Can the hamstring muscles protect the anterior cruciate ligament during a side‐cutting maneuver?

Because anterior cruciate ligament (ACL) injuries are common in European handball the present study assessed knee joint shear forces to estimate ACL loading in six elite female handball players during a side-cutting maneuver. A pilot investigation in three dimensions showed that peak moments occurred in the sagittal plane at a high velocity. Therefore, analysis of the movement was performed in two dimensions using high-speed cinematography, ground reaction forces, and electromyography (EMG). Film and force plate data allowed for calculation of net joint moments (inverse dynamics), estimates of instantaneous muscle-tendon lengths, contraction velocities, and peak loading of the ACL. During the breaking phase of the maneuver the peak knee joint moment was 239 Nm (99-309), which yielded an ACL-load of 520 N (215-673). The corresponding peak EMG amplitudes for the hamstring muscles were 34-39% of maximum EMG. During the breaking phase the quadriceps muscle contracted eccentrically with a velocity of 216-253% fiber length/s. In contrast, the hamstring muscles contracted concentrically with a velocity of 222-427% fiber length/s. These results suggest that a side-cutting maneuver produces loads that are insufficient to rupture the ACL. Furthermore, the rapid concentric hamstring contraction suggests that even during maximal activation, the ability of the hamstrings to reduce the ACL load is marginal.     

Secondary impingement in the shoulder. An improved terminology in impingement

Non-traumatic shoulder pain in the overhead athlete is a diagnostic challenge. In the last decade shoulder arthroscopy and magnetic resonance imaging (MRI) techniques have extended our knowledge. Previously unknown pathologic changes in the glenohumeral joint have been demonstrated and it is recognized that impingement symptoms and instability are often related. Shoulder dysfunction in overhead athletes may be caused by shoulder instability. However, a possible instability in the shoulder is often "silent" and difficult to demonstrate by ordinary tests and has therefore by some been termed "functional instability". It is now thought that functional instability in the shoulder may lead to a vicious cycle involving microtraumata and attenuation of the capsular complex, and may eventually lead to shoulder pain. Changes in shoulder proprioception, measured by testing kinaesthetic sense and position sense, can be related to different pathologic changes in the shoulder, and sensory motor control may be an important factor for functional stability in the shoulder. MRI and arthroscopical findings in athletes with shoulder pain are changes in the glenoid labrum, the humeral head, the rotator cuff, biceps tendon and the capsular complex. However, these findings often present other clinical entities than impingement and are not always associated with instability. Clinically, there are tests that can objectively distinguish some of the pathological findings. However, we need more exact methods to further improve our clinical diagnoses of the painful shoulder. One of the keys could be an extended knowledge about the pathophysiology behind functional instability. This review focuses on an improved terminology in impingement based on the current knowledge of impingement and instability in the shoulder.     

Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites.

Bortezomib [N-(2,3-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid] is a potent first-in-class dipeptidyl boronic acid proteasome inhibitor that was approved in May 2003 in the United States for the treatment of patients with relapsed multiple myeloma where the disease is refractory to conventional lines of therapy. Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. The development of bortezomib has provided an opportunity to describe the metabolism of a novel boronic acid pharmacophore.     

Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans.

The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile.     

Expression of zinc-positive cells and terminals in fetal neocortical homografts to adult rat depends on lesion type and rearing conditions

Zinc-positive neurons and terminals, known to be associated with the glutamatergic projections in the brain, can be demonstrated by the histochemical Timm method and later modifications thereof. The adult rat neocortex contain a uniform lamination of zinc-positive cells with specific projections to, e.g., the striatum. We have previously reported that fetal neocortical grafts implanted in the adult rat neocortex combined with rearing in an enriched environment can improve behavioral functions and reduce the secondary atrophy of thalamus after cortex infarction in adult rats. In order to examine whether the expression of zinc positivity is ontogenetically inherent to neocortical neurons we grafted fetal neocortical tissue to aspiration or ischemic lesions of the frontoparietal neocortex of adult rats, followed by histochemical visualization of the vesicular zinc pool by selenite or sulfide. One further aim of the study was to elucidate to what extent the distribution of zinc-containing neurons and terminals in the grafts depended on rearing under different environmental conditions. The foremost finding of the present study was that the overall density of zinc-containing terminals in fetal cortical transplants placed in brain infarcts of adult spontaneously hypertensive rats is higher when the rats are reared in an enriched environment. Moreover, the presence and expression of zinc-positive neurons and terminals do not seem to be ontogenetically inherent to the cortical neurons as the fetal neocortical grafts placed in aspiration lesions contained no zinc-selenide-positive neurons and few or no zinc-selenide-positive terminals. The presence or expression of zinc-positive cells may thus be induced by ingrowth of fibers and terminals from the host brain as transplants placed in the ischemic lesions expressed both zinc-positive neurons and terminals.     

21. Increased FDG uptake in Childhood CNS Tumors is Associated with Tumor Malignancy

Background: In adults PET scanning of CNS tumors with the tracer FDG (18F-flourodeoxyglucose) can provide information about the degree of malignancy, tumor extent, and dissemination. FDG PET can also be able to assess tumor response to therapy and to differentiate recurrence from necrosis. Although CNS tumors are the most common solid tumor in childhood, so far only few PET-studies have been reported. Pre-operative assessment of malignancy would facilitate surgical planning and the use of pre-operative chemotherapy.Materials and Methods: 21 children with CNS tumors were referred to clinical FDG PET prior to therapy (M/F = 12/9, median age: 9 (range 0-16)), (4 PNET/medulloblastomas; 1 gr. III ependymoma, 16 benign tumors)). Image processing included co-registration with MRI and image fusion. The FDG uptake in the tumors was ranked 0-5 by a hotspot/cortex-ratio by two observers independently. The FDG uptake in grey and white matter was used as reference for the grading system with FDG uptakes defined as 4 and 2 respectively.Results: 15 of 16 patients with tumors WHO gr. I-II had FDG-uptake of 1-2, and all 5 patients with tumors WHO gr. III-IV had FDG-uptake of 3-4. A WHO gr. I papilloma, known to have a high metabolism caused by high mitochondrial activity, had FDG uptake of 5. Except for this tumor, the FDG uptake was positively correlated with tumor malignancy. MRI/PET co-registration and image fusion increased the specificity of tumor location, as well as of tumor extent, and of heterogeneity (e.g., areas of necrosis).Conclusion: FDG PET with MRI/PET co-registration and image fusion could be an important adjunct in the diagnostic work up of pediatric CNS tumors, and could help define patients eligible for pre-operative chemotherapy.     

Sealing effect of hydroxyapatite coating: a 12-month study in canines

This study addresses the clinical problems regarding access of wear debris to the bone-implant interface and the possible dissemination of polyethylene (PE) particles to distant organs. We inserted two implants into each knee of 7 dogs allowing access of joint fluid to the bone-implant interface with a 0.75 mm initial gap around the implant. Hydroxyapatite (HA)-coated and non-coated (Ti) titanium alloy implants were randomly allocated to each distal femoral condyle. PE particles were repeatedly injected into the right knee joint 3 weeks after surgery for a period of 49 weeks, while only vehicle was injected into the left knee joint. We found huge amounts of PE particles mainly in the bone-implant interface around Ti implants. Infiltration of mononuclear inflammatory cells was present around 3 of 7 Ti implants in relation to PE particles. HA implants had approximately 70% bone ongrowth. In contrast, no bone ongrowth was seen on any Ti implants, all being surrounded by a fibrous membrane. The number of PE particles was evaluated semi-quantitatively. More PE particles were found around Ti implants than with HA implants (p < 0.002). Specimens from iliac lymph nodes, liver, spleen and lung were examined and showed dissemination of PE particles only in regional lymph nodes.     

Effects of Different Doses of Epidural Midazolam on Spinal Somatosensory Evoked Potentials

Summary  The aim of this study is to find out the effects of different doses of midazolam, when used epidurally, on somatosensory evoked potentials (SEP) by delaying neuronal conduction. Thirty two New Zeland albino male rabbits were divided into four groups. All rabbits were anesthetised with ketamine and xylasine combination and atracurium was used as muscle relaxant. 10 mg/kg/hr ketamine infusion was used for maintenance of anesthesia. After insertion of the epidural catheter surgically; Group 1 received 1.5 ml isotonic saline (Control), Group 2 received 150 μg/kg, Group 3 received 250 μg/kg, and Group 4 received 500 μg/kg midazolam epidurally. With the stimulation of sciatic nerve, SEP records were recorded from the epidural space. Records were received before the injection of the drug, and 20, 40, 60 minutes after injection of the drug.  “Latancy” results were increased according to control in all groups (including isotonic saline-control-group). Increase in latancy in the control group was interpreted as due to the effect of temperature mismatch of the saline and the rabbits. While in the first and second group amplitudes showed no differences, group 3 and 4 showed decreases of up to 50%. Epidurally administered midazolam up to 150 μg/kg caused no change in SEP records, but 250 and 500 μg/kg doses caused decreases in SEP records which can lead to misinterpretation as neurological damage.