Monocyte adhesion molecule expression in interstitial inflammation in patients with renal failure.

BACKGROUND: Patients with renal failure have an increased susceptibility to infections. We therefore studied the recruitment of monocytes and their expression of adhesion molecules CD11b and CD62L at the site of interstitial inflammation in patients with renal failure. Furthermore, we studied if the capacity of monocytes to up-regulate CD11b in interstitial inflammation was determined by the interstitial concentration of chemotactic factors. METHODS: Three intensities of interstitial inflammation (0, intermediate and intense) were established in skin blister chambers. Leukocyte count, CD11b/CD62L expression, monocyte chemotactic protein-1 (MCP-1) and blister activity in terms of CD11b mobilization were determined. RESULTS: The CD62L expression on monocytes was lower in the peripheral circulation in patients with renal failure compared with healthy subjects (P<0.005 and P<0.001). At the site of interstitial inflammation patients had a higher expression of CD62L (intermediate, P<0.05; intense, P<0.005). Furthermore, monocytes from patients had an impaired capacity to mobilize CD11b both in the peripheral circulation (P<0.005) and at the intermediate and intense sites of interstitial inflammation (P<0.005 and P<0.001, respectively) compared with cells collected from healthy subjects. We incubated monocytes in blister exudates, in order to explore whether this phenomenon is caused by cellular factors and/or to the interstitial concentration of chemotactic mediators. The expression of CD11b on monocytes from healthy blood donors incubated in blister exudates from either patients or healthy subjects in vitro was similar. The interstitial concentration of MCP-1 at the site of intermediate inflammation was significantly lower in patients with renal failure compared with the corresponding blister exudate collected from healthy subjects (P<0.05), but no differences were observed at the site of intense inflammation. Furthermore, neutralizing the action of MCP-1 in blister exudates with monoclonal antibodies did not have any impact on monocyte CD11b expression following incubation in blister exudates. CONCLUSION: These studies indicate that the impaired capacity of monocytes to mobilize CD11b at the site of inflammation in patients with renal failure is more dependent on constitutive cellular factors than the concentration of CD11b mobilizing factors in the interstitium.     

Normative values of bone parameters of children and adolescents using digital computer-assisted radiogrammetry (DXR).

PURPOSE: To verify whether estimation of bone mineral density (BMD) using digital X-ray radiogrammetry (DXR) is possible on children and to determine normative values of both such a DXR-BMD estimate and a corresponding metacarpal index (DXR-MCI) on. PATIENTS AND METHODS: In retrospect, X-rays were selected of the hands of 200 healthy Caucasian children (120 boys and 80 girls, aged 4-18 yr). The involved children were selected among a larger group of children submitted to the surgical department of our institute for evaluation of a suspected fracture after an occurred trauma. All children with a verified fracture or a chronic bone-related disease, including bone age retardation or acceleration, were excluded from the study. Furthermore, only conventional X-rays with the same film and capture parameters were included. The images were scanned and analyzed using the Pronosco X-posure system V.2 (Sectra Pronosco, Denmark). DXR-BMD, DXR-MCI, and a porosity index (DXR-PI) were automatically calculated using the midshafts of the metacarpals II-IV. Mean values of DXR-BMD and DXR-MCI were calculated separately for girls and boys in 2-yr intervals. RESULTS: In the present study the system has been demonstrated to be capable of calculating DXR-BMD from conventional X-rays of the hand from children down to approx 6 yr of age. This ability depended somewhat on the diameter and the length of the involved metacarpals. The success rate was higher for large bones than for small bones. The system succeeded in analyzing the images of 110 boys and 68 girls. Values of DXR-BMD were observed to increase with age from 0.40 g/cm2 to 0.62 g/cm2 in the male group and from 0.39 g/cm2 to 0.54 g/cm2 in the female group. Girls aged 11-12 yr had a higher DXR-BMD than did boys, corresponding to the earlier entry to puberty of girls. Standard deviations (SDs) reached values of up to 0.05 g/cm2. DXR-MCI increased with age from 0.36 to 0.47 for boys and from 0.34 to 0.49 for girls with a maximum SD of 0.06. The correlation between DXR-BMD and age was r=0.83 and r=0.84 for boys and girls, respectively. The corresponding correlations for DXR-MCI was lower, with observed correlations of r=0.63 (boys) and r=0.68 (girls), respectively, with p<0.01 in all cases. The DXR-PI did not reveal a significant correlation to age (r=-0.31 and r=0.04. respectively) and showed SDs marginally higher than the calculated mean values. CONCLUSION: The newly available DXR-methodology seems to offer the ability to determine DXR-BMD and DXR-MCI in children starting with a bone age of 6. This possibility may be of special relevance for children suffering from chronic bone diseases that require repeated X-rays of the hand (e.g. to determine bone age). The acquired normative data suggest that the measurements are of clinical value owing to low age-dependent variability (SDs) relative to an observed high increase with age. The clinical value of the porosity index (DXR-PI) remains uncertain and is limited owing to a high inter-individual variability.     

Berufsbedingte Hauterkrankungen—Paradigma der Sekundärprävention

The dermatologist's procedure was introduced in 1972 by employers' liability insurance funds in the industrial, agricultural and public sectors of Germany's statutory occupational accident insurance as a "procedure for early detection of occupational skin diseases". So far, it is still the most relevant tool for secondary prevention in occupational dermatology in Germany. According to the intention of this procedure, insured persons with a skin disease in which an occupational aetiology is suspected must be offered preventive measures and, if necessary, given appropriate treatment to avoid their losing their jobs. On the initiative of the Central Federation of Industrial Professional Associations (HVBG), a study group was set up in 1999 from among its membership in cooperation with the Working Committee of Occupational and Environmental Dermatology (ABD) and the Professional Organisation of German Dermatologists (BVDD) to improve on the efficiency of the "classic" dermatologist's procedure. The proposed "optimised" dermatologist's procedure is based on the assumption that early detection followed by competent and intensified skin protection and skin care will be successful in retarding or stopping the progression of occupational dermatoses, while later treatment is likely to be less effective. In October 2002, a pilot study started in Northwest Germany to establish by scientific evaluation whether the implementation of secondary protective measures is definitively better when the provisional "optimised" dermatologist's procedure is followed. The study results should allow detailed suggestions for an improved dermatologist's procedure before it is introduced nationwide.     

An evaluation of the cardiovascular safety profile of duloxetine: findings from 42 placebo-controlled studies.

BACKGROUND AND OBJECTIVE: In recent years, new classes of medication, such as the serotonin-noradrenaline reuptake inhibitors (SNRIs), have been developed for use in the treatment of major depressive disorder (MDD). For many years, treatment options were largely limited to the use of monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). However, there have been published reports of orthostatic hypotension, arrhythmias and corrected QT (QTc) interval changes in patients treated with TCAs. As new medications become available, it is important to understand how their cardiovascular safety profile compares with that of more established agents to aid clinicians and patients in choosing the best treatment options. This study was designed to evaluate the cardiovascular safety profile of the SNRI duloxetine through evaluation of cardiovascular-related parameters and adverse events (AEs). METHODS: The cardiovascular safety of duloxetine was assessed using all placebo-controlled duloxetine clinical trial data as of December 2005. This consisted of data from 42 placebo-controlled clinical trials of 8504 patients who were treated with duloxetine. Additional information from a high-dose clinical pharmacology study and postmarketing safety surveillance are also presented. Of the placebo-controlled trials included in this analysis, clinical indications under investigation included MDD (15 studies), diabetic peripheral neuropathic pain (3 studies), fibromyalgia (2 studies), generalised anxiety disorder (3 studies) and lower urinary tract disorders (19 studies, all related to incontinence). Cardiovascular safety was evaluated based on vital signs, ECGs and the incidence of treatment-emergent AEs potentially related to cardiovascular safety. These safety parameters were analysed across all indications. To identify both serious and non-serious cardiovascular-related AEs, as well as AEs reported as the reason for discontinuation, a comprehensive list of terms derived from the Medical Dictionary for Regulatory Activities (version 8.0) was generated and used to search the duloxetine databases for cardiovascular-related events. RESULTS: Calculation of change from baseline to maximum in ECG parameters showed significant differences between treatment groups for all parameters, with decreases from baseline in RR, QRS and QT intervals for patients receiving duloxetine and increases from baseline for patients treated with placebo. These shifts were related to small heart rate changes, but the mean differences were not considered clinically relevant. Categorical analyses of shifts from normal to abnormal (or abnormal to normal) for heart rate and QT corrected for heart rate using Fridericia's formula (QTcF) values showed that most patients did not shift from their baseline category. Patients with MDD who were treated for up to 1 year with duloxetine had blood pressure changes early in treatment that then stabilised. Even in patients with elevated blood pressure at baseline in these clinical trials, no increased risk of sustained blood pressure elevation with duloxetine treatment was found. CONCLUSION: Overall, the findings presented here support our conclusions that use of duloxetine does not appear to be associated with significant cardiovascular risks in patients with conditions for which the drug has been approved or studied.     

Entwicklung der Hornhautdicke und -endothelzelldichte nach Kataraktextraktion mittels Phakoemulsifikation

Ziel der vorliegenden Untersuchung war es, das Ausma? der Hornhautsch?digung durch eine Kataraktextraktion im Hinblick auf das Hornhautendothel und die Hornhautdicke zu untersuchen. Patienten und Methode: In einer prospektiven Untersuchung wurde die Entwicklung der Hornhautdicke und der Endothelzelldichte an 48 Patienten untersucht. Die Patienten wurden mittels Phakoemulsifikation operiert. Die Hornhautdicke wurde dabei mit einem Ultraschallpachymeter bei 12 Uhr und im Hornhautzentrum und die Endothelzelldichte mit einer Endothelzellkamera an den gleichen Me?punkten pr?operativ sowie 4 Wochen, 4 Monate und 1 Jahr postoperativ bestimmt. Ergebnisse: Ein Jahr postoperativ nahm die Hornhautdicke nach Phakoemulsifikation an der 12-Uhr-Position um ca. 9% und im Hornhautzentrum um ca. 12% im Vergleich zum pr?operativen Wert zu. Die Endothelzelldichte war 1 Jahr postoperativ an der 12-Uhr-Position um ca. 27% und im Zentrum um ca. 18% reduziert. Das Patientenalter korrelierte signifikant mit dem Zellverlust an beiden Me?punkten. Bezüglich der Dickenzunahme ist keine signifikante Korrelation festzustellen. Schlu?folgerung: Nach einer Kataraktextraktion ist der Hornhautstoffwechsel reduziert. Als Indikator k?nnen der Verlauf der Endothelzelldichte und der Dicke herangezogen werden.      

Multilevel surgery for obstructive sleep apnea: short-term results.

OBJECTIVE: To determine the efficacy of a new multilevel surgical protocol for obstructive sleep apnea (OSA). STUDY DESIGN AND SETTING: Sixty patients with moderate to severe OSA because of multilevel pharyngeal obstruction were enrolled into this prospective, controlled clinical trial after clinical examination, endoscopy, and polysomnography. Surgery included uvulaflap, tonsillectomy, hyoid suspension, and radiofrequency treatment of the tongue base (group A). A second group did not receive hyoid suspension (group B). In both groups, nasal surgery was performed if necessary. Polysomnography and Epworth Sleepines Scale (ESS) were recorded at baseline and 2 to 15 months after surgery. RESULTS: In group A, the mean apnea-hypopnea index (AHI) decreased significantly after surgery (38.9 +/- 20.0 vs 20.7 +/- 20.6, P < 0.0001), whereas in group B the AHI did not. All secondary variables (minimal oxygen saturation, mean oxygen saturation, arousal index), and the ESS significantly improved in group A with only changes in arousal index and ESS reaching levels of significance in group B. CONCLUSION: The presented protocol including the hyoid suspension proved to be effective in the treatment of OSA, whereas surgery without hyoid suspension was less successful. EBM rating: B-2b.     

The orthopan tomoscintigram — a new application of emission computed tomography for facial bone scanning

The exact regional correlation of findings of facial bone scans, planar or SPECT, to dental orthopan X-ray films (OPT) is difficult because of the very different projection techniques. To improve correlative imaging in this regard a projection algorithm was developed that uses SPECT data of the skull for reconstructing an orthopan tomoscintigraphic projection. Fourteen conventional SPECT slices of the upper and lower jaws were obtained during bone scanning. All mandibular slices were superimposed resulting in a horseshoe shaped structure, which was marked by an ROI which was divided into segments. All 14 SPECT slices were then masked by this segmental ROI, thereby marking the teeth-carrying bone in all slices. The information from this horseshoe like ROI is then transformed into lines. Line by line arrangement results in an orthopan projection, the orthopan tomoscintigram. This new display allows 1:1 true scale superimposition with the X-ray OPT and markedly facilitates correlative imaging.     

Atrial natriuretic peptide and verapamil can prevent gentamicin induced acute renal failure in the rat

Summary: Calcium channel blockers are able to improve renal function in acute renal failure (ARF) and natriuretic peptides can also exert beneficial effects. At present it is unknown whether administration of atrial natriuretic peptide (ANP) and a calcium channel blocker given before a toxic lesion can prevent gentamicin induced ARF. the mechanisms of action of natriuretic peptides and calcium channel blockers are different and, as yet, it has not been clarified if combined administration can augment the effects on renal function. After a basal period we investigated the effects of verapamil (VER, 0.66 mg/kg), ANP, (30 μg/kg) and a combination of both (identical doses as described individually). the drugs were given intravenously for a period of 40 min (infusion period) before gentamicin (15 mg/kg, i.v.) was administered for induction of ARF. Basal values for glomerular filtration rate (GFR, mL/min) were around 1.8 with no differences between the groups. At the end of the infusion period (before application of gentamicin) GFR was significantly elevated with VER + ANP (3.13 ± 0.51), ANP (2.70 ± 0.59) and VER (2.34 ± 0.47) compared to controls (saline, 1.7 ± 0.48). After application of gentamicin GFR significantly dropped in the control group (0.77 ± 0.21, 0.75 ± 0.19, respectively), indicating development of ARF. In contrast with VER + ANP, ANP and VER GFR could be maintained for 30 min (2.47 ± 0.39, 2.28 ± 0.33, 2.22 ± 0.43, respectively) and 130 min (2.11 ± 0.32, 1.86 ± 0.29, 2.11 ± 0.28, respectively) after gentamicin. Moreover ANP and VER revealed natriuretic activity and, due to their vasorelaxing potency, also influenced arterial blood pressure. We conclude that both VER and ANP are able to prevent early gentamicin induced ARF when given before the toxic lesion. Both drugs induce hyperfiltration while infused, in particular when administered in combination.