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Biomedical subjects

M Brandis

Publications and source records attributed to M Brandis.

156 records · Page 9Linked to original sources
PubMedDate not supplied

[Sclerosing peritonitis without reduced ultrafiltration as complication of peritoneal dialysis].

UNLABELLED: Peritoneal dialysis (PD) is the preferred method of renal replacement therapy in childhood and adolescence while waiting for a kidney transplant. As major complication, encapsulating peritoneal sclerosis (EPS), sometimes also referred to as "sclerosing peritonitis", may develop after prolonged periods of PD and lead to severe therapeutical problems. CASE REPORT: A 20-year-old patient with a history of three unsuccessful kidney transplants due to recurrence of his focal segmental glomerulosclerosis presented after 9 years of PD with acute abdominal pain and reduced bowel movements. Infectious peritonitis was excluded, ultrafiltration with 800-1 000 ml per day with low (1,36 %) glucose dialysate was not impaired. Plain abdominal X-ray, ultrasound and CT-scan illustrated characteristic peritoneal calcifications. Diagnosis of EPS was confirmed by peritoneal biopsy. The patients was switched to hemodialysis, enteral nutrition was continued, and the follow-up (now 16 months) was uncomplicated with the exception of a sterile ascites, which was twice relieved. Diagnostic and therapeutic options are discussed. CONCLUSION: In contrast to most reports, EPS may develop with unchanged ultrafiltration after prolonged periods of PD. We recommend regular functional and imaging studies in patients at risk.

Adolescent↗
PubMedDate not supplied

[Changes in blood coagulation in treatment with ALL-BFM-90 and NHL-BFM-90 protocols].

1. Treatment according to the ALL/NHL-BFM 90 protocol I (induction phase) caused multiple and severe coagulation changes in all 14 patients of our study. Glucocorticoids alone made Fibrinogen drop to 148 mg/dl, AT III and Protein C rise to 136% or even 179% respectively. After day 12, immediately following the start of therapy with Coli-Asparaginase (ASP), fibrinogen continued to drop to reach its lowest average value of 46 mg/dl on day 24. Anticoagulant factors like plasminogen (lowest average value: 36%), AT III (47%) and Protein C (93%) dropped abruptly. These alterations were reversed after discontinuation of Glucocorticoids and ASP. During consolidation (protocol II) similar alterations are observed as in protocol I when Glucocorticoids are applied alone. However, after Erwinia-ASP there is no fall in AT III, plasminogen, and Protein C as is observed in protocol I with Coli-ASP. 2. Severe hemorrhages or thromboses are uncommon as compared to the degree of coagulation changes which can be regularly observed. Complications occur more often in girls. Most of them are seen during the 2nd or 3rd week of simultaneous ASP-Glucocorticoid therapy. 3. To avoid twofold alteration of hemostasis it should be considered to apply Glucocorticoids and ASP separately and to replace Coli-ASP by Erwinia-ASP. The efficacy of prophylactic replacement of decreased coagulation factors has not yet been confirmed. Immunologic and infectious side effects have to be taken into consideration. 4. More definite recommendations can be given when each suspected bleeding and/or thrombosis is confirmed by imaging procedures, when it is documented and registered, and when coagulation studies are performed during the critical phase.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Stevens-Johnson syndrome during an immunosuppressive therapy with cyclophosphamide and prednisone.

Corticosteroids are often recommended for the treatment of severe Stevens-Johnson syndrome. We report about a 12 years old boy, who developed this syndrome during an immunosuppressive therapy with prednisone and cyclophosphamide for a frequent relapsing, steroid-dependent nephrotic syndrome. Most of the commonly mentioned etiologic factors for erythema exudativum multiforme could be excluded. The usefulness of corticosteroids for the therapy seems to be doubtful.

Child↗
PubMedDate not supplied

[Bacteremic episodes in pediatric oncologic patients, especially caused by the Streptococcus viridans group].

BACKGROUND: The management of infectious complications plays a major role in the care for pediatric cancer patients. The majority of infections in the neutropenic patient present as fever of unknown origin without recovering a pathogen from the blood stream. The careful evaluation of bacteremic episodes is essential, since knowledge of the bacterial spectrum expected is crucial for the successful anti-infective treatment. PATIENTS AND METHODS: From 1985 to 1995 all bacteremic episodes in pediatric oncology patients at the University Children's Hospital Freiburg were retrospectively analyzed with respect to the pathogens encountered, the antibiotic susceptibility profile and the underlying conditions. RESULTS: Overall, 113 bacteremic episodes were encountered in pediatric oncology patients, 68 of them in patients with hematological malignancies, and 45 in patients with solid tumors. In both patient groups, gram-positive bacteria were predominant with 72% and 58%, respectively. In patients with hematological malignancies, viridans streptococci were the most frequently isolated pathogens (35%) with a relevant morbidity (29% of patients developed a severe sepsis syndrome and/or ARDS), but were found only in 9% of patients with solid tumors. In 28% of patients with leukemia or lymphoma, gram-negative rods were cultured, in 6% Pseudomonas spec., in 4% Acinetobacter spec., and in 18% enterobacteria. In patients with solid tumors, in 38% gram-negative rods were isolated, 7% Pseudomonas spec., 16% Acinetobacter spec., 16% enterobacteria. In 3 patients, fungemia was observed. The antibiotic susceptibility profile was quite favorable in both, gram-positive and -negative bacteria: none of the gram-positive isolates was resistant to vancomycin, none of the Staphylococcus aureus isolates was resistant to oxacillin. All gram-negative bacteria were fully susceptible to ceftazidime, imipenem and ciprofloxacin. CONCLUSION: Gram-positive bacteria account for 2/3 of all bacteremic episodes in pediatric oncology patients. Streptococcus viridans was the most important pathogen in hematological malignancies accounting for a significant, pathogen-specific morbidity.

Adolescent↗
PubMedDate not supplied

[Miliary tuberculosis and adult respiratory distress syndrome in an infant].

We report on a 7 months old infant, who was admitted to our hospital with the tentative diagnosis of interstitial pneumonia. The infant was treated with erythromycin because of a positive mycoplasma antigen test in the nasopharyngeal mucus and the radiological findings. A tension pneumothorax led to rapid respiratory deterioration and a severe ARDS developed. A sustained respiratory stabilization could not be achieved. The diagnosis miliary tuberculosis was detected on autopsy. A parenchymal focus was found subpleurally in the left lung with a massive hematogenous spread and a tuberculous meningitis. The source of infection could not be identified in the family or in persons known to have had contact to the infant. The tuberculin skin test (PPD) was negative. Clinical, radiological and pathological findings are demonstrated.

Diagnosis, Differential↗
PubMedDate not supplied

[After-care of children and young adults surviving cancer. Initial recommendations by the late sequelae study group].

An increasing number of children suffering from cancer has been treated successfully during the last 25 years using therapy protocols of the Gesellschaft für Pädiatrische Onkologie und Hämatologie. The patients had to undergo an interdisciplinary treatment modality and a mostly intensive chemotherapy. Late effects could result from this approach for the now 20,000 survivors in the Federal Republik of Germany. The executive committee of the GPOH founded a working group for the detection of late effects stretching over all therapy studies. The first report of this group describes a spectrum of relevant late effects and proposes investigations for their detection.

Adolescent↗
PubMedDate not supplied

[Oncologic after-care--a patient-oriented concept. Basic diagnostic plan for pediatric oncology patients].

With intensive treatment many children and young adults with cancer can be cured of their disease. Therefore, the recognition of late effects of therapy will become increasingly important. Future concepts of follow-up care in pediatric oncology will have to serve two purposes: First, to determine the status of the malignant disease with early diagnosis of relapse and second, to recognize relevant side effects of treatment. We present a comprehensive approach of follow-up care which is primarily based on the definition of risk criteria for the development of relevant organ toxicity after different treatment modalities. For each patient a standardized summary of therapy delivered is documented. According to the definition of the risk criteria an individualized schedule for follow-up is decided upon. We hope that this structured concept will result in appropriate patient care while keeping the diagnostic efforts and costs limited.

Adolescent↗
PubMedDate not supplied

Inhibition of sodium-dependent transport systems in LLC-PK1 cells by metabolites of ifosfamide.

Ifosfamide (IF) is an alkylating cytostatic derived from nitrogen mustard. In addition to its well-known urotoxic effects (hemorrhagic cystitis), several cases of Fanconi syndrome following IF therapy have been reported. No information is available concerning the pathomechanisms of this tubulotoxicity. We used the permanent renal epithelial cell line LLC-PK1 in order to investigate whether major metabolites of IF (i.e. 4-OH-IF, acrolein and chloracetyldehyde) induced the transport defects most frequently detected after IF therapy in vivo. LLC-PK1 cells of passages 162-177, grown in plastic culture dishes, were used in a confluent state. Sodium-dependent and independent fluxes of l-[3H]alanine and of D-[3H]glucose were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria and of endoplasmic reticulum were determined in cell homogenates. IF itself has no detectable effect on fluxes of l-alanine and D-glucose in LLC-PK1 cells. The IF metabolite 4-OOH-IF induces a clear inhibition of sodium-dependent fluxes of both substrates after a 24-hour exposure of cells to 100 mumol/l of 4-OOH-IF. Chloracetaldehyde induces a biphasic response of sodium-dependent fluxes of l-alanine with increased uptake rates at low concentrations (< 200 mumol/l) and with a short incubation time, while higher concentrations and long exposure of the cells leads to a reduction in sodium coupled transport. Glucose transport is affected in a comparable way, however, in contrast to alanine transport, chloracetaldehyde also stimulates sodium-independent fluxes of glucose. Acrolein is the most toxic substance tested. It severely damages cell monolayers at concentrations beyond 75 mumol/l. Sodium-coupled glucose and alanine transport is inhibited by acrolein at concentrations higher than 50 mumol/l. Sodium-coupled glucose transport is more sensitive to all metabolites tested than alanine transport. While acrolein strongly affects both transport systems, marker enzymes of the apical plasma membrane, i.e. alkaline phosphatase and leucine amino-peptidase, are not significantly inhibited, suggesting a specificity of the toxic effect for the transport proteins. We conclude that LLC-PK1 cells represent a good model for further investigation of the pathogenesis of Fanconi syndrome after IF therapy. Sodium-dependent transport systems are more sensitive to acrolein than other cell surface proteins.

Acetaldehyde↗
PubMedDate not supplied

Effect of ifosfamide metabolites on sodium-dependent phosphate transport in a model of proximal tubular cells (LLC-PK1) in culture.

Ifosfamide (IF) is an alkylating cytostatic drug with urotoxic (hemorrhagic cystitis) and nephrotoxic side effects. Several cases of Fanconi syndrome in children following therapy with IF were reported. Little information is available concerning the pathomechanisms of transport inhibition by IF. We used a permanent renal epithelial cell line with proximal tubular characteristics (LLC-PK1) in order to investigate the effects of IF and some of its major metabolites (4-OH-IF, chloracetaldehyde, and acrolein). LLC-PK1 cells were used in a confluent state. Sodium-dependent and sodium-independent fluxes of 32PO4 were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria, and of endoplasmic reticulum were determined in cell homogenates. IF induces a moderate stimulation of PO4 transport. 4-OH-IF also has a stimulatory effect on transport at low concentrations (up to 200 mumol/l) and with short incubation (2h), while a 24-hour exposure of cells to 100 mumol/l of 4-OH-IF has an inhibitory effect of PO4 transport. Concentrations of 4-OH-IF which inhibit transport also reduce the activity of Na(+)-K(+)-ATPase. Chloracetaldehyde, like 4-OH-IF, induces a biphasic response of PO4 transport with stimulation in the low concentration range (up to 75 mumol/l) and inhibition at higher concentrations. Chloracetaldehyde reduces the activity of succinate-cytochrome c oxidoreductase, suggesting that a defect in ATP generation might play a role in the pathogenesis of Fanconi syndrome induced by IF. Acrolein strongly damages monolayers and reduces sodium-dependent transport of PO4 to very low levels at 150 mumol/l. It reduces the activities of both Na(+)-K+ ATPase and succinate-cytochrome c oxidoreductase. Acrolein also is the only metabolite with a moderate effect on alkaline phosphatase. We conclude that sodium-dependent transport of PO4 is highly sensitive to IF metabolites. In addition to direct toxic effects of IF metabolites on transport proteins within the apical plasma membrane, damage to mitochondrial enzymes and to Na(+)-K+ ATPase which generates the electrochemical gradients for secondary active PO4 transport may play an important role in the pathogenesis of Fanconi syndrome induced by IF.

Acetaldehyde↗
PubMedDate not supplied

Ifosfamide and mesna: effects on the Na/H exchanger activity in renal epithelial cells in culture (LLC-PK1).

Ifosfamide (IF) is an alkylating cytostatic with urotoxic and tubulotoxic side effects which may result in the development of Fanconi syndrome in children. While the urotoxicity of IF is effectively prevented by the uroprotective thiol compound sodium-2-mercaptoethanesulfonate (Mesna), tubulo-toxicity of IF may occur even in the presence of Mesna and in the absence of any signs of urotoxicity. Using the renal tubular cell line LLC-PK1, we investigated whether there is a protective effect of Mesna or of its major dimeric metabolite Dimesna against metabolites of IF with respect to the Na/H exchanger activity. We tested the major IF metabolites 4-hydroperoxy-IF (4-OOH-IF), chloroacetaldehyde (CAA), and acrolein. All metabolites significantly inhibit the Na/H exchanger activity. Half-maximal inhibition of transport occurs at concentrations of 120 mumol/l (4-OOH-IF), 80 (CAA), and 60 mumol/l (acrolein) after 2 h of incubation. The onset of the inhibitory effect of all three metabolites is rapid. Complete inhibition of Na/H exchange by acrolein and CAA is present after a 6-hour exposure to 100 mumol/l of the respective metabolite, while 100 mumol/l 4-OOH-IF causes only 50% inhibition after 24 h of incubation. Dimesna, which the proximal tubular cell has to reduce to Mesna at the expense of intracellular glutathione before it exerts a uroprotective effect, has no protective effect in LLC-PK1 cells. Dimesna (0.3 mmol/l) displaces the dose-response curve for acrolein to the left, indicating an increased toxicity of the combination of acrolein plus Dimesna. Mesna (0.3 mmol/l) has a complete protective effect with respect to acrolein and CAA, while the protective effect versus 100 mumol/l of 4-OOH-IF is incomplete. We conclude that the function of the Na/H exchanger in LLC-PK1 cells is altered by metabolites of IF. The incomplete protection against the toxic effect of 4-OOH-IF by Mesna may explain the pathomechanism by which IF causes tubulotoxicity in the absence of urotoxicity.

Acetaldehyde↗
PubMedDate not supplied

Prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in juvenile chronic arthritis.

OBJECTIVE: Sera from 66 children with active JCA of oligoarticular, polyarticular or systemic onset, 13 sera from patients in disease remission, 15 sera from patients with reactive arthritis, and 11 from Lyme arthritis patients were tested for the presence of anti-neutrophil cytoplasmic antibodies (ANCA) in order to evaluate their diagnostic significance in JCA. RESULTS: ANCA were found in 21% (14/66) of the active JCA sera, all showing an atypical pANCA staining pattern using indirect immunofluorescence on ethanol fixed granulocytes. 71% of these sera also showed antinuclear antibodies (ANA) on HEp-2 cells. By additional staining on paraformaldehyde fixed granulocytes to exclude staining artefacts due to ethanol fixation, 2 of the pANCA positive sera showed cytoplasmic staining. In no case did we find nuclear fluorescence suggesting a true cytoplasmic localization of the involved antigens. All ANCA positive sera were negative for anti-MPO and anti-LF antibodies. ANCA prevalence in our study group did not correlate with the disease subgroup, disease duration or other clinical characteristics. However, we found ANCA only in active disease. CONCLUSION: Our data suggest that the diagnostic importance of ANCA in JCA is restricted to only a few JCA patients. In these cases, however, ANCA positivity supports the diagnosis of JCA. Further studies are needed to substantiate this finding, as well as possible subgroup specificities. Standardized techniques of granulocyte fixation and antigen specific tests are needed to produce comparable results in different study groups.

Adolescent↗