Kim Thorsen

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

Abstract 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 μmol/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.

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 Jumpers 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.

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 E 2 (PGE 2 ) 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 w tendons from controls (215 vs. 69 _6;moL/L, p < 0.001). There were no significant differences in the mean concentrations of PGE 2 (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 PGE 2 levels) in ECRB tendons from patients with tennis elbow.

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.

High intratendinous lactate levels in painful chronic Achilles tendinosis. An investigation using microdialysis technique.

In this investigation the microdialysis technique was used to study the concentrations of lactate in Achilles tendons with painful chronic tendinosis and in normal pain‐free tendons. In four patients (mean age 40.7 years) with a painful thickening localized at the 2–6 cm level in the Achilles tendon (chronic Achilles tendinosis) and in five controls (mean age 37.2 years) with normal Achilles tendons, the local concentrations of lactate were registered under resting conditions. All tendons were examined using ultrasonography. In the tendons with tendinosis the painful thickening corresponded to a widened tendon and structural tendinosis changes. Normal tendons showed no widening and a normal structure. A standard microdialysis catheter was inserted into the Achilles tendon under local anesthesia. Samplings were done every 15 min during a 4 h period.

Effects of moderate endurance exercise on calcium, parathyroid hormone, and markers of bone metabolism in young women

We investigated the short-term (1 hour-3 days) effects of a 45 minute run on calcium, parathyroid hormone, the carboxyterminal propeptide of type I procollagen (PICP), and the immunoactive carboxyterminal telopeptide of type I collagen in serum (ICTP) in young females. Fourteen healthy young women, aged 25.2 ± 0.6 years (mean ± SEM) with regular menstruations, participated. The test was outdoor jogging for 45 minutes at an intensity of 50% of VO2 max. Blood samples were collected 15 minutes before the test and 1, 24, and 72 hours after the test. The measured values were adjusted for changes in plasma volume. A significant decrease of ionized calcium was observed at 1 hour (P < 0.001) and 72 hours (P < 0.05) and a significant increase of parathyroid hormone (PTH) was noted 24 (P < 0.01) and 72 hours (P < 0.05) after the test. A significant decrease of PICP at 1 hour (P < 0.05) was followed by an increase after 24 (P < 0.01) and 72 hours (P < 0.001) and a significant increase in ICTP was noted at 24 and 72 hours (P < 0.05). A strong positive correlation was found between serum levels of PICP and ICTP (r = 0.55–0.84; P < 0.05) throughout the experiment. In conclusion, young females showed biochemical signs of increased bone collagen turnover and altered homeostasis of calcium and PTH after a single bout of moderate endurance exercise.

Bone mass, muscle strength, and different body constitutional parameters in adolescent boys with a low or moderate exercise level

This study was conducted to evaluate the association between muscle strength of the thigh, different body constitutional parameters, and bone mineral density (BMD) in adolescents. The subjects were 26 healthy adolescent boys, age 15.9 +/- 0.3 years, not training for more than 3 h per week. BMD was measured in total body, head, humerus, spine, femur, and tibia/fibula. Univariate correlations were measured between the explanatory parameters height, weight, body mass index (BMI), fat mass, lean body mass, quadriceps strength, hamstrings strength, and each BMD site using Pearsons coefficient of correlation. The explanatory variables were also used in a multivariate analysis to explain each BMD site. There was a high degree of concordance when comparing the two methods of analysis. Using the multivariate analysis, quadriceps strength and lean body mass showed significant independent correlations to all BMD sites measured, the correlations being stronger for the adjacent femur and tibia/fibula than for the distant humerus and head. Hamstrings strength correlated significantly and independently with tibia/fibula BMD and spine BMD. Fat mass, BMI, and weight correlated significantly and independently to all BMD sites except femur. This study demonstrates a general relationship between BMD and different body constitutional parameters and muscle strength of the thigh.(ABSTRACT TRUNCATED AT 250 WORDS)

High Bone Mass and Altered Relationships Between Bone Mass, Muscle Strength, and Body Constitution in Adolescent Boys on a High Level of Physical Activity

We have recently demonstrated a general relationship between bone mass, muscle strength, and several body constitutional parameters in adolescent boys with a moderate exercise level. The present study was conducted to evaluate these previously described relationships in adolescent boys subjected to high physical activity and also to compare the bone mass of the same group with that of adolescents on a moderate level of physical activity. The reference group consisted of 24 boys, age 15.9 +/- 0.3 years, not training for more than 3 h per week. The ice hockey players consisted of 20 boys, age 15.9 +/- 0.3 years, from an ice hockey junior team training for about 10 h per week. The groups were matched according to age, pubertal stage, and weight. Areal bone mineral density (BMD) was measured in total body, head, humerus, spine, femur, and proximal femur using dual energy X-ray absorptiometry. BMD was significantly higher in the humerus (p < 0.01), femur (p < 0.05), and proximal femur (p < 0.05) in the high activity group. Furthermore, physical activity (h/week) was an independent predictor of humerus BMD (p < 0.01) and proximal femur BMD (p < 0.05), among all subjects investigated (n = 44). Isokinetic muscle strength of the quadriceps and hamstrings muscles was significantly higher in the high activity group (p < 0.05). In the reference group, there was a general strong independent relationship between BMD, muscle strength, and different body constitutional parameters. In the high activity group, muscle strength of the thigh independently predicted BMD of humerus and spine. Furthermore, in the same group, weight, BMI, and fat mass independently predicted only spine BMD. In conclusion, the higher BMD demonstrated in the ice hockey players seems to be site-specific and may well be associated with the type and magnitude of loading from predominantly ice hockey. High physical activity seems to weaken the relationship between BMD, muscle strength, and body constitution demonstrated in adolescent boys on a low or moderate level of physical activity.

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 (β = 0.24; P < 0.05) and femoral neck BMD (β = 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.

Local bone mineral density, muscle strength, and exercise in adolescent boys: A comparative study of two groups with different muscle strength and exercise levels

The primary objective of the present study was to evaluate the impact of physical activity and muscle strength on bone mineral density (BMD) of the tuberositas tibiac in adolescent boys. Two groups with different exercise levels were compared. The high activity group consisted of 20 subjects (age 15.9±0.3) from a junior ice hockey team. The reference group consisted of 24 volunteers (age 15.9±0.3) not training for more than 3 hours per week. The groups were matched for age, weight, and pubertal stage. BMDs (g/cm2) of the tuberositas tibiae and proximal tibia were measured using dual energy X-ray absorptiometry. Quadriceps strength was significantly higher in the high activity group (P<0.01). Univariate correlations were measured between tuberositas tibiae BMD and pubertal stage, weight, height, BMI, fat mass, lean body mass, quadriceps strength, and hamstrings strength in the high activity group and the reference group, respectively. Quadriceps strength was estimated to be the best significant predictor of BMD of the tuberositas tibiae in the reference group. A multivariate analysis confirmed this result. In the high activity group, there was no significant predictor of BMD of the tuberositas tibiae. There was no significant difference in BMD at this site when comparing the two groups. However, five of the boys in the high activity group had a former history of Mb Osgood-Schlatter with a significantly lower BMD of the tuberositas tibiae than the rest of the boys in that group. After exclusion of these boys, the remaining 15 boys were matched against 20 boys from the reference group using the previous criteria. These 15 boys then showed a significantly higher BMD of the tuberositas tibiae (P<0.05) but not of the proximal tibia than the 20 boys in the reference group. In conclusion, this study demonstrates site-specific increments of tuberositas tibiae BMD in adolescent ice hockey players unless they are affected by the negative effects on BMD by Mb Osgood-Schlatter. These increments seem primarily to be associated with forceful muscle contractions related to high quadriceps strength and not greater weight-bearing loading. Muscle strength seems to positively affect BMD of the tuberositas tibiae in adolescents, but only up to a certain level, above which additional muscle strength has no effect.