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Biomedical subjects

F Bischof

Publications and source records attributed to F Bischof.

At least 19 recordsLinked to original sources

Pathological long-bone fractures in residents with cerebral palsy in a long-term care facility in South Africa.

A high incidence of long-bone fractures has been observed in children and young adults with quadriplegic cerebral palsy in residential care. This study aimed to determine factors that contribute to these fractures and to institute preventive treatment. Twenty individuals (12 males, eight females) of a cohort of 88 residents with spastic quadriplegia in residential care in Gauteng, South Africa who had sustained fractures were compared with a random sample of age-matched control participants (10 males, 10 females) from the same facility. Participants ranged in age from 6 to 29 years (median 17.5 years). The majority of fractures were in the upper extremities. There was radiological and biochemical evidence of rickets and osteomalacia in both groups. However, the severity of the disease was more pronounced in the group with fractures. There was a significant relation (p=0.002) between the number of fractures and the use of anticonvulsant therapy (ACT). Three months of vitamin D administration (calciferol 5000 iu/day) resulted in a marked clinical improvement. There were no fractures during this period in either group. In addition, the mean serum calcium (Ca) and phosphate (Pi) levels increased (Ca from 2.17 to 2.35 mmol/L and Pi from 1.13 to 1.66 mmol/L) and mean total alkaline phosphatase level decreased (from 1123 to 423 U/L). We concluded that vitamin D deficiency was the major factor contributing to the occurrence of fractures in this population. Unless sunlight exposure can be guaranteed, vitamin D supplementation should be considered for children and adults in residential care, especially if they are on ACT, even in areas with year-round sunshine.

Adolescent↗

Specific treatment of autoimmunity with recombinant invariant chains in which CLIP is replaced by self-epitopes.

The invariant chain (Ii) binds to newly synthesized MHC class II molecules with the CLIP region of Ii occupying the peptide-binding groove. Here we demonstrate that recombinant Ii proteins with the CLIP region replaced by antigenic self-epitopes are highly efficient in activating and silencing specific T cells in vitro and in vivo. The Ii proteins require endogenous processing by antigen-presenting cells for efficient T cell activation. An Ii protein encompassing the epitope myelin basic protein amino acids 84-96 (Ii-MBP84-96) induced the model autoimmune disease experimental allergic encephalomyelitis (EAE) with a higher severity and earlier onset than the peptide. When applied in a tolerogenic manner, Ii-MBP84-96 abolished antigen-specific T cell proliferation and suppressed peptide-induced EAE more effectively than peptide alone. Importantly, i.v. administration of Ii proteins after EAE induction completely abrogated the disease, whereas peptides only marginally suppressed disease symptoms. Ii fusion proteins are thus more efficient than peptide in modulating CD4(+) T cell-mediated autoimmunity, documenting their superior qualities for therapeutic antigen delivery in vivo.

Animals↗

Aerobic thermophilic treatment of sewage sludge contaminated with 4-nonylphenol.

4-Nonylphenol (4-NP) occurs in sewage sludge as a result of the breakdown of detergents which contains nonylphenol ethoxylates (NPEs). 4-NP is of environmental concern because of its toxicity to biological systems. The present paper reports results of aerobic treatment under thermophilic conditions of sewage sludge artificially contaminated with 4-NP. Experiments were carried out using three parallel laboratory-scale batch reactors operating with blank, 50 and 100 mg/l of 4-NP concentration. For the two studied concentrations up to 66% 4-NP reduction was achieved at a specific air flow rate of 16 l/(l.h) and a thermophilic temperature of 60 degrees C, within 10 days of operation. The presence of 4-NP has minor effect on the rate of sludge oxidation and the nitrogen and phosphorous content in the sludge.

Aerobiosis↗

Thermal hydrolysis (TDH) as a pretreatment method for the digestion of organic waste.

The recycling concept under consideration is based on the process of Thermal Hydrolysis (TDH) followed by an anaerobic digestion. By increasing pressure and temperature the organic part of the waste is split up in a first step into short-chain fragments that are biologically well suited for microorganisms. The following fermentation runs much faster and more complete than in conventional digestion processes and the biogas yield is increased. Left is just a small amount of a solid residue that can be easily dewatered and utilized as surrogate fuel for incineration or as compost additive. The thermal hydrolysis process allows a complete energy recovery from organic waste. During the total procedure more energy sources are produced than are needed for running the plant. The procedure is especially suited for wet organic waste and biosolids that are difficult to compost, such as food scraps, biological waste from compact residential areas and sewage sludge. As a complete disinfection is granted due to the process temperatures the procedure is also suited for carcasses.

Bacteria, Anaerobic↗

Experimental assessment of bio-reduction of di-2-thylhexyl phthalate (DEHP) under aerobic thermophilic conditions.

The reduction of organic contaminants in sewage sludge is of great importance for a further sludge disposal or agricultural utilization. Laboratory scale batch experiments were performed to assess the potential use of the aerobic thermophilic treatment technique to reduce the concentration of difficult to degrade organic chemicals. Di-2-ethylhexyl phthalate (DEHP) was chosen as a model representative of these chemicals. The effect of the sludge temperature and aeration rate on the reduction of DEHP concentration as well as on the reduction of the organic dry solid (oDS) was investigated. With a specific air flow rate of 16 m3/m3.h and a thermophilic temperature of 63 degrees C it was possible to achieve up to 70% reduction of the DEHP concentration and 61% of oDS within 96 hours. The maximum degradation of the oDS matter occurred within the first 24 hours of operation whereby only little oDS was degraded afterward. During the experiments the reactor content was routinely monitored for pH, COD, along with the ammonia nitrogen and orthophosphate concentrations.

Aerobiosis↗

Persistent cerebellar deterioration in a patient with lobar pneumonia under lithium, carbamazepine, and trifluperidol treatment.

We report on a patient with schizoaffective disorder who was on combination therapy of lithium, carbamazepine, and the neuroleptic trifluperidol. He experienced a lobar pneumonia and developed an acute and persistent cerebellar deterioration which was most likely due to lithium toxicity, while the serum lithium level was within the therapeutic range. The combination of lithium, carbamazepine, and neuroleptics is common, and is generally considered to be safe. The reported case suggests that this regimen might increase the risk of intoxication with potentially disabling side-effects.

Anti-Bacterial Agents↗

Glucocorticoids inhibit CD40 ligand expression of peripheral CD4+ lymphocytes.

The ligand for CD40 (CD40L) is a type II transmembrane glycoprotein that belongs to the tumor necrosis factor superfamily. CD40L expression on peripheral CD4+ cells is increased upon activation and delivers signals to B lymphocytes which constitutively express CD40. We show that dexamethasone in vitro inhibits CD40L expression in a dose-dependent manner in concentrations ranging from 0.1 to 1 mg/mL. Semiquantitative analysis of CD40L mRNA by RT-PCR revealed that this effect was due to inhibition of CD40L transcription. The inhibitory effect of dexamethasone on CD40L expression was reversible and not due to affection of cell viability. Lymphocytes which have been exposed to dexamethasone in vitro retained the ability to express CD40L after incubation in medium alone for 48 h. Dexamethasone also inhibited PMA/ionomycin induced IL-2 and IFN-gamma production but not CD25 and CD69 expression. Glucocorticoids may exert their immunosuppressive effect in part by suppression of CD40L. Regulation of CD40L expression is steroid sensitive and may be similar or in part identical with IL-2 and IFN-gamma regulation.

Antigens, CD↗

Investigations on the point mutations at nt 5460 of the mtDNA in different neurodegenerative and neuromuscular diseases.

Point mutations of the mitochondrial genome are often considered to be the cause of certain neurodegenerative disorders and mitochondrial myopathies. Recently, there has been a report on Alzheimer's disease (AD) point mutations at position 5460 of the mitochondrial genome located within the ND2 gene. Using allele-specific PCR with a sensitivity of detection of less than 1% mutated mtDNA, we investigated postmortem brain samples from 48 patients with AD and blood samples of 15 patients with clinically diagnosed AD. In addition, we investigated tissue samples of patients with different neuromuscular disorders and patients with Downs syndrome. Independent of the tissue analysed very few of all the tested samples of patients showed a point mutation at nt 5460 with a base substitution from G to A. Two out of 19 brain and 48 blood samples from controls carried this mutation. The G to T transversion was not found in any of the so far tested samples. Our results do not support the previously reported significant high frequency of these mutations in AD.A polymorphism seems more likely.

Alleles↗

3.1-kb deletion of mitochondrial DNA in a patient with Kearns-Sayre syndrome.

Mitochondrial DNA (mtDNA) deletions have been found in the majority of patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. A large number of different mtDNA deletions have been identified. They generally spare the two origins of replication and are frequently flanked by direct or indirect repeats. We have found a 3.1-kb deletion of mtDNA in a patient with Kearns-Sayre syndrome that has some unusual features. First, it encompasses nucleotides 11259 to 14368, a localization that was not described before. Second, the deletion is not flanked by direct or indirect repeats, supporting the view that homologous recombination and slip-replication do not account for all mtDNA deletions.

Base Sequence↗

Subcutaneous glucose concentration in humans. Real estimation and continuous monitoring.

OBJECTIVE: To determine the real subcutaneous glucose concentration in healthy volunteers to help in the development of new calibration methods for subcutaneous glucosensors. RESEARCH DESIGN AND METHODS: We developed a new method to estimate the real subcutaneous glucose concentration based on the recirculation of phosphate-buffered saline (PBS) in a microdialysis probe inserted into the subcutaneous tissue. Tissue glucose diffuses into the probe until complete equilibration between the glucose concentration outside and inside the microdialysis probe is achieved. Later, the glucose content of the recirculated PBS is assessed in vitro. We applied the method in 10 healthy volunteers under fasting state and during a hyperglycemic clamp. In addition, we monitored the subcutaneous glucose with an enzymatic-amperometric glucosensor combined with a microdialysis probe. RESULTS: The subcutaneous glucose concentration measured by the recirculation method was 72 +/- 6 and 78 +/- 6% of the blood glucose measured in the fasting state and during the hyperglycemic clamps, respectively. On the other hand, the glucosensor's signal correlated significantly with the blood glucose. CONCLUSION: The recirculation method estimated the real subcutaneous glucose concentration, opening the way to develop new calibration procedures for subcutaneous glucosensors. However, a suitable calibration procedure is still lacking.

Adult↗

Long-term experiences with a computerized diabetes management and glucose monitoring system in insulin-dependent diabetic patients.

Only a minority of patients use diabetes management systems. In our study, 24 patients were given a memory based blood glucometer (ROMEO, Diva Medical Systems), which additionally allowed the input of insulin doses, food intake and exercise for up to four years. Eight patients returned ROMEO within one month (group I), 8 used the system as long it was available as a loan (group II) and 8 patients bought the system (group III). The patients of group III had a significantly better diabetic control (HbA1 = 7.8% +/- 0.7 (S.D.) vs. 11.7 +/- 3.6 (group I) and 10.7 +/- 2.6 (group II)) and were more reliable in their input of the data. After 3 years, however, only five patients of group III continued to use the system, but as a glucose meter only. One patient used the options of the system. These data show that glycemic control is not a question of the equipment. After a certain period, even the well-motivated patients do not use the system options routinely. Obviously, the advantages of the system are only used by a minority of patients characterized by good metabolic control and good compliance, and even these patients do not persistingly use all the options of the system after a certain period of time.

Adolescent↗

Calibration problems of subcutaneous glucosensors when applied "in-situ" in man.

Continuous glucose monitoring is the conditio sine qua non to achieve total automation in glucose-controlled insulin-delivery. Several types of glucosensors have been designed according to the enzyme-amperometric method to measure the glucose in different human compartments. However, problems such as long-term stability and calibration prevent this technique being put into practice. A feasible method is needed to calibrate the glucosensor and at the same time should be accepted by the patients. To achieve calibration we determined the absolute tissue glucose, as well as the microdialysis recovery in-vivo, in healthy subjects under normal conditions and during a hyperglycaemic clamp by applying a device based on the recirculation of phosphate buffer saline in a microdialysis probe implanted in the s.c. adipose tissue. The first experiments carried out were promising and encouraging, but further investigations are still needed to favour an ideal "before implantation, all in-vitro" method to calibrate a s.c. glucosensor.

Biosensing Techniques↗

Combination of microdialysis and glucose sensor for continuous on line measurement of the subcutaneous glucose concentration: theory and practical application.

The microdialysis technique can be used to get dialysates of the subcutaneous tissue, which can be continuously measured by an amperometric glucose sensor. In order to get further insight into the microdialysis procedure, we used a steady-state theory for microdialysis to predict the recovery of glucose in the dialysate and compared the results to experimental data obtained by a combination of the microdialysis technique with continuous amperometric glucose sensing. The recovery of glucose obtained in vitro for two different microdialysis probes was close to the theoretical predictions. When quantifying the predictions of the model with regard to the spatial concentration profile in the subcutaneous tissue, it appeared, that the presence of the microdialysis probe depressed the concentration of glucose for 0.2 mm from the probe surface. In a 24 hour in vivo experiment, there were less fluctuations in the sensor signal when the patient was lying in bed compared to the time, when the patient could move freely. In conclusion, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system. However, the microdialysis procedure itself disturbs the surrounding of the probe leading to a concentration gradient of glucose. This might explain some differences between the course of blood glucose and the course of subcutaneous glucose, measured by the combination of microdialysis and an amperometric glucose sensor. Further developments of such systems should aim at implanting microdialysis devices which have a minimal influence upon the tissue metabolism.

Biosensing Techniques↗

Quality control of intensified insulin therapy: HbA1 versus blood glucose.

Since the measurement of HbA1 has become available to the diabetologists, the physicians and patients tend to rely exclusively on this parameter for the assessment of metabolic control. Therefore, in this study, 24 hour glucose profiles of 8 selected patients (4 under intensified conventional therapy, ICT, and 4 under continuous subcutaneous insulin infusion, CSII) with HbA1 values indicating good metabolic control were taken three times at four week intervals and were compared to mean blood glucose (MBG), mean average of glucose excursions (MAGE) and Schlichtkrull's M-value. MBG of the 24 profiles was 114 +/- 21 mg/dl. The patients under CSII were somewhat lower than the patients under ICT. In 16 of the 24 profiles, there was at least one period of hypoglycemia of 50 mg/dl and below. Only in one patient, M-value and MAGE showed stable metabolic control. In conclusion, hyperglycemic excursions in patients under intensified conventional therapy or treated by continuous subcutaneous insulin infusion do escape their reflection in the HbA1 values because of low blood sugar periods following hyperglycemic swings. Undoubtedly, the partial failure of ICT and CSII to prevent diabetic complications might be ascribed to the incomplete assessment of the metabolic control based on HbA1 values exclusively.

Adolescent↗