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.     

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.

---

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.

     

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.     

Comparison of continuous-wave and pulsed excitation for interstitial neodymiurn-YAG laser-induced hyperthermia

To investigate the effect of pulsing on neodymium-YAG laser-induced hyperthermia we have exposed rat liver to low-power Nd-YAG laser light delivered via an interstitially inserted fibre. This was either continuous wave excitation or pulsed excitation at 10 or 40 Hz (pulse duration 100s) with an average power of 1W and exposure durations of 400 s. No differences were seen with respect to overall diameter of the histological damage, diameter of the central cavitation, or intrahepatic temperatures, as measured by an embedded array of microthermocouples. We conclude that with 100-s pulses, within the range of parameters studied, the pulsing rate does not influence the nature or the extent of damage seen after low-power interstitial Nd-YAG laser hyperthermia.     

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.     

Characterization of in vitro relaxant mechanisms in erectile tissue from rabbits of different ages

In the present study we investigated the in vitro relaxant response of erectile tissue obtained from rabbits of different ages (3, 7 and 24 months) in order to detect the progression with age of cavernosal activity in response to substances acting via endothelium-dependent or-independent mechanisms. Noradrenaline induced a concentration-dependent contraction (0.1 M–3 mM), with an increase in the contractility in the 24-month-old group. Acetylcholine produced a concentration-dependent relaxant effect in the three age groups, with a reduction of the maximal relaxant effect in older animals. ATP (10 M–1 mM) and adenosine (10 M–1 mM) induced a concentration-dependent relaxant effect that was higher in the older group. The presence of the NO-synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME) (0.1 mM) or of the P₂-purinoceptor antagonist suramin did not affect ATP relaxation. Relaxation induced by sodium nitrite and nifedipine was reduced in older animals. In conclusion, aging selectively alters the in vitro responsiveness of rabbit erectile tissue. Purinergic system remains more active despite a decrease in the maximal endothelial cholinergic activity and the direct smooth muscle relaxant component.     

Lipid and protein histochemistry of enamel — Effects of fluoride

Summary Staining reactions for a number of histochemical procedures for lipophilic staining and protein were studied in the enamel matrix along the length of rat incisors. Sudan Black gave a positive stain across the whole thickness of very early enamel (up to 30 m) but this staining only continued as a narrow band close to the ameloblasts as the enamel matured. A variety of tests for protein produced almost identical staining patterns in enamel matrix up to 100 m thick. Since the pattern of lipid staining persisted, after using a number of procedures which could normally be expected to remove lipid, it is suggested that Sudan Black positive staining may be due to lipophilic protein rather than lipid itself. Fluoride did not significantly alter the staining reactions for lipid and protein but did proceduce matrix which was much more effectively stained by cross-linking agents FFDNB and FF sulphene.     

In comparison: 1.064 μm-1.318 μm Nd-YAG continuous wave lasers. In vitro and in vivo experiments for endoscopic tumour therapy in the gastrointestinal tract

In in vitro and animal experiments the tissue effects of the 1.318m Nd-YAG laser were compared to those of the standard 1.064m Nd-YAG laser in order to evaluate the advantages of the new wavelength with a ten times higher absorption in water for gastroenterological tumour treatment. Under irradiation parameters related to clinical endoscopic practice, the laser of the wavelength 1.318m needs for both vaporization and coagulation significantly less energy than the 1.064m laser. Since vaporization at 1.318m is always accompanied by a higher coagulation effect compared to 1.064m the risk of late necrosis and resulting perforation appears to be increased.     

Percutaneous mid infra-red laser coronary angioplasty

Thirty patients with stenosis or total occlusion of the coronary artery were treated with mid infra-red pulsed laser angioplasty. The device consisted of a holmium-YAG laser operating at 2.1m, 500 mJ pulse^–1, 3.5 Hz, 250s pulse^–1. The laser was coupled into a multifibre catheter consisting of 37 optical fibres of 150m each concentrically arranged around a central lumen for the passage of a guidewire. This over-the-wire system allowed for safe and effective recanalization without perforation, death, arrythmia, distal embolus. Chest sensation but not pain occurred during laser emission. There was spasm in six patients which could be relieved by nitrates. In previously failed balloon angioplasty laser angioplasty allowed for successful repeat dilatation with low inflation pressure. Technical improvement should be made in reducing the dead space left in between the fibres at the distal catheter tip, in distal tip flexibility and in increasing the channel diameter for more laser stand-alone therapy.     

Penile erections induced by vasoactive intestinal peptide and sodium nitroprusside

Summary The use of vasoactive intestinal peptide (VIP), sodium nitroprusside (SNP), and the reference combination of papaverine, prostaglandin E₁, and phentolamine was studied in 22 adult cats. The maximal erectile response (intracavernous pressure, penile length, and rigidity) was produced by intracavernous injection of a combination of 1.65 mg papaverine, 0.5g PGE₁, and 25g phentolamine. This combination was considered as control in order to compare the effect of other agents. VIP and SNP increased the intracavernous pressure and caused erection in a dose-dependent manner with a maximal response obtained with 5g VIP or 10g SNP. The duration of peak erection and the total duration of drug effect were significantly shorter with VIP and SNP than with the reference combination (P<0.01). Epinephrine (30g) reversed the effects of SNP and significantly shortened the duration of peak action and total effect (P<0.05). This study supports the use of an in vivo feline model for the evaluation of vasoactive agents and demonstrates that the intracavernous injection of either VIP or SNP can induce penile erection in the adult cat.     

Diffusion theory of isotropic light dosimetry probe response

For the measurements of light energy fluence rate in tissues in vitro and in vivo we have developed an isotropic probe. The response of such a probe depends on the refractive index (n) of the medium. This has been measured in a collimated light beam with the probe in air, water (n=1.33), ehtylene glycol (n=1.43) and glycerin (n=1.46). The response as a function of n has also been calculated using diffusion theory, taking into account reflection at the boundaries. Simple formulas are proposed which very well approximate Fresnel reflection of unpolarized light, facilitating mathematical calculations. For a probe of 3.2 mm diameter with little light absorption the theoretical result depends only on n and differs from the experimental data by not more than 6 %. For a probe of 0.8 mm diameter with some light absorption excellent agreement between theory and experiment could be obtained by adjusting the (unknown) absorption and scattering coefficients ( _a, _s) of the probe material. However, a good fit was only possible within certain limits for _a, i.e. 0.35 mm^–1< _a<0.40 mm^–1, whereas _s (1-g) could be varied between at least 5 and 20 mm^–1 (g is the asymmetry parameter of the scattering function).     

Effects of laser parameters on pulsed Er-YAG laser skin ablation

Previous studies demonstrated that pulsed 2.94m Er-YAG laser radiation allows a precise etching of organic tissue with only minimal thermal damage. This makes the Er-YAG laser a promising tool for the careful removal of superficial skin lesions. In order to provide optimized laser parameters for potential clinical use and to enhance our understanding of the mid-infrared ablation process, we measured the ablation rate, temperature profile and damage zones for various pulse numbers, radiant energies and pulse repetition rates. Ablation is very efficient (about 6m J^–1 cm² for high radiant exposure) and the crater depth is exactly (1Hz) or nearly (2 Hz) linearly related to the radiant exposure. In contrast, no significant effects of the laser parameters on the thermal damage of the epidermis and the crater bottom were observed. In conclusion, for a future clinical use high radiant energies should be applicable without the disadvantage of enhanced damage.     

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.

---

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.

---

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.

---

---

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

Studies of Er-YAG laser interactions with soft tissue

The ablation efficiency and depth of secondary thermal damage have been determined for a range of cadaveric soft tissues on exposure to radiation from a pulsed Er-YAG laser operating at 2.94m. The tissues investigated included brain, small intestine, stomach, liver, heart, spleen, lung, aorta, cornea, kidney, skin and uterus. The results obtained are compared to those predicted by a simple one-dimensional model of the interaction. The amount of tissue damage varied between tissues. In cellular tissues it was approximately 20m in extent on either side of the slot and at its base. In acellular tissues (aorta, cornea, etc.) the alteration in protein structure was more variable and was dependent upon the nature of the connective tissue fibres. Corneal collagen showed changes in protein structure up to 30m from the edge of the slot, whereas aortic elastic fibres were little affected by the laser energy, apparently melting to form a coagulum that lined the slot.     

Zinc and magnesium in human seminal plasma

Several hundreds of specimens of human seminal plasma have been analyzed for zinc, magnesium, acid phosphatase activity, cholesterol and fructose. The semen was also analyzed for sperm density, motility, viability and morphology. The mean concentrations of zinc and magnesium were 129 and 106 g per ml, respectively. Zinc and magnesium concentrations were correlated (r=0.84) and both ions appear suitable for evaluation of the secretory activity of the prostate gland. Three out of four semen samples with less than 50 g Zn and/or Mg per ml had pathological spermiograms compared to 40 per cent among those with more than 100 g/ml.Presented at the VIth World Congress on Fertility and Sterility, Tel Aviv, 1968.     

Serum hippuric acid concentration in renal allograft rejection,ureter obstruction,and tubular necrosis

Plasma from 35 renal allograft recipients (21 males and 14 females) was sampled daily and analyzed for hippuric acid (HA) by highperformance liquid chromatography (HPLC) and serum creatinine. Twelve of these patients experienced an acute renal allograft rejection or a ureter obstruction as proven by clinical signs and biopsy, as well as by radiography or ultrasound, respectively. Two patients suffered from tubular necrosis followed by rejection during the postoperative period. Mean serum HA increased by 39.9 mol/l from baseline (range 20.4–115.5 mol/l) in patients with acute rejection 3 days after an initial increase that was observed 24 h before the mean serum creatinine increased by 107.1 mol/l (range 21–193 mol/l). In cases of ureter obstruction, HA rose by 1.6 mol/l (range 1–8.2 mol/l), significantly less than elevations due to rejection. The increase in creatinine, however, amounted to 65.3 mol/l (range 22–140 mol/l) and was not different from the change in rejecting patients. Successful antirejection treatment coincided with a decrease in serum HA starting 24 h earlier than the decrease in the serum creatinine concentration. Of special interest was the observation of a parallel decrease in HA with creatinine concentration in patients with tubular necrosis after allotransplantation; HA increased in cases of an additional rejection. Our data suggest that HA, which is excreted by tubular secretion and glomerular filtration, could be a sensitive and early marker of acute allograft rejection. Furthermore, it seems to discriminate between acute renal allograft rejection and ureter obstruction. It might, therefore, be of value in the diagnosis of rejection complicating tubular necrosis after transplantation.     

Effects of lead on osteoclast-like cell formation in mouse bone marrow cell cultures

To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2–10 M, whereas at 40 M Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 M Pb and decreased with increasing concentration of Pb at 10–40 M. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E₂ (PGE₂) receptor. Pb stimulated the production of PGE₂ in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE₂. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2,5-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE₂-induced increase in the levels of cyclic adenosine 3,5-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE₂ which increases the intracellular levels of cAMP and calcium ions.     

Transmission of Q-switched erbium:YSGG (λ=2.79 μm) and erbium:YAG (λ=2.94 μm) laser radiation through germanium oxide and sapphire optical fibres at high pulse energies

The erbium:YSGG and erbium:YAG lasers are used for tissue ablation in dermatology, dentistry and ophthalmology. The purpose of this study was to compare germanium oxide and sapphire optical fibres for transmission of sufficient Q-switched erbium laser pulse energies for potential use in both soft and hard tissue ablation applications. Fibre transmission studies were conducted with Q-switched (500 ns) Er:YSGG (=2.79 m) and Er:YAG (=2.94 m) laser pulses delivered at 3 Hz through 1-m-long, 450-m germanium oxide and 425-m sapphire optical fibres. Transmission of free-running (300 s) Er:YSGG and Er:YAG laser pulses was also conducted for comparison. Each set of measurements was carried out on seven different sapphire or germanium fibres, and the data were then averaged. Fibre attenuation of Q-switched Er:YSGG laser energy measured 1.3±0.1 dB/m and 1.0±0.2 dB/m for the germanium and sapphire fibres, respectively. Attenuation of Q-switched Er:YAG laser energy measured 0.9±0.3 dB/m and 0.6±0.2 dB/m, respectively. A maximum Q-switched Er:YSGG pulse energy of 42 mJ (26–30 J/cm²) was transmitted through the fibres. However, fibre tip damage was observed at energies exceeding 25 mJ (n=2). Both germanium oxide and sapphire optical fibres transmitted sufficient Q-switched Er:YSGG and Er:YAG laser radiation for use in both soft and hard tissue ablation. This is the first report of germanium and sapphire fibre optic transmission of Q-switched erbium laser energies of 25–42 mJ per pulse.     

Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC)

Objective: To determine the safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC) patients. Materials and Methods: IC patients were instilled with 50 cc of test solution containing either placebo, 0.05 M or 0.10 M RTX in the bladder. Plasma concentration of RTX and its degradant resiniferonol 9-, 13-, 14-orthophenylacetate was measured. Immediate post-treatment blood sampling and cystoscopy were performed. Symptoms were evaluated before treatment, at 4- and at 12-week follow-ups, using VAS indicator for pain, voiding diary, and OLearys IC symptom/problem indices. Results: Among 22 patients observed (ten in 0.10 M RTX, eight in 0.05 M RTX, and four in placebo groups), the most commonly reported adverse event was pain during instillation (80.0%, 87.5%, and 25.0%). No serious adverse events were reported. Conclusions: Use of intravesical RTX in IC patients is associated with important tolerability issues but safe at 0.10 M and 0.05 M.     

Serum immunosuppresive acidic protein in renal cell carcinoma

Summary Serum immunosuppresive acidic protein (IAP) was determined in 45 patients with renal cell carcinoma (20 preoperative and 25 postoperative) and 12 healthy adults. The mean values of serum IAP in patients with renal cell carcinoma of low stage (566.3±197.7 g/ml) and high stage (936.9±208.8 g/ml) were statistically higher than those of controls (368.8±84.5 g/ml). Positive rate of IAP levels was found in 58.3% and 100% of patients with low stage and high stage, respectively. The mean value of serum IAP was 756.4±361.0 g/ml in patients with metastases, while patients without metastases had a value of 434.7±170.9 g/ml. There was a statistically significant difference between the two populations. These results suggest that IAP levels appear to provide a useful diagnostic and followup marker in renal cell carcinoma patients.