The modulatory effect of endogenous parathyroid hormone on the action of hydrochlorothiazide in pseudohypoparathyroidism type I

We compared the effect of orally administered 100 mg of hydrochlorothiazide (HCTZ) among eight patients with pseudohypoparathyroidism (PHP) type I, 11 patients with idiopathic hypoparathyroidism (IHP), and 12 patients with primary hyperparathyroidism (1^oHPT). Patients with PHP type I or with IHP were studied during the treatment with 1-hydroxylated metabolites of vitamin D₃. HCTZ raised serum levels of calcium (Ca) in 1^oHPT (P<0.001) and PHP type I (P<0.01) but did not increase urinary excretion of Ca. Serum parathyroid hormone (PTH) in PHP type I decreased (P<0.02) after HCTZ administration in response to the increase in serum Ca. HCTZ did not raise serum levels of Ca in IHP but increased urinary excretion of Ca in this group (P<0.01). HCTZ suppressed tubular reabsorption of phosphate (P) in IHP (P<0.01) and 1^oHPT (P<0.05) but not in PHP type I. Urinary excretion of cAMP did not change after HCTZ administration in PHP type I, IHP, or 1^oHPT. Endogenous PTH modulated the effects of HCTZ on Ca mobilization from bone and renal reabsorption of Ca in PHP type I with normal or high serum levels of PTH and in 1^oHPT with high serum levels of PTH. The inhibitory effect of HCTZ on renal tubular reabsorption of P (probably from proximal tubules) was independent of PTH. The resistance to this inhibitory effect of HCTZ on P reabsorption in PHP type I suggested a proximal tubular dysfunction in this disorder.     

Relationship between plasma and bone concentrations of cefuroxime and flucloxacillin three different parenteral administrations compared in 30 arthroplasties

• (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin.
• (ii) Six groups of five patients participated in the study. The first three groups (A–C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D–F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously.
• (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients.
• (iv) Large inter-individual variation in bone concentration was observed.
• (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.

     

Fibrodysplasia ossificans progressiva: Still turning into wood after 300 years?

Fibrodysplasia ossificans progressiva (FOP), a rare autosomal dominant disorder, is characterized by symmetrical congenital skeletal abnormalities and progressive heterotopic ossification of the connective tissues. At present, more than 300 years after the first report by Patin in 1648 in which he described the woman who turned to wood, its pathogenesis remains largely unknown and its therapy is limited to symptom-modifying trials. However, significant progress has been recently made and new data on the molecular organization and regulation of normal and disordered bone induction are likely to lead to a more specific therapy. FOP is believed to be a genetic disorder characterized by a disturbed expression of the endochondral osteogenesis programme, and the remarkable clues from the fly reported by Kaplan et al. [8] in 1990 suggest a gain-of-function mutation in the genetic regulation of bone morphogenetic proteins.     

Hard tissue laser ablation mechanisms

The aim of this work is the experimental and theoretical investigation of the influence of variable laser parameters (wavelength, fluence, pulse repetition rate) and of the optical and thermophysical properties of bone tissue (absorption coefficient, tissue inhomogeneity) as well as of the sample thickness on ablation thresholds and ablation rate. Ablation and perforation experiments were conducted using a semiconductively pre-ionized transverse excitation atmospheric pressure (TEA) carbon dioxide (CO₂) laser (10.6m and a sliding discharge TEA [hydrogen fluoride (HF)] laser (2.9m). The experimental data are discussed with respect to the following ablation mechanisms: thermal melting and vaporization process, pressure oscillation of gases released by the thermal decomposition of collagen and/or apatite, stresses due to the expansion of superheated water.     

Impact of different doses of ethinyl oestradiol on reduction of final height in constitutionally tall girls

Fifty-two tall girls were treated for constitutionally tall stature with different ethinyl oestradiol (EE) dosages. They were divided into three different treatment groups: group B (100 g EE/day;n=11); group C (300 g;n=25) and group D (500 g;n=16) and compared with an untreated group A (n=21) matched for age, height, bone age (BA) and height prediction. Using the height prediction method TW II, EE treatment reduced final height compared with the untreated girls in a weak dose-dependent manner, 2.3 cm (100 g/day), 3.0 cm (300 g/day), and 3.8 cm (500 g/day). Such a dose dependency was not found on applying the Bayley-Pineau height prediction method (100 g/day: 4.1 cm; 300 g/day: 4.2 cm; 500 g/day: 4.5 cm). However, there was a striking inverse correlation of the BA at the onset of treatment with the height reduction achieved using the TW II method (r: –0.43;P<0.001). Importantly, girls with a BA below 12 years at the onset of treatment experienced a height reduction of more than 6 cm.The EE dose used in the range of 100–500 g/day is not crucial for the amount of height reduction in tall girls. In general high dose EE treatment should be given restrictively, and especially so in girls with a BA (TW2 RUS-ZH) above 12.0 years.     

Precision and intersite correlation of bone densitometry at the radius, tibia and femur with peripheral quantitative CT

Objective. To compare the in situ precision of peripheral quantitative CT (pQCT) at the radius, tibia and femur, and to analyze the intersite correlation, in order to determine whether measurements at the lower extremity reproduce results at the radius or are of additional informative value. Design and material. pQCT measurements were performed in 86 elderly cadavers (mean age 80.5 years) at trabecular and cortical locations in the radius, tibia and femur, determining densitometric (bone mineral content and density) as well as geometric parameters (cross-sectional area, cortical thickness, polar moment of inertia and others). In 14 cadavers, repeated measurements were obtained at all sites on four different days. Results and conclusions. At cortical sites, the precision for the densitometric and geometric variables ranged from 0.4% to 4.3%, and was similar for the radius, tibia and femur. At trabecular locations, the reproducibility of the density measurements ranged from 1.8% to 2.5% at the radius, and from 3.2% to 5.9% at the femur and tibia. The intersite correlation of the total bone mineral content ranged from 0.87 and 0.97 at cortical sites, and from 0.63 to 0.85 at trabecular locations. The trabecular density showed a higher similarity between the tibia and femur (r=0.68–0.78) than between the radius and the lower extremity (r=0.41–0.45). The results demonstrate a substantial heterogeneity of trabecular bone in elderly individuals and advocate measurements directly at the site of clinical or scientific interest. Received: 5 July 1999 Revision requested: 12 August 1999 Revision received: 31 August 1999 Accepted: 13 September 1999     

Simple, Rapid Enzyme-Linked Immunosorbent Assay (ELISA) for the Determination of Rat Osteocalcin

Determination of the concentration of osteocalcin in rat serum is frequently performed using a commercially available radioimmunoassay (RIA). However, this assay takes 3 days to complete, uses radioactive material, and has a narrow linear range. The limited range of the RIA makes it necessary to test multiple dilutions of the sample which frequently results in values that differ, depending on the dilution. In order to overcome these limitations, we have developed an ELISA that utilizes the same standards and anti-rat osteocalcin antiserum, as is used in the RIA. The principle of the ELISA is that the osteocalcin in the sample competes with osteocalcin previously immobilized on a microtiter plate to bind to the available anti-rat osteocalcin antibodies. The amount of antibody bound to the immobilized osteocalcin is determined colorimetrically using a secondary antibody coupled to alkaline phosphatase. This ELISA has a three-log linear response with a sensitivity of 0.1–0.15 ng/ml and intra- and interassay coefficient of variance (CV) values of less than 10%. Most importantly, the assay is rapid and only requires a 2-hour incubation of the sample with the antiserum. The incubation time is important since we and others have observed a significant decrease in the osteocalcin level from serum samples incubated for long periods of time with the antiserum, presumably due to degradation of the osteocalcin. In general, the commercially available RIA gives osteocalcin values that are one-half to one-fourth that of the ELISA because the RIA requires a 48-hour incubation time. Received: 14 November 1997 / Accepted: 9 July 1998     

High Bilirubin Levels Interfere with Serum Tartrate-Resistant Acid Phosphatase Determination: Relevance as a Marker of Bone Resorption in Jaundiced Patients

Serum tartrate-resistant acid phosphatase (TRAcP) activity is considered to be a biochemical marker of bone resorption. Recently, a lack of specificity of collagen-related markers for assessing bone turnover has been observed in patients with chronic liver disease. Thus, it could be of great interest to determine serum TRAcP activity in such patients. However, nonspecificity of the analytical reaction could occur when hemolyzed, lipemic, or icteric specimens are analyzed. Therefore, we have studied the interference caused by bilirubin in the measurement of serum TRAcP activity using the Hillmann method. The interference was assessed in two pools of serum containing different bilirubin concentrations but with similar total AcP levels. Mixing proportional parts of the two pools, 10 samples were also obtained. Serum activities of total AcP and TRAcP, and the concentration of bilirubin were measured in the 10 samples. Both the actual and the expected values obtained by theoretical calculations were compared. Serum bilirubin values of 2.4 mg/dl showed a negative interference of 15% in the determination of serum TRAcP activity, whereas values of bilirubin higher than 10 mg/dl interfered totally with the measurement of serum TRAcP. Bilirubin did not interfere with the total AcP determination. This study clearly shows the interference of bilirubin in the determination of serum TRAcP. This finding should be considered when bone metabolism disorders are evaluated in jaundiced patients. Received: 6 April 1998 / Accepted: 1 October 1998     

Radiation doses of yttrium-90 citrate and yttrium-90 EDTMP as determined via analogous yttrium-86 complexes and positron emission tomography

Yttrium-90 is used for palliative therapy for the treatment of skeletal metastases, but because it is a pure - emitter, data on the pharmacokinetics and radiation doses to metastases and unaffected organs are lacking. To obtain such data, the present study employed yttrium-86 as a substitute for⁹⁰Y, with detection by positron emission tomography (PET). The study compared the properties of two different⁸⁶Y complexes —⁸⁶y-citrate and⁸⁶Y -ethylene diamine tetramethylene phosphonate (EDTMP) — in ten patients with prostatic cancer who had developed multiple bone metastases (the ten patients being divided into two groups of five). Early dynamics were measured up to 1 h post injection (p.i.) over the liver region, followed by subsequent whole-body PET scans up to 3 days p.i. Absolute uptake data were determined for normal bone, bone metastases, liver and kidney. Radiation doses were calculated according to the MIRD recommendations. Based on the pharmacokinetic measurements of the distribution of the⁸⁶Y complexes, it was possible to calculate radiation doses for the bone metastases and the red bone marrow delivered by complexes containing⁹⁰Y. In 1 cm³ of bone metastasis, doses of 26±11 mGy/MBq and 18±2 mGy/MBq were determined per MBq of injected⁹⁰Y- citrate and⁹⁰Y- EDTMP, respectively. The doses to the bone marrow were 2.5±0.4 mGy/MBq for⁹⁰Y- citrate and 1.8±0.6 mGy/MBq for⁹⁰Y-EDTMP.⁸⁶Y and PET provide quantitative information applicable to the clinical use of⁹⁰Y. This method may also be useful for the design of other⁹⁰Y radiopharmaceuticals and for planning radiotherapy dosages.