Frontal bone and modified zygomatic implants for retention of a nasal prosthesis: Surgical planning using a three-dimensional computer software program

Implants integrated into bone have revolutionised the retention of total nasal prostheses. However, it may be difficult to identify available sites for placement of the implant after excision. In addition, it is ideal to minimise wide bony exposure after radiotherapy to avoid compromising the blood supply. In this paper we describe a technique for accurate placement of frontal bone and customised zygomatic implants using a computer-designed and fabricated surgical guide with a minimal access flap.     

Collagen levels are normalized after decompression of experimentally obstructed colon

Aim Our aim was to define the dynamics in collagen concentrations in the large bowel wall following decompression of experimental obstruction. Method Colonic obstruction was created in 28 male rats by the placement of a silicone ring around the distal colon. The ring was removed after 4 days to mimic endoscopical decompression by stent deployment. Colon circumference and collagen concentration were measured proximal to the obstructed segment immediately and at 3 and 10 days after decompression. The corresponding colonic sites of 23 sham‐operated and eight nonoperated control animals were subjected to identical analyses. Results Four days of obstruction resulted in a more than twofold increase in colonic circumference (20 vs 8 mm), with a concomitant 43% reduction (P = 0.001) in collagen concentration in the bowel wall proximal to the obstruction compared with sham animals. Three days after decompression, collagen concentrations remained reduced (P < 0.05), while there was no significant difference after 10 days with either sham‐operated or nonoperated controls. Colonic circumference of the obstructed colon remained slightly distended (11 mm) on day 10 and tended to correlate (r_S = 0.51, P = 0.053) with total matrix metalloproteinase activity. Conclusion The marked reduction in collagen concentration in an experimentally obstructed colon is normalized 10 days after decompression. These findings may have clinical implications for the timing of surgical resection.     

Frequency of bullying at work, physiological response, and mental health

Objective

The present study aimed to elucidate the relationship between bullying at work and cortisol secretion. Of particular interest was to examine whether frequently and occasionally bullied persons differed from nonbullied persons.

Methods

The study included 1944 employees (1413 women and 531 men) from 55 workplaces in Denmark (16 private and 39 public workplaces). During a work day three saliva samples were collected at awakening, +30 min later, and at 20:00 hours, and analyzed for cortisol concentrations. Mental health was assessed using items on somatic, cognitive, stress, and depressive mood.

Results

Of the 1944 employees, 1.1% was frequently bullied and 7.2% occasionally bullied. Frequently bullied persons reported poorer mental health and had a 24.8% lower salivary cortisol concentration compared with the nonbullied reference group. Occasionally bullied persons had a poorer self-reported mental health, but their cortisol concentrations did not deviate from the group of nonbullied persons. The associations remained significant even after controlling for age, gender, exact time of sampling, mental health, and duration of bullying. Bullying occurred at 78% of the workplaces (43 workplaces); frequent bullying occurred at 21% of the workplaces (40%).

Conclusion

Frequent bullying was associated with lower salivary cortisol concentrations. No such association was observed for occasional bullying. Whether the generally lower secretion of cortisol among the frequently bullied persons indicate an altered physiological status remains to be evaluated in future studies. Yet, the physiological response seems to underscore the possibility that bullying indeed may have measurable physiological consequences. Hence, the physiological response supports the mental symptoms found among the frequently bullied.     

A population pharmacokinetic/pharmacodynamic model of methotrexate and mucositis scores in osteosarcoma

Methotrexate, when used in high doses (12 g/m2) in the treatment of osteosarcoma, shows wide between-subject variability (BSV) in its pharmacokinetics. High-dose methotrexate is associated with severe toxicity; therefore, therapeutic drug monitoring (TDM) is carried out to guide rescue therapy and monitor for nephrotoxicity. Mucositis is a commonly encountered dose-limiting toxicity that often leads to delays in subsequent courses of chemotherapy. This, in turn, results in a reduction in the dosing intensity, which is essential in the treatment of osteosarcoma. The aims of this study were to develop a population pharmacokinetic (PK) model from TDM using physiologically relevant covariates and to investigate the correlation between mucositis scores and methotrexate pharmacokinetics. In total, 46 osteosarcoma patients (30 men and 16 women; age, 4-51 years) were recruited, and blood samples were collected for routine TDM once every 24 hours. Mucositis scores, graded according to the National Cancer Institute Common Toxicity Criteria, were recorded for 28 of the patients (18 men and 10 women; age, 8-51 years) predose and postdose. A population PK model was developed in NONMEM VI. A 2-compartment PK model was chosen, and clearance (CL) was divided into filtration and secretion/metabolism components. All parameters were scaled with body weight, and, in addition, total CL was scaled with age- and sex-adjusted serum creatinine. Between-subject variability was modeled for all parameters, and between-occasion variability was included in CL. For a typical 70 kg man of 18 years or older, the parameter estimates for the final model were CL(filt) = 2.69 L/h/70 kg, CL(sec) = 10.9 L/h/70 kg, V? = 74.3 L/70 kg, Q = 0.110 L/h/70 kg, and V? = 4.10 L/70 kg. Sequential pharmacodynamic modeling consisted of mucositis scores as 5-point ordered categorical data. A significant linear relationship between individual area under the curve (AUC) and mucositis score probability was found, and the probability of having mucositis score ≥ 1 increased with increasing AUC and was almost 50% at the average cumulative AUC after 2 consecutive methotrexate doses.     

Genetic Regulation of Bone Traits Is Influenced by Sex and Reciprocal Cross in F2 Progeny From GK and F344 Rats

A genome‐wide linkage analysis to identify quantitative trait loci (QTLs) for bone phenotypes was performed in an F₂ intercross of inbred spontaneously type 2 diabetic GK and normoglycemic F344 rats (108 males and 98 females). The aim of the study was to locate genome regions with candidate genes affecting trabecular and cortical bone and to investigate the effects of sex and reciprocal cross. pQCT was used to determine tibial bone phenotypes in the F₂ rats, comprising reciprocal crosses with divergent mitochondrial (mt) DNA. Sex and reciprocal cross‐separated QTL analyses were performed followed by assessment of specific interactions. Four genome‐wide significant QTLs linked to either cortical vBMD, tibia length, body length, or metaphyseal area were identified in males on chromosomes (chr) 1, 8, and 15. In females, three significant QTLs linked to cortical BMC or metaphyseal total vBMD were identified on chr 1 and 2. Several additional suggestive loci for trabecular and cortical traits were detected in both males and females. Four female‐specific QTLs on chr 2, 3, 5, and 10 and four reciprocal cross‐specific QTLs on chr 1, 10, and 18 were identified, suggesting that both sex and mt genotype influence the expression of bone phenotypes.     

The psychometric properties of the Swedish version of the Adolescent Drug Abuse Diagnosis (ADAD)

The psychometric properties of the Swedish version of the Adolescent Drug Abuse Diagnosis (ADAD) instrument were evaluated in two adolescent groups. The participants in the Normal group comprised 121 adolescents aged 15-17 years and the participants in the group of adolescents with antisocial problems comprised 1168 youths aged 10-21 years detained under the Swedish Care of Young Persons Act in special youth homes. The ADAD instrument produced good interrater reliability; the subscales showed moderate internal consistency and concept validity was satisfactory and comparable with American and Swiss versions. Finally, the ADAD subscales produced meaningful correlations. The interviewer rating, the adolescent's rating and the composite scores are compared and discussed. The Swedish version of ADAD appears to be a psychometrically good instrument for assessing the severity of adolescent problems and their need for treatment. However, the composite scores need to be reconstructed to be useful in future research.     

Study to prospectively evaluate reamed intramedually nails in patients with tibial fractures (S.P.R.I.N.T.): Study rationale and design

Background

Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches.

Discussion

Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention.

Summary

The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed.     

Pattern of inspiratory gas delivery affects CO2 elimination in health and after acute lung injury

Objective To avoid ventilator induced lung injury, tidal volume should be low in acute lung injury (ALI). Reducing dead space may be useful, for example by using a pattern of inspiration that prolongs the time available for gas distribution and diffusion within the respiratory zone, the mean distribution time (MDT). A study was conducted to investigate how MDT affects CO₂ elimination in pigs at health and after ALI. Design and setting Randomised crossover study in the animal laboratory of Lund University Biomedical Center. Subjects and intervention Healthy pigs and pigs with ALI, caused by surfactant perturbation and lung-damaging ventilation were ventilated with a computer-controlled ventilator. With this device each breath could be tailored with respect to insufflation time and pause time (T _I and T _P) as well as flow shape (square, increasing or decreasing flow). Measurements and results The single-breath test for CO₂ allowed analysis of the volume of expired CO₂ and the volume of CO₂ re-inspired from Y-piece and tubes. With a long MDT caused by long T _I or T _P, the expired volume of CO₂ increased markedly in accordance with the MDT concept in both healthy and ALI pigs. High initial inspiratory flow caused by a short T _I or decreasing flow increased the re-inspired volume of CO₂. Arterial CO₂ increased during a longer period of short MDT and decreased again when MDT was prolonged. Conclusions CO₂ elimination can be enhanced by a pattern of ventilation that prolongs MDT. Positive effects of prolonged MDT caused by short T _I and decreasing flow were attenuated by high initial inspiratory flow. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.