242. Korrelation klinischer und biochemischer Befunde mit dem Schweregrad einer bakteriellen Peritonitis

Zusammenfassung Anhand von Verlaufsdaten 66 chirurgischer Patienten mit einer bakteriologisch gesicherten Peritonitis sollten harte und weiche Kriterien zur Beurteilung des Schweregrades differenziert werden. Untersuchungskriterien: 1) regionale Ausbreitung, 2) Entwicklung eines Organod. Systemversagens, 3) Leukocytose/Thrombopenie, Körpertemperatur, 4) die Plasmamediatoren Endotoxin/Prostaglandin F₂ (PGF₂), 5) Anamnesedauer (Erstsymptom bis OP), 6) Anzahl erforderlicher Reoperationen und 7) Lebensalter. Zuzuordnende Schweregrade: Grad 1: überlebt, Grad 2: mit Komplikationen überlebt, Grad 3: nicht überlebt. Danach erweisen sich als harte Kriterien: 1) Lokalisation, 2) Anamnesedauer, 3) Leukocytose, 4) Endotoxin > 100 Eu/ml, PGF₂ > 500 pg/ml, 5) Körpertemperatur 38,5°C.     

Effects of transforming growth factor-β1 on formation and activation of osteoclasts

Transforming growth factor-₁ (TGF-₁) has biological functions in various types of cells. However, its roles in the regulation of osteoclast formation and function are unclear. To examine them, we employed a culture system in which unfractionated cells obtained from long bones of 13-day-old mice were cultured on a dentine slice. We found that TGF-₁ has a potent inhibitory effect on osteoclastic bone resorption at a dose of 0.2–5 ng/ml. By electron microscopy the osteoclasts appeared to have fewer mitochondria and ruffled borders than those in control cultures. But in the presence of 1,25-dihydroxyvitamin D₃, [1,25-(OH)₂D₃], TGF-₁ at a dose of 0.2–1 ng/ml stimulated the formation of osteoclasts from unfractionated bone cell cultures in which preexistent osteoclasts had degenerated. Thus, using stromal cell-free he-mopoietic blast cells, we examined the direct action of TGF-₁ on osteoclast precursors. Although TGF-₁ inhibited tartrate-resistant acid phosphatase-positive (TRAP) multinucleate cell (MNC) formation induced by 1,25-(OH)₂D₃, the conditioned medium (CM) of TGF-₁-treated MC3T3-E1 cells stimulated such formation. These results suggest that TGF-₁ inhibits osteoclastic bone resorption but stimulates osteoclast formation via the action of factor(s) produced by TGF-₁-treated osteoblasts in the presence of 1,25-(OH)₂D₃.     

Preventive treatment of nephrolithiasis with alkali citrate—a critical review

Using the keywords urolithiasis and citrate treatment, nephrolithaisis and citrate treatment, kidney stones and citrate treatment, a Medline search revealed 635 articles published between 1 January 1966 and 1 December 2004. For the present analysis, only studies meeting all of the following criteria were included: (1) publications in English or German, (2) studies on preventive alkali citrate treatment in patients with calcium oxalate, uric acid and infection stone disease, (3) clinical studies including at least ten subjects, and (4) treatment phases of at least 1 week duration. A total of 43 studies met the inclusion criteria and were further subclassified according to intermediate or ultimate endpoints as well as to study design. With stone recurrence as the ultimate endpoint, 21 uncontrolled studies in almost 1,000 patients demonstrated a reduction in stone forming rate by 47–100%. In four randomized controlled trials including 227 patients, 53.5% on alkali citrate vs 35% on placebo remained stone-free after at least 1 year of treatment (P<0.0005). Similar values (66% vs 27.5% for alkali citrate vs placebo, P<0.0005) were obtained in 104 patients from two randomized trials with dissolution/clearance of residual stones as endpoint. Unfortunately, up to 48% of alkali citrate treated patients left the studies prematurely, primarily due to adverse effects such as eructation, bloating, gaseousness or frank diarrhea.     

Acquired hydrocephalus IV. Determination of the absorption rate of albumin from the cerebrospinal fluid

Summary By quantitative isotope ventriculography (QIV), the absorption rate (₂) of albumin in the cerebrospinal fluid (CSF) was determined. Regard was paid to the rate constants for the exchange of the albumin molecule between the serum and extravascular phase.The rate constant ₂ and mean biological transit time T_mb–2 were determined in 22 patients suspected of acquired hydrocephalus. QIV revealed that 8 patients were hydrocephalic, while 13 were non-hydrocephalic, and the findings were uncertain in one.In the patients with acquired hydrocephalus, it was demonstrated that ₂ and T_mb–2 were significantly reduced as compared with the non-hydrocephalic patients. By means of QIV, a curve was calculated and plotted for the biological decay from the head—the retention curve. From the initial slope of this curve (0–24 hours), the rate constant ₄ was calculated. A comparison of ₄ and ₂ revealed a highly significant correlation, which means that the retention curve gives an acceptable measure of the absorption rate of CSF-albumin.     

Integrin laminin receptors and breast carcinoma progression

This review explores the mechanistic basis of breast carcinoma progression by focusing on the contribution of integrins. Integrins are essential for progression not only for their ability to mediate physical interactions with extracellular matrices but also for their ability to regulate signaling pathways that control actin dynamics and cell movement, as well as for growth and survival. Our comments center on the 6 integrins (61 and 64), which are receptors for the laminin family of basement membrane components. Numerous studies have implicated these integrins in breast cancer progression and have provided a rationale for studying the mechanistic basis of their contribution to aggressive disease. Recent work by our group and others on mechanisms of breast carcinoma invasion and survival that are influenced by the 6 integrins are discussed.     

381. Die operative Therapie beim Thoraxtrauma — eine retrospektive Studie

Zusammenfassung Nach multiplem Trauma sinken intracelluläre Aktivität und Konzentration der Elastase in polymorphkernigen Leukocyten (PMNL), die aus Blut ( = 67 U und 6154 g/10⁹ PMNL) und bronchoalveolärer Lavage (BAL)-Flüssigkeit ( = 44 U und 5957 g/10⁹ PMNL) isoliert wurden im Vergleich zu PMNL Gesunder ( = 106 U und 9962 g/10⁹ PMNL). Gleichzeitig wurde ein Anstieg der extracellulären Elastase-Konzentration in Plasma von = 84 g/1 auf = 399 g/1 und in BAL Flüssigkeit von = 8 g/1 auf = 561 g/1 beobachtet. Die durch Stimulation freigesetzte Elastase wird teilweise von einem spezifischen Receptor auf PMNL erneut gebunden. Die Ergebnisse unterstützen die PMNL-vermittelte ARDS-Pathogenese.     

Guidelines for a short-term therapy of a torture depression

Psychotherapeutic work with torture traumas and their aftereffects are made difficult through a number of factors. Six guiding principles are presented in this publication through which make it possible to influence the actual symptomatology within the limits of the short therapy, even under difficult conditions. Creative images, described in detail as process fantasies, are the focus of this short therapy. Situative experiences in the treatment process are not interpreted with reference to the subject or the concrete trauma. This leads to the intra-psychic patterns being unlinked from traumatic torture experience patterns. With the aid of a model which discusses the torture as a superinfection with psychogenic violence-viruses, the penetration and resistance to therapy towards the torture trauma can be illuminated so that a differentiation of social and psychological factors of the torture experience is made possible.     

Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy

Background: The anticancer role of tumor necrosis factor-alpha (TNF-) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-) activity to abrogate TNF- toxicity. Methods: C57Bl/6 mice bearing MCA 105 tumor were treated with TNF- and anti-IFN- antibody (Ab) to evaluate the effect on the acute lethality of TNF- and their efficacy as evaluated by tumor growth rate, tumor histology, and survival. Results: Anti-IFN- Ab decreased TNF- lethality. Anti-IFN- Ab alone increased tumor growth significantly more than did nonimmune IgG (p₂<0.0001). Tumor-bearing mice that received nonimmune IgG and TNF- had slower tumor growth (p₂<0.02) and a trend toward improved survival (p=0.07) compared with saline-treated controls. Anti-IFN- Ab abrogated the antitumor effect of TNF-, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN- Ab and high-dose TNF- were comparable with those in mice that received a lower, equitoxic dose of TNF- alone. Conclusions: Blocking endogenous IFN- accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF- equally. This suggests that blocking endogenous IFN- activity is not a useful strategy for limiting TNF- treatment toxicity.Presented in part at the 45th Annual Cancer Symposium of The Society of Surgical Oncology, New York, New York, March 15–18, 1992.     

Serum α1-microglobulin and β2-microglobulin for the estimation of fetal glomerular renal function

As proteins cannot cross the placenta levels of the microproteins ₁-microglobulin (₁MG) and ₂-microglobulin (₂MG) can be used to assess fetal glomerular renal function. ₁MG, ₂MG and creatinine were routinely determined in cord and maternal blood of 133 newborns [gestational age (GA) 25–42 weeks]. Twenty-nine patients with suspected impaired maternal or fetal renal function were studied separately and two fetuses were studied in utero. The mean fetal ₂MG concentration fell from 3.87±0.56 mg/l in the 25–31 weeks GA group to 2.60±0.50 mg/l in the mature newborn group. ₁MG concentration fell from 3.10±0.51 to 2.25±0.49 mg/dl. In contrast, the mean maternal ₁MG concentration rose from 1.73±0.69 mg/l in the 25–31 weeks GA group to a mean of 1.83±0.48 mg/l in the mature newborn group; ₁MG rose from 3.96±0.58 to 4.33±1.6 mg/dl. Maternal and fetal creatinine levels were identical. Fetal microprotein levels fall during intra-uterine development as glomerular filtration rate (GFR) rises. There is no correlation between cord blood and maternal ₁MG or ₂MG concentrations. In 13 children with urological anomalies only 1 had elevated microprotein levels and he later developed renal insufficiency. Determination of microprotein levels in fetal serum can be used to detect severe renal function disturbances and to estimate GFR independently of maternal renal function.     

Absorptiometry and “osteoporosis”: problems

connecting the dots between diverse clinical and other matters and an updated bone physiology reveals relationships that could modify some ideas about the roles and uses of absorptiometry in osteoporosis work. Herein, absorptiometry means that part of clinical densitometry that depends on X-ray absorption by bone and other tissues, thus excluding ultrasound methods and magnetic resonance imaging. The modifications concern, in part, some limitations of bone mineral density data, the kinds of physiological information that absorptiometry can and cannot provide, the relative importance of bone mass and whole-bone strength, how to define and study bone health and osteoporosis, and two kinds of osteoporotic fractures. As those modifications concern important national health care issues, they deserve answers based on hard evidence. Identifying those modifications might help others to evaluate them.     

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A

The levels of alpha-1 microglobulin ( ₁m) and beta-2 microglobulin ( ₂m) in serum were estimated in 77 bone marrow transplant recipients. In comparison to pretransplant levels, the highest levels of ₁m and ₂m were found during impairment of renal function, i.e., during cyclosporin-induced nephrotoxicity and during treatment with other nephrotoxic drugs (P<0.001). The ₁m levels were less elevated during infections and acute graft-versus-host disease (P<0.01), while ₂m levels were markedly elevated during the same conditions (P<0.001). The linear correlations between serum creatinine and ₁m and creatinine and ₂m were r=0.7 and 0.8, respectively (P<0.001). The overall correlation between ₁m and ₂m was 0.4 (P<0.001). It is concluded that ₁m might be a complement to serum creatinine levels in monitoring renal function after bone marrow transplantation.     

Increase in ω3 (Peripheral-Type Benzodiazepine) binding site densities in different types of human brain tumours

Summary The density of ₃ (peripheral type benzodiazepine) binding sites, a marker of reactive and tumoural cells, has been measured in different types of human brain tumours; ₃ sites were quantified autoradiographically in sections from biopsy or autopsy specimens labelled with the specific radioligand³H-PK 11195. Compared to normal brain parenchyma, up to 12-fold increase in ₃ site densities were found in appparently viable areas of high grade astrocytoma and glioblastoma specimens, whereas more limited increases (2 to 3-fold) in this marker were observed in areas of necrosis. Low grade gliomas (astrocytomas) and meningiomas exhibited only moderate increases (2 to 3-fold) in this autoradiographic marker. Metastases of lung or kidney origin were characterized by greatly elevated (up to 20-fold) ₃ site densities as compared to normal brain parenchyma. In every case, there was a good spatial correspondence between the histopathological limits of the tumour and the anatomical location of the increase in ₃ site densities. These results suggest that ₃ site densities in human brain tumours reflect their proliferative activity and point to a possible future usefulness of positron or gamma-ray emitting ₃ site ligands for the clinical investigation and detection of human brain proliferative diseases.     

Masking of physicians in the Growth Failure in Children with Renal Diseases Clinical Trial

Masking — hiding identities of treatments from the patient, physician and/or statistician — is a critical element in clinical trials. Wherever possible, masking is implemented to eliminate observational bias or systematic error. In this paper, general concepts of masking in clinical trials are examined. Specific masking procedures used in the Growth Failure in Children with Renal Diseases (GFRD) Clinical Trial are described. A method to evaluate the success of this masking procedure for physicians is introduced. For each randomized patient at each clinical center, the clinic director was asked to predict which treatment (1,25-dihydroxyvitamin D₃ or dihydrotachysterol) was assigned. Results showed that 72% of responses initially indicated absolutely no idea of treatment. Additional analyses revealed that the number and percentage of correct guesses were essentially equal for the two treatment groups and that a patient's time on treatment did not affect the mask. We conclude that the mask of physicians in the GFRD Clinical Trial was well maintained.     

Standardization of Ischemic Hepatic Failure in Pigs as a Model for Bioartificial Liver Assessment

Purpose. A standard protocol of ischemic liver failure in pigs was examined to establish a system for assessing the efficacy of a bioartificial liver, based on clinical practice. Methods. The portal blood flow was extracorporeally bypassed into the cervical jugular vein, using a centrifugal blood pump. The portal vein and hepatic artery were then ligated. Results. The maintenance protocol was established as follows: (1) the concentration of the inhaled anesthetic was decreased by 0.2% when the systolic blood pressure was 100mmHg; (2) the volume of an infusion containing 5% glucose was increased to 10ml/kg per hour when central venous pressure was 5mmHg; (3) 20ml of 50% glucose was injected intravenously when the blood glucose was 50mg/dl; (4) 2000 units of heparin was injected intravenously when the activated clotting time was 150s; (5) sodium bicarbonate was given when the blood pH was 7.3; (6) tidal volume was increased by 1ml/kg when the pCO₂ was 80mmHg; (7) oxygen was increased by 25% when the pO₂ was 100mmHg. No vasopressors were used in the experiment. Conclusion. Our protocol reduced the operating time and minimized the risk of data deviation that can arise from variations in operating techniques and individual animal conditions. This experimental model is also easy to use as a bridge to transplantation.     

Behandlung der Speichenbrüche am peripheren Ende mit dem Faustgipsverband

Zusammenfassung Es wird über die Ruhigstellung von schweren Brüchen der Speiche an ihrem peripheren Ende nach der Einrichtung mit einem kurzen Faustgipsverband berichtet. Diese Verbandanordnung hat den Vorteil, daß sich die gute Stellung der Bruchstücke nach dem Einrichten bis zu ihrer Heilung erhalten läßt. Bei richtiger Verbandtechnik, die ausführlich beschrieben wird und aktiver Bewegungstherapie kann der kurze Faustgipsverband auch bei alten Leuten ohne schädigende Folgen angelegt werden.Mit 3 Textabbildungen (11 Einzelbilder)Herrn Professor Dr. Lorenz Böhler zum 80. Geburtstag gewidmet.     

Treatment of Myoblastic C2C12 Cells with BMP-2 Stimulates Vitamin D-induced Formation of Osteoclasts

The interaction of osteoclast precursors with osteoblasts and/or stromal cells is essential for the formation of mature osteoclasts and the resorption of bone. We found that myoblastic C2C12 cells induced the differentiation of mouse spleen cells into tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated cells in the presence of 10^–7 M 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] and that C2C12 cells that had been treated with bone morphogenetic protein-2 (BMP-2) dose-dependently stimulated the formation of osteoclasts. The newly developed TRAP-positive multinucleated cells were capable of resorbing mineralized tissues. Treatment of C2C12 cells with BMP-2 for 24 h enhanced the subsequent expression in C2C12 cells of mRNA for the receptor activator of nuclear factor-B ligand (RANKL) in the presence of 1,25(OH)₂D₃. Since the formation of osteoclasts was inhibited dose-dependently by exogenous OPG, the expression of RANKL in response to BMP-2 appeared to be critical for the formation of osteoclasts. Our findings suggest that BMP-2 might play an important role in the differentiation of cells that support osteoclastogenesis.     

Modulation of vitamin D increased H2O2 production and MAC-2 expression in the bone marrow-derived macrophages by estrogen

The calcium-regulating hormone 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is recognized as an immunomodulator. Members of the macrophage-monocyte lineage are targets for 1,25(OH)₂D₃ action. The hormone enhances the ability of bone marrow-derived macrophages (BMDMs) to produce H₂O₂, increases the expression of the macrophage specific surface antigen MAC-2, increases the release of tumor necrosis factor- (TNF-), and inhibits BMDM proliferation. In the present study we examine the possibility that estrogen modulates 1,25(OH)₂D₃ effects on BMDMs. The active form, 17-estradiol, failed to affect any of the BMDM functions by itself. On the other hand, 17-estradiol increased the effects of 1,25(OH)₂D₃ production by BMDMs and on MAC-2 expression on these cells. The inactive estrogen analog 17-estradiol was unable to elicit these effects. Moreover, 17-estradiol did not affect the lipopolysaccharide (LPS)-induced increase in H₂O₂ production by BMDMs. Modulation of BMDM proliferation and TNF- release from these cells by 1,25(OH)₂D₃ were not affected by the estrogen. The experiments were performed with BMDMs harvested from vitamin D-depleted and repleted mice, and always under similar conditions, the various functions were more pronounced in the cells derived from the repleted mice. Our data are consistent with the hypothesis that 17-estradiol modulates the interactions of 1,25(OH)₂D₃ with BMDMs and consequently is able to affect biological responses to 1,25(OH)₂D₃ in these cells. We propose that this cell system is a convenient, nontransformed model for studying cellular activities of 1,25(OH)₂D₃.     

Flow cytometric study on cell kinetics of brain tumours and their cultured cells

Summary With the aid of flow cytometry (FCM), distribution of DNA content in 40 cases of brain tumour, primary culture cell, and secondary culture cell can be determined and chronological change after subculture is studied from the analysis of their cell cycle. In most primary cultures, proliferating index (PI) is likely to decrease, which suggests that environmental change might affect the growth activity. In comparison with that of the original sample, DNA-histogram of the secondary culture can be divided into the following 3 types: the type recovering to the original pattern (adapting type), in which astrocytoma, ependymoma, glioblastoma and medulloblastoma are included, 2) the type increasing more at G2 + M phase than the original (proliferating type), in which meningioma and some of glioblastoma are included, and 3) the type decreasing so far as to induce degeneration or death (degenerating type), in which pituitary adenoma and neurinoma are included. FCM is of great usefulness for the study of cell kinetics of a tumour cell undergoing culture and the present method will be available for the respective study of biological characteristics of the cultured cell, established cell line or sensitivity test for antineoplastic agents.     

Ultrastructural observations on early cartilage calcification the use of chromium sulphate in decalcification

A solution of chromium sulphate was used as a combined fixative, stain and demineralizing agent for the ultrastructural study of mineralizing cartilage. This technique revealed the presence of an organic crystal ghost associated with each crystallite. The effectiveness of chromium sulphate as a demineralizing agent is discussed.

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Zusammenfassung Bei Ultrastrukturuntersuchungen von mineralisierendem Knorpel wurde eine Chromsulfatlösung als Agens zur kombinierten Fixation, Färbung und Demineralisierung verwendet. Diese Technik zeigte das Vorhandensein eines organischen Kristallschattens, der jedem Kriställchen zugehört. Die Tauglichkeit von Chromsulfat als demineralisierendes Agens wird besprochen.

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Résumé Une solution de sulfate de chrome est utilisée à la fois comme fixateur, colorant et agent de déminéralisation pour l'étude ultrastructurale de cartilage, en voie de minéralisation. Cette technique permet de mettre en évidence un fantôme cristallin organique, en rapport avec chaque cristal. L'intérêt du sulfate de chrome comme agent de déminéralisation est souligné.

     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.