Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Beneficial Effects of Apolipoprotein A-I on Endotoxemia

Purpose. Although many studies have shown the beneficial effects of lipoproteins on animals with endotoxemia, little is known about the impact of apolipoprotein A-I (apoA-I) on tumor necrosis factor (TNF-) release in response to lipopolysaccharide (LPS). The present study was conducted to determine whether the administration of apoA-I inhibits the release of TNF- and influences the survival rate of rats with endotoxemia.Methods. Forty male Wistar rats were divided randomly into four groups. Rats in the first and second groups were given 1mg/kg LPS intraperitoneally (i.p.) and blood was collected 1h later to measure the serum levels of TNF-. Either 10mg/kg apoA-I or Tris-buffered saline was injected i.p. and the serum TNF- levels were measured again 2h later. Rats in the third and fourth groups were given 5mg/kg LPS. Following the administration of 10mg/kg apoA-I or Tris-buffered saline, animals were observed for 5 days and survival rates were determined.Results. ApoA-I inhibited the release of serum TNF- and improved the survival rates of rats with endotoxemia.Conclusion. The administration of apoA-I suppressed the TNF- release in endotoxemia and decreased the mortality rates of rats.     

Antibodies directed at mouse IL-2-R α and β chains act in synergy to abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction in vivo

The anti-mouse IL-2-R chain mAb TM-1 which, by itself, does not affect IL-2-dependent proliferation throught the high affinity mouse IL-2 receptor, was shown to cooperate in a synergistic way with a set of anti-IL-2-R chain mAbs both in vitro and in vivo. In vitro, when associated at equimolar concentrations, the TM-1/anti- mAb association was four to ten times more efficient at inhibiting the proliferation of the CTL-L2 cell line than was a similar concentration of anti- mAb alone. In addition, a bispecific antibody in which a Fab' fragment of TM-1 was covalently linked to a Fab' fragment of one of the anti- mAb (5A2) was shown to be as efficient as the TM-1/5A2 association. The association of TM-1 with 5A2 was also tested in vivo in a sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-1 which, by itself, had no effect on DTH, induced a two- to threefold decrease in the doses of 5A2 required to suppress this cell-mediated immune reaction.     

Differentiation of pancreatic ductal carcinoma cells associated with selective expression of protein kinase C isoforms

Background: The signal transduction pathways important in regulating the growth and differentiation of malignant cells are poorly understood. Recent evidence has implicated activation of the protein kinase C (PKC) family of signaling proteins in pancreatic carcinoma during cytokine-induced cytostasis and differentiation. Methods: A human pancreatic adenocarcinoma (HPAC) cell line was exposed to tumor necrosis factor- (TNF-; 40 ng/ml) for 6 days. Cytostasis and viability were confirmed by daily MTT [(3(4,5)-dimethyl-thiazol-2-yl) 2,5-diphenyl-tetrazolium bromide] and trypan exclusion assay. Protein fractions were isolated daily and subjected to immunoblot analysis for the normal (terminally differentiated) pancreatic ductal cell marker carbonic anhydrase II (CA II) as well as specific PKC isoforms (, , , , and). Results: Growth arrest occurred in HPAC cells after exposure to TNF- for 48 h, with viability maintained above 90% throughout the 6-day time course. CA II immunoreactivity was not detected in untreated controls but appeared after 2 days of TNF- exposure, peaking on day 6. Concurrently, TNF- induced the selective downregulation of PKC-, whereas PKC- levels increased. PKC- and PKC- immunoreactivity did not change. The atypical PKC- isoform developed a doublet banding pattern in response to TNF-, although overall PKC- levels did not change. Conclusions: TNF--induced growth arrest and differentiation in HPAC cells is associated with the selective downregulation of PKC- and upregulation of PKC-.Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate,benign prostatic hyperplasia and prostatic cancer

Summary The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors 1 (TGF-1), TGF-2 and TGF-3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-1 increased, whereas that of TGF-3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-1, TGF-3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.     

Detection and differentiation of lactate and lipids by single-voxel proton MR spectroscopy

The signals of lactate and lipids partially overlap in single-voxel proton MR spectroscopy (¹HMRS), sometimes making them difficult to differentiate in clinical settings. Our aim in this study was to identify lactate and lipids by varying the echo time (TE). We expect that the accurate detection of lactate and lipids will have high diagnostic value in the diagnosis of brain tumors. Following our protocol, we obtained meaningful ¹HMRS spectra from 213 patients, including 163 patients with brain tumors, between August 1999 and February 2004. ¹HMRS was performed with a TE of 144 ms followed by a TE of 30 ms and/or a TE of 288 ms, if necessary. For the 213 patients, lactate level was negative in 47 patients, positive in 131 patients, and strongly positive in 35 patients. The lipid level was negative in 90 patients, positive in 56 patients, and strongly positive in 67 patients. Based on logistic discriminant analyses of neuro-epithelial tumor WHO grade and lactate and lipid levels, lactate and lipid levels were significant between WHO grades 2 and 3 (P=0.0239) and between grades 3 and 4 (P=0.0347). Lipids are a more significant factor for the discrimination between WHO grades 2 and 3 (P=0.0073) and between grades 3 and 4 (P=0.0048). With our method of varying the TE, it is possible accurately and efficiently to detect lactate and lipids in the brain. We found a significant correlation between lactate and lipid expression and WHO grade of neuro-epithelial tumors.These data were presented at the 22nd Annual Meeting of the Japan Society for Neuro-Oncology, 17–19 October 2004 in Miyagi, Japan.     

Treatment outcomes and mortality of 94 patients with acromegaly

Summary Background. Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003.Method. The cohort consisted of 94 patients who had been followed for 0.3–31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0µg/l and a random GH value of <2.5µg/l.Findings. Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1cm), 65% with meso-adenomas (1cm to <2cm) and 27% with macro-adenomas (2cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin^® LAR^®) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2cm. The standardized mortality ratio was 1.30 (95% CI 0.52–2.67) for patients in remission and 1.38 (95% CI 0.51–3.00) for patients with persistent acromegalic activity.Conclusions. Most patients with adenomas of <2cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2cm and more than 80% of patients with adenomas of 2cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.     

Suppression of parathyroid hormone secretion in CAPD patients by intraperitoneal administration of Maxacalcitol

Background Maxacalcitol (22-oxacalcitriol; OCT) is a novel vitamin D analogue. In previous clinical studies, OCT was administered three times a week to hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in whom it acted by inhibiting parathyroid hormone secretion, as well as causing mildly elevated serum calcium. However, intravenous injection of OCT, which requires frequent visits to the outpatient clinic, degrades the quality of life of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise visit the clinic only once or twice per month. In the present study, we investigated whether transperitoneal absorption of OCT inhibited intact parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the peritoneal dialysis fluid.Methods Peritoneal dialysis fluid containing 20µg of OCT was injected into the peritoneal cavity of five CAPD patients. The serum and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured before and after treatment.Results The mean concentration of OCT in peritoneal dialysis fluid rapidly decreased, from 25268.0pg/ml at 0h to 1694.0pg/ml at 2h and 44.9pg/ml at 4h. In contrast, the mean serum OCT level increased from the pretreatment level, which was below the detection limit of the assay, to 656.0pg/ml at 0.5h and a peak of 759.0pg/ml at 1h, and thereafter gradually decreased, to 713.8pg/ml at 2h and 555.8pg/ml at 4h. Mean i-PTH significantly decreased, to 83.9% of the baseline level, at 1h (P < 0.05) and thereafter stayed at around 90%. No consistent trends in calcium and phosphate levels were observed in the five patients.Conclusions By injecting OCT into the peritoneal cavity, i-PTH levels could be significantly decreased. These findings indicate the therapeutic efficacy of intraperitoneal administration of OCT for CAPD patients.     

Sustained effects of plasma norepinephrine levels on femoral-radial pressure gradient after cardiopulmonary bypass

In order to determine the influence of the sympathetic nervous system upon the femoral-radial artery pressure gradient after cardiopulmonary bypass (CPB), we examined plasma norepinephrine levels in 34 adult male patients undergoing coronary artery bypass grafting. Cardiovascular parameters, including systolic arterial pressure, mean arterial pressure, cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary artery pressure (PAP), hemoglobin (Hb) and peak dP/dt of radial and femoral artery pressures were measured after sternotomy, and immediately after the discontinuation of CPB and 90min after CPB. Plasma norepinephrine levels were measured after sternotomy, after aortic declamping and 90min after CPB.The patients were divided into two groups. Group A consisted of 17 patients whose femoral minus radial systolic pressure difference was 15mmHg or more at 90min after CPB, while Group B consisted of 17 patients with the difference less than 15mmHg. Group A patients had significantly longer time values in the duration of both CPB (Group A 175 ± 10min; Group B 115 ± 12min, P 0.001) and aortic cross clamping (Group A 116 ± 7min, Group B 71 ± 9min, P 0.001).Although there was no significant difference in Hb or PAP of 90min after CPB in Groups A and B, the following values, listed in the order of A to B, were obtained; CI, 2.79 ± 0.10 versus 3.46 ± 0.16l·min^–1·m^–2 (P 0.01); mean radial artery pressure (MRP), 58.7 ± 2.4 versus 65.1 ± 1.8mmHg (P 0.05); peak dP/dt of radial artery pressure, 568 ± 64 versus 1026 ± 61mmHg·sec^–1 (P 0.001); and plasma norepinephrine concentration, 1.81 ± 0.25 versus 0.98 ± 0.10ng·ml^–1 (P 0.01), which were statistically significant.The higher femoral-radial artery pressure gradient after CPB was observed in patients with both a longer CPB time and a higher plasma norepinephrine concentration. These results suggest that a marked constriction of peripheral arteries might have produced a damped transmission of the pressure pulse to the radial artery.(Nakayama R, Goto T, Kukita I, et al.: Sustained effects of plasma norepinephrine levels on femoral-radial pressure gradient after cardiopulmonary bypass. J Anesth 7: 8–15, 1993)     

A prospective randomised study of the effect of nicardipine on ischaemic renal injury in renal allografts

In a prospective doubleblind trial, 127 kidneys were randomised to receive Eurocollins (n=65) or Eurocollins plus nicardipine (n=62) as a second flush solution at the time of organ retrieval. Delayed graft function occurred in 18 of 65 control kidneys (28%) and in 20 of 62 nicardipine kidneys (32%; P=0.7, Fischer's exact test). The mean (SD) serum creatinine at 6 weeks was 197 (138) mol/l in the Eurocollins group and 195 (159) mol/l in the nicardipine group (P=0.95). Eighteen recipients (28%) in the controlled Eurocollins group experienced a rejection episode in the first 6 weeks post-transplant compared to 17 (27%) in the nicardipine group (² with Yates' correction=0.027; P0.95). In this study, the addition of nicardipine to the kidney perfusion fluid did not have a beneficial effect on kidney function following transplantation.     

Hemodynamic responses during induction of anesthesia with halothane-nitrous oxide in children with or without atropine premedication

Forty three children ranged from 1yr. to 6yr. were randomly assigned to non-atropinized group (n = 20; A(–)) and atropinized group (0.015mg·kg^–1 i.m., n = 23; A(+)). Control hemodynamics were measured under 0.5% halothane and 67% nitrous oxide and 33% oxygen for three minutes, and then halothane was increased to 2.5% and maintained for 15min. In the A(–) group, stroke volume (SV) decreased to 64%, heart rate (HR) increased from 100/min to 111/min, and blood pressure (BP) decreased from 65mmHg to 62mmHg. Skin blood flow (SBF) concomitantly measured by a laser doppler flowmeter decreased to 48% and total peripheral resistance (TPR) increased to 128%. In the A(+) group, HR increased from 117/min to 132/min (P 0.05, vs. A(–) group), BP decreased from 67mmHg to 66mmHg. SV decreased to 71% (P 0.05, vs. A(–) group). Changes in SBF and TPR were 68% and 128% respectively. End-expired halothane concentration in the A(+) group increased slower than in the A(–) group but not significantly. The results indicate increased sympathetic tone would work as a compensating mechanism for decreased SV and CO. Atropine premedication attenuated cardiovascular depression by maintaing HR and possibly by delaying induction speed of anesthesia. In conclusion, halotane-nitrous oxide anesthesia decreased SV without a marked decrease in heart rate and blood pressure in children. This decrease in SV and BP was attenuated by atropine premedication.(Kawana S, Namiki A, Morita Y, et al.: Hemodynamic responses during induction on anesthesia with halothane-nitrous oxide in children with or without atropine premedication. J Anesth 6: 63–68, 1992)     

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.     

173. Tierexperimentelle Ergebnisse mit einem voll implantierbaren Distraktionsgerät zur operativen Beinverlängerung

Zusammenfassung Zur operativen Beinverlängerung wurde ein neues Femur-Distraktionsgerät entwickelt. Das Gerät besteht aus einem elektronisch programmierbaren Distraktionsaggregat einschließlich Kraftquelle und einer zweiteiligen Führungsschiene. Das Gesamtsystem ist voll versenkbar und schafft Übungsstabilität während der Distraktionsphase. Die Funktionen Vorlauf — Stop —Rücklauf können transcutan induktiv gesteuert werden. Ein für das Tierexperiment speziell entwickelter Prototyp des Gerätes wurde an Schafen erfolgreich erprobt.     

Parathyreoidektomie und Autotransplantation beim renalen Hyperparathyreoidismus

Zusammenfassung Im Rahmen der totalen Parathyreoidektomie und Autotransplantation wegen therapieresistentem renalen Hyperparathyreoidismus wurden bei 35 Hämodialysepatienten (normocalciämisch:n =14; hypercalciämisch:n = 21) insgesamt 140 vergrößerte Epithelkörperchen entfernt und am Querschnitt intraoperativ klassifiziert. Ohne Hilfsmittel war nur die Unterscheidung von diffusen (Typ 1) und nodulär hyperplastischen (Typ 2) Drüsen möglich. Innerhalb der Typ 1-Drüsen konnten unter Verwendung einer Stereolupe (10-und 16fache Vergrößerung) in Typ 1a- (Fettzellen!) und Typ 1b-Drüsen (Fehlen von Fettzellen!) differenziert werden. Ähnlich aufgebaute Areale fanden sich auch zwischen den Knoten der inhomogen aufgebauten Typ 2-Drüsen. Nodulär hyperplastische Drüsen kamen signifikant häufiger bei hypercalciamischen Patienten vor ( ²-Test:p <0,001). Unterschiedliche Farbschattierungen am frischen Querschnitt der Typ 2-Drüsen erlaubten Rückschlüsse auf den cellulären Aufbau der durch Bindegewebssepten isolierten Knoten (dunkel: oxyphile Zellknoten; mittel: Hauptzellknoten; hell: Knoten aus überwiegend degenerierenden` oxyphilen Zellen). Vor allem in Typ 1b-Düsen und Typ 1bähnlichen Arealen sowie in den isolierten Knoten der Typ 2-Drüsen fand sich ein erhöhter Mitoseindex (> 1:10 000) als Zeichen einer erhöhten Proliferation. Diese Areale sollten von einer Autotransplantation ausgeschlossen werden.

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Parathyroidectomy and autotransplantation in renal hyperparathyroidism: I. Morphological studies for tissue selection

Summary During total parathyroidectomy and autotransplantation 140 enlarged glands were removed in 35 hemodialyzed patients (normocalcemic:n =14; hypercalcemic:n = 21). The crosssections of all glands were classified intraoperatively. Diffuse hyperplastic (type 1) and nodular hyperplastic (type 2) glands could be distinguished. Using a stereo-magnifier (magnification: × 10 – × 16), type 1a- (stromal fat cells!) and type lbglands (without stromal fat cells!) could be differentiated. Those areas were also found between the nodules of type 2-glands. Significantly, nodular hyperplastic glands predominated in hypercalcemic patients ( ²-Test:p < 0.001). The colour of the nodules on the cross-sections of type 2-glands correlated with the predominating cell type (dark: nodule of oxyphile cells; medium: nodule of chief cells; light: nodule of degenerating oxyphile cells). As sign of proliferation the mitotic index was elevated (>1:10000) in type 1b-glands, in type 1 b-like areas and in nodules of type 2-glands. These areas should not be used for autotransplantation.

     

Comparison of Precuffed and Vein-Cuffed Expanded Polytetrafluoroethylene Grafts for Infragenicular Arterial Reconstructions:A Case-Matched Study

Distal vein cuff interposition is often added to prosthetic infragenicular arterial reconstruction in an attempt to improve hemodynamics and patency rates. The purpose of this study was to compare the outcome of a precuffed expanded polytetrafluroethylene (ePTFE) graft with a vein-cuffed ePTFE graft for infragenicular bypass. We reviewed the clinical outcome of 77 patients with critical limb ischemia without available autologous vein conduits who underwent arterial reconstruction of 80 limbs to below-knee popliteal or tibioperoneal vessels using either ePTFE precuffed graft (precuffed group, 38 patients 40 limbs) or ePTFE vein-cuffed graft (vein-cuffed group, 39 patient, 40 limbs). Precuffed group patients were enrolled in a prospective cohort study. Vein-cuffed group patients consisted of consecutive case-matched patients operated on during the same study period. End points were primary graft patency and limb salvage rates. There were 42 males and 35 females with a mean age of 73.4 years (range, 44-92 years). Both groups were matched to demographics, risk factors for atherosclerosis, previous ipsilateral reconstruction, and location of the distal anastomosis. Proximal anastomosis was to the common (n=68) or superficial (n=12) femoral arteries. Distal anastomosis was to the below-knee popliteal (n=28), anterior tibial (n=12), posterior tibial (n=15) and peroneal (n=25) arteries. Operative mortality was 1.3%. Graft patency at dismissal was 90% and 95% in the precuffed and vein-cuffed groups, respectively. The mean follow-up was 25.7 months (range, 2.4-61 months). Primary patency rates at 1 and 3 years were 70% and 57% in the precuffed group, and 78% and 54% in the vein-cuffed group (p=0.32). Limb salvage rates at 1 and 3 years were 97% and 70% in the precuffed group, and 95% and 81 % in the vein-cuffed group (p=0.49). Overall patient survival at 1 and 3 years was 81 % and 57%, respectively. In this case-control study, results of precuffed ePTFE graft were similar to those obtained with vein-cuffed ePTFE grafts. The precuffed ePTFE graft is an adequate alternative conduit for infragenicular arterial reconstruction in patients with critical limb ischemia and no available autologous veins.Presented at the 32^nd Annual Symposium on Vascular Surgery, Society for Clinical Vascular Surgery, Rancho Mirage, CA, March 10–13, 2004.     

The Contribution of Familial Resemblance to Variation in Circulatory Levels of Tissue Inhibitors of Metalloproteinases and Transforming Growth Factor-?1

This study attempted to elucidate the genetic and environmental factors influencing interindividual variation of circulating TIMP-1, TIMP-2 and TGF-1 and to clarify the relationship between the latter biochemical indices and hand osteoarthritis in an ethnically homogeneous sample. Plasma levels of each of the above biochemical indices were measured in 401 healthy individuals (aged 18–75 years) belonging to 90 nuclear and more complex families. Variance component analysis showed that a major part of the interindividual differences in TGF-1, TIMP-1 and TIMP-2 levels was credibly attributable to genetic and familial factors. Adjusted for significant covariates, the putative genetic effects on the above three amounted to 0.40 ± 0.10, 0.47 ± 0.11 and 0.72 ± 0.10, respectively. Common environmental factors, shared by members of the same household, also contributed significantly (P < 0.01) to variation of each of the biochemical indices and explained between 27.6% (TIMP-2) and 38.7% (TGF-1) of their variation. A bivariate analysis revealed a strong and highly significant correlation between TIMP-1 and TGF-1 (r = 0.58, P < 0.001), which was due to common genetic and environmental sources (r_G = 0.62 ± 0.09, r_E = 0.31 ± 0.11, both P < 0.001). The analysis also detected modest but significant genetic correlation between TIMP-1 and TIMP-2 (r_G = –0.307 ± 0.108, P < 0.01). The present study evinces a strong genetic dependence for the plasma levels of both TIMPs and TGF-1 and provides a basis for the further analysis of genetic variation affecting and regulating the circulatory concentrations of TIMPs and TGF-1 in healthy humans.     

55. Organisationsfragen in der Intensivmedizin

Zusammenfassung Der Begriff Intensivmedizin gliedert sich in die Intensivüberwachung und die Intensivbehandlung. In der klinischen Praxis gehen zwar beide Bereiche oft ineinander über, trotzdem sind sie wegen der unterschiedlichen Anforderungen begrifflich klar voneinander zu trennen. Der Gesamtbettenbedarf für die Intensivmedizin beträgt in der allgemeinen Chirurgie 7–10%, für die Intensivbehandlung im engeren Sinne 3–5%. Die Besetzung mit Pflegepersonal richtet sich in der Intensivüberwachung nach einem Personal: Bettenschlüssel von 1:1, in der Intensivbehandlung von 2:1. Für die Intensivüberwachung wird 1 Arzt auf 3 Betten, für die -behandlung neben dem ärztlichen Leiter der Betteneinheit 1 Arzt auf 2 Betten benötigt. Aus organisatorischen Gründen besitzen die Intensiveinheiten der meisten Krankenhäuser interdisziplinären Charakter. Das bedingt neue Formen ärztlicher Zusammenarbeit; aus dem konsiliarisch zugezogenen Arzt wird der mitbehandelnde Arzt, der für seinen Teil der Therapie die volle Verantwortung übernimmt. Trotzdem muß die ärztlich-organisatorische Leitung der Betten-einheit in einer Hand liegen. Die Befugnisse dieses ärztlichen Leiters berühren aber nicht die Fachkompetenzen der anderen beteiligten Ärzte.

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Organizational problems of intensive care

Summary The term Intensive Care includes both Intensive Observation and Intensive Therapy.In clinical practice, however, those two terms are not distinctly defined although they must be clearly separated because of their different characteristics.The number of beds required for Intensive Care amounts to 7 to 10% for general surgery, whereas 3 to 5% are needed for Intensive Therapy. The ratio of nurses to beds is 1 to 1 for Intensive Observation and 2 to 1 for Intensive Therapy. For Intensive Observation one doctor is needed for 3 beds while for Intensive Therapy one doctor is needed for 2 beds each in addition to a head physician in charge of the Intensive Care ward. For organizational reasons the Intensive Care wards of most hospitals are inter-departmental. This calls for new forms of cooperation among doctors; the consulting doctor is also a doctor in charge who shall be fully responsible for his part in the therapy. Nevertheless, the medical and organizational administration of the Intensive Care ward must be in the hands of one person whose competences, however, do not coincide with the expert competences of the other doctorsin charge.

     

Increased urinary albumin indicating urothelial leakage following intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer

Summary This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL) 1, IL2, IL6, and tumor necrosis factor alpha (TNF) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24h thereafter. The mean concentration of albumin in pre-therapy specimens was 112±118 (range 2–432) g albumin/ml urine, approximating 14±14 g/ mol creatinine (creat) (n=15), which was comparable to the mean pre-instillation value of 16±32 g/mol creat (n=96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P<0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3–6. A significant correlation between albumin and concentration of the cytokines IL1, IL2, IL6, and TNF was found (P<0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n=418), respectively. During the first 24h after instillation cytokines and albumin peaked in the following order: TNFIL2albuminIL6IL1. TNF peaked most frequently after 2–4h and IL1 after 6h, while IL2, albumin, and IL6 peaked between these time points. In conclusion, the presence of albumin in urine indicates a leakiness of the bladder wall after repeated BCG instillations. Since albumin was shown to be stable in urine and the assay is relatively simple and cheap, it may be performed in most hospitals. This will allow largescale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy.     

Potentiation of transforming growth factor (TGF-β1) by natural coral and fibrin in a rabbit cranioplasty model

The association of a biodegradable material and a growth factor could be of clinical value for treating bone defects. We therefore tested the association of transforming growth factor (TGF-1) in fibrin glue and coral granules to heal skull defects in rabbits. Adult rabbits underwent a double trepanation symmetrically in both parietal bones. Using histomorphometry, we compared bone repair after 1 month in control animals (n=5) and in animals treated with either TGF-1 as a single injection of 1 g in methylcellulose (n=5) or in fibrin glue (n=5), or with coral granules in fibrin glue (n=4) or with coral granules and TGF-1 1 g in fibrin glue (n=5). We measured the diameter of the remaining defect and the surface of the bone growth. TGF-1 without coral in either methyl cellulose or fibrin induced a partial closure of the defect as assessed by a significant decrease in the defect diameter, compared with the control group. However, the association of TGF-1 in fibrin and coral induced an area of the bone growth higher than in any other groups (P<0.05). Two months after surgery, this triple association induced a better healing of the defect than coral alone or control group. In each group treated with TGF-1, the mineralization rate was increased not only at the treated side but also in the contralateral defect which was untreated, suggesting a diffusion of the growth factor. Indeed, when pooled together, the diameter of the defect at the contralateral side of 14 animals that had received TGF-1 was reduced compared with the control group. Significant coral granules resorption occurred between month 1 and 2 and was unchanged by the addition of TGF-1. In conclusion, the triple association of coral granules and TGF-1 in fibrin could be of interest for treating bone defects.     

Seasonal changes of serum 25-hydroxyvitamin D and intact parathyroid hormone levels in a normal Japanese population

We conducted an observational study in order to assess the prevalence of hypovitaminosis D and its seasonal changes, in the Tokai area (N35.3 E137.0), in 197 normal subjects in Japan. The mean serum 25-hydroxyvitamin D (25-OHD) level measured by direct radioimmunoassay (RIA) was lowest at the end of winter, and highest at the end of summer (15.1 ± 7.1ng/ml in March; 21.5 ± 5.5ng/ml in June; 31.6 ± 5.6ng/ml in September; 23.1 ± 5.3ng/ml in December; mean ± SD). The prevalence of hypovitaminosis D (<20ng/ml) was 86.7%, 33.4%, 1.0%, and 26.0% in March, June, September, and December, respectively. Mean plasma intact parathyroid hormone (iPTH) concentration was lowest at the end of summer and highest at the end of winter (28.2 ± 9.3pg/ml in March; 21.7 ± 7.0pg/ml in June; 19.8 ± 6.9pg/ml in September; and 25.7 ± 9.2pg/ml in December; mean ± SD). Serum 25-OHD was inversely associated with iPTH (coefficient, –0.223; r = 0.251; P < 0.001). Serum 25-OHD levels were higher in men than in women. The serum 25-OHD level was positively associated with age, body weight, and body mass index, but not with body fat content. These results suggest a high prevalence of hypovitaminosis D associated with elevation of iPTH in Japan, in winter, even in a sunny area.