Taxol inhibits osteoclastic bone resorption

Summary We have examined the effect of the anti-tumor compound taxol, on osteoclastic bone resorption. In the bone slice assay, taxol (0.1–0.001 M) dose-dependently inhibited bone resorption with an IC₅₀ of 0.08 M. Osteoclast survival on bone slices was unaffected by 0.01–1 M taxol, but 10 M was cytotoxic. Taxol (1 M) also ihibited osteoclast spreading (45%) on fibronectin-coated slides. The antiproliterative effects of taxol are due to its unique ability to stabilize microtubules. Primary osteoclasts are nonproliferating end cells, so taxol probably inhibits bone resorption by intertering with other microtubule-dependent functions such as cell polarization, motility or vesicle exocytosis. Since these inhibitory effects on osteoclasts in vitro are seen with therapeutically relevant concentrations, taxol therapy may have beneficial side-effects e.g. inhibition of hyperealcemia and bone metastases.     

A quantitative study of the structure of trabecular bone in man,rhesus monkey,beagle and miniature pig

Summary This paper reports a quantitative comparison of trabecular bone structures in 4 mammalian species in terms of both measured path-length distributions across the trabeculae and marrow cavities as well as structural parameters derived from the pathlength data, that is, mean path lengths, percentage bone volume and the ratio of endosteal surface to bone volume. The path-length measurements have been made by scanning radiographs of thin sections of bone using an object-plane scanning microscope. Results are given for sets of up to 9 bones of a 9-year-old child, a 44-year-old man, a beagle, a rhesus monkey and a miniature pig. Mean cavity path lengths range typically from 1200 m in the adult man to 350 m in the miniature pig; mean trabecular path lengths range typically from 190 m in the child to 280 m in the miniature pig. Percentage bone volumes are lowest in adult man (16%) and highest in the miniature pig (45%) and the ratios for surface to volume show an opposite trend. Tentative estimates of skeletal values of surface-to-volume ratio are given, namely around 190 cm²/cm³ for all species studied except the miniature pig (130 cm²/cm³). Finally, an appendix illustrates the considerable effects of structural differences on radiation dosimetry.     

Scanning electron microscopy-electron probe microanalysis study of the interface between apatite and wollastonite-containing glass-ceramic and rabbit tibia under load-bearing conditions after long-term implantation

Glass-ceramic implants containing oxy- and fluoroapatite [Ca₁₀(PO₄)₆(O, F₂)] and -wollastonite (CaSiO₃) were studied under load-bearing conditions in a segmental replacement model in the tibia of the rabbit. A 16-mm segment of the middle of the tibial shaft was resected at a point distal to the junction of the tibia and the fibula. The defect was replaced by a 15 mm-long hollow, cylindrical implant that was fixed by intramedullary nailing using Kirschner wire. The implants were 9 mm in diameter and 15 mm long bearing a central hole 3.05 mm in diameter. The rabbits used were killed 6 months, 1 year, 18 months, and 2 years after implantation. The interface between the bone and the glass-ceramic was investigated by scanning electron microscopy-electron-probe microanalysis (SEM-EPMA).None of the glass-ceramic implants broke, and the glass-ceramic had bonded directly to the bone tissue without any intervening soft tissue. A calcium-phosphorus layer (Ca-P layer) was observed at the glass-ceramic/bone interface. This layer was 30–100 m thick at 6 months after implantation, 60–110 m thick at 1 year after implantation, 80–200 m thick at 18 months, and 120–350 m thick at 2 years. At the lateral surface of the glass-ceramic uncovered by the bone, the calcium-phosphorus layer was 50–80 m thick at 6 months after implantation, 250–450 m thick at 1 year, 300 400 m thick at 18 months, and 300 m thick at 2 years. The thickness of the calcium-phosphorus layer increased moderately after long-term implantation. However, it was difficult to estimate the rate of increase in the thickness of calciumphosphorus layer.     

Local application of basic fibroblast growth factor into the bone increases bone mass at the applied site in rabbits

The effect of basic fibroblast growth factor (bFGF) applied locally into the bone under physiological conditions was investigated. An aqueous solution containing Og (vehicle), 100 g or 400 g recombinant human bFGF was percutaneously applied through a needle into the right ilium in rabbit, and the ilia were harvested 4 weeks after the application. Compared with vehicle-treated animals, bone mineral density measured by dual-energy X-ray increased in the 400 g bFGF group. The width of trabeculae in the bFGF-treated groups was greater than in the vehicle group. These results showed that bFGF applied locally into the bone under physiological conditions affected bone formation, and suggested that such an application might have potential for increasing bone.     

Effect of second messenger systems on oxalate uptake in renal epithelial cells

The oxalate transport system along with protein phosphorylation appears to be deranged in stone formers. This study was undertaken to characterize in LLC-PK₁ cells in culture the effect of altering specific intracellular second messenger systems on oxalate uptake. Cellular uptake experiments were performed at 37°C in buffer [265 mM mannitol, 5 mM NaOH, 5 mM KOH, 10 mM Ca-EGTA, 25 mM HEPES/TRIS, pH=7.4 or in Hank's balanced salt solution (HBSS)] containing 200 M labeled oxalate (1-¹⁴C, 0.3 Ci). Cells were preincubated with DAG (final concentration of 100 M), phorbol myristate acetate (10 M), forskolin (50 M), 8-bromo-cyclic AMP (50 M), trifluoroperazine (20 M) and low molecular weight heparin (1 mg/ml) for 10 min in the presence and absence of the anion transport inhibitor DIDS (100 M) and the effect(s) on oxalate uptake at 10, 25 and 45 min incubation were determined. Chemicals (DAG, forskolin, TPA and 8-bromo-cAMP) which stimulate protein kinase A or C activity resulted in an increased uptake of oxalate while inhibitors of these systems (trifluoroperazine and low molecular weight heparin) resulted in decreased oxalate uptake. The results dernonstrate that oxalate uptake in renal tubular cells is modulated by protein kinase C and A dependent mechanisms.     

Penetration of cefazolin,ceftriaxone, cefoperazone,and ceftazidime into human gallbladder tissue and bile

Forty patients underwent elective cholecystectomy following administration of a single intravenous dose of cefazolin, ceftriaxone, cefoperazone, or ceftazidime. Mean gallbladder bile concentrations of cefoperazone (398.8 g/ml and ceftriaxone (153.4 g/ml) were significantly higher than those of cefazolin (12.3 g/ml) and ceftazidime (3.08 g/ml) (p<0.008). Mean gallbladder tissue levels of cefazolin (30.1 g/g), ceftriaxone (50.5 g/g), and cefoperazone (91.0 g/g) exceeded that of ceftazidime (7.25 g/g) (p<0.001). When adjusted for known in vitro activity against biliary pathogens, these data suggest that cefoperazone and ceftriaxone are superior to ceftazidime and cefazolin for prophylaxis in elective biliary surgery.

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Resumen Las nuevas cefalosporinas de tercera generación poseen actividad contra una variedad de bacterias, incluso la mayoría de los patógenos biliares comunes. Hemos realizado un estudio prospectivo sobre el grado de penetración de la cefazolina, la ceftriaxona, la cefoperazona, y la ceftazidima en el tejido y la bilis de la vesícula biliar en pacientes sometidos a colecistectomía electiva.Cuarenta pacientes recibieron una dosis única de la cefalosporina dentro de la hora anterior a la colecistectomía. Las concentraciones medias en la bilis de la vesícula biliar fueron significativamente mayores para la cefoperazona (398.8g/ml) y la ceftriaxona (153.4g/ml) que para la cefazolina (12.3g/ml) y la ceftazidima (3.08g/ml) (p<0.008). Los niveles medios en el tejido de la vesícula biliar fueron superiores para la cefalozina (30.1g/g), la ceftriaxona (50.5g/g), y la cefoperazona (91.0g/g que para la ceftazidima (7.25g/g) (p<0.001). Al ajustar estos datos contra valores conocidos de actividad in vitro contra patógenos biliares, aparece que la cefoperazona y la ceftriaxona son superiores a la ceftazidima y la cefazolina en cuanto a profilaxis en cirugía biliar electiva.

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Résumé Quarante patients ont été cholécystectomisés après administration intraveineuse d'une dose unique de céfazoline, de ceftriaxone, de céfapérazone ou de ceftazidine. La concentration moyenne de la bile vésiculaire en céfopérazone (398.8g/ml) et en ceftriaxone (153.4g/ml) était significativement plus élevée que la concentration en céfazoline (12.3g/ml) et en ceftazidine (3.08g/ml) (p<0.008). Les concentrations tissulaires vésiculaires moyennes de céfazoline (30.1g/g), de ceftriaxone (50.5g/g), et de céfopérazone (91.0g/g) étaient plus importantes que la concentration de ceftazidine (7.25g/g) (p<0.001). Lorsque ces antibiotiques sont sensibles in vitro contre des germes pathogènes, nos résultats suggèrent que le céfopérazone et la ceftriaxone sont meilleurs que la ceftazidine et la céfazoline dans la prophylaxie antibiotique de la chirurgie biliaire élective.

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Presented at the Société Internationale de Chirurgie in Sydney, Australia, September, 1987.     

Responses of fetal rat bone cells and bone organ cultures to the ionophore,A23187

The ionophore A23187 produced a rapid transient increase in the rate of calcium uptake by isolated fetal rat bone cells. There was no effect on calcium efflux or total cellular calcium. The magnitude of the effect on influx was amplified when the cell were incubated at 4°C. Cellular metabolic functions and resorption of cultured fetal rat bones (release of⁴⁵Ca from pre-labeled long bone) were affected by A23187 in a biphasic manner: cell cyclic AMP (cAMP) was increased by 0.1 and 0.3 g/ml of the ionophore, whereas 10 g/ml was either ineffective or lowered the cAMP levels. The high A23187 concentration abolished the stimulatory effects of parathyroid hormone and methylisobutylxanthine. Concentrations of 0.1 and 0.3 g/ml A23187 stimulated bone resorption. The effect was abolished by calcitonin. Ionophore concentrations above 1 g/ml produced less bone resorption. These higher concentrations antagonized the bone-resorbing effect of parathyroid hormone and 1,25-dihydroxyvitamin D₃. A23187 at 5 and 10 g/ml decreased bone cell lactate and ATP. Thus at low concentrations, A23187 produced effects on bone similar to those of parathyroid hormone, suggesting that calcium is the primary initiator of PTH-induced bone resorption. At the higher concentrations A23187 may have a general inhibitory effect on cell metabolism.     

Demonstration of calmodulin-sensitive calcium translocation by isolated osteoclast plasma membrane vesicles

Summary Plasma membrane vesicles were prepared from chicken osteoclasts, and active calcium transport was demonstrated in a spectrofluorimetric assay using the fluorescent calcium concentration indicator, fura-2. Transport activity was inhibited by quercetin (10 M), sodium vanadate (10 M), and the anticalmodulin agents, compound 48/80 (20 and 200 g/ml) and calmidazolium (10 and 20 M). The transport rate (V_max, 1.3 nmol/mg protein/min) was not altered in the presence of the protonophore, nigericin (1 M), indicating that proton transport was not driving calcium transport. Release of accumulated calcium in the vesicles occurred with the addition of bromo-A23187 (5 M) or ionomycin (5 M). Increasing calcium transport occurred with increasing calcium concentration. Finally, the calmodulin content of the vesicles was demonstrated to be 54–134 U/mg protein. These results demonstrate that a calmodulin-sensitive, ATP-dependent calcium transporter is present in the osteoclast plasma membrane.     

Tetracycline double-labeling of iliac trabecular bone in 41 normal adults

Summary A histomorphometric evaluation of the iliac crest trabecular bone remodeling was performed after tetracycline double-labeling in 41 normal Danes (12 males and 29 females) aged 19 to 56 years. The fraction of formative (osteoid covered) and resorptive surfaces was unrelated to age but higher in males than in females (P<0.02 andP<0.05, respectively). The appositional rate (0.65±0.12 m/day) was unrelated to age and sex, whereas the fractional labeled surfaces were higher (P<0.01) in the males (0.18±0.08 m²/m²) than in the females (0.12±0.05 m²/m²), and among the females inversely related to age (R=–0.38,P<0.05). The bone formation rate at BMU level (0.50±0.20 m³/m²/day) was unrelated to sex, but among the females inversely related to age R=–0.49,P<0.01). The bone formation rate at tissue level was higher (P<0.02) in the males (0.13±0.07 m³/m²/day) than in the females (0.07±0.03 m³/m²/day) and among the females inversely correlated to age (R=–0.43,P<0.05). The age- and sex-dependent variations in the dynamic parameters underline the importance of a more elaborated normal material.     

Pattern of elevation of urine catecholamines in intracerebral haemorrhage

Summary Autonomic nervous system dysfunction is a common complication of severe intracranial disease. The aim of this study was to reveal the autonomic changes in patients suffering from acute intracerebral haemorrhage (ICH). 25 patients with spontaneous ICH within 24 hours of onset of symptoms were included. All patients were treated with standardised medical management and the meta- and normetanephrines were detected by high performance liquid chromatography (HPLC) in 24-hour urine every day.The mean level of normetanephrine (709±579 g/day) and metanephrine (244±161 mg/day) were significantly elevated in comparison with a control group, p0,01. The norepinephrine elevation was of greater diagnostic and prognostic importance. Maximum urinary catecholamine metabolite levels occurred between day 3 to 10 after the bleeding.Normetanephrines correlated with the prognosis and the complications of ICH: intraventricular involvement resulted in significantly elevated normetanephrine levels (896±520 g/day versus 311±78 g/day) p0,01. Patients with a great volume of haematoma developed severe autonomic dysregulation (normetanephrines 1114±493 g/day), whereas patients with smaller haematoma did not (339±125 g/day) p0,0001; patients with bad outcome (1014±620 mg/day) had higher levels of normetanephrines than those with a good prognosis (322±110 g/day) p0,001. A close relationship to elevated intracranial pressure was established.This study demonstrated the feasibility of detecting autonomic nervous system dysfunction in neurological intensive care patients by means of examination of the metabolites of the catecholamines in the urine. The pattern of elevation in ICH and the relation to the clinical situation is presented. Norepinephrine offers the chance of simple and feasible monitoring of autonomic dysfunction.     

27. Nachkontrolle und Rezidivprophylaxe nach Strumaresektion

Zusammenfassung Da die Strumaresektion nur eine symptomatische Maßnahme ist, kommt es bei etwa 15 %. zu einem Rezidiv. Der erhöhte TSH-Spiegel (Jod- oder Hormonmangel) muß daher lebenslang durch Substitution gesenkt werden: a) euthyreote Strumen: beginnend pop. 2 × wöchentl. 100 g T4 oder 100 g T4 mit 20 g T3. b) hyperthyreote Strumen: nach 2 – 3 Monaten Vorgehen wie a). c) Nach Op. tox. Adenome beginnend 14 Tage pop. wie a). Im eigenen Krankengut beträgt durch die systematische Rezidivprophylaxe die Rezidivquote 1,7 %. Die Organisation der Rezidivprophylaxe mit sogenannten Strumakarten wird demonstriert.     

Serum levels of bone GLA protein (osteocalcin,BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegly: Effects of long-term octreotide treatment

Summary We measured serum concentrations of bone Glaprotein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150–450 g/day for 6–33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2±4.2 g/liter versus 8.0±3.3 g/liter, P<0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r=0.67, P<0.001). Also IGF-I concentrations were positively correlated with BGP (r=0.66, P<0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146±46 g/liter versus 127±44 g/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.     

Secretory territories and rate of matrix production of osteoblasts

The secretory territories of rat osteoblasts on the parietal bone were measured directly using scanning electron microscopy. The mean territory of 4620 cells in 19 fields was 154 m² per osteoblast. The range for the fields was 136 to 177 m² per osteoblast. Four hundred cells were measured individually—for these the mean value per osteoblast was 143 m² with a standard deviation of 33. The daily rate of apposition over an 8 day period was 3.12 m (standard deviation 0.22) measured by tetracycline marking of the mineral front. This gave a daily matrix production rate of approximately 470 m³ per osteoblast.

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Zusammenfassung Die Ausscheidungsbereiche von Ratten-Osteoblasten des Scheitelbeines wurden mit dem Raster-Elektronenmikroskop direkt gemessen. Der durchschnittliche Bereich von 4620 Zellen in 19 Gesichtsfeldern war 154 m² per osteoblast. Der Streubereich lag in den verschiedenen Gesichtsfeldern zwischen 136 und 177 m² per Osteoblast. 400 Zellen wurden einzeln gemessen. Bei diesen war der Durchschnittswert per Osteoblast 143 m², mit einer Standard-Abweichung von 33. Die tägliche Anlagerungsrate während einer Periode von 8 Tagen war 3,12 m (Standard-Abweichung 0,22); sie wurde mittels Tetracyclinmarkierung der Mineralisierungsfront gemessen. Dies ergab eine tägliche Produktionsrate der Matrix von etwa 470 m³ per Osteoblast.

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Résumé Les territoires sécrétoires des ostéoblastes d'os pariétal de rats sont déterminées en utilisant la microscopie électronique à balayage. Le territoire moyen de 4.620 cellules, dans 19 territoires, est de 154 m² par ostéoblaste. Les valeurs extrêmes par champ varient de 136 à 177 m² par ostéoblaste. Quatre cent cellules sont mesurées individuellement; la valeur moyenne par ostéoblaste est de 143 m³ avec une déviation standard de 33. Le taux d'apposition journalier, mesuré par la tétracycline pendant 8 jours, est de 3.12 m (déviation standard 0.22). Ce qui correspond à une production matricielle journalière d'environ 470 m³ par ostéoblaste.

     

Comparison of Microcomputed Tomographic and Microradiographic Measurements of Cortical Bone Porosity

Cortical bone is perforated by a network of canals that have a significant impact upon its material properties. Microcomputed tomography offers the possibility of noninvasively visualizing and quantifying cortical pores in both two and three dimensions. Establishing how two-dimensional (2D) microcomputed tomographic (CT) analysis compares with conventional methods for analyzing cortical porosity is an important prerequisite for the wider adoption of this technique and the development of three-dimensional (3D) analysis. Therefore, we compared porosity-related parameters from 2D microcomputed tomographic images with those from matching microradiographic sections. Samples from five human femora were scanned at a 10-m resolution and then sequentially sectioned and microradiographed. An average of eight image pairs were produced from each femur (total, n = 41). The repeatability and comparability of the two techniques was assessed for three parameters; cortical porosity (%), mean pore area (m²), and pore density (pores/mm²). For repeatability, no significant difference (P > 0.05) was found between the two methods for cortical porosity and mean pore area; however, pore density differed significantly (P < 0.001). For comparability, the bias (± error) between the methods was found to be 0.51% (±0.31%) for cortical porosity and –155 m² (±293 m²) for mean pore area. The bias for pore density was dependent upon measurement size with microcomputed tomographic images having 14% (±9.3%) fewer pores per millimeter squared. The qualitative and quantitative similarities between the two techniques demonstrated the utility of 2D microcomputed tomographic for cortical porosity analysis. However, the relatively poor results for pore density revealed that a higher resolution (<10 m) is needed to consistently visualize all cortical pores in human bone.     

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.     

Pharmacokinetics of methylmethacrylate monomer during total hip replacement in man

Summary The concentration of methylmethacrylate monomer (MMA) in the blood stream after implantation of the components of 15 total hip prostheses using bone cement was determined in the pulmonary artery, the radial artery, and the superior vena cava after cement application, and correlated with the observed drop in blood pressure and the increase in the pulmonary arterial pressure. In all samples MMA was found. The values ranged from 0.02 g/ml to 59 gg/ml. The mean maximum value after implantation of the stem was measured to be 7.8g/ml in the pulmonary artery, 4.6 g/ml in the radial artery, and 1.75 g/ml in the superior vena cava. After implantation of the cup the values were clearly lower. The simultaneously recorded blood pressure decreased slightly during the first 3 min and then returned to previous values. The pulmonary arterial mean pressure increased from 18 to 20mmHg during the first 10 min. Although in some patients a drop in blood pressure started at the same time as MMA reached maximum values, high concentrations did not result in a greater effect on the circulatory parameters. Statistical analysis by the Spearman test revealed no correlation between MMA concentrations and the decrease in blood pressure or the increase in the pulmonary arterial pressure.

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Zusammenfassung Während der Implantation von fünfzehn Totalendoprothesen mit Knochenzement wurden die Konzentrationen von Methylmethacrylatmonomer (MMA) in der Arteria pulmonalis, der Arteria radialis and der Vena cava superior bestimmt und mit dem beobachteten Blutdruckabfall and dem Anstieg des pulmonalarteriellen Druckes korreliert. In den Proben konnten MMA-Konzentrationen zwischen 0,02 g/ml and 59 g/ml nachgewiesen werden. Die mittlere Maximalkonzentration betrug nach Implantation des Schaftes 7,8 g/ml in der Pulmonal-, 4,6 g/ml in der Radialarterie und 1,75 g/ml in der Vena cava superior. Die Konzentrationen nach Implantation der Pfanne waren deutlich geringer. Der gleichzeitig aufgezeichnete Blutdruck fiel geringgradig während der ersten drei Minuten and kehrte dann auf Ausgangswerte zuriick. Der pulmonalarterielle Mitteldruck stieg von 18 auf 20 mm Hg während der ersten zehn Minuten. Obwohl bei einigen Patienten der Blutdruckabfall mit dem Auftreten maximaler MMA-Konzentrationen zusammenfiel, hatten höhere MMA-Konzentrationen keinen größeren Effekt auf die zirkulatorischen Parameter. Bei der statistischen Analyse mit dem Spearman Test bestand keine statistische Korrelation zwischen den MMA-Konzentrationen und dem Abfall des Blutdruckes bzw. dem Anstieg des pulmonalarteriellen Druckes.

     

Influence of intravesical administration of tumor necrosis factor α and systemic γ-interferon on murine bladder cancer: Lack of dose response

Summary The effect of intravesical administration of high dose recombinant tumor necrosis factor- (rTNF) and in combination with systemic recombinant -interferon (rIFN) on murine bladder cancer was studied. RTNF was given at 12.5 g/mouse on days 7, 11 and 15 after tumor instillation or at 2.5 g/mouse on days 7, 9, 11, 13 and 15. Some groups were also injected i.v., 24-h prior to each rTNF treatment with rIFN at a dose of 1.3 g/mouse. RTNF treatment suppressed tumor growth up to 48% of control, although the difference was not statistically significant. Combined administration of rIFN did not provide additional benefit.     

Technical Considerations for Microstructural Analysis of Human Trabecular Bone from Specimens Excised from Various Skeletal Sites

The purpose of this study was to test the effect of repositioning, systematic displacements of the region of interest (ROI), and acquisition parameters (scan mode and integration time) on quantitative analysis of human trabecular bone microstructure at various skeletal sites, using microcomputed tomographic (CT) technology. We investigated 28 cylindrical specimens of human trabecular bone (length 14 mm, diameter 8 mm) from four skeletal sites (femoral neck, greater trochanter, second lumbar vertebra, and distal radius). These specimens were selected from over 200 CT measurements, in order to cover a large range of bone volume fraction (BV/TV) observed at each site. Cylindrical ROIs (length 6 mm, diameter 6 mm) were examined twice at an isotropic resolution of 26 m, 8 weeks apart. In addition, comparative analyses were performed for displacements of the volumes of interest (VOIs) by 1, 2, 3, and 4 mm (83.4%, 66.6%, 50%, and 33.3% overlap), respectively. Eventually, comparative measurements were obtained at different resolution scan modes and integration times. The results show that CT measurements are highly reproducible (range of the root mean square coefficient variation % (RMS CV%) = 0.64% to 1.29% for BV/TV at different sites). Displacements of the VOI of up to 4 mm generally led to non significant systematic differences in mean values of <10%. When comparing various combinations of resolution scan modes and integration times, the use of an integration time of 100 ms was found to be preferable for determining microstructural parameters from human samples with this CT scanner.     

Effects of cyclosporin A on rat osteoblasts (ROS 17/2.8 cells) in vitro

Summary The effects of the immunosuppressive drug cyclosporin A (CsA) were evaluated on ROS 17/2.8 cells in vitro. ROS cells were treated with CsA (0, 0.5, 1.0, 5.0 g/ml) for 3 days with and without bovine parathyroid hormone (bPTH) (1–34) 10 nM. CsA at 0.5, 1.0, 5.0 g/ml without PTH and at 5.0 g/ml in the presence of PTH significantly inhibited proliferation, as determined by a tetrazolium colorimetric assay. In addition, ROS cell number was significantly reduced at 3 and 4 days with CsA (5.0 g/ml) without affecting cell viability. Incorporation of [³H]-thymidine into DNA was significantly reduced by 3.0 and 5.0 g/ml CsA after 12 and 24 hours exposure. Basal and 1,25-dihydroxyvitamin D₃-stimulated alkaline phosphatase levels in confluent ROS cells were reduced (P<0.05) with CsA (1.0 and 3.0 g/ml). Pretreatment of ROS 17/2.8 cells with CsA did not alter PTH-stimulated cAMP levels or [¹²⁵I]-PTHrP binding to ROS cells. CsA treatment of ROS 17/2.8 cells induced a spindle-shaped appearance with loss of attachment in confluent cultures. When ROS cells were cultured in CsA-containing media, cellular attachment at 6 and 12 hours was reduced (P<0.05) compared with untreated ROS cells. These findings indicate that CsA was capable of inhibiting proliferation, cell number, mitogenesis, alkaline phosphatase levels, and cell attachment of ROS cells without affecting PTH binding or cAMP levels. This direct effect of CsA on osteoblasts may be important in changes of bone remodeling observed in CsA-treated humans and animals.     

A comparative study of coagulation effects on the cortex of the rat using Nd-YAG (1.32 μm), Nd-YAG (1.06 μm) and CO2 lasers

This paper represents a comparative study on brain tissue of three lasers: Nd-YAG (1.32m); Nd-YAG (1.06 m); and CO₂ laser. The experimental studies were performed on rats. They consisted of a comparison between the thermal effects and the consequent histological lesions produced. The surface temperature of the cortex induced by each laser shot was measured with an infrared camera. The results show that there exists an excellent correlation between surface temperature and the histology of the lesions produced. It appears that for equivalent surface temperatures the cortical lesions 8 days after irradiation were similar for Nd-YAG (1.32m) and for CO₂ lasers but significantly different for the Nd-YAG (1.06m) laser. For example the depth of coagulation necrosis varied between 20 to 250m with the CO₂ laser using the power of 3 to 10 W at an exposure of 0.05 s with a fluence of 5J/cm² and varied from 210 to 260m using the Nd-YAG (1.32m) with the power of 5 to 14 W with an exposure of 0.4 s with a fluence of 50–170 J/cm². With the Nd-YAG (1.06m) the depth of coagulation necrosis varied from 490m to 550m using a power of 12 to 19 W with an exposure of 0.4 s with a fluence of 150–250 J/cm². It would appear that the Nd-YAG laser at a wavelength of 1.32m should be valuable in neurosurgery as this wavelength is highly absorbed by brain parenchyma and is transmissible with a fibre optic delivery system.

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Résumé Les auteurs presentent une étude comparative de la coagulation du parenchyme cérébral au moyen de différents lasers. Les études expérimentales ont été effectuées sur le cortex du rat. Elles ont consisté à comparer les effets thermiques et histologiques de 3 longueurs d'onde: Nd-YAG (1.32m), Nd-YAG (1.06m) et CO₂ (10.6m). La température corticale de surface induite par le tir laser a été mesurée au moyen d'une caméra infrarouge. Les courbes du profil thermique de chaque tir et de son évolution au cours du temps ont ainsi été obtenues. Les résultats montrent qu'il existe une excellente corrélation entre les données thermiques et les données histologiques recueillies pour chaque tir. Il apparaît ainsi que pour des augmentations de température équivalentes, les lésions corticales 8 jours après le tir sont similaires pour les lasers Nd-YAG (1.32m) et CO₂, mais significativement différentes pour le laser Nd-YAG (1.06m).Par exemple, le profondeur de nécrose varie entre 200 et 250m pour le laser CO₂ utilisé avec une puissance de 3 à 10 W, un temps d'exposition de 0.05 s et une fluence de 5 J/cm². La profondeur de nécrose varie entre 210m et 260m lorsqu'on utilise le laser Nd-YAG (1.32m) avec une puissance de 5 à 14 W, un temps d'exposition de 0.4 s et une fluence de 50 à 170 J/cm². Avec le laser Nd-YAG (1.06m), la profondeur de nécrose est beaucoup plus importante. Elle varie entre 490m et 550m pour une puissance comprise entre 12 et 19 W, un temps d'exposition de 0.4 s et une fluence de 150 à 250 J/cm².Ces résultats expérimentaux montrent que la longueur d'onde 1.32m est bien adaptée à la neurochirurgie puisqu'elle est bien asbsorbée par le parenchyme cérébral et qu'elle est transmissible par une fibre optique.