Effect of vitamin D3 treatment on bone density in neurofibromatosis 1 patients: A retrospective clinical study

ObjectivesWe have previously demonstrated reduced bone density and an increased incidence of 25-hydroxy vitamin D₃ (25-OH D₃) deficiency in adults with neurofibromatosis 1 (NF1) compared to healthy controls. Vitamin D₃ is a cheap, safe, and effective supplement in the general population, but its value in NF1 patients has not been demonstrated. This study investigates the therapeutic potential of oral vitamin D₃ on bone mineral density (BMD) in NF1 patients with vitamin D₃ deficiency.MethodsWe measured serum 25-OH D₃, parathyroid hormone, calcium, and bone alkaline phosphatase concentrations, urinary deoxypyridinoline concentrations, and BMD in 35 adults with NF1. Nineteen patients received vitamin D₃ supplementation for 2 years, six patients received supplementation for 1 year and 10 patients received no supplementation. Supplementation was administered in a dose that maintained the serum 25-OH D₃ level above 30 μg/l. BMD was measured again at 1 and 2 years, and biochemical assessments of bone metabolism were measured at least every half year during therapy.ResultsTreated subjects had significantly reduced loss of BMD, as measured by T score at the hip (p = 0.011) and lumbar spine (p = 0.022). The effect on hip BMD was apparent at 1 year in comparison to baseline (p = 0.02) and was greater at 2 years in comparison to measurements at 1 year (p = 0.02).ConclusionsVitamin D₃ supplementation improves BMD in adult NF1 patients. Further studies are needed to elucidate the mechanisms responsible for reduced BMD in NF1 patients.     

Use of Imatinib in the Prevention of Heterotopic Ossification

Background

Heterotopic ossification (HO) is a common complication following orthopedic and trauma surgery, which may have substantial negative effects on the postoperative outcome. Angiogenesis appears to play a critical role in heterotopic ossification. One of the involved signaling molecules is platelet-derived growth factor (PDGF) which may be inhibited by imatinib.

Questions/Purposes

Our goal was to prevent HO by pharmacologically interfering with the molecular signaling pathways involved in the developmental process. We hypothesized that by administering a proven inhibitor of PDGF expression, heterotopic bone formation may be prevented.

Methods

The effect of imatinib on HO formation was studied in a murine model which reliably produces islets of HO within the soft tissue following Achilles tenotomy. The control group underwent Achilles tenotomy only. The imatinib group received imatinib mesylate. After trial completion, the limbs were harvested and scanned by micro-CT. Heterotopic bone volume was then identified and quantified.

Results

The mean volume of heterotopic bone formed in the control group was 0.976mm³ compared to 0.221 mm³ in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group.

Conclusions

The administration of imatinib was associated with a significantly reduced volume of HO. This may be due to the inhibitory effect of imatinib on the PDGF signaling pathway during development of HO.

Clinical Relevance

The successful reduction of HO formation following imatinib administration has led to further insight concerning the pathogenesis of HO which in the future may lead to new clinical approaches towards the prevention of HO.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9335-y) contains supplementary material, which is available to authorized users.     

Oral High-Dose Vitamin D Dissolved in Oil Raised Serum 25-Hydroxy-Vitamin D to Physiological Levels in Obese Patients After Sleeve Gastrectomy—A Double-Blind,Randomized, and Placebo-Controlled Trial

Background

Osteomalacia and cardiometabolic disorders are favored in morbidly obese patients due to an inadequate vitamin D (VD) status. Former trials supplementing orally VD (20–50 μg/day) in crystalline form after sleeve gastrectomy (SG) could not stabilize serum 25-hydroxycholecalciferol levels at predefined concentrations (≥50 nmol/l). We hypothesized that VD in an oily suspension would increase its bioavailability resulting in normal serum VD levels minimizing markers of cardiometabolic risk.

Methods

Morbidly obese patients (n?=?94, BMI 51.8?±?11.5 kg/m²) received orally 80 μg/day VD₃ dissolved in oil or placebo (pure oil) in a randomized, double-blind, parallel-group study for 12 weeks after SG. 25-hydroxycholecalciferol, parathyroid hormone, albumin, alkaline phosphatase, phosphate, magnesium, calcium, creatinine, C-reactive protein, lipids, glucose, and glycated hemoglobin were determined in serum/plasma before surgery and after 4 and 12 weeks of supplementation. Intake of energy, fat, and VD were monitored using a 3-day food record.

Results

Seventy-nine patients were included in statistical analysis. Preoperatively, 77.2 and 40.5 % presented 25-hydroxycholecalciferol levels <75 and <50 nmol/l, respectively. After 12 weeks of supplementation, significantly more patients in the VD group exhibited levels >50 nmol/l (92 %) and >75 nmol/l (68 %) compared to the placebo group (54 and 22 %, respectively). Parameters of mineral metabolism and cardiometabolic risk were not modulated by intervention.

Conclusion

Supplementation of 80 μg/day VD₃ by oil is an effective and safe measure to prevent VD deficiency and to treat a preexisting undersupply in patients after SG. Cardiometabolic risk factors were, however, not affected; probably, higher VD doses might be necessary.

Clinical Trial Registration

This trial was registered retrospectively on November 14, 2014, at the German Clinical Trials Register as DRKS00007143.

     

Wie häufig werden Patienten mit depressiven Störungen in der hausärztlichen Praxis erkannt?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Hausärzte sind als Primärversorger für Patienten mit depressiven Störungen entscheidende Weichensteller...     

Case reports

The clinical presentation of lead intoxication may vary widely and in the absence of a high clinical index of suspicion, the diagnosis may be missed. The effects of lead on mitochondrial oxidative phosphorylation and its interaction with calcium-mediated processes explain the heterogenous presentation. In this case report, the diagnosis was finally made when bilateral wrist drop developed on top of abdominal cramps and anemia. Before, ascites raised the suspicion of a tumor. Therefore, each element of the triad of unexplained anemia, abdominal cramps, and bilateral wrist (or foot) drop should lead any physician to consider the diagnosis of lead intoxication. This case also illustrates the importance of a careful and meticulous social history in patient management.     

Voiding and sexual dysfunction after deep rectal resection and total mesorectal excision

OBJECTIVE: Voiding and sexual dysfunction after deep rectal resection have been described with various frequencies in the literature. In this study, we prospectively evaluated the baseline preoperative voiding and sexual function in a cohort of patients undergoing deep rectal resection with mesorectal excision to determine any pre-existing abnormalities. Postoperatively, we sought first to determine the frequency of a urinary or sexual dysfunction, secondly whether there is a time-dependent change of a dysfunction and thirdly whether there is a relationship between postoperative urological dysfunction and the patient's age. PATIENTS AND METHODS: Fifty-two patients (36 men and 16 women) with a primary rectal carcinoma were prospectively examined directly before and after the operation, as well after the third and sixth postoperative month. The preoperative urological evaluation consisted of a careful voiding and sexual history, uroflowmetry and a sonographic residual urine determination. A detailed sexual history was obtained via the use of a questionnaire. RESULTS: Urological dysfunction: Preoperatively, 49 of the 52 patients had a completely normal bladder function and three patients had post void residual >100 ml. Postoperatively, 12 of the 49 patients with normal preoperatively urinary function had voiding dysfunction, but only four male patients had residual urine in the third postoperative month. Therefore, in about 90% of the patients, postoperative bladder function became normal and only 10% suffered from vesical denervation after 6 months. We could not determine a relationship between the degree of bladder dysfunction and the patient's age due to a relatively small patient cohort in this study. Sexual dysfunction: Preoperatively, 36 (seven women, 29 men) of the 52 patients were potent and had regular sexual intercourse. Eleven men specified a limited erection, but all had occasional sexual intercourse. One of the potent men experienced no ejaculation. Postoperatively, eight of the 29 men were impotent and two of the 29 men experienced retrograde ejaculation. Therefore, 30% of the preoperatively potent men had sexual dysfunction postoperatively. There was no correlation between the postoperative impotence and the age of the patients at the time of surgery. Although it is likely that the potency may diminish with advanced age, the incidence of impotence was not higher in the older patients of our study. CONCLUSIONS: The results of our study underline the importance of risk estimation for possible postoperative urological dysfunction by means of preoperative urologic evaluation in this patient collective. Of patients with postoperative bladder dysfunction, 90% improved within 6 months after surgery and only 10% continued to have bladder dysfunction beyond 6 months, indicating irreversible nerve damage.     

Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology

Cytokines released by infiltrating T cells may contribute to the hepatic injury in chronic hepatitis. Therefore, we characterized peripheral blood- and liver-infiltrating T cells from patients with chronic hepatitis of different etiology and determined the T cell phenotypes and the cytokine release. Liver tissue and peripheral blood-derived T cells from patients with autoimmune hepatitis and primary biliary cirrhosis predominantly expressed CD4-molecules and the α- and β-chains of the T cell receptor (TCR). In chronic viral hepatitis B and C, liver- and blood-derived T cells were preferentially CD8+ T cells expressing the αβ TCR. Mitogenic stimulation with irradiated Daudi lymphoma cells and phytohemagglutinin led to a strong release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) by T cells in patients with chronic hepatitis and in healthy controls. T cells from patients with primary biliary cirrhosis and some patients with autoimmune hepatitis showed a significantly higher secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10) than T cells from patients with chronic viral hepatitis or healthy controls. Histologic inflammatory activity did not correlate with the amount of cytokines released after mitogenic activation. In conclusion, liver tissue and peripheral blood T cells of patients with autoimmune hepatitis and primary biliary cirrhosis were dominated by CD4+ TCR αβ+ T helper/inducer cells, whereas in chronic viral hepatitis an enrichment of CD8+ TCR αβ+ cytotoxic/suppressor T cells was observed. In addition, analysis of the cytokine release showed that T cells in autoimmune and chronic viral liver diseases secreted high amounts of IFN-γ and TNF-α, cytokines predominantly secreted by T_hl-like cells. The secretion of the T_h2 cytokines. IL-4 and IL-10, however, was increased in autoimmune hepatitis and primary biliary cirrhosis. These data show that in autoimmune and chronic viral liver diseases different functional T cell subsets are activated.     

Comparing the predictive value of the pelvic ring injury classification systems by Tile and by Young and Burgess

Introduction

Radiology-based classifications of pelvic ring injuries and their relevance for the prognosis of morbidity and mortality are disputed in the literature. The purpose of this study was to evaluate potential differences between the pelvic ring injury classification systems by Tile and by Young and Burgess with regard to their predictive value on mortality, transfusion/infusion requirement and concomitant injuries.

Patients and methods

Two-hundred-and-eighty-five consecutive patients with pelvic ring fractures were analyzed for mortality within 30 days after admission, number of blood units and total volume of fluid infused during the first 24 h after trauma, the Abbreviated Injury Severity (AIS) scores for head, chest, spine, abdomen and extremities as a function of the Tile and the Young–Burgess classifications.

Results

There was no significant relationship between occurrence of death and fracture pattern but a significant relationship between fracture pattern and need for blood units/total fluid volume for Tile (p < .001/p < .001) and Young–Burgess (p < .001/p < .001). In both classifications, open book fractures were associated with more fluid requirement and more severe injuries of the abdomen, spine and extremities (p < .05). When divided into the larger subgroups “partially stable” and “unstable”, unstable fractures were associated with a higher mortality rate in the Young–Burgess system (p = .036). In both classifications, patients with unstable fractures required significantly more blood transfusions (p < .001) and total fluid infusion (p < .001) and higher AIS scores.

Conclusions

In this first direct comparison of both classifications, we found no clinical relevant differences with regard to their predictive value on mortality, transfusion/infusion requirement and concomitant injuries.