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.

     

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.     

Neurosurgical lasers for tumour removal

The early 1970s saw the birth of microscopic neurosurgery and the late 1970s the birth of laser neurosurgery. For more than 10 years now, laser radiations have been used during neurosurgical procedures: mostly for tumoral removal concerning essentially benign lesions. The reference laser has been and still is the CO₂ laser, which has a limited penetration into CNS tissues. Until recently the Nd-YAG laser was used with its normal spectral transition, 1.064 m. Because of its important diffusion in the CNS, it cannot be widely used except for shrinking large vascularized tumours such as meningiomas. The technological evolution has brought the laser specialists—physicists, medical doctors and surgeons—new concepts and new wavelengths which will progressively broaden laser applications and surgical procedures towards greater effectiveness, security and simplification. Holmium-YAG (2.1 m), Erbium-YAG (2.9 m) or long Nd-YAG wavelengths (1.44 or 1.32 m) have been studied by different teams. The 1.32 m Nd-YAG transition has been clinically used for about 2 years by a few neurosurgical teams (Beck in Munich, Roux in Paris, and more recently Lombard and Fasano in Torino, Ascher in Gratz).Laser radiations can be useful essentially during the removal of benign tumours, mostly if they are well vascularized and placed near functional structures such as the brain stem, the cranial nerves, the spinal cord: the CO₂ laser is most efficient for vaporization; 1.06 Nd-YAG is effective for coagulation; 1.32 Nd-YAG provides very satisfactory photoevaporation effects if used with a superpulsed emission, and/or with a focusing handpiece, it also has good haemostatic properties with a c.w. output.The development of new optic fibre conducted wavelengths appears to be a possible answer to new requisites which should lead to the development of endoscopic neurosurgery (intraventricular tumours, discal herniations) and sterotaxic laser surgery (deep-seated intra-cerebral lesions).     

Preliminary experience with the 1.32 μm neodymium-YAG laser in the treatment of tracheobronchial malignancy

Endoscopic laser treatment for tracheobronchial malignancy is usually given with the neodymium-YAG laser using the 1.064m output beam. However, recent experimental work suggests that the 1.32m output beam of this laser has more desirable tissue effects. We have now treated 55 patients with the 1.32m Nd-YAG laser (MBB-Medizintechnic) under general anaesthesia, using power settings of 10–20 W and pulse durations of up to 1 s. The indications for treatment were localized airway obstruction in each case. Airway calibre was improved in 46 (84%) patients and this was associated with an improvement in symptoms of cough and breathlessness. Patients with tracheal and carinal obstruction exhibited the most striking clinical improvements with up to four-fold increases in peak expiratory flow. In patients with more peripheral endobronchial obstruction, treatment improved airway calibre less frequently and resulted in a smaller clinical improvement. Of 11 patients with obstruction of a main bronchus and lung collapse, treatment led to partial or complete re-expansion in 10 cases (91%). The 1.32m wavelength allows treatment to be conducted efficiently and safely but at a considerably lower power than is required for the 1.064mwavelength. The ability to use low powers has the apparent advantage of generating only negligible quantities of smoke. Our experience with this new laser system demonstrates its considerable potential in the management of tracheobronchial malignancy.     

A comparative study of etching enamel by acid and laser

Acid etching is regarded as one of the main means of providing additional retention in aesthetic dentistry. Alternative methods of achieving bonding to tooth tissue which have been proposed include laser etching. Conflicting results on bond strength to enamel have been reported for laser etching. Here the tensile bond strength of composite resin to acid- and laser-etched enamel was measured and the topographical differences between the surfaces were evaluated using the scanning electron microscope. The laser used was a pulsed Nd-YAG laser at 10 pulses per second with a pulse length of 150s, 80mJ pulse^–1, 1.064m wavelength. The results obtained indicate that the bond strength of laser-etched enamel was significantly lower than that of acid-etched enamel. In this study the difference may be attributable to the chromophore used. Variations in the rate of traverse of the laser tip across the surface did not appear to produce significant alterations in the bond strength.     

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.     

A thermal appraisal of the ablation process in canine aorta in vivo using a 100 μm pulsed Nd-YAG laser

A model has been developed to calculate distal tissue necrosis in vascular tissue after application of a 100 laser pulse from a Nd-YAG laser (5 kW peak pulse power on a 0.13 mm² spot size). The model assumes that the temperature profile in the tissue is proportional to the laser light fluence rate and that the distal tissue necrosis depth is that depth in the tissue where there is a temperature increase of 42 °C minus the etch rate (ablation depth per laser pulse). The fluence rate has been calculated using the diffusion approximation to the radiative transport equation. The tissue optical parameters (absorption and reduced scattering coefficients) have been derived from published data. The etch rate used (10m per pulse) is derived from in vivo experimental results. The model predicts a damage depth varying between 0 and 2.33 mm (mean 1.10 mm) and this is compared with an experimental result (0.77 mm) in dog aorta.     

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.     

Laser synovectomy of the knee joint

The clinical impact of laser-assisted synovectomy was investigated in a two-part study consisting of a morphological part with morphometric measurements and an in vivo part using an animal model. A continuous wave Nd:YAG laser ( = 1064 nm; power density 18–106 W/mm²; exposure 0.5–5 s) and a XeCl excimer laser ( = 308 nm; pulsewidth 20 ns; repetition rate 10–70 Hz; energy density 20–45 mJ/mm²; exposure 10–60 s) were employed in combination with a fused silica fiber with diameters of 600 m and 800 m, respectively. In vitro study. Under light microscopy, synovium exposed to Nd:YAG laser energy presents a transitional band (with a mean diameter of 2 mm) with three zones: a carbonized area, a vesicular zone, and a coagulated part. In contrast, pulsed UV-laser irradiation leads only to a narrow transitional zone extending 10–70 m. Scanning electron microscopy reveals a clear-cut surface following excimer synovectomy, whereas Nd:YAG laser irradiation forms an irregular surface with numerous bursts due to vaporizing activity. In vivo study. Partial synovectomy of the knee joint was performed in two groups of 14 New Zealand white rabbits with a 1064-nm Nd:YAG laser and a 308-nm XeCl excimer laser. Another 14 animals synovectomized in a conventional technique served as a control. Morphological examination and histopathological scoring of the synovial membrane were performed 4 days to 6 months after the operation. The progress of synovial regeneration following excimer laser synovectomy did not differ from observations in the control group. However, Nd:YAG laser irradiation led to a significantly delayed formation of a neosynovium. In addition, Nd:YAG laser application provided an efficient hemostasis. In conclusion, the Nd:YAG laser is a suitable instrument for synovectomy and is superior to conventional techniques, as it provides sufficient hemostasis, an appropriate extent of synovial resection, and delayed formation of a neosynovium, thus interrupting the vicious cycle that may lead to an early recurrence of synovitis.     

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.     

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.     

Human pancreatic tumor GH-releasing factor

Summary Within the past year, three similar peptides with specific growth hormone (GH) releasing effects have been extracted from human tissue, identified, and synthesized. Human pancreatic tumor GH releasing factor (1–40)-OH (hpGRF-40) was the sole hpGRF isolated from the pancreatic tumor of a patient in Charlottesville and was the predominant peptide isolated from the pancreatic tumor of a patient in Lyon. The Lyon tumor also contained hpGRF(1–37)-OH and hpGRF(1–44)-NH₂. Both immunological and biochemical data suggest that hpGRF-40 and hpGRF-44 are present in the human hypothalamus and may be the human GH releasing hormone(s) (GHRH).In cultures of rat pituitary cells, hpGRF stimulates GH but affects neither basal and dopamine-inhibited prolactin release nor basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. hpGRF stimulates cyclic AMP production within seconds, an effect which is blocked by somatostatin. In contrast, while hpGRF stimulates phosphatidylinositol turnover in the pituitary, the effect is not inhibited by somatostatin.In the human, hpGRF-40 (1 g/kg) given intravenously (i.v.) stimulates GH release within 5 minutes. hpGRF-40 does not elevate serum prolactin levels, thyrotropin (TSH), LH, or corticotropin (measured indirectly through plasma cortisol), or blood glucose or plasma concentrations of insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, or somatostatin. When graded doses of hpGRF (0.1–10 g/kg) are given i.v., no differences are noted in the maximal levels of serum GH achieved. Doses of 1, 3.3 and 10 g/kg hpGRF-40 elicits a prolonged and biphasic pattern of GH release. Twenty-four hours after hpGRF-40 administration, serum somatomedin C is increased in 66% of subjects tested. Side effects including a feeling of warmth and facial flushing are observed in 66% (3.3 gmg/kg) and 100% (10 g/kg) of men given hpGRF-40. hpGRF-40 (3.3 g/kg, i.v.) selectively stimulates GH release and somatomedin C production in normal women, although no differences are found in GH responsivity during the menstrual cycle. hpGRF-40 given intranasally to normal men (30 g/kg) stimulates GH release within 30 minutes. The calculated metabolic clearance rate for hpGRF-40 is 194±17.51/m²/d; the disappearance rate occurs as two phases: an initial equilibration phase (7.6±1.2 minutes) and a subsequent elimination phase (51.8±5.4 minutes). hpGRF-40 administered i.v. stimulates the release of GH in some adult patients with GH deficiency documented in childhood. Serum somatomedin C concentrations may increase in patients in whom hpGRF-40 fails to stimulate GH release. If patients with GH deficiency who do not respond to hpGRF-40 administration (10 g/kg i. v.) are given the peptide (0.33 g/kg i. v. every 3 hours) for five days, some will respond to a subsequent 10 g/kg challenge. Of those who do respond initially, the response to the subsequent challenge may be greater. Serum somatomedin C increases significantly following the 5 days of intermittent administration of hpGRF-40.hpGRF-40 and/or hpGRF-44 may be the long sought GHRH. Clinical studies with hpGRF suggest that GH deficiency may often result from hypothalamic GHRH deficiency rather than pituitary disease. hpGRF and its analogues and antagonists may find therapeutic application in the treatment of GH deficiency and in other disorders in which an increase or decrease in the secretion of GH would be beneficial.     

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.     

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.     

Experience with a new solid phase enzyme immunoassay for prostatic acid phosphatase

Summary In recent years, the value of prostatic acid phosphatase (PAP) as a tumor marker for early prostatic cancer (CaP) has been the subject of controversial discussion. Investigation of sera from patients with pathohistologically proven localized CaP and from those with benign prostatic hyperplasia (BPH) has demonstrated a lack of discrimination between these groups of patients. Earlier investigations have demonstrated that the turnover rate of PAP in a conventional enzyme immunoassay (EIA) was limited by the release of the phosphate from the active center of the enzyme. However, a transfer of the activated phosphate on n-butanol or n-pentanol could increase the turnover rate to about 150%. Based on these observations 1-butanol was added to a solid-phase direct EIA in order to increase the sensitivity. PAP was assayed in 177 healthy male donors, 33 patients with benign prostatic hyperplasia and 33 patients with CaP. In 10 out of 21 patients with localized CaP (T1-3N0M0), the tumor stage was based on pathohistological examination. The upper limit of discriminative normal value was set at 0.65 g/l. The values of normal donors ranged between 0.07 and 0.6 g/l (mean 0.27 g/l), while the values for patients with BPH were slightly higher (mean 0.5 g/l). Only one patient with BPH had an elevated serum level (0.7 g/l). Out of 33 patients with CaP, 31 were found to have PAP values higher than 0.65 g/l. In one patient with CaP, pT2pN0M0 and one other patient with CaP T1N0M0, serum PAP levels were slightly lower than 0.65 g/l. This study indicates that an increase in the sensitivity of PAP determination might yield a valuable tool even in the diagnosis of early CaP.     

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.

     

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.     

Interactive computerized morphometric analysis for the differential diagnosis between dysplasia and well differentiated adenocarcinoma of the prostate

Summary To distinguish prostatic dysplasia (or adenosis) from well differentiated adenocarcinoma on transrectal needle biopsy, a morphometric study was conducted on 20 cases of adenosis and 20 cases of well differentiated adenocarcinoma of the prostate. About 100 cells for each patient were analyzed by means of a computerized image analyzer, and mean nuclear diameter, mean nuclear area, mean form factor and number of cells in eight classes of nuclear diameter were studied. The best predictors of malignancy (evaluated by means of Receiver Operating Characteristics curves) were mean nuclear area >28², presence of more than 5% of cells with nuclear diameter>6.15 , and mean nuclear diameter>. Using these diagnostic criteria the probability of malignancy for a positive specimen rises from 14% (pre-test) to 75% (post-test).Supported by a grant from Associazione Italiana per la Ricerca sul Cancro     

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).     

Aminoalkylbisphosphonates,potent inhibitors of bone resorption,induce a prolonged stimulation of histamine synthesis and increase macrophages,granulocytes, and osteoclasts in vivo

Summary Aminoalkyl derivatives of bisphosphonates are potent inhibitors of bone resorption. A single I.P. injection of 4-amino-1-hydroxybutylidene-1,1-bis-phosphonate (AHBuBP) induced a prolonged enhancement of histidine decarboxylase (HDC) activity in the bone marrow, spleen, lung, and liver of mice and resulted in an increase in histamine. The induction of HDC by the agent was dose dependent (16–80 mol/kg) and peaked 3–4 days after its injection (40 mol/kg). Repeated S.C. injections of smaller doses of AHBuBP (0.32 or 1.6 mol/kg/day) for 4 days also enhanced HDC activity. However, the minimum dose capable of inhibiting bone resorption (0.064 mol/kg/day) was lower than that inducing HDC. Unexpectedly, AHBuBP, at the doses inducing HDC, increased macrophages, granulocytes, and even osteoclasts. The size of osteoclasts was also enlarged by the agent. Another aminobisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, but none of nonamino derivatives, also exhibited essentially the same effects as those of AHBuBP. These results indicate that in spite of increase in osteoclasts and their enlargement, bone resorption is still inhibited by amino bisphosphonates. As granulocyte and granulocyte-macrophage colony-stimulating factors and interleukin-3 induce HDC in hematopoietic organs, and histamine has a hematopoietic activity, the HDC induction by aminobisphosphonates may be relevant to the proliferation of progenitor cells of macrophages, granulocytes, and osteoclasts.