Contrast media injection in the rat after multiple renal insults no evidence of additional nephrotoxicity

Experiments were performed to determine whether water-soluble contrast media (CM) show nephrotoxic properties when injected into rats after multiple renal insults. The latter consisted of combinations of prostaglandin synthesis inhibition (with indomethacin) and/or salt depletion and/or uninephrectomy. Renal function was evaluated by standard clinical methods to measure parameters such as urinary output, urinary osmolality, urinary creatinine excretion and serum creatinine. CM injected after prostaglandin synthesis inhibition alone did not influence urinary creatinine excretion or serum creatinine. After a combination of renal insults a significant increase in median serum creatinine values from 61.88 mol/l [interquartile range (IR) 17.68] [0.70 mg% (IR 0.20)] to 97.24 mol/l (IR 79.56) [1.10 mg% (IR 0.90)] was observed but CM or sham injections did not prevent a normalization of serum creatinine. The pattern of recovery of serum creatinine was not influenced by previous kidney mass reduction. It is concluded that the nephrotoxic properties of CM cannot be detected with standard clinical methods in rats after multiple renal insults.     

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.

     

Investigations of the efficacy of ascorbic acid therapy in cystinuria

Summary We investigated ascorbic acid therapy for cystinuria in a study of seven healthy control persons and seven cystinuric patients. The study lasted 9 days. During the first period, we collected 24-h urine specimens from all subjects on 3 consecutive days. Starting on day 4, all were given 5 g ascorbic acid/day for a period of 6 days. On the last 3 days, 24-h urine specimens were again collected. Quantitative amino acid determination was performed using an HPLC method described elsewhere. During ingestion of ascorbic acid, the mean excretion of cysteine by the control group increased from 134.1 to 159 mol/ day, whereas the excretion of cystine decreased from 107.1 to 82 mol/day. The corresponding values for the cystinuric patients increased from 352.4 to 452.1 mol/ day for cysteine and decreased from 4,131.6 to 3,663.2 mol/day for cystine. Thus, ascorbic acid seems to have only mild reducing properties in respect to cystine.     

Atrial natriuretic peptide (ANP) attenuates brain oedema accompanying experimental subarachnoid haemorrhage

Summary The effects of centrally administered atrial natriuretic peptide (ANP) on the brain water and electrolyte contents were investigated in a rodent subarachnoid haemorrhage (SAH) model. SAH caused statistically significant increases in the brain sodium and water contents, while the potassium content did not change significantly, indicating that the brain oedema could be classified as having a primarily vasogenic component. Two g or 5 g of rat ANP administered into the lateral ventricle at the time of SAH induction statistically significantly decreased the water and sodium accumulation measured 90 minutes following SAH. The same treatment did not inhibit development of brain oedema measured 3 hours following SAH. However, when 5 g of ANP was administered intraventricularly at the time of SAH induction and also 90 minutes later, the brain oedema 3 hours following SAH was again reduced statistically significantly. These effects of ANP were found not to be mediated by primary changes in serum osmolality and electrolyte concentrations.The present results confirm that centrally administered ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation in SAH-induced brain oedema. The potentials of influencing the central neuro-endocrine system as a novel way of the treatment of brain oedema are discussed.Supported by Grant OTKA I/3 2728 and ETT T110/ 1990.     

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.

     

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.

     

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.     

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.     

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.     

Effects of needle shape on the integrity of the vascular endothelium

Summary Lesions generated by the passage of micro-needles through vessel walls are of concern because any lesion may significantly alter hemodynamics of an anastomosis. To study this problem, three different needles were tested on the exposed carotid arteries of 30 rats: the 100 taper point, the 100 cutting point, and the 75 taper point. Trauma generated by the penetration of needles was tested first as the needle and its attached suture was passed through the vessel, then the suture was left in place. One hour after penetration, the arteries were prepared for scanning electron microscopy.Differences between the 100 taper point and the 75 taper point were significant in terms of size and extent of lesions. An arc of endothelial cells surrounding the wounds showed flattening, tissue destruction and clotting. To minimize endothelial trauma, taper point needles are superior to cutting needles. The 100 cutting needle caused damage to the vessel wall in tissue cutting on needle penetration, causing a slit-like incision, and in aggregation of platelets at the puncture site.Supported in part through an American Heart Association Student Clerkship in Cerebrovascular Disease Award, 1981. Additional support received from the Bauervic Foundation, West Bloomfield, Michigan and Sheldon Hayes Stroke Fund, Detroit, Michigan and Medical Materials & Devices, Inc., Pittsburgh.     

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.     

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.     

Connective tissue metabolism in children with chronic renal failure

To assess the characteristics of connective tissue metabolism in chronic renal failure (CRF), urinary excretion of glycosaminoglycan (GAG) fractions and hydroxyproline (HYP) was determined in ten patients with CRF and in ten age-matched healthy children. CRF was found to be associated with elevated free HYP (19.9±6.1 vs 9.8±3.6 mol/day,P<0.05) and depressed peptide HYP excretion (33.1±13.5 vs 225.2±17.7 mol/day,P<0.01), a low rate of total GAG excretion (7.0±2.4 vs 16.1±1.9 mol uronic acid/day,P<0.05) with low chondroitin 4 — sulphate + chondroitin 6 — sulphate (Ch-Ss) (14.0±9.9 vs 65.0±22.1%) and a high proportion of non-sulphated or under-sulphated fractions, i.e. hyaluronic acid + chondroitin + heparan sulphate (HA+Ch+HS) (75.3±11.4 vs 31.5±5.7%). Urinary 3-methyl-histidine (3-met-HIS) excretion and plasma essential free amino acids did not differ in the two groups. In response to haemodialysis no consistent change occurred in urinary excretion of 3-met-HIS, peptide-bound HYP, total GAG or percentage distribution of individual GAG fractions. After haemodialysis all plasma amino acids decreased significantly, and there was a significant increase in urinary excretion of free HYP (P<0.05). We conclude that the alterations in urinary excretion of total and individual GAGs observed in CRF may reflect disturbed connective tissue metabolism which does not appear to be accounted for by protein malnutrition or enhanced protein breakdown and remains uninfluenced by haemodialysis therapy.     

Effect of transdermal l7β-estradiol and oral conjugated equine estrogens on biochemical parameters of bone resorption in natural menopause

Summary Objective: To evaluate and compare the effects or oral and transdermal estrogen replacement therapy on biochemical markers of bone resorption in early postmenopausal women Design: Controlled, randomized group comparison. Setting: Outpatient clinic for menopausal women and research into osteoporosis. Subjects: Sixty healthy women menopausal for less than 5 years and who had never received any medications interfering with bone metabolism. Interventions: The 60 women were randomly allocated to 3 months therapy with either oral conjugated estrogens (0.625 mg/day) (n = 28) or transdermal estradiol (50 jig/day) (n = 32) in cyclical combination with medroxyprogesterone acetate (5 mg/day). Main outcome measures: Traditional (urinary calcium/creatinine and hydroxyproline/creatinine) and the new specific (urinary pyridinoline/creatinine and deoxypyridinoline/creatinine) markers of bone resorption were determined before and after 3 months of treatment. Results: In both groups, circulating levels of estrone and estradiol were significantly (P < 0.001) increased during treatment. In women treated with oral conjugated equine estrogens, urinary calcium/creatinine and hydroxyproline/creatinine ratios were significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 69.1 (4) [mean (SEM)] to 50 (4) mol/mol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 10.8 (1) [mean (SEM)] to 8.3 (0.8) mol/mol (P < 0.01). In the group treated with transdermal estradiol, urinary hydroxyproline/creatinine ratio was significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 66.3 (4) [mean (SEM)] to 46.2 (3) mol/mol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 11.5 (1.5) [mean (SEM)] to 7.7 (0.6) mol/mol (P < 0.01). There were no differences between the evolution of the biochemical variables in the two groups. Conclusion: These results suggest that oral conjugated equine estrogens and transdermal estradiol, in the given doses, are equally effective in reducing postmenopausal bone resorption.     

Urinary thromboxane B2 as an indicator of acute rejection in human liver transplantation

Urinary thromboxane B₂ (u-TXB₂) was measured and analyzed after a human liver transplantation in 28 patients (30 transplantations) who underwent an orthotopic liver transplantation. Our results showed that the u-TXB₂ levels exceeded 3.0g/mmol creatinine in only 2 of the 13 cases that had a favorable postoperative course. In 10 of the 11 episodes of acute rejection, the u-TXB₂ levels exceeded 3.0g/mmol creatinine. In 6 episodes of acute rejection, the TXB₂ levels were more than 5.0. In 4 out of 6 episodes of infection unassociated with rejection, the u-TXB₂ values were between 3.0 and 4.9g/mmol creatinine. In 2 episodes of liver necrosis the TXB₂ value reached 5.3 in one and 0.9 in the other. In conclusion, the u-TXB₂ level was observed to be elevated in cases of acute rejection, infection, or necrosis. The diagnosis of acute rejection on the basis of u-TXB₂ showed a sensitivity of 58.8%, a specificity of 93.3%, and an accuracy of 75.0% for a threshold level of 3.0g/mmol creatinine, and a sensitivity of 85.7%, a specificity of 79.2%, and an accuracy of 80.6% for a threshold level of TXB₂ of 5.0g/mmol creatinine. These results indicate that the serial determination of u-TXB₂ is a useful diagnostic means for predicting acute rejection after liver transplantation.     

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.     

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.     

Pharmacokinetic profile of a new fluoride preparation: Sustained-release monofluorophosphate

The pharmacokinetic profiles of a sustained-release monofluorophosphate (MFP-SR) preparation (76 mg) and of plain MFP (76 mg) were compared in six osteoporotic females. These studies were performed in a randomized, crossover, double-blind design to select a preparation that would result in therapeutic serum levels while avoiding high serum peak values. Following a single dose of 76 mg MFP-SR, the serum fluoride levels remained within the accepted therapeutic range (5–10 M/liter) for 24 hours. In contrast, following a single dose of 76 mg plain MFP, serum fluoride levels exhibited a wide circadian fluctuation and serum levels approximately threefold higher than those of the MFP-SR preparation (9.5±1.6 vs 3.5±0.8 M/liter, P<0.005). Compared with plain MFP, the sustained-release MFP had a significantly lower peak concentration (C_max MFP-SR: 10.6 ±3 vs C_maxMFP: 18.9±5 M/liter, P<0.005) and a significantly longer absorption lag time (T_maxMFP-SR 7.3±1.6 vs T_maxMFP: 3.0±0.6 h, P<0.05). Twenty-four-hour urinary fluoride excretion after ingestion of plain or SR fluoride was significantly increased from pretreatment values documenting absorption with either MFP formulation. Our results show that the use of sustained-release MFP preparation that we tested prevents the development of high peak levels associated with the use of plain MFP preparations. Furthermore, a single dose of MFP-SR resulted in serum fluoride levels within the accepted range of 5–10 M/liter for 24 hours.     

Study of the microstructure of renal stones: Uric acid and calcium oxalate

This paper represents the results of experimental study on the microstructure of uric acid and calcium oxalate crystallites in renal stones. The size distribution parameters and morphological characteristics of the microcrystals forming the stone were determined using SEM and image analysing system. Information on the fabric of the renal stones examined indicates that the mean volume diameter is 15.5 m for uric acid and 32 m for calcium oxalate stones. The polydispersity index , the shape factor , and the distribution of particle shape show close similarity. Quantitative studies on stone microstructure could furnish valuable information on stone genesis.This work was supported by the Kidney Foundation and by the Medical Research Council of Canada.     

Urinary protein excretion and renal function in children with IgA nephropathy

Renal haemodynamics and the pattern of urinary protein excretion were studied in 38 children (21 boys, 17 girls) with biopsy-proven IgA nephropathy (IgAN), 0.4–16.8 (median 5.3) years after onset of the disease. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were evaluated by clearances of inulin and para-aminohippuric acid. Serum and urinary albumin, IgG and beta₂-microglobulin (2) were determined and the excretion rates, clearances, and fractional clearances were calculated. The patients were grouped according to the type and the amount of proteinuria. Mean GFR and ERPF were significantly decreased (107±3 and 580±17 ml/min per 1.73 m², respectively) versus controls (119±2 and 627±14 ml/min per 1.73 m², respectively). Grouped according to albumin excretion rates, non-albuminuric patients had normal GFR, while mean GFR was reduced in patients with micro-albuminuria (106±3 ml/min per 1.73 m²) and albuminuric patients (92±7 ml/min per 1.73 m²). IgG excretion increased with increasing albuminuria, but the selectivity index was lower in albuminuric patients than in patients with micro-albuminuria. Albuminuric patients had also higher blood pressure than those with micro-albuminuria. 2 excretion did not discriminate between patients with impaired renal function. The results suggest that childhood IgAN is not a benign kidney disease. After a median duration of 5 years of the disease a number of children had impaired renal function. Mean GFR was reduced most in the albuminuric patients but was also decreased in micro-albuminuric patients, indicating that micro-albuminuria may be a predictor of more severe disease.