Norethisterone Treatment, a Major Risk-Factor for Veno-Occlusive Disease in the Liver After Allogeneic Bone Marrow Transplantation

In this single-center study, we retrospectively analyzed incidenceand risk factors for hepatic veno-occlusive disease (VOD) in 249 consecutive patients who underwent allogeneic hematopoietic stem celltransplantation between January 1990 and June 1995. Twenty-four of the249 transplanted patients developed VOD. The probabilities ofdeveloping VOD were 17% among women and 7% in men (P = .01). In women treated with norethisterone, the incidence was 27%compared with 3% in women without this treatment (P = .007).One-year survival rates were 17% and 73% in patients with (n = 24)or without VOD (n = 225), respectively. The use of heparin prophylaxis (100 IE/kg/24 hours for 1 month) did not alter the incidence or 1-year mortality of VOD. In multivariate analysis, thefollowing risk factors were significant: norethisterone treatment (P < .001), bilirubin >26 µmol/L before bone marrowtransplantation (BMT) (P = .002), one HLA-antigen mismatch(P = .003), previous abdominal irradiation (P = .02), and conditioning with busulphan (P = .02). Ourconclusion is that norethisterone treatment should not be used inpatients undergoing BMT and heparin prophylaxis did not affect theincidence or mortality of VOD.     

No effect of risedronate on femoral periprosthetic bone loss following total hip arthroplasty: A 4-year follow-up of 61 patients in a double-blind,randomized placebo-controlled trial

Background and purpose

We have previously shown that during the first 2 years after total hip arthroplasty (THA), periprosthetic bone resorption can be prevented by 6 months of risedronate therapy. This follow-up study investigated this effect at 4 years.

Patients and methods

A single-center, double-blind, randomized placebo-controlled trial was carried out from 2006 to 2010 in 73 patients with osteoarthritis of the hip who were scheduled to undergo THA. The patients were randomly assigned to receive either 35 mg risedronate or placebo orally, once a week, for 6 months postoperatively. The primary outcome was the percentage change in bone mineral density (BMD) in Gruen zones 1 and 7 in the proximal part of the femur at follow-up. Secondary outcomes included migration of the femoral stem and clinical outcome scores.

Results

61 of the 73 patients participated in this 4-year (3.9- to 4.1-year) follow-up study. BMD was similar in the risedronate group (n = 30) and the placebo group (n = 31). The mean difference was −1.8% in zone 1 and 0.5% in zone 7. Migration of the femoral stem, the clinical outcome, and the frequency of adverse events were similar in the 2 groups.

Interpretation

Although risedronate prevents periprosthetic bone loss postoperatively, a decrease in periprosthetic BMD accelerates when therapy is discontinued, and no effect is seen at 4 years. We do not recommend the use of risedronate following THA for osteoarthritis of the hip.Adaptive bone remodeling around the femoral stem following total hip arthroplasty (THA) results in regional loss of bone mass, especially in proximal parts of the femur—most of which takes place within the first postoperative year (Bodén et al. 2006, Sköldenberg et al. 2006). Periprosthetic bone loss may predispose to periprosthetic fracture, aseptic loosening, and difficulties at revision surgery (Lindahl 2007, Streit et al. 2011, Sköldenberg et al. 2014).The bisphosphonate (BP) risedronate has been used successfully to prevent osteoporotic fractures, mainly in the hip and vertebrae, by inhibiting osteoclast activity (McClung et al. 2001). In recent years, the possible use of BPs to prevent or ameliorate periprosthetic adaptive bone resorption, osteolysis, and implant migration has been investigated thoroughly in animal models and humans. The short-term results of several studies showing the effects of postoperative BP treatment in reducing periprosthetic bone loss up to a year after the arthroplasty have already been published (Venesmaa et al. 2001, Wilkinson et al. 2001, Hennigs et al. 2002, Wilkinson et al. 2005, Arabmotlagh et al. 2006).We have previously found that risedronate given once a week for 6 months after THA reduces periprosthetic bone resorption around an uncemented femoral stem in the first and second postoperative year (Sköldenberg et al. 2011). We now report the 4-year outcome in the same cohort.     

Somatostatin receptor 1–5; expression profiles during rat development

Background

Somatostatin acts through five receptor subtypes (SSTRs 1–5). We aimed to investigate SSTRs mRNA expression and protein distribution in whole rat embryos, with special emphasis on the pancreas.

Material and methods

Rat embryos were collected on embryonal days 10, 11, 12, 14, 15, 17, 19, 21, and at birth. Presence of SSTRs was investigated with RT-PCR techniques and immunohistochemistry.

Results

There was no SSTR5 mRNA expression in the whole rat embryos. All SSTR1–5 proteins were observed at embryonal day 10, but the localization varied between the different subtypes. From day 11 to birth SSTRs protein presence increased with time in major structures such as skin and cartilage. It remained similar over time in the heart and liver. In the fetal pancreas mRNA expression of SSTR2 and 4 was detected at day 14, and there was an increase up to birth. Only SSTR1 protein co-localized to a higher extent with the islet hormones studied. SSTR2 was present in all islet endocrine cells except for β-cells. In contrast, the immunostaining for SSTR3–4 was co-localized with insulin and PP, and, finally, SSTR5 with glucagon and pancreatic polypeptide. In mRNA isolated from whole rat embryos SSTR1-2 and SSTR4 expression showed a peak at day 14, while SSTR3 mRNA was not present until day 15.

Conclusion

The present data suggest a role for SSTRs during the development of the rat embryo. Subsequent functional studies may elucidate regulatory roles of specific SSTRs for the growth and differentiation of the pancreas as well as other organs.     

Entrapment of circular mapping catheter in the mitral valve

BACKGROUND: Ablation procedures in the left atrium for treatment of atrial fibrillation are becoming increasingly common. The procedure often involves placing one or two circular mapping catheters in the left atrium. Entrapment of an ablation catheter in the mitral valve during ablations of left-sided accessory pathways by the retrograde approach has been described in two earlier published reports. More recently, several reports describe similar entrapment of a mapping catheter. In a recently published review, however, only one case of unspecified valve damage was registered among 8745 atrial fibrillation procedures. OBJECTIVE: The purpose of this study was to evaluate patients with entrapment. METHODS: Retrospective analysis of electrophysiological results. RESULTS: We describe three patients with entrapment during ablations for atrial fibrillation. The entrapments occurred with three different operators at three different electrophysiological laboratories within 2 years. The complication described here may be more common than is widely appreciated. CONCLUSIONS: From our figures, we estimate the incidence of the complication to 0.9% (95% confidence interval, 0.2-2.5%).     

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

ObjectiveIt has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women.Methods20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions.ResultsEpisodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri.ConclusionsDiet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.Key Words: Functional magnetic resonance imaging, Episodic memory, Obesity, Diet interventions, Hippocampus