The BFM relapse studies in childhood ALL: concepts of two multicenter trials and results after 2 1/2 years.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
R Hartmann
Publications and source records attributed to R Hartmann.
Urecholine prophylaxis for urinary retention in anorectal surgery.
A randomized prospective trial with 108 patients undergoing anorectal surgery was conducted comparing the use of Urecholine orally or subcutaneously to no treatment controls. There was no difference in postoperative urinary retention rates and caudal or general anesthesia, nor was there an earlier postoperative bowel movement with Urecholine. The volume of intravenous fluids significantly affected retention rates.
Anal Canal↗
Rat cytosolic epoxide hydrolase.
Rat liver microsomal and cytosolic epoxide hydrolase may be distinguished through differences in substrate specificity: styrene 7,8-oxide is preferentially hydrolyzed by the microsomal form, while trans-stilbene oxide is the preferred substrate for cytosolic epoxide hydrolase. Large interindividual differences in the specific activity of Sprague-Dawley (outbred strain) liver cytosolic epoxide hydrolase were observed, varying from 2 to 77 pmol/min X mg protein. Interindividual variations were much lower for microsomal epoxide hydrolase. The specific activity of Fischer F-344 (inbred strain) liver cytosolic epoxide hydrolase varied only by a factor of 2. The specific activity of cytosolic epoxide hydrolase using trans-stilbene oxide as the substrate was highest in kidney and heart, followed by liver, brain, lung, testis, and spleen. For microsomal epoxide hydrolase, the specific activity was much lower in extrahepatic tissues than in liver. None of the commonly used inducers of xenobiotic metabolizing enzymes caused significant changes in rat liver cytosolic epoxide hydrolase. However, peroxisome proliferating drugs were found to drastically increase cytosolic epoxide hydrolase activity. Treatment for one week with a diet containing clofibrate (0.25%), tiadenol (0.5%) or acetylsalicylic acid (1%) caused a 8, 13 and 5 fold increase in cytosolic epoxide hydrolase activity respectively in the liver which parallelled the induction of peroxisomal beta-oxidation activity (13, 19 and 5 fold, respectively).
Animals↗
Prevalence and development of retinopathy in children and adolescents with type 1 (insulin-dependent) diabetes mellitus. A longitudinal study.
In 231 subjects with Type 1 diabetes mellitus aged 17.6 +/- 4.0 years, with a diabetes duration of 8.5 +/- 4.9 years at the end of the study, the prevalence and the development of retinopathy during a period of 5 years were studied. All patients were examined between one and six times both by ophthalmoscopy and fluorescein angiography. A total of 626 fluorescein angiographies were evaluated. By the end of the study, 109 out of 231 patients (47%) had developed retinal changes, half of which were classified as minimal (less than 5 microaneurysms). Thirty-eight patients (35% of those affected) had background (n = 28) or proliferative (n = 10) retinopathy. In subjects less than 15 years of age and diabetic for less than 5 years, retinal lesions were rare. With increasing age and duration of diabetes, both the prevalence and severity of retinal changes increased markedly. Life-table analysis was used to calculate the median individual risk for the development of early retinal changes, which was 9.1 years of diabetes duration. This risk differed in sub-groups with different ages at onset of diabetes, i.e. 12.1, 8.9 and 6.6 years (p less than 0.0001), with diabetes starting below 4, between 5 and 9, and after 10 years of age respectively. After 18 years of diabetes, every patient demonstrated at least incipient structural changes. Fluorescein angiography allowed the detection of retinopathy, on average, four years earlier than with ophthalmoscopy. The median interval between the 'onset' of retinopathy, as indicated by a few microaneurysms, and background retinopathy was 5 years.
Actuarial Analysis↗
Risk factors for the development of retinopathy in children and adolescents with type 1 (insulin-dependent) diabetes mellitus.
In our preceding paper, the prevalence and development of retinopathy in 231 Type 1 diabetic children and adolescents were reported to be associated with the duration of diabetes and its age at onset. This paper analyses the relationships between the development of retinopathy and the following factors: age, sex, puberty, blood pressure, insulin dosage, HLA antigens, long-term glycaemic control, and serum cholesterol and triglycerides. All these variables were longitudinally evaluated in a cohort of 322 insulin-dependent patients aged 16.2 +/- 4.9 years with diabetes for 7.4 +/- 5.2 years, including those 231 subjects whose eyes were examined once or repeatedly by ophthalmoscopy and fluorescein angiography. Long-term glycaemic control from the onset of diabetes to the retinal examination was assessed by both an arbitrary score comprising different parameters and by mean values of glycosylated haemoglobin, and was categorised as good, fair, and poor. With life-table analysis, the overall median individual risk for developing early retinal changes (9.1 years) was found to be significantly influenced by glycaemic control. Minimal lesions developed earlier (8.0 years) with poor control, but later with fair (10.5 years) and good glycaemic control (12.5 years) (p less than 0.01). Mean HbA1 values below 10% delayed the onset of both incipient (10.8 years) and background retinopathy (16.6 years), while values above 10% advanced it (8.0 and 11.8 years respectively) (p less than 0.05 and less than 0.008). By multivariate regression and stepwise discrimination analyses, only 4 out of 14 variables were found to exert significant independent influences on the development of retinopathy: diabetes duration, long-term glycaemic control, serum triglycerides and age.(ABSTRACT TRUNCATED AT 250 WORDS)
Actuarial Analysis↗
Annual progression of retinopathy in conventionally treated children and adolescents with type I diabetes mellitus.
In a cohort of 268 type I diabetic patients, aged 19.6 +/- 4.1 years (Mean +/- 1 SD), with a diabetes duration of 10.4 +/- 4.9 years, treated by the same team, using the same conventional treatment regime during the total observation period, the progression rate of early retinopathy within the first two decades of diabetes was deduced from observed transitions of the retinal status from one stage of retinopathy (as defined by fluorescein angiography) to a higher one (Malone et al., 1977) within one year. A total number of 83 such events were evaluated. After a gradual development of earliest changes within the fifth year of diabetes, the median annual rate of progression was found to be 12-13%, independent of the previous duration of diabetes and the actual retinal state.
Adolescent↗
Discharge patterns of cat primary auditory fibers with electrical stimulation of the cochlea.
Intact and destroyed cat cochleae were electrically stimulated through round window electrodes. Intact cochleae provided information about fiber properties with acoustic stimuli. With sinusoidal currents thresholds for synchronization were 4-68 microA rms. Thresholds were independent of the fiber's characteristic frequencies and thus of their places of origin in the intact cochleae. This shows large current spread. Phase-locking of the responses to electric stimulation was much stronger than it was to acoustic stimulation. Destroyed cochleae had no spontaneous activity and showed even stronger phase-locking. Thresholds obtained using 0.2 ms per phase biphasic pulse stimuli were 60-350 microApp. Action potentials were found to be released with as little as 0.3 ms latency. The neuronal responses to any electric stimulus differed considerably from the responses to corresponding acoustic stimuli. Vestibular fibers were easily activated by electric stimulation.
Acoustic Stimulation↗
A new embedding medium for cryo-sectioning eggs of high yolk and lipid content.
Eggs can be cryo-sectioned without rupture of the yolk- and lipid-containing areas after embedding in a mixture of polymerized acrylamide, crosslinked gelatine, 'Jung' medium and buffer. For initial fixation of the section on the slide a fixative containing glue is employed, followed by postfixation treatment. The new technique improves sectioning of large eggs including embryonic stages for histological and histochemical studies. It is especially useful for eggs containing large amounts of yolk (insects, snails, fishes and newts) and for secretory organs containing high levels of proteinaceous material.
Acrylic Resins↗
Use of monoclonal and polyclonal antibodies as structural and topographical probes for hepatic epoxide hydrolase.
Monoclonal antibodies have been prepared against rat liver epoxide hydrolase (EH), some of which gave precipitation lines on immunodiffusion against pure EH suggesting the presence of repetitive structural domains on the enzyme. Using ELISA, with polyclonal antibodies to rat and rabbit liver EH, reactivity and therefore structural similarities between EH of all species tested, including human, were observed. This was in contrast to immunodiffusion results demonstrating the limitations of the latter technique. Using monoclonal antibodies in ELISA, greatest structural similarity was between rat, mouse, and Syrian hamster EH and relatively little between rat and human. Two of the antibodies reacted with nearly all species tested and may be directed towards critical sites on the enzyme. This and most of the EH molecule would appear to be localised on the cytoplasmic surface of the endoplasmic reticulum.
Animals↗
Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure.
A sodium dodecyl sulfate-gel electrophoretic procedure which allows the separation of isolated cytochrome c oxidase from different mammalian sources into 13 different polypeptides is described. Application of the silver-staining procedure results in the same protein pattern as obtained by Coomassie blue staining. From the correlation of the gel bands with 12 isolated polypeptides from which the complete amino acid sequence is known, it is concluded that mammalian cytochrome c oxidase consists of 13 different polypeptides which can all be separated by the described procedure.
Animals↗
Tissue-specific genes code for polypeptide VIa of bovine liver and heart cytochrome c oxidase.
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Amino Acid Sequence↗
Comparison of auditory single fiber responses during acoustic and electric stimulation of the intact cat cochlea.
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Acoustic Stimulation↗
Lithium carbonate in patients with small cell lung cancer receiving combination chemotherapy.
Lithium administration has been shown to attenuate the leukopenia associated with systemic chemotherapy. The results of a randomized trial of lithium in 45 patients with small cell lung cancer who received combination chemotherapy and radiation therapy are reported. Patients randomized to receive lithium were started on 300 mg three times daily for 18 days of every 21 day chemotherapy cycle. Patients who received lithium experienced significantly less mid-cycle leukocyte and neutrophil count depression and spent fewer days with leukopenia and neutropenia than control patients regardless of age or extent of disease. Patients who received lithium spent fewer days hospitalized and fewer days with fever in the presence of severe neutropenia than control patients. The cumulative risk of fever with signs of infection was greater in control patients regardless of age, disease extent or the presence of marrow involvement. Patients who were given lithium received significantly more chemotherapy than control patients. Patient survival was greatest in those with limited disease, in complete responders and in those who received more than 75 percent of their induction chemotherapy although it did not differ between the two study groups. The majority of patients required either reduction or discontinuation of lithium. Those who received lithium continuously demonstrated a higher objective response rate and longer survival than either patients in whom the lithium had to be discontinued or those randomized to the control group. Infection was an important cause of death in the control group and cardiovascular event occurred frequently in the lithium group, but the major cause of death in this patient population remains progressive malignant disease.
Carcinoma, Small Cell↗
Discharge properties of afferent fibres of the goldfish semicircular canal with high frequency stimulation.
The horizontal semicircular canals of goldfish were sinusoidally stimulated 0.07 and 63 Hz (about 3 decades). Single afferent fibre recordings showed sinusoidal modulation of discharges. Above 4 Hz the discharges became phase-locked to the stimulus. With increasing frequency the number of spikes per period decreased so that finally only one spike per period remained. At 63 Hz a stimulus of as little as 0.005 degrees was sufficient to drive the units to far above their spontaneous activity. As cupular deflection is less than the angle of body movement, the cupular deflection threshold for modulation of afferent discharges must be much less than 0.005 degrees. Transfer functions of afferent activity were determined. The simple pendulum model does not fit the data. Additional introduction of a third time constant and the low pass properties of the receptor cell membrane, the synaptic delay and the leaky integrator of the post synaptic afferent terminal improve the fit.
Animals↗
Efferent activity in the goldfish vestibular nerve and its influence on afferent activity.
Out of 326 fibres in the horizontal semicircular canal branch of the goldfish vestibular nerve, 7 fibres could be identified as efferents. They showed irregular spontaneous activity and responded to rotatory stimuli with double frequency. Additionally in the central stump of the dissected nerve, efferent fibres were found, the spontaneous and stimulus modulated activity of which could not be differentiated from afferents. Efferents could be driven by a number of stimuli (vestibular, visual, somatosensory). Disruption of the efferent influence upon the receptors by dissection of the nerve or by pharmacological means (Gallamine) led to an increase of spontaneous afferent activity by 50%, showing that there is tonic efferent inhibition. Transfer functions of afferents were not changed after release from efferent influence. Electrical stimulation of efferents in 41% of the fibres led to an increase of afferent activity instead of the expected inhibition, which was seen in another 32%.
Animals↗
Anaerobic growth of halobacteria.
An energy-transducing pathway in halobacteria is described. Arginine mediates substrate level phosphorylation and allows the cells to grow anaerobically. Bacteriorhodopsin plus light can function as an alternative energy source under these conditions, provided the cells contain the pigment when transferred to the anaerobic environment. Therefore the selection of mutants functionally defective in ATP synthase or bacteriorhodopsin becomes possible.
Adenosine Triphosphate↗
Kala-azar as a cause of disseminated intravascular coagulation.
With our present day highly mobile population, the diagnosis of kala-azar must be considered in any patient presenting with fever, enlarged liver and spleen, anemia and leukopenia who has visited a region where this disease is endemic, particularly since the incubation period may be as long as a year. We report a case in which disseminated intravascular coagulation was an unusual complication.
Child, Preschool↗
[Physiological basis for a cochlear prosthesis (author's transl)].
For the attempt to develop a cochlear prosthesis, which allows some understanding of speech, it seems--at least for the first attempts--to be appropriate to mimic natural conditions as far as possible. The auditory nerve contains about 30,000 afferent fibres. Qualitatively, their behavior is similar but quantitative measures show considerably differences (2.3). Nothing certain can be said at present however about the spiral fibres originating from the outer hair cells. The quantitative differences between single afferents concern tuning, frequency selectivity, thresholds, intensity functions and--of particular interest for electrical stimulation--differences in timing of the activity pattern, brought about by differences in travelling time along the cochlear duct (2.3). The time differences seen in the activity pattern of different fibres are in the order of several ms (2.3.6;2.3.7). Actionpotentials elicited by natural acoustic stimuli show probabilistic behavior, that is they are not strictly determined. It is obvious that with artificial electrical stimulation not every surviving single fibre can be selectively stimulated. An electrode will always stimulate a group of fibres simultaneously. With any conceivable electrical stimulation all fibres in the suprathreshold region of the electrode will be synchronously activated (3.2); a fundamental difference to the natural situation. To estimate the number of channels, necessary to stimulate the auditory nerve with sufficient accuracy to allow speech perception we consider some psychoacoustic data. These have shown that the auditory system possesses the ability to differentiate a great number of different pitches, but on the other hand it is capable of integrating different frequency areas to a so called critical bandwidth. Sound energy falling into one critical bandwidth is integrated to a uniform auditory sensation. If one is to integrate various fibres of the auditory nerve to one channel of stimulation it seems to be adequate to use the critical bandwidth as a measure (3.1). According to this criterion 15 channels would have to be introduced into the speech region of the cochlea. This would allow 1.2 mm of cochlear length for each channel. Perfect electrical separation of the channels is required. Considering the severe distortions in neuronal activity pattern, introduced by electrical stimulation in comparison to the natural conditions it is not clear even whether the number given would be sufficient. On the other hand, current spreading would appear to prohibit any higher electrode density. As far as coding of sound parameters within one channel is concerned it is proposed that full use should be made of frequency analysis according to the place principle. In respect to coding of periodicity and loudness it is proposed to approach natural conditions as far as possible (3.3). Here delay times between the individual channels and a probabilistic character of the stimuli should be introduced to avoid dominance of periodicity pitch...
Action Potentials↗