Chemotherapy and radiotherapy causing radiation myelopathy: what is to blame?
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Biomedical subjects
Publications and source records attributed to J Walther.
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A 30-year-old man with underlying Wiskott-Aldrich syndrome, which is a rare X-linked congenital immunodeficiency syndrome characterized by recurrent infections, thrombopenia, eczema and hematopoietic malignancies, presented with bloody diarrhea. Endoscopic and histological evaluation was compatible with ulcerative colitis. Congenital immune defects are paralleled by enterocolitis mimicking inflammatory bowel disease in a substantial number of patients. Despite therapy with prednisolone and 5-ASA compounds, the patient described here experienced a relapse of the colitis twice. Subsequently a JC virus infection of the central nervous system was diagnosed, and he died due to progressive multifocal leukencephalopathy.
Tumors of the diaphragm are rare and caused by there special localisation difficult to diagnose. We describe the case of a 31 year old man with a choristoma of the left diaphragmal crux where the localisation and genesis could only be cleared through lateral thoracotomy. Nor the CT guided puncture or the laparoscopy-although sufficient samples for the pathology could be gained-allowed the right diagnose. The importance of good diagnostic approach to select the right operative procedure-in this case the anterolateral thoracotomy-is described.
BACKGROUND: Sleep related hypoxemia (SRH) in chronic obstructive pulmonary disease (COPD) can be easily detected by pulse-oximetry and may contribute to the development of pulmonary hypertension (PH). Since several parameters for the quantification of SRH are in use, we investigated which of these parameters has the strongest relation to the awake pulmonary arterial pressure (PAP) and is able to distinguish between patients without and with PH. PATIENTS AND METHODS: 44 COPD-patients (awake PaO2 > or = 60 mm Hg) were investigated. PAP at rest (PAP; pathological threshold > 20 mm Hg) and under physical exercise (PAPB; p.t. > 28 mm Hg) were determined during daytime by Swan-Ganz-catheter. To quantify the degree of SRH the following parameters of nocturnal pulse-oximetry were used: mean nocturnal oxygen saturation (SaO2 m; p.t. < 90%), nadir SaO2 (SaO2 min; p.t. < 85%), and mean time of SaO2 < or = 90% in relation to total time of registration (t90; p.t. > 30%). Linear correlations and regressions as Chi 2-respectively Fisher-test were used for statistical analysis (p < 0.05). RESULTS: Generally there was only a weak relation between PAP and SRH. The best linear correlation at rest respectively under physical exercise was found between PAP and SaO2 min (r = -0.529 resp. -0.541, p < 0.001). Using the above defined thresholds for PAP and SaO2 patients could be most precisely separated into those without and with PH using SaO2 min with a threshold for the pathological range of < 85% (p = 0.030 resp. 0.002). t90 with a threshold > 30%, however, had a much worse selectivity (p = 0.487 resp. 0.057). CONCLUSIONS: In COPD-patients with SRH the closest relation can be found between nadir SaO2 and PAP resp. PAPB. Furthermore nadir SaO2 (< 85%) could more precisely separate patients into those without and with pulmonary hypertension than t90. The overall weak relation between nocturnal oxygenation and pulmonary hypertension shows, however, that other factors such as daytime PaO2, hypercapnia or emphysema are involved in the development of pulmonary hypertension in COPD.
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Mitochondria cannot maximize energy production, efficiency, and the cellular ATP phosphorylation potential all at the same time. The theoretical and observed determinations of coupling of oxidative phosphorylation in mitochondria from rat liver, heart, and brain were compared using classical and nonequilibrium thermodynamic measures. Additionally, the optimal thermodynamic efficiency and flow ratios were determined for control of the two energy-converting complexes of the respiratory chain: complex I (NADH), which reflects the integrated cellular pathway, and complex II (FADH2), the predominantly tricarboxylic acid (TCA) cycle pathway. For all three organs, the cellular respiratory pathway was more tightly coupled than the TCA pathway and resulted in a greater optimal efficiency. Liver mitochondria are the most thermodynamically efficient at ATP production using oxidative phosphorylation. Heart and brain mitochondrial systems utilize more oxygen, but can produce ATP at a faster rate than liver systems. Per the theory of economic degrees of coupling, isolated rat liver mitochondrial systems are designed for the economic production of ATP for use in cellular processes. In the brain, the mitochondrial TCA cycle pathway promotes the maximal maintenance of the cellular energy state for cellular viability, whereas in the heart the TCA cycle pathway maximizes the production of ATP. The coupling of oxidative phosphorylation not only can be expected to change with substrate availability but may also reflect an ontogenetic response of mitochondria to fit specific organ roles in the rat.
UNLABELLED: In eyes lacking adequate posterior capsular support, fixation of posterior chamber intraocular lenses (IOL) by iris sutures has become one of the methods available. Ultrasound biomicroscopy (UBM) allows detection of the haptic position postoperatively and determination of its relationship to adjacent intraocular structures. METHODS: Thirteen patients with iris-sutured IOLs were examined pre- and postoperatively with UBM. The examination included locating the haptic and tracing the haptic to the position closest to other uveal structures. RESULTS: The position of all 26 haptics was determined. All haptics were in touch with the iris. In the 12-clock position 11 haptics did not touch other intraocular structures. In one case the haptic was located in the ciliary sulcus, and in another case it touched the ciliary body. In the 6-clock position two haptics were located in the sulcus region, and seven were located posterior to the ciliary processes. Four haptics did not touch any other intraocular structures. CONCLUSIONS: In most cases surgical placement of iris-fixed lenses is a blind procedure. UBM is an adequate method of determining the position of IOL haptics postoperatively.
In an attempt to reestablish normal hematopoiesis in symptomatic myelodysplasia (MDS) and to show the tolerability of a combination treatment of low-dose cytosine arabinoside (LD AraC) and interleukin-3 (IL-3), we treated 31 patients (pts., median age 65 years) who had more than 10% blasts in the bone marrow (BM) and hematopoietic failure with LD AraC (2 x 10 mg/m2 sc, day 1-14) plus IL-3 (once daily sc, day 8-21) at different dose steps (1.0, 2.5, 5.0, and 10.0 micrograms/kilogram body weight). The numbers of each 21-day cycle varied between 1 (3 pts.), 2 (6 pts.), 3 (8 pts.), 4 (1 pt.), 5 (5 pts.), and 6 (8 pts.), in total 116 cycles on an outpatient basis. Subjective tolerability was good in 20 cases (65%). Toxicities were fever (29 pts.), flu-like symptoms (17 pts.), infections (15 pts.), hepatic toxicity (10 pts.), and skin reactions (8 pts.). Overall response was seen in 13 cases (42%) and 5 complete responses (CR), while 10 pts. had stable disease (SD), 5 progressed (2 to acute leukemia), 2 were considered toxic deaths, and 1 died due to the disease. Median survival is 18 months, progression-free survival is 12.5 months (18.0 months in responding pts.), with an actuarial follow-up of 31 months. The data from this phase I/II study show that a combination of LD-AraC and IL-3 is well tolerated and that stable responses can be achieved in MDS by means of an easy outpatient therapy.
As the quality of water in the dialysis fluid varies considerably, dialysis fluid is contaminated with a high percentage of bacteria and endotoxins. The bacterial populations contained in the dialysis fluid are as heterogeneous as the chemical structure of the endotoxins that result. The latter can pass through the dialysis membrane whereby high-flux membranes permit a larger number of retransportable molecules than low-flux membranes. A central aim toward a future, safe dialysis process should, therefore, be the production of a dialysate that is free of bacteria and endotoxins. As we were able to demonstrate in various examinations, this goal is most likely to be achieved with the aid of sterile filtration using hollow fiber modules of polyamid. To avoid disinfection of the polyamid membrane, as this would only reach bacteria but not endotoxins, the filter was changed after at most 10 h. The achieved dialysis fluid was free of bacteria and endotoxins. We were also able to show that the release of interleukin-1 was reduced. In addition, side-effects, such as a drop in blood pressure, headaches, muscular cramps, and nausea, were reduced.
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Modern combination chemotherapy cures about one third of patients with non-Hodgkin's lymphomas (NHL) [3]. Attempts to increase this proportion by more intensive chemotherapeutic regimens have failed so far in randomized trials [4, 5]. Dose intensity has been reported to be important for cure [8]--a factor which can be enhanced by hematopoietic growth factors--but addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to intensive chemotherapy did not improve response on survival in a controlled study published recently [10]. Therefore, we tried to design a regimen which might be more appropriate for combination with growth factors, using pulse chemotherapy rather than continuous treatment and employing drugs of low stem-cell toxicity. Ifosfamide (Ifo) appeared to be ideal because it is effective even in some resistant cases [1] and might act synergistically with anthracyclines by reducing intracellular glutathione levels [9]. Epirubicin (Epi) was favored because of its low hemato- and cardiotoxicity [2]. These drugs, together with etoposide (VP-16) had been found to be very effective in relapsed cases [7]. Methotrexate (Mtx) was added because it penetrates the spinal fluid. Moreover, we chose granulocyte/macrophage colony-stimulating factor (rhGM-CSF) as an adjunct cytokine because this not only enhances neutrophil regeneration [6] but might also have antitumor effects, as suggested by an uncontrolled study in sarcomas [11]. This report summarizes our experiences regarding feasibility, toxicity, and responses with this new regimen obtained in a pilot study.
As the quality of water in dialysis fluid varies considerably, and, in view of the fact that endotoxin or active derivates can cause acute and chronic side effects in patients under hemodialysis treatment, the dialysis fluid must be sterile and endotoxin-free. The predialyzer fluid in 20 hemodialysis patients was investigated. The bacterial loading was between 5/ml and 12,000/ml, the endotoxin concentration was high and extremely variable. Therefore we introduced the ultrafiltration of the dialysis fluid by a polyamide hollow fiber membrane before entering the dialyzer. All samples were free of bacteria, and the concentration of endotoxin was lower than the detectable limit. With this procedure we can obtain sterile dialysis fluid, which is endotoxin free. Our preliminary results showed that Interleukin-1 in the patients was significantly (p less than 0.005) lower under ultrafiltration of the dialysis fluid than without ultrafiltration.
Electromyography of the duodenums was performed in dogs, using two bipolar electrodes placed 5 and 10 cm aborally of the pylorus on the serosa of the duodenums. 10 days after implantation and 24 hours after the last meal the duodenal motility was registered in 9 bastard dogs for 5 hours. Pentagastrin, given as a 1-hour intravenous infusion, changed the interdigestive motility to an irregular (postprandial) pattern, which continued up to the end of measurement or was followed by a prolonged phase III with return to cyclic activity. Infusion of somatostatin for 1 hour interrupted the interdigestive motility leading to a prolonged phase I pattern and to partial discoordination. After the end of infusion phase III motility returning to cyclic activity or irregular activity were registered. A standard relaparotomy 10 days after implantation was performed in 3 dogs. Up to the second day of the postoperative period interdigestive cycles of duodenal motility were not obtained.
As the quality of water in the dialysis fluid varies considerably, and in view of the fact that endotoxin or active derivates can cause acute and chronic side effects in patients under chronic hemodialysis treatment, the dialysis fluid must be sterile and endotoxin free. The predialyzer fluid in 20 hemodialysis patients was investigated. The bacterial load was between 5/ml and 12,000/ml, the endotoxin concentration was high and extremely variable. Therefore, we introduced the ultrafiltration of the dialysis fluid by a polyamide hollow fiber membrane before entering the dialyzer. All samples were free of bacteria, and the concentration of endotoxin was lower than the detectable limit. With this procedure, we can obtain sterile dialysis fluid, which is endotoxin free. Our preliminary results showed that interleukin-1 in the patients was significantly (p less than 0.005) lower under ultrafiltration of the dialysis fluid than without ultrafiltration.
The influence of a mechanical disturbance of the duodenum on the motility of the antrum and duodenum was investigated by means of the electromyography and the perfusion manometry. Thereby the effect of the pentagastrin stimulating the motility of the unstriated muscles of the gastro-intestinal tract was used for testing the function reserve of the antrum- and duodenal-muscles. After one and a half month of establishing the passage obstacle there occurs a complex disturbance of the electrical activity; the unstriated muscles does not react on a stimulating excitation.
The binding of antigen-loaded carrier to mononuclear cells of heart transplant recipients has been investigated by means of an antigen-specific rosette technique. The increase of rosette forming cells and the inhibition of this reaction with monoclonal antibodies against activated T-cells is a sign of a beginning rejection. 3-6 days later infiltrating immunological competent cells are seen in biopsy.