Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Peters.
Explore the source record for details and available documents.
New Zealand White rabbits were used to investigate the influence of increasing dietary P concentrations on growth performance, mineral balance, kidney calcification and bone development. The minimum dietary P requirement of 0.22 % (National Research Council) is usually exceeded in commercial natural-ingredient chows, leading to undesirable kidney calcifications. In order to study the optimal dietary P level, rabbits were fed semi-purified diets with four different P levels (0.1, 0.2, 0.4, and 0.8 %; w/w) at a constant dietary Ca concentration (0.5 %) during an 8-week period. Body weight and growth were not influenced by the dietary P level. During two periods (days 20-23 and 48-51), faeces and urine were collected quantitatively for the analysis of Ca, Mg and P and balances were calculated. Increased dietary P intake caused increased urinary and faecal P excretion and P apparent absorption and retention. Faecal Ca excretion increased with higher dietary P levels, whereas urinary Ca excretion reacted inversely. The apparent absorption of Ca became reduced at higher dietary P concentrations, but Ca retention was unchanged. The response of Mg was in a similar direction to that of the Ca balance. Kidney mineral content increased with higher dietary P levels, indicating the presence of calcified deposits. Nephrocalcinosis became more severe in kidney cortex and medulla at increasing dietary P levels, as was confirmed by histological analysis. Femur bone length was not differentially influenced by dietary P. Bone density (g/cm(3)) of the femur diaphysis became significantly lower at the 0.8 % dietary P level as compared with the 0.2 % P group only. The bone Mg content was significantly increased on the 0.8 % P diet, both in the diaphysis and epiphysis. Plasma P concentration increased and plasma Ca decreased with higher dietary P levels, whereas plasma Mg levels were unaffected. The present study shows that the current recommended minimum dietary P level of 0.2 % for rabbits, as advised by the National Research Council in 1977, leads to a normal growth and bone development, but also causes some degree of kidney calcifications at a dietary Ca level of 0.5 %. As the dietary P level of 0.1 % virtually prevented kidney calcification and at the same time did not give evidence for any deleterious effects on growth and bone development, this indicates that the current recommended dietary P level for rabbits should be regarded as a maximum advisable concentration, and that a lower P level may be more optimal.
UNLABELLED: Long standing confusion exists in the terminology of hypokalaemic salt-losing tubulopathies (SLTs). SLTs are autosomal recessively transmitted and characterized by normotensive secondary hyperreninism/hyperaldosteronism with hypokalaemic metabolic alkalosis. Historically, four phenotypical variants have been described: (1) the (classic) Bartter syndrome (cBS), (2) the hypomagnesaemic hypocalciuric Gitelman syndrome (GS), (3) the hypercalciuric hyperprostaglandin-E-syndrome (HPS) or antenatal Bartter syndrome (aBS) and (4) the hyperprostaglandin-E-syndrome with sensorineural deafness (HPS + SND). The latter two syndromes are the most severe variants with antenatal manifestation with polyhydramnios and life-threatening course of salt- and water-loss. Defects in five renal membrane proteins involved in electrolyte reabsorption have been identified: In HPS-patients mutations in (1) either the furosemide-sensitive sodium-potassium-chloride cotransporter NKCC2, or (2) in the potassium channel ROMK have been identified, and (3) HPS + SND is caused by mutations in the beta-subunit of the chloride channels ClC-Kb and -Ka (named barttin), all mimicking the major pharmacological effects of furosemide with minor potassium-wasting in ROMK-patients as seen in patients treated with simultaneous furosemide and amiloride, and minor calcium-wasting in Barttin-patients resembling the combination of furosemide and thiazides. (4) cBS is caused by mutations in the chloride channel ClC-Kb with similar clinical characteristics as seen under combination of thiazides and furosemide, (5) GS is caused by mutations in the thiazide-sensitive sodium-chloride cotransporter NCCT resembling the effect of long-term thiazide administration. CONCLUSION: The combination of pharmacology and genetics suggests a new terminology for the above described SLTs: Furosemide-like-SLT for HPS caused by NKCC2-mutations, furosemide/amiloride-like-SLT for HPS caused by ROMK-mutations, furosemide/thiazide-like-SLT for HPS + SND, thiazide/furosemide-like-SLT for cBS, and thiazide-like-SLT for GS.
This study was conducted to evaluate the effect of an unaware carriership on the delay in diagnosis of haemophilia and the resulting effect of this delay on morbidity. Information on 73 haemophilia patients (<18 years) and their mothers was gathered from data of patients' medical records and completed by interviews with the parent(s). Although a positive family history was present in 52 gravidae, 16 of them (31%) were not aware of their carrier status at moment of delivery. Fifteen of these 16 unaware carriers, were carriers of a non-severe form of haemophilia. In mothers who were unaware of carriership for haemophilia instrumental delivery occurred more frequently than in mothers who knew they were carriers. This is disquieting since instrumental delivery poses a significant risk (relative risk: 17.8, 95% CI: 4.0-78.4) for intra- or extracranial bleedings in newborn haemophiliacs in comparison to spontaneous deliveries or caesarean sections. In 83% of the patients with a positive family history, diagnosis was established before the first bleeding episode. Patients diagnosed by bleedings presented more often with iatrogenic bleedings (38%) then patients who were diagnosed because of a positive family history (9%) (P < 0.05). In comparison to previous studies, more patients had a positive family history and in more haemophiliacs with a positive family history diagnosis was established before the first bleeding episode. Although this reflects the yield of improved diagnostic methods, further reduction of iatrogenic bleeding is possible by intensifying counselling of mild haemophilia carriers.
We evaluated inhibitor formation in a group of patients with mild haemophilia A caused by an Arg593 to Cys mutation. A remarkably high cumulative inhibitor incidence of 14% over 22 years was observed. Three of 49 patients developed transient, low-titre inhibitors, which remained below 2.0 BU mL(-1). Four patients with an Arg593 to Cys mutation developed high-titre inhibitors (>5.0 BU mL(-1)). Three of these patients have been described previously. In this study, we characterized inhibitory antibodies in a fourth patient with high-titre inhibitors. Epitope mapping studies revealed that antibodies were predominantly directed to the A2 domain of factor VIII. We addressed the role of human leucocyte antigen (HLA) class II alleles in inhibitor development in patients with an Arg593 to Cys mutation by HLA genotyping. In the group of inhibitor patients raised frequencies of HLA-DRB1*01 and HLA-DQB1*05 were observed that did not reached statistical significance. Our data suggest that inhibitor development in mild haemophilia A patients with an Arg593 to Cys mutation is not linked to HLA class II profile.
Seven neonates required intensive care at our institution with enterovirus myocarditis, 2001-2003. Presentation was at a median age of 9 days. All had ischaemic electrocardiograms, poor ventricular function, raised creatine kinase, and enterovirus RNA detected by reverse transcriptase polymerase chain reaction. Four survived. Enterovirus myocarditis may be an under recognised cause of neonatal collapse.
Mucociliary clearance (MCC) is an important mechanism for removing inhaled particles, secretions and cellular debris from the respiratory tract. Here, a direct measurement of tracheal mucus velocity (TMV) for assessment of MCC, suitable for clinical and research use, is reported, and a comparison is made of TMV in normal subjects and patients with chronic obstructive pulmonary disease (COPD). A 0.1-mL bolus of radiolabelled (2-5 MBq), technetium-labelled macroaggregated human albumin (99mTc MAA) was injected through the cricothyroid membrane into the trachea of 20 young (< 50 yrs) and 12 older (> 50 yrs) normal subjects and 34 patients with COPD. Repeat studies were carried out in 13 normal subjects and 16 COPD patients. Movement of the bolus in the trachea was recorded (15 min) using a gamma camera interfaced to a computer. Data were analysed using specifically designed software. The test was well tolerated by subjects and patients, and no significant adverse events were reported. No significant differences were observed between data recorded from different regions of the bolus (leading edge, peak, trailing edge) by analysis of variance (ANOVA). Bland-Altman plots of the repeat studies indicated that data were more variable in normal subjects (coefficient of repeatability (COR) 10.3 mm.min-1) than in COPD patients (COR 5.5 mm.min-1). TMV (mean +/- SD) in young normal subjects (n = 20) was 10.7 +/- 3.5 mm.min-1. TMV was reduced in older normal subjects (n = 12; 6.5 +/- 2.6 mm.min-1) and further reduced in COPD (n = 34; 2.1 +/- 2.7 mm.min-1). In conclusion, this technique can be used to measure tracheal mucus velocity rapidly and safely in healthy subjects and patients with respiratory tract disease. This study has confirmed that tracheal mucus velocity declines with age and is further impaired in patients with chronic obstructive pulmonary disease.
Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation is directed at the identification of treatable subset. Accurate diagnostic workup is crucial because both prognosis and survival rates depend mainly on detection of the primary tumor site. Although these patients undergo extensive imaging procedures, nuclear medicine techniques are under-utilized despite their ability of providing molecular information. Positron emission tomography has an emerging role in this clinical challenge along with other nuclear medicine methods including, bone scan, thyroid scintigraphy.
In 13 German Holstein calves from two different dairy farms arthrogryposis of the front legs, facial scoliosis and torticollis were observed. Obvious environmental reasons could not be found. Chromosomal anomalies in two affected calves were not detectable. A striking feature was the high frequency of affected calves among the offspring of one natural service sire. A plausible explanation of the congenital anomalies observed is a dominantly inherited mutation restricted to germ cells.
The efficacy of sequencing batch reactors (SBRs) to provide high levels of biological nutrient removal has been extensively demonstrated around the world. Environmental Solutions International (ESI) has now constructed over 20 full-scale SBR plants and has confirmed that nutrient removal is enhanced via the process of simultaneous nitrification and denitrification. Over 18 months of operational data from two plants, operating in distinctly different catchments, processing an average of between 2,000 and 2,500 m3/d of wastewater, has clearly shown the efficacy and robustness of the ESI SBR-BNR process. Median effluent total nitrogen and total phosphorus values of 3 mg/L and <0.6 mg/L, respectively, were demonstrated over the 18-month period. This high level of nutrient removal is attributed to the design of the bio-selector which maximises carbon storage for the subsequent denitrification reactions, the effective aeration control which ensures no over-aeration during the air-on cycle as well as the level of operational control provided at these two plants.
AIM: Osteodystrophy is a well known complication of cholestatic liver diseases such as primary biliary cirrhosis (PBC), although the factors predisposing to the development of metabolic bone disease and its natural history have not been well studied. METHODS: We followed a cohort of patients, predominantly post-menopausal females, for changes in bone mineral density over a period of up to 8 years. RESULTS: We found that most patients with PBC have relatively stable lumbar bone density over time, even in the face of progressive liver disease. Only 2 of 22 patients experienced fractures. Both of these patients had low initial bone density measurements. CONCLUSIONS: We recommend that all patients with newly diagnosed PBC undergo bone mineral density measurement so as to identify those at greatest risk of pathological fractures.
Tissue cysts of parasites of the genus Hammondia are rarely described in naturally or experimentally infected intermediate hosts. However, ultrastructural examinations on tissue cyst stages of Hammondia sp. are needed, e.g. to compare these stages with those of Neospora caninum and other related parasites. We describe a cell culture system employed to examine the in vitro development of tissue cysts of a Hammondia sp.-like parasite (isolate FOX 2000/1) which uses the European fox as a definitive host. Cells of a diploid finite cell line from embryonal bovine heart (KH-R; CCLV, RIE 090) were infected by inoculation of sporozoites und cultivated for up to 3 months. Transmission electron microscopic examination of 17 day old cell culture material revealed the presence of cyst walls. Infected cell cultures cultivated for 2 months were used to feed a fox. Six to 13 days post infection the fox shed large numbers (n=1.2 x 10(7)) of Hammondia-sp. like oocysts which could not be distinguished from those used to infect the cell culture as determined by DNA sequencing of the internal transcribed spacer 1 and the D2/D3 domain of the large subunit ribosomal DNA. To find out the proportion of parasitophorous vacuoles that had developed into tissue cysts, the expression of bradyzoite markers was examined by probing infected cell cultures with mouse polyclonal antibodies against Toxoplasma gondii bradyzoite antigen 1 (anti-BAG1) and rat monoclonal antibodies against a cyst wall protein (mAbCC2). Nineteen and 90 days post infection all parasitophorous vacuoles in the cell cultures were positive with anti-BAG1 and mAbCC2. This shows that biologically viable (i.e. infectious) tissue cysts of a fox-derived Hammondia sp. isolate (FOX 2000/1) can be efficiently produced in this cell culture system. Since in vitro cystogenesis of dog-derived Hammondia heydorni has not been observed yet, in vitro cyst formation might be one trait to separate fox-derived Hammondia sp. from H. heydorni on a species level.
An intracranial epidermoid cyst was diagnosed in a Haflinger gelding aged 12 years suffering from episodes of neurological disturbance, apathy and fever. The extracerebral cyst was located in the region of the tentorium cerebelli and measured 9 x 8 x 5 cm. It displaced the cerebral hemispheres anteriorly and compressed the cerebellum and brainstem underneath. Histologically, the cyst was lined by keratinizing, stratified squamous epithelium and contained keratin scales, debris, focal haemorrhages, and degenerating inflammatory cells. The epithelium was supported by a vascularized fibrous capsule that firmly adhered to the dura mater. Multifocal haemorrhages and moderate lymphohistiocytic infiltrations were present in the capsule. The basement membrane was disrupted focally, and single or clustered cytokeratin-positive epithelial cells were detected in the fibrous capsule, suggesting a possible transition to malignancy.
The referral of critically ill cancer patients to an intensive care unit (ICU) is a matter of controversial debate. This study was conducted by an interdisciplinary clinical group to evaluate the outcome of ICU treatment in cancer patients according to their characteristics at the time of referral. A retrospective analysis was used to identify relevant subgroups among 189 consecutive cancer patients referred as emergencies to one of four ICUs during a 2-year period. Reasons for ICU referral were pneumonia (29.6%), sepsis (27.0%), fungal infection (11.1%), another infection (9.5%), gastrointestinal emergency (16.9%), treatment-related organ toxicity (6.9%), or other, non-infectious complications (43.9%). Vasopressor support was required in 50.3%, mechanical ventilation in 49.7%, and haemodialysis/-filtration in 26.5% of the patients. Overall, 41.3% died during ICU treatment, 12.2% died after transfer from ICU to a non-ICU ward, and 35.4% were discharged alive. Sepsis, mechanical ventilation, vasopressor support, renal replacement therapy and neutropenia were independent risk factors for fatal outcome, but no single risk factor unequivocally predicted death. All patients with fungal infection who required vasopressor support and either had sepsis (n=13) or needed mechanical ventilation (n=14) died during ICU treatment, while all non-septic patients. who did not require mechanical ventilation, were younger than 74 years of age and had a non-infectious underlying complication (n=29), survived. This analysis may help to early identify relevant subgroups of cancer patients with different prognoses under ICU treatment. A prospective study to confirm the predictive usefulness of this approach is needed. Cancer patients should not be excluded from referral to the intensive care unit in an emergency solely due to their underlying malignant disease or a single unfavourable prognostic factor.
AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance study, 70 previously treated haemophilia A patients were included (73% severe, 14% moderate and 13% mild haemophilia A). Most of these patients were followed during 4 years for the appearance of adverse events, possible transmissions of blood-borne viruses and the occurrence of antibodies against FVIII. The efficacy of treatment was determined in each patient by the in vivo recovery of FVIII. During this study, only six adverse events, possibly related to the use of AAFACT, were reported. None of these were indicated as serious. Transmissions of HIV, HAV, HBV and HCV in the seronegative patients have not been observed. In none of the patients, inhibitors to FVIII were detected. The in vivo recovery of FVIII during this study was not different from the in vivo recovery observed in eight patients during the preregistration study. There was a correlation of in vivo recovery with age and body weight. From these results, we conclude that the clinical usage of this human plasma-derived FVIII product is efficient and safe.
A 14-year-old standardbred mare with clinically suspected acute bronchitis was killed because of rapidly progressing central nervous disturbances. Necropsy revealed systemic granulomatous inflammation and vasculitis involving the lungs, thoracic lymph nodes, ribs, and liver. In the cerebrum there was a severe subacute bilateral encephalitis and malacia predominately affecting the white matter, and vasculitis with perivascular infiltration of lymphocytes, macrophages, and giant cells. A causative infectious agent could not be detected by Ziehl-Neelsen, Grocott, or Giemsa stains, by periodic acid-Schiff reaction of tissue sections, nor by bacterial and fungal cultures. Therefore, idiopathic systemic granulomatous disease (ISGD) was diagnosed and an immune-mediated pathogenesis was suspected. Inflammatory involvement of the brain has hitherto not been reported in cases of equine ISGD. This case seems to be an uncommon variant of ISGD with encephalitis and lack of dermal involvement.
In a colony of 11 harbour seals (Phoca vitulina Linné 1758) two episodes of central nervous disorders occurred within 2 years causing fatalities in seven adult animals. Clinical signs comprised dyspnoea, anorexia, apathy, incoordination and lateral recumbency. Vitamin B complex therapy was successful once. Pathomorphological examination of seven carcasses revealed acute and subacute malacia of the cerebellar grey matter. Additional acute malacic lesions located in the cerebral cortices and basal ganglia were observed. Mesencephalic nuclei were less severely affected and displayed acute changes. Despite intense search for environmental toxins and infectious agents, the cause of the fatalities remained undetermined. However, the type and pattern of the lesions are most suggestive of a thiamine deficiency.
The objective of this study was to gain insight into the patients' decision-making for migraine and chronic daily headache management. Patients were recruited by theoretical sampling in Surrey (UK). Semi-structured and tape-recorded interviews (n = 13) were conducted, transcribed verbatim, coded and analysed according to the grounded theory methodology. Thirteen patients (8 migraine and 5 chronic daily headache) described their management. All patients employed multiple behaviours to manage their headaches. From the patients' descriptions emerged their decision-making. Based on experience, perceptions and new information, the decision-making process involved four stages: headache severity, evaluation, decision making and behaviours. Although the participants were passive with regards to certain management strategies, overall they were actively involved in treating and preventing their headaches. Furthermore, they were active decision-makers in choosing appropriate management. Migraine and chronic daily headache patients are actively involved in managing their headaches. They are key decision-makers and should not be overlooked as a resource for effective management.