Performance and outcome evaluation of emergency resuscitative thoracotomy in a Norwegian trauma centre: a population-based consecutive series with survival benefits.

BACKGROUND: Emergency resuscitative thoracotomy (ERT) is a lifesaving procedure for select indications in severely injured patients. The main body of the literature stem from regions with a high prevalence of penetrating injuries, while data from European institutions remain scarce. We aimed to evaluate a decade of ERT in a Norwegian trauma centre. METHODS: A prospectively collected series from the institutional trauma registry of all consecutive trauma patients who had an ERT at Stavanger University Hospital (SUH) from 2006 to 2018. Data were extracted using both registry and electronic patient record (EPR) data, including injury profile, demographics and outcomes. Comparison of groups were done by descriptive statistics. RESULTS: A total of 26 ERTs were performed during the study period, of which 20 were men (75%) and 6 women (25%). Five patients (19%) survived to hospital discharge, of which 3 men and 2 women with a median age of 46 years (range 24-68). All survivors had thoracic injury as location of major injury (LOMI.). Of the five survivors, four suffered blunt injury and one patient penetrating injury. At one-year of follow-up of the survivors, three patients scored 8/8 on Glasgow outcome scale-extended, 1 patient scored 7/8 and one patient 5/8. CONCLUSION: In this study, ERT conferred good outcome with survival in one of every five procedures. Performing ERT in severely injured patients presenting in extremis appears to be justified even in low-volume centres and in blunt trauma.

Long-Term Mortality in Patients Operated for Perforated Peptic Ulcer: Factors Limiting Longevity are Dominated by Older Age, Comorbidity Burden and Severe Postoperative Complications.

BACKGROUND: Perforated peptic ulcer (PPU) is a surgical emergency associated with high short-term mortality. However, studies on long-term outcomes are scarce. Our aim was to investigate long-term survival after surgery for PPU. MATERIALS AND METHODS: A population-based, consecutive cohort of patients who underwent surgery for PPU between 2001 and 2014 was reviewed, and the long-term mortality was assessed. Survival was investigated by univariate analysis (log-rank test) and displayed using Kaplan-Meier survival curves. Multivariable analysis of risk factors for long-term mortality was assessed by Cox proportional hazards regression and reported as hazard ratio (HR) with 95 % confidence intervals (CI). RESULTS: A total of 234 patients were available for the calculation of ninety-day, one-year and two-year mortality, and the results showed rates of 19.2 % (45/234), 22.6 % (53/234) and 24.8 % (58/234), respectively. At the end of follow-up, a total of 109 of the 234 patients (46.6 %) had died. Excluding 37 (15.2 %) patients who died within 30 days of surgery, 197 patients had long-term follow-up (median 57 months, range 1-168) of which 36 % (71/197) died during the follow-up period. In multivariable analyses, age >60 years (HR 3.95, 95 % CI 1.81-8.65), active cancer (HR 3.49, 95 % CI 1.73-7.04), hypoalbuminemia (HR 1.65, 95 % CI 0.99-2.73), pulmonary disease (HR 2.06, 95 % CI 1.14-3.71), cardiovascular disease (HR 1.67, 95 % CI 1.01-2.79) and severe postoperative complications (HR 1.76, 95 % CI 1.07-2.89) during the initial stay for PPU were all independently associated with an increased risk of long-term mortality. Cause of long-term mortality was most frequently (18 of 71; 25 %) attributed to new onset sepsis and/or multiorgan failure. CONCLUSION: The long-term mortality after surgery for PPU is high. One in every three patients died during follow-up. Older age, comorbidity and severe postoperative complications were risk factors for long-term mortality.

Predicting outcomes in patients with perforated gastroduodenal ulcers: artificial neural network modelling indicates a highly complex disease.

PURPOSE: Mortality prediction models for patients with perforated peptic ulcer (PPU) have not yielded consistent or highly accurate results. Given the complex nature of this disease, which has many non-linear associations with outcomes, we explored artificial neural networks (ANNs) to predict the complex interactions between the risk factors of PPU and death among patients with this condition. METHODS: ANN modelling using a standard feed-forward, back-propagation neural network with three layers (i.e., an input layer, a hidden layer and an output layer) was used to predict the 30-day mortality of consecutive patients from a population-based cohort undergoing surgery for PPU. A receiver-operating characteristic (ROC) analysis was used to assess model accuracy. RESULTS: Of the 172 patients, 168 had their data included in the model; the data of 117 (70%) were used for the training set, and the data of 51 (39%) were used for the test set. The accuracy, as evaluated by area under the ROC curve (AUC), was best for an inclusive, multifactorial ANN model (AUC 0.90, 95% CIs 0.85-0.95; p < 0.001). This model outperformed standard predictive scores, including Boey and PULP. The importance of each variable decreased as the number of factors included in the ANN model increased. CONCLUSIONS: The prediction of death was most accurate when using an ANN model with several univariate influences on the outcome. This finding demonstrates that PPU is a highly complex disease for which clinical prognoses are likely difficult. The incorporation of computerised learning systems might enhance clinical judgments to improve decision making and outcome prediction.

Strategies to improve the outcome of emergency surgery for perforated peptic ulcer.

BACKGROUND: Perforated peptic ulcer (PPU) is a common surgical emergency that carries high mortality and morbidity rates. Globally, one-quarter of a million people die from peptic ulcer disease each year. Strategies to improve outcomes are needed. METHODS: PubMed was searched for evidence related to the surgical treatment of patients with PPU. The clinical registries of trials were examined for other available or ongoing studies. Randomized clinical trials (RCTs), systematic reviews and meta-analyses were preferred. RESULTS: Deaths from peptic ulcer disease eclipse those of several other common emergencies. The reported incidence of PPU is 3.8-14 per 100,000 and the mortality rate is 10-25 per cent. The possibility of non-operative management has been assessed in one small RCT of 83 patients, with success in 29 (73 per cent) of 40, and only in patients aged less than 70 years. Adherence to a perioperative sepsis protocol decreased mortality in a cohort study, with a relative risk (RR) reduction of 0.63 (95 per cent confidence interval (c.i.) 0.41 to 0.97). Based on meta-analysis of three RCTs (315 patients), laparoscopic and open surgery for PPU are equivalent, but patient selection remains a challenge. Eradication of Helicobacter pylori after surgical repair of PPI reduces both the short-term (RR 2.97, 95 per cent c.i. 1.06 to 8.29) and 1-year (RR 1.49, 1.10 to 2.03) risk of ulcer recurrence. CONCLUSION: Mortality and morbidity from PPU can be reduced by adherence to perioperative strategies.

A basic set of homeostatic controller motifs.

Adaptation and homeostasis are essential properties of all living systems. However, our knowledge about the reaction kinetic mechanisms leading to robust homeostatic behavior in the presence of environmental perturbations is still poor. Here, we describe, and provide physiological examples of, a set of two-component controller motifs that show robust homeostasis. This basic set of controller motifs, which can be considered as complete, divides into two operational work modes, termed as inflow and outflow control. We show how controller combinations within a cell can integrate uptake and metabolization of a homeostatic controlled species and how pathways can be activated and lead to the formation of alternative products, as observed, for example, in the change of fermentation products by microorganisms when the supply of the carbon source is altered. The antagonistic character of hormonal control systems can be understood by a combination of inflow and outflow controllers.

Robust adaptation and homeostasis by autocatalysis.

Robust homeostatic mechanisms are essential for the protection and adaptation of organisms in a changing and challenging environment. Integral feedback is a control-engineering concept that leads to robust, i.e., perturbation-independent, adaptation and homeostatic behavior in the controlled variable. Addressing two-component negative feedback loops of a controlled variable A and a controller molecule E, we have shown that integral control is closely related to the presence of zero-order fluxes in the removal of the manipulated variable E. Here we show that autocatalysis is an alternative mechanism to obtain integral control. Although the conservative and marginal stability of the Lotka-Volterra oscillator (LVO) with autocatalysis in both A and E is often considered as a major inadequacy, homeostasis in the average concentrations of both A and E ( and ) is observed. Thus, autocatalysis does not only represent a mere driving force, but may also have regulatory roles.

Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways.

Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer types. Here we utilize Illumina Beadchip methylation array analysis to identify LRES across 800 kb of chromosome 5q31 in colorectal adenomas and carcinomas (n=34) relative to normal colonic epithelial DNA (n=6). This region encompasses 53 individual protocadherin (PCDH) genes divided among three gene clusters. Hypermethylation within these gene clusters is asynchronous; while most PCDH hypermethylation occurs early, and is apparent in adenomas, PCDHGC3 promoter methylation occurs later in the adenoma-carcinoma transition. PCDHGC3 was hypermethylated in 17/28 carcinomas (60.7%) according to methylation array analysis. Quantitative real-time reverse transcription-polymerase chain reaction showed that PCDHGC3 is the highest expressed PCDH in normal colonic epithelium, and that there was a strong reciprocal relationship between PCDHGC3 methylation and expression in carcinomas (R=-0.84). PCDH LRES patterns are reflected in colorectal tumour cell lines; adenoma cell lines are not methylated at PCDHGC3 and show abundant expression at the mRNA and protein level, while the expression is suppressed in hypermethylated carcinoma cell lines (R=-0.73). Short-interfering RNA-mediated reduction of PCDHGC3 led to a decrease of apoptosis in RG/C2 adenoma cells, and overexpression of PCDHGC3 in HCT116 cells resulted in the reduction of colony formation, consistent with tumour suppressor capabilities for PCDHGC3. Further functional analysis showed that PCDHGC3 can suppress Wnt and mammalian target of rapamycin signalling in colorectal cancer cell lines. Taken together, our data suggest that the PCDH LRES is an important tumour suppressor locus in colorectal cancer, and that PCDHGC3 may be a strong marker and driver for the adenoma-carcinoma transition.

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes.

Aberrant activation of the Wnt signaling pathway is causally involved in the formation of most colorectal cancers (CRCs). Although detailed knowledge exists regarding Wnt-regulated protein-coding genes, much less is known about the possible involvement of non-coding RNAs. Here we used TaqMan Array MicroRNA Cards, capable of detecting 664 unique human microRNAs (miRNAs), to describe changes of the miRNA transcriptome following disruption of beta-catenin/TCF4 activity in DLD1 CRC cells. Most miRNAs appeared to respond independent of host gene regulation and proximal TCF4 chromatin occupancy as inferred from expression microarray and ChIP-chip data. A module of miRNAs induced by abrogated Wnt signaling in vitro was downregulated in two independent series of human primary CRCs (n=76) relative to normal adjacent mucosa (n=34). Several of these miRNAs (miR-145, miR-126, miR-30e-3p and miR-139-5p) markedly inhibited CRC cell growth in vitro when ectopically expressed. By using an integrative approach of proteomics and expression microarrays, we found numerous mRNAs and proteins to be affected by ectopic miR-30e-3p levels. This included HELZ and PIK3C2A that were directly repressed by several miRNA binding sites as confirmed by luciferase reporter assays in combination with mutational analyses. Finally, small interfering RNA-mediated downregulation of PIK3C2A, but not HELZ, was sufficient on its own to restrict CRC cell growth. Collectively, our study demonstrates that multiple miRNAs are upregulated as a consequence of forced attenuation of Wnt signaling in CRC cells, and some of these miRNAs inhibit cell growth with concomitant suppression of several growth-stimulatory cancer-related genes.

Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells.

BACKGROUND: The KIAA1199 transcript is upregulated in colon adenomas and downregulated upon ß-catenin knockdown. METHODS: Transcript profiling was performed on >500 colon biopsies, methylation profiling data were compared with transcript data. Immunohistochemistry assessed KIAA1199 protein expression in 270 stage II/III tumours (>3 years follow-up). The effects of stable KIAA1199 knockdown in SW480 cells (three different constructs) were studied using transcriptional profiling, proliferation and protein analysis. RESULTS: The KIAA1199 transcript was strongly upregulated in 95% of adenocarcinomas. Absent expression in normal mucosa correlated with KIAA1199 promotor methylation. Nuclear and cytoplasmic KIAA1199 protein expression was identified in colon adenocarcinomas and other types of cancers. A subpopulation of patients with tumours strongly expressing KIAA1199 in the nucleus showed a better outcome with regard to recurrence as lung or liver metastases. The KIAA1199 knockdown affected the cell cycle and the Wnt-signalling pathway. Reduced cellular proliferation and decreased KI67, phosphorylated retinoblastoma, ß-catenin and ASCL2 protein expression supported these findings. Eighteen Wnt-signalling genes differentially expressed upon KIAA1199 knockdown correlated with the KIAA1199 expression profile in clinical specimens. CONCLUSION: The KIAA1199 knockdown attenuates the effects of the Wnt/ß-catenin signalling and it may thus be regarded as a regulatory part of this pathway.

Clinical and cellular effects of hypothermia, acidosis and coagulopathy in major injury.

BACKGROUND: Hypothermia, acidosis and coagulopathy have long been considered critical combinations after severe injury. The aim of this review was to give a clinical update on this triad in severely injured patients. METHODS: A non-systematic literature search on hypothermia, acidosis and coagulopathy after major injury was undertaken, with a focus on clinical data from the past 5 years. RESULTS: Hypothermia (less than 35 °C) is reported in 1·6-13·3 per cent of injured patients. The occurrence of acidosis is difficult to estimate, but usually follows other physiological disturbances. Trauma-induced coagulopathy (TIC) has both endogenous and exogenous components. Endogenous acute traumatic coagulopathy is associated with shock and hypoperfusion. Exogenous effects of dilution from fluid resuscitation and consumption through bleeding and loss of coagulation factors further add to TIC. TIC is present in 10-34 per cent of injured patients, depending on injury severity, acidosis, hypothermia and hypoperfusion. More expedient detection of coagulopathy is needed. Thromboelastography may be a useful point-of-care measurement. Management of TIC is controversial, with conflicting reports on blood component therapy in terms of both outcome and ratios of blood products to other fluids, particularly in the context of civilian trauma. CONCLUSION: The triad of hypothermia, acidosis and coagulopathy after severe trauma appears to be fairly rare but does carry a poor prognosis. Future research should define modes of early detection and targeted therapy.

Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer.

The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51 TFs displaying differential transcript levels between normal mucosa and CRC. For a subset of these we provide in vitro evidence that deregulation of the Wnt signalling pathway can lead to the alterations observed in tissues. Furthermore, in two independent cohorts of microsatellite-stable stage II cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2-6.0; P=0.01). Analyses of approximately 1000 stage I-III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly better overall survival rate (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate analyses revealed that a high CBFB protein level was an independent predictor of survival. In conclusion, several of the identified TFs seem to be involved in the progression of CRC.

Current physical activity is related to bone mineral density in males but not in females.

The purpose of the present study was to investigate the association between high-, medium-, and low-impact physical activity in males and females at the time of peak bone mineral density in young adulthood. The cohort consisted of 62 male medical students (aged 28.1 +/- 3.9) and 62 female medical students (aged 25.1 +/- 3.9). The bone mineral density (aBMD, g/cm (2)) of the total body, femoral neck, and lumbar spine, and the bone mineral content (BMC, grams) and area (cm (2)) of the femoral neck and lumbar spine was measured using dual energy X-ray absorptiometry. Volumetric BMD (vBMD, mg/cm (3)) of the femoral neck and lumbar spine was estimated. The total amount of physical activity per week, which was recorded in a questionnaire, was divided into high-impact, medium-impact, and low-impact activity. In the male cohort, hours of high-impact physical activity per week was associated with aBMD and BMC of all sites (r=0.27 - 0.53, p<0.05) and bone area of the femoral neck (r=0.38, p<0.01). Total amount of physical activity per week was associated with aBMD of the total body and femoral neck, BMC of femoral neck and lumbar spine, femoral neck vBMD, and the lumbar spine area (p<0.05 for all). Using multiple linear regression, high-impact physical activity was independently associated with aBMD (beta=0.27, p<0.05) and BMC (beta=0.34, p<0.01) of the femoral neck. In the female cohort there was no association between amount or type of physical activity to aBMD, BMC, vBMD, or the bone area of any site. Instead body weight, lean body mass, or fat mass were significantly related to aBMD and all BMC sites in this group. The results of the present study suggest that present physical activity level has a stronger relation to different aspects of bone mass in the male compared to the female adult skeleton.

A 3-year longitudinal study of the effect of physical activity on the accrual of bone mineral density in healthy adolescent males.

It has previously been suggested that physical activity predominantly influences the accumulation of bone density before puberty. The purpose of the present study was to examine the effect of physical activity on the accumulation of bone mass in male athletes between 16 and 19 years of age. The cohort studied consisted of 12 badminton players (aged 16.1 +/- 0.5), 20 ice hockey players (aged 16.1 +/- 0.5), and 24 age-matched controls (aged 16.1 +/- 0.6). The bone mineral density (BMD, g/cm2) of the total body, spine, dominant and nondominant humerus, head and femoral neck was measured twice with a 3-year interval by dual energy X-ray absorptiometry (DXA). In addition, at the femoral neck, volumetric bone mineral density (vBMD, mg/cm3) was estimated. At baseline, the athletes as a whole group had significantly higher BMD at the total body (P = 0.03), dominant (P = 0.006) and nondominant humerus (P = 0.009) and femoral neck (P = 0.007) compared to the controls. At the 3-year followup, the athletes had significantly higher BMD at all sites (total body; P = 0.003, spine; P = 0.02, dominant humerus; P = 0.001, nondominant humerus; P = < 0.001, femoral neck; P = 0.001) except for the head (P = 0.91) compared with controls. The athletes also had higher vBMD at the femoral neck compared with the controls (P = 0.01). Furthermore, to be an athlete was found to be independently associated with a higher increase in nondominant humerus BMD (beta = 0.24; P < 0.05) and femoral neck BMD (beta = 0.30; P < 0.05) compared with the controls, during the study period. In summary, these results suggests that it is possible to achieve continuous gains in bone mass in sites exposed to osteogenic stimulation after puberty in males by engaging in weight-bearing physical activity.

In vivo microdialysis and immunohistochemical analyses of tendon tissue demonstrated high amounts of free glutamate and glutamate NMDAR1 receptors, but no signs of inflammation, in Jumper's knee.

This investigation describes, to our knowledge, the first experiment where the microdialysis technique was used to study certain metabolic events in human patellar tendons in combination with immunohistochemical analyses of tendon biopsies. In five patients (four men and one woman) with a long duration (range 12-36 months) of pain symptoms from Jumper's knee (localized tenderness in the patellar tendon verified as tendon changes with ultrasonography or MRI), and in five controls (four men and one woman) with normal patellar tendons, a standard microdialysis catheter was inserted into the patellar tendon under local anestesia. The local concentrations of glutamate (excitatory neurotransmitter) and prostaglandin E2 (PGE2) were registered under resting conditions. Samplings were done every 15 min during a 2 h period. In all individuals (patients and controls) biopsies were taken for immunohistochemical analyses. The results showed that it was possible to detect and measure the concentrations of glutamate and PGE2 in the patellar tendon with the use of microdialysis technique. There were significantly higher concentrations of free glutamate, but not PGE2, in tendons with tendinosis compared to normal tendons. In the biopsies, there were no inflammatory cell infiltrates, but, for the first time, it was shown that there was immunoreaction for the glutamate receptor NMDAR1 in association with nerve structures in human patellar tendons. These findings altogether indicate that glutamate might be involved in painful Jumper's knee, and further emphasizes that there is no chemical inflammation (normal PGE2 levels) in this chronic condition.

Glutamate NMDAR1 receptors localised to nerves in human Achilles tendons. Implications for treatment?

In this investigation, we show the presence of both free glutamate (microdialysis) and glutamate NMDAR1 receptors (immunohistochemical analyses of tendon biopsies), in tendons from patients with chronic Achilles tendon pain (Achilles tendinosis) and in controls (pain-free tendons). The NMDAR1 immunoreaction was usually confined to acetylcholinesterase-positive structures, implying that the reaction is present in nerves. Glutamate is a potent pain mediator in the human central nervous system, and in animals it has been shown that peripherally administered glutamate NMDA receptor antagonists diminish the response to formalin-induced nociception. Our present finding of glutamate NMDA receptors in human Achilles tendons might have implications for pain treatment.

Bone mineral density and muscle strength in female ice hockey players.

The purpose of this study was to investigate bone mineral density (BMD) at different sites in female ice hockey players as well as to study the relationship between BMD, muscle strength, and body composition parameters. The study group consisted of 14 female ice hockey players (age 22.2 +/- 4.3 years) which was compared with 14 inactive females (age 21.5 +/- 3.8 years). The two groups were matched for age and weight. Areal bone mineral density was measured in total body, head, lumbar spine, femoral neck, Ward's triangle and the trochanter, using dual energy X-ray absorptiometry. Body composition parameters were derived from the total body scan. Isokinetic concentric peak torque of the left quadriceps and hamstrings muscles was measured using an isokinetic dynamometer. Compared to the inactive group, the ice hockey players had significantly higher BMD of all of the bone sites measured, except for the head, (total body 6.9%, head -2.6%, lumbar spine 8.9%, femoral neck 17.6%, Ward's triangle 20.4%, and trochanter 21.7%). The hockey players also had significantly higher peak torque in the quadriceps and hamstrings muscles. In the ice hockey group, a significant positive correlation was found between BMD of the femoral neck and hamstrings peak torque at 225 degreesisecond (r = 0.67, P < 0.01). In the inactive group, significant positive correlations were found between BMD and peak torque in the hamstrings muscles (90 degrees/second: r = 0.6-0.8, P<0.05 (total body, trochanter) and P<0.01 (spine, neck), 225 degrees/second: r = 0.5-0.8, P<0.05 (total body, Ward's triangle, trochanter) and P< 0,01 (spine, neck)). In the inactive group significant positive correlations was also found between lean body mass and BMD of the trochanter (r = 0.58, P < 0.05). In young females it appears that training and playing ice hockey might influence BMD and muscle strength in a positive direction. The correlation between BMD and muscle strength seems to weaken with increased exercise level.

In vivo investigation of ECRB tendons with microdialysis technique--no signs of inflammation but high amounts of glutamate in tennis elbow.

We used the microdialysis technique to study concentrations of substances in the extensor carpi radialis brevis (ECRB) tendon in patients with tennis elbow. In 4 patients (mean age 41 years, 3 men) with a long duration of localized pain at the ECRB muscle origin, and in 4 controls (mean age 36 years, 2 men) with no history of elbow pain, a standard microdialysis catheter was inserted into the ECRB tendon under local anesthesia. The local concentrations of the neurotransmitter glutamate and prostaglandin E2 (PGE2) were recorded under resting conditions. Samplings were done every 15 minutes during a 2-hour period. We found higher mean concentrations of glutamate in ECRB tendons from patients with tennis elbow than in tendons from controls (215 vs. 69 micromoL/L, p < 0.001). There were no significant differences in the mean concentrations of PGE2 (74 vs. 86 pg/mL). In conclusion, in situ microdialysis can be used to study certain metabolic events in the ECRB tendon of the elbow. Our findings indicate involvement of the excitatory neurotransmitter glutamate, but no biochemical signs of inflammation (normal PGE2 levels) in ECRB tendons from patients with tennis elbow.

The relation between bone mineral density, insulin-like growth factor I, lipoprotein (a), body composition, and muscle strength in adolescent males.

Osteoporosis is the most common metabolic bone disease. A low peak bone mass is regarded a risk factor for osteoporosis. Heredity, physical activity, and nutrition are regarded important measures for the observed variance in peak bone mass. Lp(a) lipoprotein is a well-known risk factor for atherosclerosis. Serum insulin-like growth factor I (IGF-I) has been found to be increased in males with early cardiovascular disease. In this study, we evaluated the association between bone mass, body constitution, muscle strength, Lp(a), and IGF-I in 47 Caucasian male adolescents (mean age, 16.9 yr). Bone mineral density (BMD) and body composition were measured by dual x-ray absorptiometry, muscle strength of thigh using an isokinetic dynamometer, IGF-I by RIA, and Lp(a) by enzyme-linked immunosorbent assay. IGF-I was only associated with Lp(a) (r = 0.38, P < 0.01). Lp(a) was related to total body (r = 0.40, P < 0.01), skull (r = 0.45, P < 0.01), and femoral neck BMD (r = 0.44, P < 0.01). Lp(a) was also related to fat mass (r = 0.34, P < 0.05) and muscle strength (r = 0.30-0.42, P < 0.05). After multiple regression and principal component (PC) analysis, the so-called PC body size (weight, fat mass, lean body mass, and muscle strength) was the most significant predictor of BMD (beta = 0.28-0.51, P < 0.05-0.01), followed by the so-called PC physical activity (beta = 0.28-0.38, P < 0.05-0.01, weight-bearing locations). However, the PC analysis confirmed that Lp(a) was an independent predictor of total body, skull, and femoral neck BMD (beta = 0.33-0.36, P < 0.01). The present investigation confirms that BMD, body size, and muscle strength are closely related and that the level of physical activity is a major determinant of BMD. However, the positive relation of Lp(a), a major risk factor for cardiovascular disease, to BMD has not previously been described. The importance of this observation has to be further investigated.

Treatment of tear of the anterior cruciate ligament combined with localised deep cartilage defects in the knee with ligament reconstruction and autologous periosteum transplantation.

An acute tear of the anterior cruciate ligament (ACL) is frequently associated with injuries to the joint cartilage and subchondral bone. These injuries may progress to deep cartilage defects, causing disabling pain, and represent a therapeutic challenge in patients with the combination instability and pain. At our clinic we treat patients with the combined injury with simultaneous ACL reconstruction and autologous periosteum transplantation of the cartilage defect. This report describes the technique for periosteum transplantation of full-thickness cartilage defects in the medial femoral condyle. Our clinical report includes the first 7 patients (6 men and 1 woman, mean age 29.1 years at operation) who have been followed for 2 years or longer of 14 consecutive patients (12 men and 2 women). All patients had suffered a total tear of the ACL and a full-thickness defect of the cartilage at the medial femoral condyle. The cartilage defects had a mean area of 7.3 cm2 (range 1.0-13.5 cm2). All patients had disabling instability and medial knee pain when walking. The anterior cruciate ligament was reconstructed with a bone-tendon-bone graft of the central third of the patellar ligament. After preparation of the cartilage lesion, the periosteum transplant was anchored to the underlying bone with suture anchors and fibrin glue. Postoperatively, these patients (n = 7) were initially treated with continuous passive motion, followed by active flexibility training and slowly progressing strength training and weight-bearing activities. At follow-up a mean of 31.3 months (range 24-38 months) later, 6 patients evidenced subjectively stable knees, no pain during rest or when walking, and had returned to not too heavy knee-loading work. One patient had a subjectively stable knee, but felt medial knee pain. Meticulous surgical technique and rigorous postoperative rehabilitation are probably of the greatest importance in this procedure. With the use of suture anchors and fibrin glue, the periosteum transplant can be well adapted to the condylar subchondral bone bed.

In situ microdialysis in tendon tissue: high levels of glutamate, but not prostaglandin E2 in chronic Achilles tendon pain.

This investigation was to our knowledge the first to use the microdialysis technique to study concentrations of substances in a human tendon. In four patients (mean age 40.7 years) with a painful nodule in the Achilles tendon (chronic Achilles tendinosis) and in five controls (mean age 37.2 years) with normal Achilles tendons (confirmed by ultrasonography) the local concentrations of glutamate and prostaglandin E2 were measured under resting conditions. A standard microdialysis catheter was inserted into the Achilles tendon under local anesthesia. Sampling was performed every 15 min over a 4-h period. The results showed significantly higher concentrations of glutamate in tendons with tendinosis than in normal tendons (196 +/- 59 vs. 48 +/- 27 mumol/l, P < 0.05), and there were no significant changes in glutamate concentration over the period of investigation. There were no significant differences in the mean concentrations of prostaglandin E2 (83 +/- 22 vs. 54 +/- 24 pg/ml) between tendons with tendinosis and normal tendons. In conclusion, in situ microdialysis appears a useful method to study certain metabolic events in tendon tissue. The higher concentrations of the excitatory neurotransmitter glutamate in Achilles tendons with a painful nodule may possibly be involved in the pain mechanism in this chronic condition. Furthermore, there were no signs of inflammation in the tendons with painful nodules, as indicated by the normal prostaglandin E2 levels.