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Selected Abstracts

Comparison between different dialysate calcium concentrations in nocturnal hemodialysis

HEMODIALYSIS INTERNATIONAL, Issue 2 2007
Nigel D. TOUSSAINT
Abstract Benefits of dialysate with greater calcium (Ca) concentration are reported in nocturnal hemodialysis (NHD) to prevent Ca depletion and subsequent hyperparathyroidism. Studies with patients dialyzing against 1.25 mmol/L Ca baths demonstrate increases in alkaline phosphatase (ALP) and parathyroid hormone (PTH) and increasing dialysate Ca subsequently corrects this problem. However, whether 1.5 or 1.75 mmol/L dialysate Ca is most appropriate for NHD is yet to be determined, and differences in the effect on mineral metabolism of daily vs. alternate daily NHD have also not been well defined. We retrospectively analyzed mineral metabolism in 48 patients, from 2 institutions (30 at Monash and 18 at Geelong), undergoing home NHD (8 hr/night, 3.5,6 nights/week) for a minimum of 6 months. Thirty-seven patients were dialyzed against 1.5 mmol/L Ca bath and 11 patients against 1.75 mmol/L. We divided patients into 4 groups, based on dialysate Ca and also on the hours per week of dialysis, <40 (1.5 mmol/L, n=29 and 1.75 mmol/L, n=8) or ,40 (n=4 and 7). We compared predialysis and postdialysis serum markers, time-averaged over a 6-month period, and the administration of calcitriol and Ca-based phosphate binders between 1.5 and 1.75 mmol/L Ca dialysate groups. Baseline characteristics between all groups were similar, with a slightly longer, but nonsignificant, duration of NHD in both 1.75 mmol/L dialysate groups compared with 1.5 mmol/L. The mean predialysis Ca, phosphate, and Ca × P were similar between the 1.5 and 1.75 mmol/L groups, regardless of NHD hr/week. Postdialysis Ca was significantly greater, with 1.75 vs. 1.5 mmol/L in those dialyzing <40 hr/week (2.64±0.19 vs. 2.50±0.12 mmol/L, p=0.046), but postdialysis Ca × P were similar (2.25±0.44 vs. 2.16±0.29 mmol2/L2, p=0.60). Parathyroid hormone was also lower with 1.75 vs. 1.5 mmol/L baths in the <40 hr/week groups (31.99±26.99 vs. 14.47±16.36 pmol/L, p=0.03), although this difference was not seen in those undertaking NHD ,40 hr/week. Hemoglobin, ALP, and albumin were all similar between groups. There was also no difference in vitamin D requirement when using 1.75 mmol/L compared with the 1.5 mmol/L dialysate. Multivariate analysis to determine independent predictors of postdialysis serum Ca showed a statistically significant positive association with predialysis Ca, dialysate Ca, and total NHD hr/week. An elevated dialysate Ca concentration is required in NHD to prevent osteopenia but differences in serum markers of mineral metabolism between 1.5 and 1.75 mmol/L Ca dialysate in NHD in our study were few. This was similar for patients undertaking NHD <40 or ,40hr/week, although differences in the frequency of NHD may also be as important as dialysate Ca with regard to serum Ca levels. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown and further studies addressing bone metabolism with larger NHD numbers are required. [source]

The Expression of an Alcohol Deprivation Effect in the High,Alcohol-Drinking Replicate Rat Lines Is Dependent On Repeated Deprivations

ALCOHOLISM, Issue 6 2000
Zachary A. Rodd-Henricks
Background: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of alcohol/total fluid intake and voluntary intake of ethanol (EtOH) solutions over baseline drinking conditions when EtOH access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. In the current study, we examined the effects of initial deprivation length and number of deprivation exposures on the ADE in the replicate lines of the high,alcohol-drinking (HAD) rats. Methods: Adult male HAD-1 and HAD-2 rats received 24 hr free-choice access to 10% (v/v) EtOH and water for 6 weeks. Rats were then assigned to groups deprived of EtOH for 0 (control), or 2 to 8 weeks. All deprived groups were then given 24 hr access to EtOH for 2 weeks before being deprived of EtOH for another 2 weeks. This cycle of 2 weeks of access and 2 weeks of deprivation was carried out for a total of four deprivations. Results: After the initial EtOH deprivation period, EtOH consumption in HAD-1 and HAD-2 rats returned to baseline levels but failed to exhibit either an early onset ADE (initial 2 hr) or prolonged ADE (24 hr). An ADE was observed in two of the four deprived groups for the HAD-1 rats (2 week and 6 week groups) and in all deprived groups for the HAD-2 rats after a second deprivation, and in all deprived groups of both lines after a third deprivation. In the HAD-2 line, but not in the HAD-1 line, the duration of the ADE was prolonged into the second reinstatement day after the fourth deprivation. Conclusions: The expression of an ADE was observed only after repeated deprivation periods in the HAD lines. The duration of the ADE was prolonged in the HAD-2 line, but not in the HAD-1 line, with repeated deprivations, which suggests a dissociation between selection for alcohol preference and the effects of repeated deprivations on the duration of the ADE. [source]

Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2009
K. Gebauer
Summary Background, Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency. Objectives, To evaluate dosing frequency response of imiquimod 5% for treatment of AK. Methods, This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with , 10 but , 50 clinical AKs, one of which was histologically confirmed, were randomized (4 : 1) to 2,6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment. Results, One hundred and forty-nine (94 men and 54 women) white subjects, with a mean ± SD age of 71 ± 10·2 years, were enrolled. Twenty-eight subjects (18·8%) discontinued from study: 0%, 3·1%, 6·9%, 30·0% and 33·3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3·2%, 6·9%, 3·3% and 6·7% of subjects, and partial clearance (, 75% lesion reduction) in 0%, 22·6%, 24·1%, 20·0% and 36·7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively. Conclusions, Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0·002). [source]

Biodegradable polylactide membranes for bone defect coverage: biocompatibility testing, radiological and histological evaluation in a sheep model

CLINICAL ORAL IMPLANTS RESEARCH, Issue 4 2006
Gerhard Schmidmaier
Abstract: Large bony defects often show a delayed healing and have an increasing risk of infection. Several materials are used for the coverage of large defects. These materials must be biocompatible, easy to use, and must have an appropriate stability to present a mechanical hindrance. Aim of this study was to investigate two different biodegradable membranes for defect coverage in a sheep model. Round cranial defects (1.5 cm diameter) were created in sheep. Six different treatments were investigated: defects without membrane, defects covered with a poly(d,l -lactide) or with a 70/30 poly(l/d,l -lactide) membrane and all defects with or without spongiosa filling. The sheep were sacrificed 12 or 24 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on CT radiographs. Histomorphometry and host-tissue response were evaluated by light microscopy. The biocompatibility was investigated by analyzing the amount of osteoclasts and foreign body cells. Both membranes served as a mechanical hindrance to prevent the prolapse of soft tissue into the defect. The biocompatibility test revealed no differences in the amount and distribution of osteoclasts at the two investigated time points and between the investigated groups. No negative effect on the tissue regeneration was detectable between the investigated groups related to the type of membrane, but a foreign body reaction around the two membrane types was observed. In the membrane-covered defects, the spongiosa showed a progressing remodeling to the native bony structure of the cranium. The groups without spongiosa partly revealed new bone formation, without complete bridging in any group or at any time point. Comparing the 12 and 24 weeks groups, an increased bone formation was detectable at the later time point. In conclusion, the results of the present in vivo study reveal a good biocompatibility and prevention of soft tissue prolapse of the two used membranes without differences between the membranes. An enhanced remodeling of the spongiosa into native bony structures under the membranes was detectable, but no osteopromoting effect was observed due to the membranes. [source]