Osteopathien und Calcium-Phosphat-Stoffwechsel bei chronischer Hämodialyse

Zusammenfassung Unter chronischer Hämodialyse-Behandlung wurden 13 Fälle auf Knochenveränderungen unter Berücksichtigung des Calcium-Phosphat-Stoffwechsels untersucht. Die Knochenveränderungen wurden histomorphometrisch definiert. Bestimmt wurden die prozentualen Anteile der neutralen Oberflächen, des Osteoids, der aktivierten Osteoblasten, der Resorptionslacunen und der mehrkernigen Osteoclasten an den endostalen Oberflächen, sowie die mittlere Breite der Osteoidsäume. Außerdem wurden Formation und Resorption des Knochens mittels quantitativer Mikroradiographie sowie die volumetrische Dichte der Spongiosa gemessen.Beiallen Fällen konnten unterschiedlich schwere Knochenveränderungen nachgewiesen werden (60% schwere und 40% leichte), wobei die stets pathologisch erhöhte Knochenresorption als Ausdruck eines regulativen sekundären Hyperparathyreoidismus gewertet wurde. Eine direkte Beziehung zwischen Calciumspiegel und Schwere der renalen Osteopathie ließ sich nicht beweisen. Die Hyperphosphatämien, die bei allen Patienten unter der Hämodialyse-Behandlung unverändert blieben, ergaben mit den ansteigenden Serumcalciumwerten pathologische Calciumphosphatprodukte. Bei einem Teil der Patienten kam es zu extraossären Verkalkungen, die unter kontrollierter Behandlung mit Aluminiumhydroxyd und abfallendem Calciumphosphatprodukt eine erhebliche Rückbildungstendenz zeigten. Wegen der Gefahr derartiger Calcifizierungen verbot sich in unserem Krankengut eine Vitamin D-Behandlung. Die Indikation einer totalen oder subtotalen Parathyroidektomie wurde in Abhängigkeit vom Ausmaß der Osteopathie und einer möglichen Nierentransplantation erörtert.

---

Bone Disease and Calcium-phosphate Metabolism in Chronic Hemodialysis

Summary 13 patients under chronic hemodialysis were studied for changes in the bone, whereby calcium and phosphorus metabolism were given special attention. The changes in the bone were defined histomorphometrically. The percentage of the neutral surfaces, the osteoid, the activated osteoblasts, the resorption lacunae and the polynuclear osteoclasts of the endosteal surfaces were determined as well as the medium width of the osteoid seams. Moreover, formation and resorption of the bone were assessed by quantitative microradiography and the volumetric density of the cancellous bone was measured. Inall cases, bone changes of various degree were observed (60% of serious and 40% of slight changes), whereby the constantly increased bone resorption was considered as expression of a regulative secondary hyperparathyroidism. A direct relationship between serum calcium levels and the degree of seriousness of renal osteopathy could not be established. Hyperphosphatemia remained unchanged and with increasing serum calcium levels, the calcium phosphorus product became abnormally high in all subjects under hemodialysis. Extraosseus calcifications developed in some cases and were reduced to a considerable degree by controlled treatment with aluminiumhydroxide in connection with a fall of the calcium phosphorus product. Because of the risk of such calcifications, vitamin D treatment were out of question. Total or subtotal parathyroidectomy was discussed in relation to the degree of osteopathy and the possibility of a kidney transplantation.

---

---

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Cadmiumkonzentrationen im blut von stadt- und inselbewohnern in Schleswig-Holstein

Zusammenfassung Die Cadmiumkonzentrationen im Blut von Kindern and Erwachsenen der Landeshauptstadt Kiel and der Nordseeinsel Pellworm (Schleswig-Holstein, Norddeutschland) wurden gemessen. Die Teilnahme an einem Programm der externen Qualitätskontrolle der Europäischen Gemeinschaft sicherte die Richtigkeit der Analysen. Bei den repräsentativen Stichproben von 35 Kindern aus Kiel and 25 von Pellworm im Alter zwischen 7 und 16 Jahren Bowie 45 Kieler and 53 Pellwormer Erwachsenen lagen alle Meßwerte zwischen 0,1 and 4,0 g Cd/l Blut. Kinder sind in beiden Regionen geringer belastet als Erwachsene. Eine Gefährdung durch das Schwermetall Cadmium konnte bei diesen fur Schleswig-Holstein typischen Bevölkerungs-gruppen nicht festgestellt werden, obwohl die Cadmiumbelastung des Blutes durch Zigarettenrauchen signifikant zunimmt.     

Acoustic voice analysis by means of the hoarseness diagram.

The hoarseness diagram (Michaelis, Fr?hlich, & Strube, 1998a) has been proposed as a new approach to describe different acoustic properties of voices. To test its performance in the analysis of pathologically disturbed and normal voices five requirements are suggested that should be met by any acoustic voice-analysis protocol to be used in voice research and clinical practice. The hoarseness diagram is then tested with regard to these requirements. Individual voices are found to show a satisfactory localization in the diagram. Aspects of stationarity are discussed in the context of four case studies. The different cases illustrate that changes in the acoustic analysis results are observed if the voice-generation conditions change, whereas results are stationary if phonation conditions do not change. Different pathological voice groups defined on grounds of the specific phonation mechanism are found to map to specific regions of the hoarseness diagram, with differences between group locations being significant. All results can be interpreted without exceptions if the two hoarseness diagram coordinates are taken to reflect the vibrational irregularity of the voice-generation mechanisms on the one side and the degree of closure of the vibrating structures on the other side. The hoarseness diagram and its underlying algorithms are thus shown to constitute a useful approach to acoustic voice analysis in research and clinical practice. The tests themselves demonstrate several application possibilities, including the quantitative monitoring of individual voices.     

Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin

PURPOSE: To investigate the effect of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2-E) on degradative functions of lysosomes in human retinal pigment epithelial (RPE) cells and to evaluate its mechanism of action. METHODS: A2-E was coupled to low-density lipoprotein (LDL). Human RPE cell cultures were loaded with the A2-E/LDL complex, and controls were run with medium containing LDL alone. To determine whether A2-E accumulated in lysosomes, cells were fractionated in a Percoll gradient, and protein degradation was determined by metabolic labeling and measurement of the release of low-molecular-weight radioactivity. Lysosomal degradation was distinguished from nonlysosomal degradation by inclusion of NH4Cl in the medium. The metabolism of sulfated glycosaminoglycans was studied by radiosulfate incorporation in pulse-chase experiments. Intralysosomal pH was determined using a fluorescent lysosomotropic pH indicator. RESULTS: A2-E accumulated almost exclusively in the lysosomal compartment. Lysosomal protein degradation was reduced in a dose-dependent fashion in A2-E-treated cells. The selectivity of A2-E on lysosomal function was demonstrated by its lack of effect on degradation of extralysosomal protein. Lysosomal glycosaminoglycan catabolism of RPE cells was also strongly inhibited by A2-E. Lysosomal pH was increased by A2-E. CONCLUSIONS: The findings indicate that accumulation of A2-E in RPE cells interferes with lysosomal functions as exemplified by its inhibitory effect on protein and glycosaminoglycan catabolic pathways. The quaternary amine character of the A2-E apparently causes a perturbation of the acidic intralysosomal milieu, resulting in diminished hydrolase action and consequent accumulation of undegraded material. Such mechanism could be operative in retinal diseases associated with excessive lipofuscin accumulation including age-related macular degeneration.     

In vivo significance of ICAM-1--dependent leukocyte adhesion in early corneal angiogenesis

PURPOSE: Numerous investigations have stressed the significance of leukocytes in early angiogenesis. Leukocytes invade the cornea, and the location of their extravasation corresponds to the site of vessel ingrowth. The interactions between leukocytes and vascular endothelium are mediated by various proteins, including adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). In this study, the role of ICAM-1 during early corneal angiogenesis was evaluated in vivo. METHODS: Corneal neovascularization was induced in New Zealand White rabbits by use of intrastromal pellets containing 750 ng vascular endothelial growth factor (VEGF). The fluorescent dye rhodamine 6G was used to stain leukocytes in vivo. Leukocyte adhesion and vessel growth were quantified in vivo by high-resolution fluorescence angiography. To inhibit ICAM-1 interactions a microemulsion containing anti-ICAM-1 antibody was applied topically. RESULTS: Limbal vessels showed increased leukocyte adhesion 24 hours after pellet implantation: The number of rolling and sticking leukocytes was significantly increased compared with the number in control animals (P < 0.01). Treatment with anti-ICAM-1 antibody resulted in reduced leukocyte sticking and increased leukocyte rolling. The area covered by new blood vessels was significantly diminished in eyes treated with anti-ICAM-1 (P < 0.05). CONCLUSIONS: The results support the hypothesis that ICAM-1-mediated leukocyte adhesion is a key event in early angiogenesis. This model may serve for investigation of the significance of adhesion molecules by in vivo observation and quantification.     

Topical application of methotrexate for inhibition of corneal angiogenesis

· Purpose: Methotrexate (MTX) is a folic acid antagonist used in chemotherapy regimens. Additional therapeutic applications have been suggested based on effect as an immuno-modulating drug in systemic rheumatoid disease and associated uveitis. Since chronic inflammatory disease is often associated with a neovascular response, we investigated the use of MTX for treatment of corneal angiogenesis.· Methods: Neovascularizations were induced by fibroblast growth factor in a corneal pocket model. Vessels were examined biomicroscopically. MTX was applied topically to rabbit corneas in a concentration of 0.2 mg/day. MTX level was measured in aqueous humor and plasma. · Results: On day 9 the vascularized area was 12.0±6.9 mm² in control eyes and significantly smaller, 2.2±1.86 mm², in treated eyes. Treated animals showed no local side effects such as epithelial defects. Although therapeutic levels were measured in the aqueous humor, MTX could not be detected in the serum of treated animals.· Conclusion: The antiangiogenic mechanism of MTX might be due to inhibition of both macrophage invasion during early angiogenesis and endothelial cell proliferation. The high levels in the aqueous humor indicate a possible application of topical MTX for inflammations of the anterior segment of the eye. Received: 4 March 1999 Revised version received: 6 May 1999 Accepted: 6 May 1999     

Financing the World Health Organisation: global importance of extrabudgetary funds

From 1948, when WHO was established, the Organisation has relied on the assessed contributions of its member states for its regular budget. However, since the early 1980s the WHO World Health Assembly has had a policy of zero real growth for the regular budget and has had to rely increasingly, therefore, on attracting additional voluntary contributions, called extrabudgetary funds (EBFs). Between 1984-85 and 1992-93 the real value of the EBFs apparently increased by more than 60% and in the 1990-91 biennium expenditure of extrabudgetary funds exceeded the regular budget for the first time. All WHO programmes, except the Assembly and the Executive Board, receive some EBFs. However, three cosponsored and six large regular programmes account for about 70% of these EBFs, mainly for vertically managed programmes in the areas of disease control, health promotion and human reproduction. Eighty percent of all EBFs received by WHO for assisted activities have been contributed by donor governments, with the top 10 countries (in Europe, North America and Japan) contributing about 90% of this total, whereas the UN funds and the World Bank have donated only about 6% of the total to date. By contrast, about 70% of the regular budget expenditure has been for organisational expenses and for the support of programmes in the area of health systems. Despite the fact that the more successful programmes are heavily reliant on EBFs, there are strong indications that donors, particularly donor governments, are reluctant to maintain the current level of funding without major reforms in the leadership and management of the Organisation. This has major implications for WHO's international role as the leading UN specialised agency for health.     

Techniques for vascular access when venous entry is impossible. Route depends on urgency and the agent to be administered

When a patient requires parenteral fluid or drug administration and venous cannulation cannot be performed, consider less typical routes. Intraosseus infusions are usually more effective in children than adults, but intraosseus cannulation failure may occur in as many as 20% of patients. Intra-arterial infusions are possible if pump pressures are kept high. Hypodermoclysis (infusion into the subcutaneous tissues) can correct moderate dehydration. Administering resuscitative drugs endobronchially is usually safe and effective, although pulmonary function may be somewhat compromised. A number of drugs may be given sublingually, either by injection or topical application. Finally, the corpora cavernosa of the penis may be used for short-term, large-volume fluid administration.     

Bladder Cancer and Arsenic Exposure： Differences in the Two Populations Enrolled in A Study in Southwest Taiwan

Objective Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400 μg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis.     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.