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul devido à dificuldade de locomoção, fraqueza nos membros pélvicos e disquesia havia 15 dias. Já estava recebendo tratamento medicamentoso sem sucesso. Ao exame clínico, notou-se aumento de volume sólido na região perineal direita, e foram solicitados exames complementares de imagem. A radiografia da região sugeriu hérnia perineal direita ou neoplasia. O cão foi encaminhado para cirurgia, na qual foi removida uma estrutura tumoral, arredondada, de aspecto ossificado. O exame histopatológico diagnosticou a estrutura como um cisto ósseo aneurismático em tecido mole, e o paciente recuperou-se totalmente após a excisão cirúrgica.(AU)

This paper describes the diagnosis and treatment of a dog with a rare aneurysmal bone cyst in soft tissue. The patient was attended in the Veterinary Clinic Hospital at the Fedral University of Rio Grande do Sul due to limited mobility, weakness in hind limbs, and dyschezia for 15 days. It was already receiving medical treatment without success. Upon clinical examination a solid increase volume in the right perineal region was detected, and complementary imaging tests were requested. Radiography of the region suggested right perineal hernia or neoplasia. The dog was submitted to surgery, and a rounded and ossified tumoral structure was removed. The histopathological exam diagnosed the structure as an aneurysmal bone cyst in soft tissue, and the patient recovered fully after surgical excision.(AU)

Muscle strain injuries of the hindlimb in eight horses: diagnostic imaging, management and outcomes.

OBJECTIVE: To describe the clinical presentation, ultrasound findings, management and outcome in horses with muscle tear injuries of the hindlimbs. DESIGN: Retrospective case series Procedure Medical records of eight horses were reviewed and information on signalment, history, presenting complaint, physical examination findings and further diagnostic tests were recorded. Diagnosis of muscle injury was determined by the presence of abnormal ultrasound findings, compared with the contralateral limb, and, when required, nuclear scintigraphy. Follow-up information was obtained via telephone interviews with owners, trainers and referring veterinarians. RESULTS: Muscle tears causing lameness were identified in the middle gluteal (3), semitendinosus (1), semimembranosus (2) and gracilis (2) muscles. Tears were classified by ultrasound imaging as partial (6) or complete (2). The degree of lameness did not appear to be indicative of the extent of injury or of completion of healing. Long-term follow-up was available for seven horses and the outcome was favourable in six cases. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonography is useful in the diagnosis and assessment of moderate to severe muscle strain injuries. The prognosis appears to be favourable in most cases, although recurrence of injury and lameness can delay the return to athletic activity and an inferior outcome with persistent gait abnormality may occur.

Associations between physiotherapy findings and subsequent diagnosis of pelvic or hindlimb fracture in racing Thoroughbreds.

REASONS FOR PERFORMING STUDY: Physiotherapists who work in racehorse training yards routinely treat horses' backs and hindquarters and may be able to recognise signs that indicate the presence of (impending) pelvic or hindlimb fracture before it becomes catastrophic. OBJECTIVE: To establish whether physiotherapy assessment findings in Thoroughbred racehorses referred for routine physiotherapy could be predictive of subsequent (within 30 days) pelvic or hindlimb fracture diagnosis. METHODS: Retrospective veterinary and physiotherapy data from a cohort of Newmarket (UK) Thoroughbred racehorses, were used. A case-control study compared physiotherapy assessment findings of racehorses with and without a subsequently diagnosed pelvic or hindlimb fracture. Uni- and multivariable logistic regression was used to investigate and quantify the strength of association between physiotherapy findings and subsequent fracture diagnosis. Statistical significance was set at P<0.05. RESULTS: A total of 513 horses provided 14 fracture cases for analysis. Presence of pelvic bony asymmetry, muscle atrophy of the quarters, reduced reflex movements of dorsi- and/or ventroflexion and spasm or tenderness on palpation of the gluteal muscles were significantly associated with subsequent fracture diagnosis in univariable analysis. Multivariable analysis indicated that horses subsequently diagnosed with pelvic or hindlimb fracture were 11.1 times more likely to show pelvic bony asymmetry, 4.7 times more likely to display muscle atrophy of the quarters and 6.6 times more likely to have spasm or tenderness on palpation of the gluteal muscles than those that were not. CONCLUSIONS: Racehorses presented for physiotherapy that show pelvic bony asymmetry, muscle atrophy of the quarters and/or spasm or tenderness on palpation of the gluteal muscles should alert the physiotherapist to the potential presence of (impending) pelvic or hindlimb fracture. POTENTIAL RELEVANCE: Earlier detection of (impending) pelvic or hindlimb fracture in racing Thoroughbreds could reduce the incidence of catastrophic fractures.

Combination antiretroviral therapy without a nucleoside reverse transcriptase inhibitor: experience from 334 patients in three cohorts.

BACKGROUND: Toxicity and resistance may limit the use of HIV nucleoside reverse transcriptase inhibitors (NRTIs). We assessed the safety and activity of regimens that did not include an NRTI. METHOD AND PATIENTS: We analysed NRTI-sparing regimens using pooled data from three cohorts in Australia and France where HIV RNA viral load, CD4 lymphocyte count and metabolic parameters are assessed prospectively. The inclusion criterion was the commencement of any antiretroviral combination excluding NRTIs. RESULTS: A total of 334 (3.9%) of 8477 patients were included in the present study for a median follow-up time of 105 weeks. Therapeutic combinations were one nonnucleoside reverse transcriptase inhibitor (NNRTI) plus one protease inhibitor (PI) (58%), two PIs (26%), one PI (16%), and one NNRTI plus two PIs (8%). At baseline, the median CD4 lymphocyte count was 264 cells/muL (interquartile range 164-446 cells/muL) and 25% of patients had plasma HIV RNA below 500 HIV-1 RNA copies/mL. In intent-to-treat analysis, 64% of patients had HIV RNA <500 copies/mL at 6 months and 68% at 24 months. The mean CD4 lymphocyte count increase was 60 cells/microL (95% confidence interval 41-76 cells/microL) at 6 months and 111 cells/microL (95% confidence interval 82-140 cells/microL) at 24 months. Prognostic factors for having HIV RNA <500 copies/mL at 6 months included independently having undetectable HIV RNA at baseline and being naïve for NNRTIs. The proportion of patients with triglycerides >2.3 mmol/L increased from 32% to 63% at 6 months and to 62% at 24 months (P-trend=0.002), and those with total cholesterol >6.2 mmol/L increased from 18% to 38% at 6 months and to 44% at 24 months (P-trend <0.001), with an increased risk for patients treated with NNRTI+PIs. Forty-one per cent of patients discontinued their NRTI-sparing regimen. CONCLUSION: In these antiretroviral-experienced patients, NRTI-sparing therapy appeared to have satisfactory virological and immunological efficacy. However, hyperlipidaemia was frequent and requires monitoring of cardiovascular risk factors.

Role of monoamine oxidase inhibition and monoamine depletion in fenfluramine-induced neurotoxicity and serotonin release.

The role of both monoamine synthesis and monoamine oxidase inhibition in mediating the fenfluramine-induced damage to serotonin neurones was examined; as pretreatment agents, both alpha-methyl-para-tyrosine (AMPT) and parachlorophenylalanine (PCPA) were used to deplete dopamine and serotonin, respectively, while clorgyline and deprenyl were used to inhibit monoamine oxidase types A and B. While both AMPT and deprenyl did not alter fenfluramine induced serotonin or 5-hydroxyindoleacetic acid (5-HIAA) depletion in any area, PCPA did partially reduce the serotonin depletion in the hippocampus and hypothalamus. Although pretreatment with clorgyline did not significantly alter fenfluramine-induced serotonin depletion, it did produce a 65% mortality rate in animals treated with both drugs. Both PCPA and clorgyline significantly increased the depletion of striatal 5-HIAA concentration consequent to fenfluramine; however, these drugs also produced a long-term depletion of striatal 5-HIAA when administered alone, therefore, the changes seen after the coadministration with fenfluramine may be viewed as additive. Finally, acute PCPA pretreatment attenuated the rapid rise in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (homovanillic acid) induced by fenfluramine, and acute clorgyline reversed the drop in serotonin and rise in 5-HIAA induced by fenfluramine. These results indicate that the rapid increase in dopamine activity induced by fenfluramine is partially dependent on serotonin concentration and release and that the mechanism of fenfluramine-induced toxicity is unlike that of the other substituted amphetamines.

Combined radiochemotherapy with docetaxel in patients with unresectable locally advanced head and neck tumors.

BACKGROUND: As the treatment with docetaxel in metastatic head and neck cancer resulted in an encouraging response rate, the following phase-I study examined the effects of a combined radiochemotherapy with weekly docetaxel in patients with inoperable advanced head and neck tumors. PATIENTS AND METHODS: Six patients with Stage IV head and neck cancer were included into the study. Within the treatment regimen the primary tumor and the involved lymph nodes were irradiated up to a total dose of 70 Gy, the non involved cervical and supraclavicular lymph nodes received 50 Gy in conventional fractionation. Simultaneously docetaxel was given 1 hour before radiotherapy. The initial dose was 15 mg/m2. RESULTS: A dose escalation was impossible because of several dose limiting toxicities (NCI-CTC) already in the first dose level. Two patients showed skin reactions Grade 4, 2 patients pulmonary complications Grade 4, 2 patient neurologic side effects Grade 3 and 1 a thrombocytopenia Grade 3. The response rate resulted in 3 complete and 1 partial remission, 1 death, 1 patient was not evaluable. CONCLUSION: Unexpectedly already in the first dose level several dose limiting toxicities were evaluated. For that reason the treatment scheme is not feasible.

Selenoproteins are expressed in fetal human osteoblast-like cells.

Selenoproteins are involved in mechanisms of cell differentiation and defense. We investigated the expression of glutathione peroxidases, as well as other selenoproteins, in fetal human osteoblasts (hFOB-cells). Using 75-selenium metabolic labelling of viable hFOB-cells, we identified several selenoproteins in cell lysates of about 45-80 kDa and in the migration range of 14 kDa to 24 kDa. Cells expressed low mRNA levels of both cellular glutathione peroxidase and plasma glutathione peroxidase mRNA as analysed by Southern analysis of RT-PCR products. Basal cellular glutathione peroxidase enzyme activity in hFOB-cells (19.7 nmol NADPH oxidised per min and microg protein) was further increased 2.5-fold by the addition of 100 nM sodium selenite to the culture medium for 3 days. Furthermore, expression of selenoprotein P mRNA was demonstrated by RT-PCR. hFOB-cells did not show activities of the selenoproteins type I or type II 5'-deiodinase. In summary, we identified cellular glutathione peroxidase, plasma glutathione peroxidase and selenoprotein P among of a panel of several 75-selenium labelled proteins in human fetal osteoblasts. The expression of selenoproteins like glutathione peroxidases in hFOB-cells represents a new system of osteoblast antioxidative defense that may be relevant for the protection against hydrogen peroxide produced by osteoclasts during bone remodelling.

Stability of mono- and bisbenzyloxime ethers of the acetylcholinesterase reactivator TMB-4.

Mono- and bisbenzyloxime ethers of the bispyridinium derivative TMB-4 (UNO, DUO) are potent allosteric modulators of the muscarinic receptor attracting clinical interest in case of organophosphate poisoning. In order to work out the stability of these compounds oximes, different oxime ethers and potential degradation products were synthesized and UV- and NMR-spectroscopically characterized. The process of degradation of all compounds was observed under stress conditions at varying pH-values and different temperatures by means of time-dependent NMR- und UV-measurements. The pyridinium aldoxime turned out to be rather stable, whereas the oxime ether and cyano derivatives convert to the pyridone at high pH-values and high temperature. The mechanism of degradation is discussed.

Changes in condylar postition and occlusion associated with maxillary expansion for correction of functional unilateral posterior crossbite.

The purpose of this study was to confirm that correction of functional posterior crossbite through maxillary expansion is associated with a change in condylar position and occlusal relationships, and to determine whether maxillary expansion is associated with autonomous increase in mandibular arch width. Pretreatment and posttreatment study models of 61 patients ages 4.1 to 12.0 years (mean 8.5 years, SD 1.5) were available after maxillary expansion with a Quad Helix or a Haas expander for correction of a functional posterior crossbite. Pretreatment and posttreatment tomograms were available for 22 of the patients. Tomographic evaluation revealed that the condyles moved posteriorly and superiorly on the noncrossbite side from before to after treatment (p < 0.05). No differences were observed on the crossbite side. Superior joint space was greatest on the noncrossbite side before treatment, whereas, conversely, it was greatest on the crossbite side after treatment (p < 0.05). Relative condylar position was more anterior on the noncrossbite side before treatment (p < 0.05), but similar on both sides after treatment. Molar and canine relationships were more Class II on the crossbite side before treatment (p < 0.01 and < 0.05, respectively) and similar on both sides after treatment. A significant reduction in midline deviation was seen from before to after treatment (p < 0.001). A small, but significant autonomous increase in mandibular intermolar width (p < 0.001) occurred concomitant with the maxillary expansion.

Effect of head orientation on posterior anterior cephalometric landmark identification.

This study examined the effect of head rotation about the vertical and transverse axes on posterior anterior cephalometric landmarks. Radiographs were taken on 25 skulls, first in a normal position, then in four positions each rotated 5 degrees from normal. The identification errors of 52 bilateral and midline landmarks were determined in the horizontal and vertical dimensions. The landmark identification errors for each of the five orientations were compared and those landmarks affected by 5 degrees rotation were identified. Landmarks with significantly larger identification error in a rotated position were: nasal cavity, mandible/occiput, foramen rotundum and orbitale. Best fit vertical and horizontal reference lines were determined, and the effect of head rotation on the choice of best fit reference lines was assessed. Rotation about the transverse axis did not affect the relationship of landmarks to the best vertical or horizontal lines. Rotation about the vertical axis did not affect the relationship of landmarks to the best horizontal line but did affect their relationship to the best vertical line.

Terminal care of the very old. Changes in the way we die.

BACKGROUND: This study examines the use of advance directives, limitations of treatment, and medical interventions during the terminal hospitalization of the old-old. Study periods before and after the implementation of the Patient Self-Determination Act of 1990 were chosen to determine if there has been a change in terminal care. METHODS: Chart review was performed for all patients 85 years and older who died in the hospital during 1988 and 1993. Patient characteristics, presence of advance directives, do-not-resuscitate orders, and other treatment limitations were noted as were interventions listed in the Medical Directive. RESULTS: Less than 12% of the 167 study patients had an advance directive. Length of stay for these terminal admissions decreased from 18.5 to 9.6 days. Ninety-five percent of the patients were "do not resuscitate" by time of death, but orders were written sooner in 1993--75% within 24 hours of admission. Patients with early do-not-resuscitate orders had fewer high-intensity interventions. More patients had "comfort measures only" during the study period. An overall decrease in high-intensity interventions and a specific decrease in the use of transfusions, invasive tests, minor surgery, and cardiopulmonary resuscitation was seen. CONCLUSION: Patients 85 years and older are receiving fewer high-intensity interventions during their terminal hospitalizations. More attention is being paid to comfort and few are receiving cardiopulmonary resuscitation. There is little reference to formal advance directives in decision making for these patients.

Carmoxirole inhibits platelet aggregation in vitro and ex vivo.

The influence of carmoxirole, a new antihypertensive DA2-agonist on human platelet aggregation was studied in vitro and ex vivo. In an open study 15 patients with essential hypertension received 3 doses of carmoxirole, 0.5, 1 and 2 mg daily, each for a 2-week period, following a 2-week placebo phase. At the end of each 2-week period blood pressure, platelet aggregation, plasma carmoxirole and plasma catecholamines were measured. Preliminary experiments in vitro showed that 10 microM carmoxirole inhibited the adrenaline induced aggregation velocity by 10%: Increasing the carmoxirole concentration caused dose dependent inhibition which was complete at 1 mM. Carmoxirole itself caused a weak aggregating effect on human platelets in vitro. Blood pressure was reduced from 163 +/- 11/103 +/- 3 before treatment to 155 +/- 11/97 +/- 4, 148 +/- 11/93 +/- 4 and 143 +/- 11/90 +/- 6 mmHg following 2 weeks of 0.5, 1 and 2 mg oral carmoxirole, respectively. Carmoxirole plasma levels 2 1/2 h after the last capsule administration were 0.37 +/- 0.612, 0.95 +/- 1.045 and 3.69 +/- 2.570 ng/ml following treatment with 0.5, 1 and 2 mg carmoxirole, respectively. No influence of carmoxirole on plasma catecholamines could be established. Compared to 100% before treatment, the 5-hydroxytryptamine induced platelet aggregation velocity ex vivo decreased to 70%, 38% and 69% after the administration of 0.5, 1 and 2 mg carmoxirole, respectively. The adrenaline induced aggregation velocity was reduced in the same manner. These results show that carmoxirole is an antihypertensive agent with antithrombotic potential.

Platelet aggregation after naftidrofuryl application in vitro and ex vivo.

Naftidrofuryl has been shown to inhibit the interaction between platelets and damaged endothelium, which may lead to thrombosis and is mediated by the 5-hydroxytryptamine. (5-HT2) receptor. This study was designed to investigate the effects of naftidrofuryl on 5-HT induced platelet aggregation. In vitro experiments were carried out on platelets from healthy laboratory personnel. Naftidrofuryl (0.0625-100 microM) caused a continual increase in in vitro inhibition, whereby the inhibition at 0.0625 microM was already significant when compared to control (p < 0.05). The IC50 was approximately 10 microM induced aggregation. Subsequently, ex vivo effects of naftidrofuryl on 5-HT induced platelet aggregation of healthy volunteers together with naftidrofuryl plasma levels were measured. Twelve healthy volunteers received either 400 mg naftidrofuryl or placebo in this double-blind, crossover study. Blood samples for determination of aggregation and naftidrofuryl plasma levels were taken before, 0.5, 1, 2, 3, 4, 5, 6.5 and 9 h after medication application. One hour after application of 400 mg naftidrofuryl a maximal plasma level of approximately 380 ng/ml was measured. Under control conditions the aggregation (Vmax) increased from an arbitrary 100% at 8:00 am to about 150% by 10:00 am, remaining at this level until 5:00 pm. Application of 400 mg naftidrofuryl p.o. resulted in a 50% decrease in Vmax 2 h after drug application. Thereafter, the aggregation rose to the initial 100% value 4 h after drug application and remained at this level during the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyenylphosphatidylcholine improves the lipoprotein profile in diabetic patients.

Patients with diabetes mellitus commonly exhibit pathological lipoprotein profiles and concomitant cardiovascular or peripheral atherosclerotic complications. Thirty non-insulin-dependent diabetics with secondary hyperlipidemia received 2.7 g 3-sn-polyenylphosphatidylcholine (PPC) or placebo daily, orally over a 2-month period under randomized, double-blind trial conditions, to investigate the efficacy and tolerance of the treatment. This period was followed by a one-month observation phase without investigational medication. Serum LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides were determined on days 1, 14, 28, 56 and 84. After 56 days of treatment with PPC, the primary variable of effectiveness, LDL cholesterol, decreased significantly (p = 0.0174) by 17% from 191 +/- 31 to 159 +/- 36 mg/dl, whereas values did not change in the placebo group. Total cholesterol (TC) in serum decreased by 16% from 303 +/- 22 to 255 +/- 23 mg/dl with PPC. In the placebo group, only a slight decrease from 292 +/- 27 to 289 +/- 41 mg/dl occurred. Mean serum triglyceride (TG) levels fell by 9% from 194 +/- 32 to 177 +/- 27 mg/dl in the PPC group. In the control group, values increased from 193 +/- 34 to 202 +/- 41 mg/dl. The differences in LDL, TC and TG between the treatment groups were statistically significant; p = 0.0014, p = 0.0001 and p = 0.007, respectively. HDL cholesterol in serum increased 12% from 50 +/- 10 to 55 +/- 13 mg/dl after PPC application. The control group did not show any alteration of mean HDL cholesterol level at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Landmark identification error in posterior anterior cephalometrics.

This study was designed to quantify the intraexaminer and interexaminer reliability of 52 commonly used posterior anterior cephalometric landmarks. The horizontal and vertical identification errors were determined for a sample of 33 skulls and 25 patients. The results show that there is a considerable range in the magnitude of error with different horizontal and vertical values. Interexaminer landmark identification error was significantly larger than intraexaminer error for many landmarks. The identification error was different for the skull sample compared to the patient sample for a number of landmarks. The relevance of knowing the identification error for each landmark being considered in a particular application was discussed.