Correction to: Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone.

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Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone.

Loading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels. INTRODUCTION: Osteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone. METHODS: Right tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with µCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure). RESULTS: The cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (-14 and -3%, p < 0.01, respectively) and crystallinity (-1.4 and -0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites. CONCLUSION: Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.

Association studies on 11 published colorectal cancer risk loci.

BACKGROUND: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort. METHODS: The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed. RESULTS: Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age. CONCLUSIONS: Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.

Testing the SF-36 in Parkinson's disease. Implications for reporting rating scale data.

Rating scales are increasingly the primary outcome measures in clinical trials. However, clinically meaningful interpretation of such outcomes requires that the scales used satisfy basic requirements (scaling assumptions) within the data. These are rarely tested. The SF-36 is the most widely used patient-reported rating scale. Its scaling assumptions have been challenged in neurological disorders but remain untested in Parkinson's disease (PD). We therefore tested these by analyzing SF-36 data from 202 PD patients (54% men; mean age 70) to determine if it was legitimate to report scores for the eight SF-36 scales and its two summary measures of physical and mental health, and if those scores were reliable and valid. Results supported generation of the eight SF-36 scale scores and their reliabilities were generally good (> or = 0.74 in all but one instance). However, we found limitations that question the meaningfulness of four scales and other limitations that restrict the ability of four scales to detect change in clinical trials (floor/ceiling effects, 19.6-46.2 %). The two SF-36 summary measures were not found to be valid indicators of physical and mental health. This study demonstrates important limitations of the SF-36 and provides the first evidence-based guidelines for its use in PD. The limitations of the SF-36 demonstrated here may explain some unexpected findings in previous studies. However, the main implication is a general one for the clinical research community regarding requirements for reporting rating scale endpoints. Specifically, investigators should routinely provide scale evaluations based on data from within major clinical trials.

Deep-brain stimulation in the subthalamic nuclei improves balance performance in patients with Parkinson's disease, when tested without anti-parkinsonian medication.

OBJECTIVE: To evaluate the effect of bilateral deep-brain stimulation (DBS) in the subthalamic nucleus (STN) on balance performance in patients with severe Parkinson's disease (PD), when tested without anti-parkinsonian medication. MATERIAL AND METHODS: Thirty-one patients (median age 65 years, range 50-77) were included. Assessments were made after 10-12 h withdrawal of medication, before and 6 and 12 months after surgery. Postoperative evaluations were performed with DBS on and off. Balance performance was evaluated with the Berg Balance Scale (BBS). Motor symptoms and postural stability (item 30) were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS III). RESULTS: DBS in STN improved balance performance as well as postural stability and motor symptoms significantly (P

Neurosurgery for movement disorders.

Movement disorders have been treated neurosurgically since the 1930s. Current diagnoses for neurosurgical interventions are Parkinson's disease, essential tremor, multiple sclerosis, and some dystonic disorders such as idiopathic torsions dystonia. By using stereotactic image-guided techniques, targets can be chosen to treat different symptoms: the ventrointermediate nucleus of thalamus for tremor; the internal globus pallidus for dyskinesia, dystonia, rigidity, akinesia, and tremor; and the subthalamic nucleus for all cardinal symptoms in advanced Parkinson's disease, including drug-induced hyperkinesia (secondary to reduced drugs). The surgical approaches can be divided into three main groups: destructive (e.g., lesional surgery), reversible and adjustable (e.g., permanent electro-inhibition/stimulation), and reconstructive (e.g., fetal nerve cell transplantation). Reconstructive procedures, which are not discussed here, are still in the early developmental phase. All the methods have advantages and disadvantages; therefore, it is important that the right target and technique be chosen for each patient.

Biapenem versus imipenem/cilastatin in the treatment of complicated intra-abdominal infections: report from a Swedish Study Group.

118 patients with complicated intra-abdominal infections participated in an open randomized comparative multicenter trial in order to compare the clinical and microbiological efficacy and safety of biapenem with imipenem/cilastatin (Tienam). 31 men and 27 women (mean age 52.3 years) were enrolled in the biapenem group, and 43 men and 17 women (mean age 52.3 years) in the imipenem/cilastatin group. The patients received either biapenem 500 mg every 8 h or imipenem/cilastatin 500 mg/500 mg every 6 h by intravenous infusion for up to 13 days (mean 6.5 days). 28/43 evaluable patients (65.1%) receiving biapenem and 27/40 evaluable patients (67.5%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 28/43 evaluable patients (65.1%) receiving biapenem and in 27/40 evaluable patients (67.5%) receiving imipenem/cilastatin. No significant differences in clinical or microbiological efficacy between the two treatment groups were found. The present study shows that biapenem may be useful in the treatment of intra-abdominal infections.

Timing of antibiotic treatment in non-perforated gangrenous appendicitis.

OBJECTIVE: To assess whether antibiotic treatment with cefuroxime and tinidazole started during the operation was as effective as treatment started before operation in patients with gangrenous non-perforated appendicitis. DESIGN: Prospective randomised study. SETTING: University hospital, Sweden. SUBJECTS: 114 patients with gangrenous, non-perforated appendicitis who had had antibiotics started before operation and 120 whose treatment was started during operation out of a total of 575 who presented with a presumptive diagnosis of appendicitis. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: There were no deaths, and the rates of infective complications were 1/114 (0.9%) and 3/120 (3%), respectively. The median hospital stay was four days in both groups. CONCLUSION: Antibiotic treatment started during the operation is not significantly worse at preventing infective complications in non-perforated, gangrenous appendicitis than treatment started before the operation.

Cytogenetic analysis of 52 colorectal carcinomas--non-random aberration pattern and correlation with pathologic parameters.

Cytogenetic analysis of short-term cultures from 52 colorectal carcinomas revealed a normal karyotype in 13 and clonal chromosome aberrations in 39 tumors. In the abnormal group, 13 tumors had simple numerical changes only, whereas 26 had at least one structural rearrangement with or without concomitant numerical changes. The most common numerical abnormalities were, in order of decreasing frequency, +7, -18, -Y, +8, +13 and -14. The most common structural rearrangements affected, again in order of decreasing frequency, chromosomes 8, 1, 6, 7, 17, 3, 11, 13, 14, 16, 2 and 10. The chromosome bands most frequently involved in the structural changes were 8q10, 17p11, 11q13, 8p11, 6q21, 7p15, 7q36, 12q13, 13q10, and 16q13. The most frequent genomic imbalances brought about by the structural rearrangements were losses from chromosome arms 8p, 1p, 6q, 17p, 7p, and 16q, as well as gains of 7q, 8q, 13q, and 11q. A statistically significant (p < 0.05) correlation between the karyotypic pattern and tumor grade was found, with the poorly differentiated carcinomas generally having more massive chromosomal abnormalities.

Bacterial load and inflammatory reaction in the bowel wall after colonic obstruction. An experimental study in rats.

To quantify the inflammatory reaction to obstruction, alkaline phosphatase and myeloperoxidase activities were measured in specimens of colonic wall from 60 rats. Twenty rats had undergone laparotomy and band obstruction, 20 laparotomy without obstruction and 20 had no operation. The mean activities of both enzymes were increased proximal but not distal to the obstruction, that of alkaline phosphatase significantly so. Despite increase in the number of bacteria, both proximal and distal to the obstruction, no signs of bacterial invasion of the bowel wall were seen either on histological examination or culture. These findings indicate that mechanical factors may be more important than bacteria in causing the increased inflammatory reaction in bowel wall proximal to an obstruction.

Peroperative contamination and anastomotic leakage after resection for left colon stenosis. An experimental study in the rat.

In this experimental study the effect of peroperative faecal soiling on immediate postoperative anastomotic leakage after resection and primary anastomosis of a left colon obstruction was evaluated. Faecal soiling was quantified by a standardized irrigation of the abdominal cavity and then culturing of the fluid. An increased peroperative soiling was found after resection of a stenosis compared to resection of a non-stenotic bowel. Anastomotic complications were correlated to the degree of bacterial contamination and a breakpoint of 10(4) CFU/ml was found. Immediate postoperative leakage, tested with the bacteria Serratia marcescens, was not increased in the stenosis group. Thus, peroperative bacterial contamination seems to be one important factor in developing anastomotic complications after resection of colonic obstruction while an immediate leakage of bacteria through the anastomosis seems to be less important.

The effect of diverting colostomy on anastomotic healing after resection of left colon obstruction. An experimental study in the rat.

A standardized stenosis of the left colon was created in the rat model. After four days the stenosis was resected and a primary anastomosis made. Half of the animals (n = 21) were randomized to a proximal diverting colostomy and the other half to a non-colostomy control group. On postoperative days two and seven anastomotic complications were recorded and anastomotic strength was determined. Collagen content in the anastomotic area was measured. In the colostomy group no anastomotic complications occurred, while 6/21 (29%) animals in the non-colostomy group had complications. On day two there was no difference between the groups as regards anastomotic strength and collagen content. After a week, however, the control group showed a significant increase in both anastomotic strength and collagen content which was not observed in the colostomy group. The absence of increase in anastomotic strength in the colostomy group had no adverse effect on anastomotic healing, as judged by complications. Thus, a diverting colostomy may be of value in reducing anastomotic complications after resection of a left colon obstruction.

Impact of bacteria on metabolism of collagen in colonic obstruction in rats.

The influence of bacteria on metabolism of collagen in the colonic wall under normal conditions and after obstruction was evaluated by using germ-free and conventionally bred rats. Under normal conditions, no differences in synthesis and content of collagen or tissue dry weight in the colonic wall were found between germ-free and conventionally bred rats. After obstruction, both groups reacted similarly with an equally increased collagen synthesis. The findings imply that bacteria do not play any major role in the regulation of collagen metabolism in the colonic wall, neither under normal conditions nor in the strained situation with colonic obstruction and fecal impaction.

Anastomotic healing after resection of left-colon stenosis: effect on collagen metabolism and anastomotic strength. An experimental study in the rat.

Anastomotic breaking strength and collagen metabolism in the colonic wall were studied after resection of a standardized left-colon stenosis in the rat. An increased complication rate was found in the stenosis group compared with the control group (27 percent vs. 2 percent) and the complications arise soon after surgery. The collagen turnover in the anastomotic area, as well as the changes of breaking strength, were equal between the groups in the early healing course, implying that the stenosis group, as an entity, did not show impairment in the studied parameters predisposing for complications. Other factors such as mechanical strain by the increased fecal bulk and increased bacterial load may contribute to occurrence of the anastomotic complications.

The effect of stenosis on collagen metabolism in the colonic wall. Studies in the rat.

The influence of colonic stenosis resulting in faecal loading was investigated in regard to collagen metabolism in the intact colonic wall. The collagen content was increased in the left colon proximal to the stenosis, due to enhanced collagen synthesis. The collagen concentration fell significantly, however, as noncollagenous substances increased more than collagen. Collagen concentration clearly can be misleading as an indication of the actual amount of collagen. The enhanced rate of collagen turnover with collagen accumulation proximal to stenosis requires further analysis in regard to its importance for healing capacity.

Long-term effects on bacterial sensitivity patterns of preoperative antibiotic prophylaxis in colorectal surgery.

Since 1973, when doxycycline was introduced as preoperative prophylaxis in elective colorectal surgery at Malmö General Hospital, Sweden, there has been an unchanged and low rate (8% to 12%) of septic complications in colonic surgery. For treatment of postoperative infections, ampicillin and cefuroxime have been used since 1973 and 1980, respectively. The sensitivity of Escherichia coli to these three antibiotics used for prophylaxis and treatment was followed for five years (1981-1985). Only minor changes were observed during the period. A lower frequency of antibiotic resistance was found in bacterial strains isolated peroperatively than in strains isolated postoperatively after colorectal surgery or from infections in other patients. Considering the low frequency of postoperative infectious complications and the low frequency of antibiotic resistance in peroperative isolates, doxycycline still remains an alternative for prophylaxis in bowel surgery.

Long-term effects on bacterial sensitivity patterns of preoperative antibiotic prophylaxis in colorectal surgery.

Since 1973, when doxycycline was introduced as peroperative prophylaxis in elective colorectal surgery at Malmö General Hospital, Sweden, there has been an unchanged and low rate (8-12%) of septic complications in colonic surgery. For treating postoperative infections ampicillin, cefuroxime and piperacillin have been used since 1973, 1980 and 1982 respectively. The sensitivity pattern of E. coli and Klebsiella against these four antibiotics used for prophylaxis and treatment has been followed for the past five years and only minor changes have occurred through the period. However, a lower frequency of antibiotic resistance was recorded for bacteria isolated peroperatively than postoperatively after colorectal surgery or from infection sites from other patients presumably mostly due to selection caused by antibiotics used within the hospital. Due to the good clinical outcome and seemingly lack of development of antibiotic resistance in peroperative isolates, doxycycline still remains a choice for prophylaxis in bowel surgery.

Antibiotic treatment during surgery for diffuse peritonitis: a prospective randomized study comparing the effects of cefuroxime and of a cefuroxime and metronidazole combination.

In a prospective randomized open study of patients operated upon for diffuse peritonitis, the effects of two different antibiotic regimens were evaluated. Cefuroxime given as a single drug (Group I; n = 59) was compared with a combination of cefuroxime and metronidazole (Group II; n = 63). Bacteriological cultures, both aerobic and anaerobic, were obtained peroperatively and in the event of any complication. The antibiotic sensitivities of isolated bacteria, and the serum and tissue concentrations of cefuroxime were determined. Postoperative infectious complications occurred in 22 per cent of Group I patients (cefuroxime), and in 17.5 per cent of Group II (cefuroxime plus metronidazole). The mortality rates were 5 per cent for Group I and 8 per cent for Group II. Tissue concentrations of cefuroxime were well above the MIC (minimal inhibiting concentration) values for most of the bacteria isolated. From a few patients in Group I, however, cultures were obtained with isolates sensitive to metronidazole but resistant to cefuroxime. Our findings suggest that, in the antibiotic treatment of patients operated for diffuse peritonitis, an agent which is primarily effective against aerobic bacteria (but not entirely without effect on anaerobes) is as effective as combination therapy covering both aerobic and anaerobic bacteria.

Histamine2-receptor antagonists in gastroduodenal ulcer haemorrhage.

This paper reviews randomised trials in which the effects of histamine2-receptor antagonists have been studied in gastroduodenal ulcer haemorrhage. There is a trend in these studies that histamine2-receptor antagonists may reduce the number of rebleedings, especially in elderly patients with gastric ulcers. A randomised trial comparing cimetidine and ranitidine in high risk patients with massive gastroduodenal haemorrhage is also presented. The total mortality in this study was 12%, 15% for gastric ulcer patients and 11% for duodenal ulcer patients. There was no difference in mortality, amount of blood transfusion required, rebleedings or need for emergency surgery between the two treatment models.