PubMed Health⌕ Search

Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 55 records · Page 3Linked to original sources

Effects of chronic haloperidol and clozapine treatment on AMPA and kainate receptor binding in rat brain.

BACKGROUND: Alterations in AMPA and kainate receptor binding have been revealed in post-mortem schizophrenic brains. As most patients had been treated with antipsychotics, medication effects cannot be excluded as a possible explanation for these results. METHODS: Within the framework of this animal study, we investigated [3H]AMPA and [3H]kainate receptor binding in different rat brain regions following 6 months of oral treatment with either haloperidol (1.5 mg/kg/day) or clozapine (45 mg/kg/day). RESULTS: AMPA receptor binding was increased after haloperidol treatment in the striatum, nucleus accumbens, cingulate cortex, and insular cortex. Clozapine showed increased AMPA receptor binding only in the anterior cingulate cortex. Kainate receptor binding was increased by both drugs in all hippocampal subfields. CONCLUSIONS: This altered receptor binding may be related to beneficial neuroleptic effects and side effects. Furthermore, neuroleptic therapy may contribute to some of the post-mortem findings in the striatum in schizophrenia.

Animals↗

Sexual dimorphism in the osteoarthritis of STR/ort mice may be linked to articular cytokines.

BACKGROUND: STR/ort mice spontaneously develop degenerative changes of the knee joints resembling human osteoarthritis (OA), with the males being more severely affected than the females. OBJECTIVE: To analyse the early changes leading to OA by examining the articular cytokine expression and degenerative changes in STR/ort mice. METHODS: 122 STR/ort mice of both sexes aged between 2 and 15.5 months were included. Thin sections of the knees were analysed for osteoarthritic changes by haematoxylin/eosin staining. The articular cytokine expression was investigated by immunohistochemical staining using monoclonal antibodies specific for interleukin (IL)6, tumour necrosis factor alpha, transforming growth factor beta1 (TGFbeta1), IL1beta, IL4, and IL10, respectively. RESULTS: Both cartilage degeneration and articular cytokine expression differ between the sexes. The protection from cartilage degeneration in the female mice correlates with an increased expression of TGFbeta1 and IL4 at 2 months of age. CONCLUSION: The increased expression of TGFbeta1 and IL4 in young STR/ort female mice suggests that the sexual dimorphism is mediated through the articular expression of cytokines involved in cartilage metabolism.

Animals↗

Impaired recycling of surfactant-like liposomes in type II pneumocytes from injured lungs.

BACKGROUND: Surfactant synthesis and secretion has been shown to be impaired in type II cells from diseased lungs. The mechanism of surfactant lipid recycling, which is an important physiological process in surfactant treatment, was studied in type II cells isolated from injured lungs. METHODS: Different stages of lung injury were induced by exposing rats to 10 ppm nitrogen dioxide (NO(2)) for 3, 20, and 28 days. Type II cells were isolated from these lungs and recycling of (3)H-DPPC labelled surfactant-like liposomes was studied in vitro. RESULTS: Uptake of liposomes (150 micro g/ml) for 20 minutes in the absence and presence of surfactant protein-A (SP-A, 5 micro g/ml) was higher in cells from NO(2) injured lungs (63-78%) than in control cells. There was no difference in liposome uptake between the groups with NO(2) exposure of different duration. After liposome uptake, most of the internalised label remained in the phosphatidylcholine (PC) fraction and increased with duration of exposure to NO(2). After 20 minutes internalisation, cells were allowed to resecrete lipids for a further 20 minute period. In cells from controls and from all stages of lung injury, liposomes that had been internalised in the presence of SP-A were resecreted to a greater extent than those internalised without SP-A. However, cells from lungs exposed to NO(2) resecreted less lipid than cells from control lungs. Again, there was no difference in resecretion between the groups with NO(2) exposure of different duration. CONCLUSION: Type II cells from injured lungs internalise more surfactant-like liposomes than cells from controls, suggesting a putative therapeutic significance to cope with limited alveolar surfactant pools in lung injury.

Animals↗

HHV-8 DNA sequences in the peripheral blood and skin lesions of an HIV-negative patient with multiple eruptive dermatofibromas: implications for the detection of HHV-8 as a diagnostic marker for Kaposi's sarcoma.

BACKGROUND: Multiple eruptive dermatofibroma (MEDF) is a rare disorder seen in immunocompromised patients, simulating Kaposi's sarcoma (KS). Whereas KS is strongly associated with human herpesvirus 8 (HHV-8), the virus has never been detected in MEDF until now. OBJECTIVE: To present a patient with MEDF who showed no signs of immunodeficiency but was seropositive for HHV-8 antibodies and demonstrated HHV-8 DNA both in the peripheral blood and lesional skin of MEDF. METHODS: Clinical, histological and serological investigations were performed as well as polymerase chain reaction (PCR) studies and in situ hybridization (ISH). RESULTS: A 35-year-old white man with suspected KS was referred for evaluation of multiple pigmented nodules and patches. Biopsies revealed features of dermatofibroma, superficial fibrosing dermatitis and scar. One of the nodular lesions harbored HHV-8 DNA sequences. A faint amplification product was detected in the superficial fibrosing dermatitis lesion, while no HHV-8 sequences were found in normal skin and scar. Whole-blood samples and serum were positive for HHV-8. None of the skin lesions shown to harbor HHV-8 DNA sequences by nested PCR displayed a signal for HHV-8 RNA by ISH. Repetitive peripheral blood examinations did not reveal any serum antibodies against or antigens of HIV. Serum antibodies against the HHV-8 capsid antigen orf 65.2 were detected. CONCLUSION: Results of PCR studies and ISH indicate that the presence of HHV-8 in the lesional tissue was probably blood-borne due to viremia and not due to viral replication in tumor cells. The presence of HHV-8 is not fully restricted to KS. The differential diagnosis of KS and its simulators should be based on an integrative analysis of all available clinicopathological and molecular data and should not rely exclusively or predominantly on the presence or absence of HHV-8.

Adult↗

Immunoneutralization of procalcitonin as therapy of sepsis.

Prior studies have demonstrated that the prohormone, procalcitonin (ProCT), and its component calcitonin precursors (CTpr) are increased in the serum of septic patients, correlate with the severity of the illness, and persist for relatively long periods of time. Animal studies in septic hamsters have revealed that the administration of ProCT is toxic and that immunoneutralization with IgG that is reactive to this molecule significantly improves survival. A large animal model of a very rapidly lethal polymicrobial sepsis has been developed in the pig in order to measure continuous physiological and metabolic parameters and also to compare the effects in this animal of an immunoneutralization, which is performed late in the course of the disease, to an identical, but early, therapy. Based upon the physiological and metabolic parameters, the late therapy, which was initiated during the fourth hour at a time when pigs were nearly moribund, was found to be as beneficial as early therapy. In both late and early therapy, the only animals to survive at the predetermined time of euthanasia were those which had received immunoneutralization therapy.

Animals↗

Selection of chloroplasts by laser microbeam microdissection for single-chloroplast PCR.

Laser microbeam microdissection and laser pressure catapulting offer the possibility of separating cell compartments, thus allowing for contamination-free analysis. Using these methods, we were able to select single chloroplasts of Nicotiana tabacum. Starting from homogenized leaf material, chloroplasts were purified by differential centrifugation and applied directly onto a poly-ethylene-naphthalate membrane that was mounted on a microscope slide. Single chloroplasts were dissected under microscopic control and catapulted into a PCR tube. Subsequent PCR of a spacer region between the trnT and trnF genes verified the successful amplification of DNA from a single chloroplast. The advantage of this method compared to the use of capillaries or optical tweezers is that one is able to prepare high numbers of samples in a short time.

Base Sequence↗

[The paradox of TSH elevation in Sheehan's syndrome].

HISTORY AND CLINICAL FINDINGS: A 59-year-old woman was examined because of weight gain, increasing fatigue and secondary amenorrhoea, which occurred after a complicated delivery at age 18. The finding of an increased TSH concentration was initially considered as primary hypothyroidism and substitution therapy was commenced. Because of the concomitant secondary amenorrhoea the patient was referred for additional endocrinological investigations. INVESTIGATIONS: Biochemical analysis confirmed the increase in TSH concentrations, and revealed a gonadotropin deficiency, a decrease in IGF-I concentration and a free urinary cortisol concentration at the lower end of the normal range. Dynamic testing of pituitary function (insulin tolerance test) confirmed a severe growth hormone deficiency and partial secondary adrenal insufficiency. An MRI study of the pituitary showed an empty sella with some remaining pituitary tissue at the bottom of the sella. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: The laboratory findings of pituitary insufficiency with an empty sella on MRI scan suggested Sheehan's syndrome despite an increase in thyrotropin level. Pituitary replacement therapy was started with hydrocortone, combined estrogens and progesterone in addition to levothyroxin, which considerably improved clinical symptoms. CONCLUSION: A history of secondary amenorrhoea after a complicated delivery including significant bleeding or septic complications suggest Sheehan's syndrome, which can result in partial or complete panhypopituitarism. In such circumstances the pituitary hormone levels are usually reduced. TSH concentrations, however, may be increased.

Amenorrhea↗

Phenotypic features of myoclonus-dystonia in three kindreds.

BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with involuntary jerks and dystonic contractions. Autosomal dominant alcohol-responsive M-D is associated with mutations in the epsilon-sarcoglycan gene (SGCE) (six families) and with a missense change in the D2 dopamine receptor (DRD2)gene (one family). OBJECTIVE: To investigate the clinical phenotype associated with M-D including motor symptoms, psychiatric disorders, and neuropsychological deficits. METHODS: Fifty individuals in three M-D families were evaluated and a standardized neurologic examination and DNA analysis were performed. Psychiatric profiles were established with the Diagnostic Interviews for Genetic Studies (DIGS) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Cognition was evaluated with standardized neuropsychological tests. RESULTS: Distinct truncating mutations in the SGCE gene were identified in each family. Additionally, a missense alteration in the DRD2 gene was previously found in one family. Motor expression was variable, with onset of myoclonus or dystonia or both affecting the upper body and progression to myoclonus and dystonia in most cases. Psychiatric profiles revealed depression, obsessive-compulsive disorder, substance abuse, anxiety/panic/phobic disorders, and psychosis in two families, and depression only in the third family. Averaged scores from cognitive testing showed impaired verbal learning and memory in one family, impaired memory in the second family, and no cognitive deficits in the third family. CONCLUSIONS: Cognitive deficits may be associated with M-D. Psychiatric abnormalities correlate with the motor symptoms in affected individuals. Assessment of additional M-D families with known mutations is needed to determine whether these are characteristic phenotypic manifestations of M-D.

Adult↗

[Unusual manifestations of autoimmune thyroiditis].

Autoimmune thyroid disease (AITD) is quite common and comprises goitrous and nongoitrous eu- and hypothyroid Hashimoto's Disease with or without preceding thyrotoxicosis, classical hyperthyroid Graves' Disease and its rarer eu- and hypothyroid variants. There is no generally accepted international classification of AITD. Important aspects of the pathogenesis of AITD have been elucidated in the past two decades. AITD may be explained by an excess of either stimulating and/or destructive/blocking immune processes or by a balanced coexistence of various of these pathological autoimmune features. The HLA (DQA1*0501) is involved in determining the susceptibility to AITD. The measurement of antibodies against thyroidal peroxidase and TSH receptor has become the cornerstone in the diagnosis of AITD. Antibodies directed against TSH receptors are stimulating (TSAb) or blocking (TSBAb). In routine measurements they are determined by a radioligand assay which does not distinguish between these two different types of antibodies. A valid interpretation of antibody results is therefore only possible in connection with the clinical findings and the results of thyroid hormone measurements. We present here four unusual cases with AITD which illustrate its complexity and summarize the present state of knowledge on this disease.

Adult↗

[Hypophyseal incidentaloma in a patient with autosomal dominant polycystic kidney disease].

The prevalence of incidentally discovered lesions within the pituitary (pituitary incidentalomas) is about 10%. The most common form of sellar mass are clinically nonfunctioning adenomas (less than 10 mm); functioning adenomas, however, are rare. Incidentally discovered pituitary microadenomas causing growth hormone hypersecretion are uncommon. In addition, the association of autosomal dominant polycystic kidney disease with acromegaly is exceptional and has not yet been reported to our knowledge.

Acromegaly↗

Resorbable defect analog PLGA scaffolds using CO2 as solvent: structural characterization.

After tooth extraction, the immediate wound treatment by implanting an exact copy of the root could prevent alveolar bone atrophy. The implant should have an interconnected porosity in order to promote tissue in-growth. This communication reports a novel method to realize such net-shaped porous scaffolds fabricated within a few minutes. Porosity and micro-architecture are evaluated by Hg-porosimetry and by image analysis of electron and light microscopy as well as by computed micro-tomography. The total porosity of the scaffold corresponds to (63 +/- 3)%, mainly related to open interconnected porosity. Micro-tomography, as a noninvasive 3D method, is best suited to uncover pores of about 100 microm, a diameter especially important for tissue in-growth. The differentiation between open and closed porosity, however, depends on the method chosen. This effect is attributed to the spherical pores with an orifice only detected in the 3D analysis. Consequently, the closed porosity is overestimated by 8% evaluating 2D images. Finally, the mean pore diameter is found to be 106 and 100 microm for 2D and 3D analysis, respectively. Although the porosity of the scaffold needs to be further optimized for clinical applications, the procedure proposed is a promising route in manufacturing open porous implants without the use of any organic solvent.

Alveolar Bone Loss↗

[Sympathetically maintained pain (SMP): phentolamine test vs sympathetic nerve blockade. Comparison of two diagnostic methods].

The objective of our study was to clarify whether the phentolamine test is as suitable as sympathetic blockade in diagnosing cases of sympathetically maintained pain. The specificity and the sensitivity of both procedures were examined within a prospective and randomized study. Both a local sympathetic blockade and an intravenous phentolamine infusion were carried out in 29 patients with persistent pain in the area of the upper or lower extremities. A significant improvement was defined as reduction of pain of at least 50%. There were no complications in either test procedure. The phentolamine test registers sympathetically maintained pain well when it has a positive result (specificity of 83%). However, the phentolamine test shows only a low sensitivity of 69%. The phentolamine test, on the other hand, can be realized very easily and safely. Therefore, based on the results obtained, it is recommended that the phentolamine test be applied for primary diagnosis. In case of a negative result, further diagnosis should follow subsequently, for example with local sympathetic blockade.

Adrenergic alpha-Antagonists↗

Primary subcutaneous follicular centre cell lymphoma with involvement of the galea: a case report and short review of the literature.

Primary cutaneous follicular centre cell lymphoma (FCCL) is a distinct subtype of cutaneous lymphoma that originates from germinal centre cells. Histologically, the disease is typified by a bottom-heavy infiltrate with a diffuse or follicular growth pattern situated in the mid or deep dermis. In some cases, the neoplastic infiltrate may involve the underlying subcutaneous tissue, but so far primary subcutaneous FCCL has not been reported. We report the first case of primary FCCL located primarily in the deep subcutis with extension into the galea and review the literature on primary subcutaneous B-cell lymphomas.

Female↗

Basal TSH levels compared with TRH-stimulated TSH levels to diagnose different degrees of TSH suppression: diagnostic and therapeutic impact of assay performance.

BACKGROUND: The estimated prevalence of endogenous subclinical hyperthyroidism varies from 4% to 6% and a basal thyroid stimulating hormone (TSH) level < 0.5 mU L-1 may be associated with increased mortality in subjects over 60 years of age who are not on thyroid medication. Exogenous TSH suppression is a mainstay in the treatment of thyroid cancer. Because of recent concerns about potential adverse effects, especially of endogenous TSH suppression on bone, the cardiovascular system and cognitive functions, subclinical hyperthyroidism obtained new clinical importance. We therefore re-evaluated the diagnostic value of basal and thyrotrop in TRH-stimulated serum TSH measurements using TSH assays with different sensitivities. MATERIALS AND METHODS: A total of 805 oral and nasal TRH stimulation tests were performed on 409 ambulatory subjects with low basal serum TSH concentrations of less than 0.1 mIU L-1. Basal serum TSH was measured either using a second generation assay (functional sensitivity > 0.03 mIU L-1) or two third generation assays (functional sensitivity 0.01 mIU L-1 and 0.007 mU L-1, respectively). Serum TSH concentration was determined before and 3 h after oral administration of 40 mg of TRH and before and 30 min after nasal administration of 2 mg of TRH. RESULTS: In the oral testing group, the basal TSH levels measured by the different TSH assays were 0.06 +/- 0.03, 0.04 +/- 0.02 and 0.03 +/- 0.02, respectively, whereas the peak TSH levels were 0.4 +/- 0.6, 0.4 +/- 0.6 and 0.3 +/- 0.5 in the patients with subclinical hyperthyroidism. In overt hyperthyroidism, the basal TSH levels were 0.06 +/- 0.02, 0.03 +/- 0.02 and 0.03 +/- 0.02, whereas the peak TSH levels were 0.19 +/- 0.3, 0.16 +/- 0.3 and 0.15 +/- 0.2, respectively. Basal TSH values could discriminate between different degrees of TSH suppression if measured with a third generation assay (P < 0.001), but not with a second generation assay. There was only a weak correlation between basal TSH and peak TSH when measured by a second generation assay (n = 126; r = 0.3; P < 0.001) in contrast to the strong correlation found using the third generation assays (n = 128; r = 0.7; P < 0.001 and n = 69; r = 0.8; P < 0.001, respectively). CONCLUSIONS: In view of the recent concerns about potential adverse effects in TSH suppression and based on our data, it is mandatory to select a TSH assay with a functional sensitivity of < or = 0.01 mIU L-1 for optimal titration of L-T4 suppressive therapy, especially in patients with thyroid cancer. If, however, only a second generation TSH assay is available, additional TRH testing allows a more careful titration of suppressive thyroxine therapy.

Administration, Intranasal↗

[Diagnosis and embryogenesis of partial anomalous pulmonary venous connection].

In Anomalous Pulmonary Venous Drainage one or more pulmonary veins are not connected with left atrium, but drain into systemic circulation or right atrium. The clinical signs of the shunt between pulmonary and systemic circulation increase during lifetime, thus the abnormality gets late or not diagnosed. Partial Anomalous Pulmonary Venous Drainage is a developmental disorder, according to embryogenesis we recommend a classification of this abnormality. Two case reports are given to illustrate difficulties in diagnosis of this relatively common abnormality. A diagnostic standard of assessment of pulmonary venous disorders is discussed. The "Gold Standard" of selective pulmonary Angiography in combination with oxygen measurement is widely used for diagnosis of Partial Anomalous Pulmonary Venous Drainage. In the future improvement and common use of modern cross sectional imaging techniques will redefine the value of conventional Angiography.

Adolescent↗

Association of HLA-DRB1*02 with osteoarthritis in a cohort of 106 patients.

OBJECTIVE: We have previously shown that the inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 or IL-1beta are up-regulated in chondrocytes of patients with osteoarthritis (OA). However, the inflammatory responses associated with OA are of low grade and restricted. To investigate the involvement of the immune system in the pathogenesis of OA, we analysed patients for their HLA-DRB1 haplotypes. METHODS: Combining single-stranded oligo or sequence-specific primer typing procedures, 139 randomly selected controls and 106 OA patients were typed for their HLA-DRB1 alleles. RESULTS: The OA cohort showed statistically significant differences in the frequencies of the DR2 and DR5 alleles compared with the controls. While the frequency of the DR2 allele was elevated among the OA patients, the DR5 allele was negatively associated with the disease. The P values for differences from the controls were 0.0431 for DR2 and 0.0386 for DR5 and the odds ratios for the two alleles were 1.58 and 0.54 respectively. CONCLUSION: The association of DR2 and DR5 with OA hints at linkage disequilibrium between HLA-DRB1 genes and genes involved in the pathogenesis of OA. Alternatively, DR2 has a direct role in restricting immunological responses to the low-grade inflammation characteristic of OA.

Aged↗