Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Acquired dyschromatopsia in combined exposure to solvents and alcohol

Hypothesis: Does occupational exposure to solvents in combination with alcohol intake give rise to acquired color vision defects? Method: A total of 138 individuals exposed to solvents (toluene, xylene, trichloroethylene, tetrachloroethylene) were examined using Lanthony’s D-15 test and compared with 100 nonexposed controls. The extent of color vision loss was quantitatively assessed based on Bowman’s color confusion index (CCI). A cumulative exposure index was calculated from the hours of exposure per day and the years of exposure. In 30 persons who were exposed to trichloroethylene and tetrachloroethylene, urinary trichloroacetic acid was assessed as a parameter of exposure. Alcohol intake was calculated as based on interviews of patients in grams of ethyl alcohol per week. Results: Individuals who consumed more than 250 g alcohol/week and were simultaneously exposed to solvents showed a significantly elevated CCI (P = 0.0044). No significant correlation emerged between trichloroacetid acid excretion in the urine or the cumulative exposure index and the CCI. Conclusion: The combination of alcohol intake and occupational exposure to solvents discloses the risk of acquired subclinical color vision defects.     

Ergebnisse der strukturierten Konsensuskonferenz „Bild gebende Verfahren in der Unfallchirurgie“ und Methodik zur Messung der Akzeptanz unter Tagungsteilnehmern

Existing knowledge and present experience relating to the indications for imaging techniques in trauma surgery were summarised, screened and considered in different ways by representatives of various professional scientific bodies, with the aim of finding what procedures should be implemented as the primary examination techniques after a careful clinical examination when particular posttraumatic situations affecting the knee, foot, ankle, or hand were found. In the course of an interdisciplinary consensus conference the evidence-based recommendations prepared by a panel were discussed and modified, giving rise to statements on the suitability of the given imaging techniques in 28 different clinical situations immediately after a clinical examination, based on scientific evidence and medical consensus. The degree of consensus was measured and carefully documented. These statements were transformed into decision algorithms and presented to doctors working in accident and emergency medicine during a conference on trauma surgery, with the aim of.measuring the acceptance of the statements among those attending the trauma surgery meeting. The remarks made by the participants during the discussion and the results of the acceptance measurements clearly show the need for further discussion among experts.     

Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey--the Rotterdam Study.

Serum ALP may be a good indicator of Paget's disease in epidemiologic studies. Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP. INTRODUCTION: Evidence from radiographic surveys of limited skeletal sites has shown that Paget's disease of bone (PDB) is common in the elderly and has a distinct geographic variation. There is no information, however, about the relation of serum alkaline phosphatase (ALP) activity, a marker of the disease, and its prevalence in the population. MATERIALS AND METHODS: We analyzed data from a well-defined Dutch population cohort (the Rotterdam study) with the following specific aims: (1) to assess the relationship between serum ALP activity and prevalence of radiographically diagnosed PDB, (2) to estimate the overall prevalence of the disease in the Netherlands, and (3) to assess the appearance of the disease with time. Using a nested case-control design, subjects with an increased serum ALP and normal serum liver enzymes were matched for gender and age (1 to 6) with subjects with normal serum ALP activity. Radiographs of the thoracic and lumbar spine, pelvis, proximal femurs, knees, wrists, and hands were taken. RESULTS AND CONCLUSIONS: PDB was diagnosed in 20.5% of subjects with elevated serum ALP activity and in 2.3% in those with normal serum ALP activity, increasing with age in both groups. The relative risk (RR) for PDB in the presence of raised serum ALP activity was 10.9 (95% CI, 4.8, 24.9). The estimated prevalence of PDB in the population was 3.6%, and the large majority (about 86%) had normal serum ALP activity, contrasting findings in bone clinics where the opposite is the case. Finally, in subjects with normal and raised serum ALP activity but no PDB at baseline, radiographs taken 6-9 years later showed no evidence of the disease. This study demonstrated that serum ALP activity is a sensitive marker of PDB in men and women >55 years of age, but the majority of those affected have normal serum ALP activity.     

Resorption rate and biocompatibility characteristics of two polyester ventilation tubes in a guinea pig model

OBJECTIVES: Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation. STUDY DESIGN AND SETTING: 50/50 poly (D, L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination. RESULTS: The PLA tubes remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy. CONCLUSIONS AND SIGNIFICANCE: Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA-approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. EBM RATING: B-2.     

Antimuscarinic Effects of (R)- and (S)-Oxyphencyclimine Hydrochloride

The (R)-( + )- and (S)-( – )-enantiomers of the anticholinergic compound, oxyphencyclimine, were synthesized from (R)-( – )- and (S)-( + )-2-cyclohexyl-2-hydroxy-2-phenylethanoic acid, respectively. The potencies of the enantiomers were compared using a cholinergic receptor binding assay. The (R)-( + )-enantiomer inhibited binding 29 times more potently than the (S)-( – )-enantiomer.     

Statistical vs Clinical Significance in Product Testing: Can They Be Designed to Satisfy Equivalence?

Statistical issues associated with demonstrating significance between treatment groups (efficacy or superiority) and nonsignificance (equivalence) are presented and discussed. Methodologies for demonstrating efficacy of a product are proposed and contrasted, incorporating clinical and statistical criteria, with emphasis on situations in which placebo groups are precluded from the study design. Distinctions are drawn between study designs for demonstrating superiority and those for equivalence, including the determination of sample sizes needed for the different approaches. The "at least as good as" criterion is proposed as a reasonable alternative to that of equivalence in active control equivalence studies for demonstrating that dental product modifications or new products are efficacious.     

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of ²⁰¹Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the ²⁰¹Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of ²⁰¹Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of ²⁰¹Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of ²⁰¹Tl derived from healthy volunteers who underwent the same combined protocol.