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P Meissner

Publications and source records attributed to P Meissner.

36 records · Page 2Linked to original sources

Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen. A possible mechanism for the acute attack of variegate porphyria.

Variegate porphyria (VP) is characterized by photocutaneous lesions and acute neuropsychiatric attacks. Decreased protoporphyrinogen oxidase activity results in accumulation of protoporphyrin (ogen) IX and coproporphyrin (ogen) III. During acute attacks delta-aminolevulinic acid and porphobilinogen also increase, suggesting that porphobilinogen deaminase (PBG-D) may be rate limiting. We have examined the effects of porphyrinogens accumulating in VP on PBG-D activity in Epstein-Barr virus-transformed lymphoblast sonicates from 12 VP and 12 control subjects. Protoporphyrinogen oxidase activity was decreased and protoporphyrin increased in VP lymphoblasts. PBG-D in control lymphoblasts obeyed Michaelis-Menten kinetics (Vmax 28.7 +/- 1.8 pmol/mg per h, Hill coefficient 0.83 +/- 0.07). VP sonicates yielded sigmoidal substrate-velocity curves that did not obey Michaelis-Menten kinetics. Vmax was decreased (21.2 +/- 2.0 pmol/mg per h) and the Hill coefficient was 1.78 +/- 0.17. Addition of protoporphyrinogen IX and coproporphyrinogen III to control sonicates yielded sigmoidal PBG-D substrate-velocity curves and decreased PBG-D Vmax. Addition of porphyrins or uroporphyrinogen III did not affect PBG-D activity. Removal of endogenous porphyrin (ogens) from VP sonicates restored normal PBG-D kinetics. Purified human erythrocyte PBG-D obeyed Michaelis-Menten kinetics (Vmax 249 +/- 36 nmol/mg per h, Km 8.9 +/- 1.5 microM, Hill coefficient 0.93 +/- 0.14). Addition of protoporphyrinogen yielded a sigmoidal curve with decreased Vmax. The Hill coefficient approached 4. These findings provide a rational explanation for the increased delta-aminolevulinic acid and porphobilinogen during acute attacks of VP.

Cell Line, Transformed↗

[Long-term treatment of sleep apnea with evening administration of oral retard theophylline].

In 776 patients suffering from sleep apnoea long-term treatment with sustained-release theophylline was investigated. Responders show a significant reduction of apnoea phases. Using an individual theophylline dosage with morning theophylline concentrations between 5 and 8 micrograms/ml, only few side effects occurred. Positive effects on cardiopulmonary capacity were seen.

Administration, Oral↗

Physical and tumor biological aspects and calculation model of dosage in boron neutron capture therapy (BNCT).

Fundamentally different aspects apply to dosage in boron neutron capture therapy (BNCT) compared to that in the case of normal radiotherapy with photons, electrons or heavy particles such as neutrons. The reason is that the latter only requires a knowledge of the stochastic distribution of the absorbed dose within cells, radiation quality and atomic composition of tissue in the regions of interest, whereas for the former the absolute concentration and microscopic distribution of 10B atoms in inter- and intracellular spaces of tumor and healthy cells is additionally of equal importance. The effects of radiation without 10B must always be superimposed on those of heavy particles resulting from neutron capture reactions on 10B atoms. Complex geometrical calculations are necessary with respect to ranges of the heavy particles smaller than a cell diameter. Apart from the direct effects of radiation without 10B, the dosage therefore depends on thermal neutron fluence, 10B concentration, its extreme inhomogeneous macroscopic distribution in the tumor tissue, the cellular localization of the 10B atoms in the large intercellular space, the cell membrane, within cytoplasm or the cell nucleus, the geometrical probability of hitting the cell nucleus, and that such a hit finally results in a cell killing, and a Poisson statistical enhancement factor, which describes the dose-effect relation for cell survival. The calculations necessary are demonstrated in the case of a normal and a tumor cell type, each with representative cell diameter and nucleus size. It is evident that the microscopic distribution of 10B atoms is one of the most critical parameters which is still insufficiently known.

Boron Neutron Capture Therapy↗

[The physical and technical outlook for neutron therapy in Germany].

All five fast neutron therapy centres in Germany use low energy cyclotrons or neutron generators and are, therefore, at the low energy end of the 21 neutron therapy facilities presently in use worldwide. The depth dose characteristics are worse than for 60Co gamma rays, the absorbed dose rate is too low and the treatment is technically restricted because of the lack of those modern features like multileaf collimators and full gantry rotation that are available with modern linear accelerators. A survey of the statistical and methodical data on the neutron treatment in Germany is presented. To avoid masking the potential biological benefits of high LET neutron irradiation by the use of suboptimal equipment and to utilise the real therapeutical benefit for specific tumor types, the German neutron therapy centres urgently need modernization of their outdated facilities. Specific recommendations of how to meet the requirements of modern neutron therapy are given.

Fast Neutrons↗

Alcoholic beverages in acute porphyria.

Alcohol consumption habits and the clinical consequences of intake of alcoholic beverages were examined in 254 individuals with a diagnosis of acute intermittent porphyria or variegate porphyria, using a questionnaire. The study failed to demonstrate a connection between the amount of ethanol consumed, or the frequency of ingestion, and the development of symptoms of acute porphyria, other than in extreme consumption patterns. It was concluded that agents in alcoholic beverages other than ethanol play important roles in precipitating the porphyric symptoms. A majority of the individuals were able to identify alcoholic beverages that were less well tolerated and those that were better tolerated. The results suggest that polyphenolic compounds and 3 to 5 carbon chain hydrophobic alcohols may be responsible for the induction of clinical symptoms in acute porphyria by some alcoholic beverages. On the basis of these findings advice is proposed on alcohol counseling in inducible porphyria.

Acute Disease↗

Maximizing the functional status of geriatric patients in an acute community hospital setting.

Patients (n = 103) admitted to an inpatient geriatric care unit focusing on restoration of functional status were compared to similar patients (n = 75) admitted to a control-unit. Study unit patients showed significantly greater improvement in basic functional capabilities from admission to discharge than did control-unit patients. A mixed picture evolved when length of stay and total charges of study and control-unit patient were compared by diagnostic-related groups.

Activities of Daily Living↗

Cost-effectiveness of routine and campaign vaccination strategies in Ecuador.

A national household coverage survey of 3697 Ecuadorean children, carried out in July 1986, provided an opportunity for a cost-effectiveness analysis of (1) routine vaccination services based in fixed facilities and (2) mass immunization campaigns. A major purpose of the campaigns was to complement the routine services and to accelerate immunization activities. Based on the coverage survey, the Program for Reduction of Maternal and Childhood Illness (PREMI) and earlier campaigns increased the proportion of children under 5 years who were fully vaccinated from 43% to 64%. In one year, the PREMI campaign was responsible for fully vaccinating 11% of children under one year, 21% of 1-2-year-old children, and 13% of all children under 5 years. The campaign also helped ensure that vaccinations were completed when children were still very young and at greatest risk. The average cost per vaccination dose (in 1985 US$ prices) was approximately $0.29 for fixed facilities and $0.83 for the PREMI campaign. Total national costs were $675,000 and $1,665,000 for routine and campaign services respectively. The cost per fully vaccinated child (FVC) was $4.39 for routine vaccination services and $8.60 for the campaign. The cost per death averted was about $1900 for routine vaccination services, $4200 for the PREMI campaign, and $3200 for the combined programme. Because of Ecuador's lower mortality rates, the costs per death averted in Ecuador from both vaccination strategies are not as low as those from studies of vaccinations in Africa. The campaigns, though less cost-effective than routine services, significantly improved the vaccination coverage of younger children who had been missed by the routine services. The costs per FVC of both the campaign and the routine services compare favourably with such programmes in other countries.

Child↗

Infrared and visible thermoluminescence signals of Tm-doped CaF2 measured by a semiconductor photodiode.

A silicon semiconductor photodiode was used to measure the TL-signal of TLD-300 (CaF2:Tm) detectors irradiated with 60Co gamma rays and 226Ra alpha particles. The applied dose values varied from 0.12 to 14.3 Gy for gamma rays and from about 50 to 300 Gy for alpha particles. Because of the infrared sensitivity of the photodiode the infrared emission of the planchet and the TLD-detector produced a high output signal above about 200 degrees C. In addition to this background signal an infrared emission from the TLD-300 detectors could be detected. This infrared TL-signal exhibited the same dose dependences as the visible signal, but the amplitude was higher than that of the visible TL-signal. For the applied photodiode the ratio of the infrared TL-signal to the visible TL-signal was about 24 for the 100 degrees C peak, about 15 for the 150 degrees C peak and 6 for the 240 degrees C peak.

Alpha Particles↗

Physiological and biochemical measurements during a 4-day surf-ski marathon.

We studied competitors in the 1983 Texan Challenge surf-ski paddle marathon to determine the effects of 4 days prolonged paddling on sweat rates, rectal temperatures, renal function, serum glucose, free fatty acid, porphyrin and C-reactive protein levels and serum creatine kinase activity. Sweat rates during the race varied from 0.5 to 1.0 l/h, and peak rectal temperatures did not exceed 38 degrees C, even in the most dehydrated subjects. Renal function was unchanged during the race. Plasma renin activity remained low during the race but C-reactive protein levels and serum creatine kinase activity were elevated. Seventy per cent of the subjects had immediate post-exercise blood glucose levels below 3.9 mmol/l after the 1st and 4th days, and 27% had values below 3.0 mmol/l, one competitor requiring intravenous glucose therapy on the beach. Surf-ski paddling is therefore associated with low sweat rates, low levels of dehydration, low body temperature and unchanged renal function. The low post-exercise blood glucose levels indicate that competitors must eat high-carbohydrate diets for the duration of the event and must either eat carbohydrate-containing foods or drink concentrated carbohydrate solutions while paddling.

Blood Glucose↗

[Digital recording of glow curves of the TLD-300 thermoluminescent dosimetry detector by adaptation of a sum of Gauss function to the measured values].

Calciumfluoride doped with Thulium (TLD-300) can be used to measure simultaneously with one detector neutron and photon absorbed dose in mixed neutron-photon beams. The accuracy in dose measurements can be increased by use of a computer. Additionally the number of data needed to store a glow curve can be reduced from 240 to 24 by fitting a sum of Gauss functions to the measured glow curve.

Calcium Fluoride↗

Dosimetrical verification of calculated total and gamma absorbed dose distributions DT, respectively DG, for fast neutron therapy.

The physical part of treatment planning for neutron therapy is highly important but quite more complicated than for photons and electrons due to the necessity of separation of total and gamma absorbed dose distributions (DT and DG). Therefore, dosimetrical verifications of dose distributions of complex treatment plans are very rare, and the experimental difficulties are enormous. A method using TLD-300 (CaF2: Tm) detectors is described with the ability to provide from each detector's readings both DT and DG using the different LET dependence of the main glow-curve peaks. The principle of an on-line computer program is given for an automatic mathematical glow-curve analysis which is necessary to achieve the accuracy of about +/- 5% (DT) and +/- 10% (DG) in single fixed fields. Dosimetrically relevant features of the TLD-300 method are discussed. Examples of dosimetrical verifications of calculated dose distributions (DT and DG) for a treatment with one single fixed field, with two wedge filter fields and with a rotational field with d(14)+Be neutrons are shown. Deviations exceeding significantly the uncertainties above are found only in the case of the wedge filter treatment for the absolute (quite less for the relative) values of the DG dose distribution. Probable reasons are mostly the reduced contribution of scattered radiation for phantom sizes, which laterally scarcely exceed the useful beam, and slight neutron energy spectrum changes by the wedge filter.

Dose-Response Relationship, Radiation↗

A small-scale neutron dosimetry intercomparison between Essen, Amsterdam and Edinburgh.

An intercomparison of neutron dose measurements was made at Essen by visiting groups from Amsterdam and Edinburgh to compare measurements of the neutron and photon absorbed doses in a phantom in the neutron beam. An intercomparison of the photon calibration of the tissue-equivalent chambers was also made. Differences in the measurements of total absorbed dose in the neutron beam of up to 4.7% were observed. These were consistent with the observed differences in the photon calibrations. A summary is given of the different calibration methods used by each group. Greater discrepancies (up to 18%) were seen in the measurement of the photon contribution to the absorbed dose in the neutron beam and these were in part due to insufficient shielding of the GM counter from thermal neutrons.

Germany, West↗

Proposal for a practical dose calculation scheme for neutron irradiations.

Dose calculations for neutron therapy irradiations should be based on the dosimetrically best accessible parameters "total absorbed Dose Dt" and "gamma ray absorbed dose Dgamma". By adequate standardization it should be possible, that only one single reference parameter contains all deviations of calibration, while a table of relative factors, only once to be determined, gives all long-term constant dependencies for all field sizes and phantom depths. A standardization is proposed for the irradiation technique with fixed fields at a constant focus-skin distance, giving rise to especially simple equations for the absorbed doses Dt and Dgamma. It is as well easy to get by these doses and mean relative biological effectivenesses rn for neutrons and rgamma for gamma rays the "total effective absorbed dose De", being an opportune quantity for the biologically weighted absorbed dose. The practical application of equations and tables is demonstrated for an opposing field irradiation as example. Adequately standardized "reference tissue air ratios" and corresponding equations are given for isocentric fixed or rotating beam irradiations and used for the example of a dose calculation within a phantom at the isocentre.

Humans↗