Does oral antipsychotic pre-treatment influence outcome of a switch to long-acting injectable risperidone in patients with schizophrenia?

INTRODUCTION: The objective of this open-label study was to evaluate treatment benefits of risperidone long-acting injectable (RLAI) in patients with schizophrenia following direct transition from oral risperidone (RIS) compared with transition from other oral second generation antipsychotics. METHODS: Stable in- or outpatients (n=206) receiving RIS or OQAZ (olanzapine, quetiapine, amisulpride, ziprasidone) were transitioned to RLAI for 12 weeks. The primary outcome was the between-group treatment difference in change in PANSS total score from baseline to endpoint. Secondary outcomes included health-related quality-of-life and therapeutic alliance. RESULTS: Mean between-group difference in the change in PANSS total score from baseline to endpoint was -6.1 (CI: -17.6, 5.4), suggesting greater improvement in OQAZ than RIS patients. Due to the pre-specified non-inferiority margin of 5.1, it could not be concluded that OQAZ pre-treatment results in an at least non-inferior PANSS reduction versus RIS pre-treatment. Patient satisfaction with medication and change in quality-of-life subscores showed advantages for OQAZ patients. DISCUSSION: Compared to RIS pre-treatment, clinically stable patients with schizophrenia who are pre-treated with OQAZ might draw a stronger clinical benefit from direct transition to RLAI.

Neurological and psychiatric practitioners' views on Alzheimer's disease and treatment thereof.

BACKGROUND: General views of practitioners shape medical routine. This study surveyed general views of neurological and psychiatric practitioners in Germany on Alzheimer's disease (AD). METHODS: 850 surveys were distributed and 637 (75%) recovered. RESULTS: 36% of practitioners reported not having used therapies for medical conditions other than dementia in patients with AD for reasons of limited compliance in these patients. Efficacy of antidementia drugs (donepezil, galantamine, memantine, rivastigmine) was rated on a 5-point scale (very good, good, satisfactory, sufficient, insufficient) regarding memory, attention and concentration, aggression, depression, activities of daily living, and dependency on caregivers. 87% of practitioners reported an at least satisfactory effect on at least 2 domains. Practitioners estimated that about 20% of caregivers are treated for psychiatric disorders such as depression. Practitioners that were more aware of caregivers' needs for psychiatric treatment more frequently reported positive feedback of caregivers concerning improvement of the patients in everyday life. Nursing home admission was estimated to result from both progression of dementia and diminished forces of the caregivers. CONCLUSIONS: Neurological and psychiatric practitioners perceive antidementia drugs as effective in multiple domains in AD. Appreciation of the overall success of treatment requires consideration of the patient-caregiver dyad.

Quantitative parameters for light microscopic assessment of the tubuli seminiferi.

For quantitative, histologic assessment of the testis tubuli there are four suitable parameters: diameter of tubulus, area of tubulus, number of cell nuclei per tubulus, and area of nuclei of the various cells participating in spermatogenesis. For estimating areas, the integrative method of measurement, either with a grid or with the aid of the manual optical picture-analysis system, is proposed. The tubulus diameter can be determined rapidly and easily, although the tubulus size can be assessed more accurately by area estimation. An assessment of reproductive capacity in detail is possible by means of rather time-consuming determination of cell nucleus number and nuclear area, whereby the stages of the cycle of the seminiferous epithelium must be considered.

Localization and characterization of cytochrome P450 in the brain. In vivo and in vitro investigations on phenytoin- and phenobarbital-inducible isoforms.

The antiepileptic drug phenytoin is known to be substrate as well as inducer of cytochrome P450 (P450) in the mammalian liver. We were able to show the expression of P450 species immunorelated to the main phenytoin-induced hepatic isoforms in mice (CYP2C29) and rats (CYP2B1,2) also in the central and peripheral nervous system and primary cultures of cell types from the brain. The 2B1,2 related protein showed only a weak constitutive expression in vivo and in vitro analyzed by immunocytochemistry, in situ hybridization, Northern blot and RT/polymerase chain reaction (PCR). Contrary, the CYP2C29 related form is inducible by phenytoin at about 1.5-fold starting from an already higher constitutive level. This protein is characterized by a remarkable tendency to dissociate from the endomembranes during tissue homogenization. The supernatant of microsomal pellet is able to metabolize phenytoin in a reconstitutive system.

[Experimental torsion of the spermatic cord. Histological and histochemical studies (author's transl)]. / Experimentelle Hodentorsion. Histologische und enzymhistochemische Untersuchungen.

In 40 male adult rats on unilateral torsion of the spermatic cord was initiated by operation. In the first group (4 x 5 animals) the testes were removed after 3, 6, 12, 24 hours. The treatment of the animals in the second group (4 x 5 animals) was untwisting of the torsion after 3, 6 12, 24 hours. Three months later both testes were removed. Histological and enzymehistochemical results are as follows: 1. The extend of acute damage to the affected testis depends on the length the torsion lasted. 2. The delay of time of untwisting the testis probably does not influence the degree of later regeneration. 3. Even short duration of torsion of the affected testis results in damage to the contralateral testies.

[Shwachman-diamond syndrome as cause of infantile eczema associated with failure to thrive]. / Shwachman-Diamond-Syndrom als Ursache eines Säuglingsekzems mit begleitender Dystrophie.

BACKGROUND: Shwachman-Diamond syndrome is an autosomal recessive multisystem disorder involving an insufficiency of the exocrine pancreas and haematological problems as main symptoms. Frequently, ichthyosiform skin lesions are described but are usually not the leading symptom of the disease. CASE REPORT: We report on a 6-months-old boy suffering from ichthyosiform and eczematous skin eruptions beginning at the age of 3 months which were accompanied by failure to thrive. Because of an atopic predisposition and a sensitisation to hen's egg the diagnosis atopic dermatitis with food allergy was established. We describe the steps leading to the diagnosis Shwachman-Diamond syndrome. CONCLUSION: Shwachman-Diamond syndrome may present with skin eruptions as main symptom. A mixed clinical picture with an atopic dermatitis may occur and can aggravate skin symptoms. Additional medical problems like failure to thrive or neutropenia should lead to further diagnostic procedures to exclude Shwachman-Diamond syndrome.

Detection of herpesvirus DNA in cerebrospinal fluid and correlation with clinical symptoms.

BACKGROUND: Novel PCR techniques can detect minute quantities of herpesvirus DNA in cerebrospinal fluid (CSF). The clinical significance of such findings is not always clear. PATIENTS AND METHODS: (a) Investigation of clinical characteristics of 76 patients with herpesvirus DNA detection in CSF. (b) Screening for herpesvirus DNA in CSF samples of 208 patients without clinical signs of herpesvirus infection. RESULTS: (a) Eleven of 76 herpesvirus-DNA-positive patients did not show symptoms usually associated with the detected virus (HSV-1/2, n = 5; EBV, n = 6). (b) Two of 208 patients without hint for herpesvirus infection had HHV-6 DNA of low concentration in CSF. CONCLUSIONS: The detection of low-level herpesvirus replication in CSF by highly sensitive PCR assays requires critical evaluation.

Genetic analysis of MAPT haplotype diversity in frontotemporal dementia.

The H1 haplotype of the tau gene, MAPT, has been linked to the sporadic tauopathies corticobasal degeneration and progressive supranuclear palsy; however, there have been inconsistent findings regarding association with frontotemporal dementia (FTD). We investigated MAPT haplotype diversity, in 171 sporadic FTD and 186 healthy controls individuals, and report no single marker or haplotype association with increased risk or changes in age at onset. These findings do not support an association of MAPT with FTD but do not rule out its association with other tauopathies.

Clioquinol treatment in familiar early onset of Alzheimer's disease: a case report.

Recently the metal chelator clioquinol (CQ) has been suggested as a possible option for treatment of Alzheimer's disease (AD). We report two patients with early onset of AD [one with a mutant amyloid-precursor-protein (APP) gene] who received long-term treatment with CQ. In both cases focally augmented cerebral glucose metabolism and stabilization but no amelioration of the clinical impression were observed without signs of neurotoxicity. In one case CSF-tau and beta-Amyloid (42/40) concentrations changed during CQ treatment.

[New views on the significance and treatment of undescended testis (author's transl)]. / Neue Aspekte zur Bedeutung und Behandlung von Hodendescensusstörungen

Undescended testis is of clinical importance because there are increased risks of milignancy and torsion and disturbances of fertility and psychosexual development. New quantitative morphologic investigations show that human prepubertal testicular maturation does not occur in phases but is continuous. This made it necessary to investigate afresh the causes of disturbance of fertility and the treatment of indescended testis. Our own investigations show that damage to the germ epithelium need not be congenital but may develop because of its ectopy. If, in dogs, a testis is placed into the abdomen, not only this but also the normally placed testis in the scrotum is damaged. The diameter of the tubules and their surfaces as well as the numbers of pachtenous primary spermatocytes are significantly reduced both in the displaced and the normally placed testis. Nuclear surfaces and density of the cells involved in spermatogenesis differ from those in the controls. The findings support the plea for early hormonal or surgical treatment in order to prevent later disturbances of fertility.

Stages of the cycle of the seminiferous epithelium in the dog.

In principle, the spermatogenesis of the dog resembles that of other animals. It consists of 6 consecutive, differentiating spermatogonia generations (A1-A4, Im, B). The number of ensuing spermatogenetic cell generations corresponds to that of other mammals. We divided the spermatogenesis of the dog into 10 stages in order to attain a precise systematization. The cell-divisions of the successive spermatogonia occur in stages II, III, V, VI, VII, and VIII. Stages V a and V c are characterized by the meiotic divisions.

Effect of human chorionic gonadotrophin on the dog seminiferous tubule, with and without experimental unilateral cryptorchism.

The effect on human chorionic gonadotrophin (HCG) on the testes of pubertal and postpubertal Beagle dogs was studied, in the one instance in bilaterally normotopic testes and in the other on the still scrotally located gonad of dogs which had been subjected to unilateral experimental cryptorchism. The area of the cross-sectioned seminiferous tubules served as a parameter for evaluating the effect of HCG. Administration of therapeutic doses of HCG produced, in animals with bilaterally normotopic testes, a marked diminution of the area of the seminiferous canals. This means that HCG application at normal dosage impairs the seminiferous tubules in the dog. In animals with unilateral cryptorchism, HCG application produced no significant change in the tubule area of the scrotally located testis beyond that which is ascertainable anyway on the orthotopic testis following translocation of the contralateral gonad to within the abdominal cavity. Hence, HCG does not influence the degenerative change in the orthotopic testis in experimental unilateral cryptorchism. Rather, an adverse effect of HCG on the seminiferous tubule is evident, independently of the hitherto published reports of successfully attained descent.

Hospital admission circumstances and prevalence of frontotemporal lobar degeneration: a multicenter psychiatric state hospital study in Germany.

Frontotemporal lobar degeneration (FTLD) is a heterogenous, non-Alzheimer's disease, dementia complex with variable clinical presentation. We carried out a prospective nationwide hospital-based clinico-epidemiologic study in geriatric psychiatry to estimate the prevalence and admission circumstances of patients with FTLD. During a 4-week period 33 patients with clinical FTLD were prospectively ascertained in 36 psychiatric state hospitals in Germany with a total catchment area of >20,000,000 people. The relative portion of FTLD patients within the primary dementia population accounted for 1.9%. The estimated prevalence of FTLD in Germany was 47.9/100,000 population aged between 45 and 79 years. The admission circumstances were mainly behavioral disturbances (54.5%), unclear syndromes of dementia (18.1%) and further remarkably heterogeneous psychiatric syndromes. FTLD is a common cause of dementia in geriatric psychiatry with a variable clinical presentation that could mimic most of the major psychiatric diseases. Patients with FTLD may be older than previously assumed (mean age at admission 63.9 years) and show their maximum age-related prevalence between 60 and 70 years (78.7/100,000).

Does the pattern of atrophy of the Corpus callosum differ between patients with frontotemporal dementia and patients with Alzheimer's disease?

The pattern of callosal atrophy might be useful for the differentiation between frontotemporal dementia (FTD) and Alzheimer's disease (AD) in advanced cases. However, it is unclear whether the pattern of callosal atrophy differs between patients with FTD and patients with AD in mild to moderate stages. Volumetric MR images were recorded from 48 probands (12 with FTD, 12 with late-onset AD, and 24 controls). All patients were in a mild or in a moderate stage. The corpus callosum was divided into five segments. A repeated-measures analysis of variance showed that there was no difference in the pattern of callosal atrophy between the groups. We provide evidence that patients with FTD and patients with late-onset AD do not differ in the pattern of callosal atrophy on condition that: (1) FTD patients and AD patients are in a mild to moderate stage and (2) FTD patients and AD patients differ in age.

Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer's disease.

[18F]FDG positron emission tomography (PET) scans of 14 patients comprising the clinical prototypes of dementias that are considered to be associated with frontotemporal lobar degeneration (FTLD) were compared to a population of 15 patients with early onset Alzheimer's disease (EOAD). The FTLD group included patients with frontotemporal dementia (FTD), semantic dementia (SD), and primary progressive aphasia (PPA). A voxel to voxel group comparison identified metabolic impairment in the bilateral ventromedial frontal area, the left anterior insula, and inferior frontal cortex, and indicated the right middle temporal gyrus to exhibit increased activity in FTLD compared to EOAD patients. All identified cortical structures are considered to be critically involved in neuropsychological features associated with FTLD (altered social behavior, aphasia) and EOAD (impaired linguistic and visuo-constructive abilities). In conjunction with recent insights from neuropathologic investigations, these results implicate that the a priori heterogeneous prototypes of FTLD (FTD, SD, PPA) may share more common ground than previously assumed, and therefore would become distinguishable as an entire group from EOAD.

Patterns of referring of patients with frontotemporal lobar degeneration to psychiatric in- and out-patient services. Results from a prospective multicentre study.

Dementia with frontotemporal lobar degeneration (FTLD) is clinically characterized by the occurrence of various psychiatric symptoms. In a recent study, the hospital-based prevalence of FTLD and the circumstances of the patients' admission to German psychiatric state hospitals were estimated. On the basis of further continuous assessment, this original FTLD group (n = 33) has been enlarged to 58 patients. The authors here present demographic and clinical data, and reasons for admission to geriatric psychiatry hospitals in comparison with 17 patients, who primarily attended the Memory Disorders Clinic of the University of Regensburg. The results implicate that both institutions see patients with different clinical syndromes: (1) patients were primarily referred to the Memory Disorders Clinic presenting memory and/or speech difficulties as the leading symptoms; (2) major reasons for hospitalisation of patients with FTLD in geriatric psychiatry hospitals were behavioural disturbances; (3) late-onset FTLD (>65 years) was more common than previously assumed in both institutions, and (4) increasing age at admission increased the likelihood to obtain a limited diagnostic approach of brain imaging (only cranial computer tomography) to evaluate the cause of dementia.

Identification of novel mutations in the NPC1 gene in German patients with Niemann-Pick C disease.

Niemann-Pick disease type C (NPC) is an inherited neuro-degenerative disorder associated with intracellular cholesterol trafficking defects. Mutations in two distinct genes, NPC1 and HE1, have recently been shown to cause this disease. We have analysed the NPC1 gene in five German patients with NPC from four unrelated families. We identified a total of five novel mutations in the coding region of the NPC1 gene (G231V, D874V, 1642M, 11094T and R116stop). All affected individuals displayed compound heterozygosity. The mutated alleles were transmitted by the nonaffected parents with the exception of one patient, in whom a de novo mutation (G231V) had occurred. Interestingly, the G231V/P237S NPC1 genotype in this individual is associated with an early-onset form of NPC. In contrast, we found that the D874V/D948N genotype, observed in another NPC patient, is characterized by a late onset of clinical symptoms that presents with a pronounced white-matter disease. Our results will contribute to defining the association between the clinical phenotypes and the genetic abnormalities in Niemann-Pick C disease.

Effect of phenytoin on cytochrome P450 2B mRNA expression in primary rat astrocyte cultures.

Studies on cytochrome P450 2B (CYP2B) in the brain have essentially been focused on protein characterization and regional distribution. Due to the high sequence homology between the closely related CYP2B1 and 2B2 isoforms and the low amounts of the corresponding mRNAs few efforts have been made to analyze the expression, regulation, and inducibility of these P450 genes in a specific cell type. In the present study, we investigated CYP2B mRNA expression in primary rat astrocyte cultures under the influence of the anti-epileptic drug phenytoin, which is known to be a CYP2B inducing agent in liver. In situ hybridization with a digoxigenin (DIG)-labeled cRNA probe demonstrated that 30-40% of the astrocytes strongly expressed a CYP2B mRNA-specific signal within the first week of cultivation. With increasing age (> 14 days) a greater percentage of cells (>90%) expressed mRNA for P450 2B. However, the level of transcriptional activity was substantially lower than in younger cultures. To discriminate between the 2B1 and 2B2 isoforms the reverse transcription/polymerase chain reaction (RT/PCR) procedures were proved for rat hepatic mRNA as a control assay. Subsequently, the application of this method on cultured astrocytes confirmed that these brain cells may express CYP2B1 mRNA. CYP2B2 mRNA could not be detected in astrocyte cultures at any age examined. Phenytoin led to the down regulation of CYP2B1 mRNA, which contrasts with the drug inducing effect on hepatic CYP2B1 and 2B2 levels. After 4 hr of exposure of phenytoin to the astrocytes no amplification product could be detected at all. Phenytoin did not induce either CYP2B1 or 2B2 expression.

[Presenile dementia in polycystic lipomembranous osteodysplasia]. / Präsenile Demenz bei polyzystischer lipomembranöser Osteodysplasie.

We present a 36-year-old woman with a 3-year history of cognitive decline followed by development of a small stepped gait and urinary and fecal incontinence. Workup revealed multiple bone cysts documented by X-ray and idiopathic hyperprolactinoma. An MRI confirmed the CT finding of massive bilateral basal ganglia calcification. This is the first case of polycystic lipomembranous osteodysplasia described in Germany. We conclude that patients with presenile dementia, psychosis, or early-onset Parkinsonism associated with basal ganglia calcification should undergo X-rays of hand and feet to rule out polycystic lipomembranous osteodysplasia.