Pancreatic islet circulation in relation to the diabetogenic action of streptozotocin in the rat

A possible relationship between pancreatic islet blood flow (IBF) and the diabetogenic action of streptozotocin (STZ) has been investigated in rats injected ip with saline, glucose, propranolol, phentolamine, yohimbine, or adrenaline. A low dose (25 mg/kg BW) of STZ was given iv 10 min later, and serum glucose concentrations were determined after 3 and 7 days. Measurements of IBF were performed in separate experiments with a microsphere technique 10 min after injection of the drugs. Administration of phentolamine, glucose, or yohimbine was followed by overt diabetes, whereas animals injected with saline, adrenaline, or propranolol failed to become diabetics. Blood flow measurements showed an increase in IBF 10 min after the injection of glucose or propranolol, while there were no significant effects of the other drugs. It is concluded that changes in IBF are of minor importance for the action of agents modulating the diabetogenic effect of STZ. However, the potentiated hyperglycemic effects by glucose, phentolamine, or yohimbine in combination with STZ seemed to coincide with increased insulin secretion, as reflected by elevated serum insulin concentrations at the time of STZ administration.     

Sports activities after medial unicompartmental knee arthroplasty Oxford III—What can we expect?

Purpose

Excellent long-term results have been reported for implantation of unicompartmental knee arthroplasty (UKA). In many patients the desire for improvement in function often includes an aspiration to return to sports. The purpose of our study was to evaluate physical activities after medial Oxford-III (Biomet) UKA surgery.

Methods

Patients’ physical activity before and after the surgery was assessed using a self reporting questionnaire. We used the Oxford knee scoring system (OKS), the WOMAC-, the Knee society- (KSS) and the UCLA-score to assess postoperative knee function. The mean follow-up was 4.2 years. The female-to-male ratio was 1.3:1. The mean age at surgery was 65.3 years.

Results

Of the 131 patients studied 78 participated in some kind of sports before surgery (mean age 64.4 years), while 53 patients did not perform any sports (mean age 66.5 years) (p > 0.05). At follow-up the patients in the active group were significantly younger than the patients in the inactive group (p < 0.05). The majority of patients (80.1 %) returned to their level of sports activity after UKA surgery. Six patients took up sports after surgery while 15 patients stopped their sports. Among the active patients we found a shift from high- towards low-impact sports. The active patients had significantly higher scores for the OKS, KSS, WOMAC and UCLA score. The complication rate was comparable in both groups.

Conclusion

Our study demonstrates that a high degree of patient satisfaction in terms of sports activity can be achieved using the Oxford-III UKA for medial osteoarthritis.     

Dynamic MR imaging of the pelvic floor performed with patient sitting in an open-magnet unit versus with patient supine in a closed-magnet unit

PURPOSE: To compare open-magnet magnetic resonance (MR) imaging performed with the patient sitting with dynamic closed-magnet MR imaging of the pelvic floor performed with the patient supine. MATERIALS AND METHODS: Thirty-eight patients underwent dynamic 1.5-T closed-magnet pelvic floor MR imaging while in the supine position. Midsagittal T2-weighted single-shot fast spin-echo and T1-weighted multiphase spoiled gradient-recalled-echo (SPGR) MR images were obtained before and after rectal contrast agent administration, respectively, with the patient at rest, straining, and maximally contracting the sphincter. Subsequently, the patient was transferred to an open 0.5-T system. Midsagittal multiphase T1-weighted SPGR MR images were then obtained every 2 seconds with the patient sitting while at rest, maximally contracting the sphincter, straining, and defecating. Images were analyzed with regard to presence of enteroceles, anterior rectoceles, intussusceptions, rectal descents, bladder descents, and vaginal vault descents. RESULTS: All intussusceptions were missed at supine MR imaging. With sitting MR imaging as the reference standard, the sensitivity of supine MR imaging was 79% for depiction of bladder descents. When MR findings were graded and clinically irrelevant MR findings were excluded, sensitivity increased to 100% for depiction of bladder descents and anterior rectoceles and to 96% for depiction of rectal descents. CONCLUSION: Dynamic supine MR imaging performed with a closed-configuration unit before and after rectal contrast agent administration appears to be an alternative to sitting MR defecography performed with an open-configuration unit for diagnosis of clinically relevant pelvic floor abnormalities.     

Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate-high risk, based on stratified genetic information. METHODS: The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION: Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.     

Use of Heparin-bonded Circuits in Cardiopulmonary Bypass Improves Clinical Outcome

Objective : The use of heparin-coated surfaces in cardiopulmonary bypass has been shown to decrease the inflammatory response imposed by the contact between blood and artificial surfaces. One would expect this reaction to improve clinical outcome. However, this has been difficult to verify. This investigation is based on an aggregation of two randomized studies from our institution and highlights possible effects of heparin coating on a number of clinically oriented parameters. Design : Departmental analysis of patients subjected to coronary artery bypass surgery using heparin-coated circuits. Cardiopulmonary bypass was employed using either the Carmeda or Duraflo heparin coatings compared with a control. The systemic heparin dose was reduced in the heparin-coated groups (ACT > 250 s) vs control group patients (ACT > 480 s). The effects of heparin coating related to clinical outcome were studied. Results : The use of heparin-coated circuits reduced the mean length of stay in hospital from 7.8 &#45 2.5 to 7.3 &#45 1.8 days ( p = 0.040) and postoperative ventilation time from 9.7 &#45 9.2 to 8.2 &#45 8.5 h ( p = 0.018), blood loss 8 h post surgery from 676 &#45 385 to 540 &#45 245 ml ( p = 0.001), individual perioperative change of haemoglobin loss ( p = 0.001), leukocyte count ( p = 0.000) and creatinine elevation ( p = 0.000), proportion of patients exposed to allogenous blood transfusions 39.2 vs 23.9% ( p = 0.001), postoperative coagulation disturbances 4.4 vs 0.4% ( p = 0.006), postoperative deviations from the normal postoperative course 47.2 vs 36.7% ( p = 0.035), neurological deviations 9.4 vs 3.9% ( p = 0.021) and atrial fibrillation 26.4 vs 18.0% ( p = 0.041). No effects were found with respect to perioperative platelet count, postoperative fever reaction and 5-year survival. Conclusion : Based on several indicators, the use of heparin coating in cardiopulmonary bypass is associated with improved clinical results.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.     

Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis

Introduction

The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC).

Material and methods

Newborn Sprague–Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression.

Results

The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p < 0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1.

Discussion

Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.     

Glucose modulates food‐related salience coding of midbrain neurons in humans

Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low‐caloric food (LC), high‐caloric food (HC), and non‐food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment‐specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376–4384, 2016. © 2016 Wiley Periodicals, Inc.     

Heat distribution of polymerisation temperature of bone cement on the spinal canal during vertebroplasty

Purpose  

In the last 15 years, vertebroplasty and kyphoplasty have become established operative procedures for treating osteoporotic vertebral-body fractures and vertebral bodies afflicted with metastases. These procedures are quickly performed with few personnel and material resources and have a low rate of complications. However, cases of neurological impairment are reported in the scientific literature. We analysed whether potentially harmful heat is radiated/conducted by the polymerisation temperature of polymethylmethacrylate (PMMA) bone cement in the spinal canal.     

Epidemiology of adult ankle fractures in Sweden between 1987 and 2004: a population-based study of 91,410 Swedish inpatients

Background and purpose

Previous national epidemiological data on the characteristics and trends of patients with ankle fractures have been limited. We therefore analyzed data on Swedish inpatients with ankle fractures in this nationwide population study, based on data from 1987 through 2004.

Patients and methods

Data on all inpatients aged 15 years and older with ankle fracture were extracted from the Swedish National Patient Register for the period 1987–2004.

Results

We identified 91,410 hospital admissions with ankle fracture, corresponding to an annual incidence rate of 71 per 10⁵ person-years. During the study period, the number of hospital admissions increased by 0.2% annually, mainly from increase in fracture incidence in the elderly women. Mean age at admission was 45 (SD 19) years for men and 58 (18) for women. The major mechanism of injury was falling at the same level (64%).

Interpretation

This nationwide study of inpatients with ankle fractures showed an increase in fracture incidence, particularly in elderly women.Ankle fractures are among the most common fractures treated in orthopaedic surgery today. They are also a significant source of morbidity in both the young and the elderly (Donaldson et al. 1990, Jones et al. 1994, van Staa et al. 2001). Previous epidemiological studies have shown trends of increasing incidence over time, mainly in elderly women (Bengnér et al. 1986, Daly et al. 1987, Baron et al. 1996, Kannus et al. 1996, Court-Brown et al. 1998, van Staa et al. 2001, Kannus et al. 2002). However, most of these studies have included limited numbers of patients, and mostly originated from single hospitals or limited areas.Basic epidemiological data such as incidence, fracture type, age and sex distribution, mechanisms of injury, and surgical procedures can provide estimates when discussing disease burden and in the planning and provision of healthcare.The purpose of this study was to perform an epidemiological analysis of all adult ankle fractures requiring hospital admission in Sweden from 1997 through 2004, including incidence, causes of fracture, surgical procedures, patient characteristics, and trends over time.