Asymptomatic Achilles, patellar, and quadriceps tendinopathy: a longitudinal clinical and ultrasonographic study in elite fencers.

Lower limb tendon changes detected at imaging are common among asymptomatic athletes. We aimed to prospectively assess the clinical status, tendon structure, and vascularity of lower limb tendons of elite fencers, and predict the risk of developing symptoms over time. Clinical examination, changes at ultrasonography (US), and Power Doppler (PD) flow of both the Achilles, patellar, and quadriceps tendon were assessed in 37 elite fencers in January 2007 and 3 years after. Two hundred and twenty-two tendons were examined. At the last appointment, patellar tendons diagnosed as abnormal at baseline were more likely to develop symptoms than those normal at baseline (P < 0.05, Fisher's exact test), while US and PD abnormalities on Achilles and quadriceps tendons were no predictive for development of symptoms over years. A very low percentage of tendons diagnosed as normal at baseline (1.45%) showed US abnormalities at 3-year follow-up. In asymptomatic elite fencers, structural changes are relatively common at US and PD assessment of Achilles, quadriceps, and patellar tendons. It seems unlikely that additional PD investigations provide further information or change prognosis in patients with US diagnosis of tendinopathy.

Store-dependent Ca(2+) entry in endothelial progenitor cells as a perspective tool to enhance cell-based therapy and adverse tumour vascularization.

Endothelial progenitor cells (EPCs) have recently been employed in cell-based therapy (CBT) to promote neovascularization and regeneration of ischemic organs, such as heart and limbs. Furthermore, EPCs may be recruited from bone marrow by growing tumors to drive the angiogenic switch through physical engrafting into the lumen of nascent vessels or paracrine release of pro-angiogenic factors. CBT is hampered by the paucity of EPCs harvested from peripheral blood and suffered from several pitfalls, including the differentiation outcome of transplanted cells and low percentage of engrafted cells. Therefore, CBT will benefit from a better understanding of the signal transduction pathway(s) which govern(s) EPC homing, proliferation and incorporation into injured tissues. At the same time, this information might outline alternative molecular targets to combat tumoral neovascularization. We have recently found that store-operated Ca(2+) entry, a Ca(2+)-permeable membrane pathway that is activated upon depletion of the inositol-1,4,5-trisphosphate-sensitive Ca(2+) pool, is recruited by vascular endothelial growth factor to support proliferation and tubulogenesis in human circulating endothelial colony forming cells (ECFCs). ECFCs are a subgroup of EPCs that circulate in the peripheral blood of adult individuals and are able to proliferate and differentiate into endothelial cells and form capillary networks in vitro and contribute to neovessel formation in vivo. The present review will discuss the relevance of SOCE to ECFC-based cell therapy and will address the pharmacological inhibition of store-dependent Ca(2+) channels as a promising target for anti-angiogenic treatments.

Assessment of vascular function: flow-mediated constriction complements the information of flow-mediated dilatation.

OBJECTIVE: To determine whether vascular function assessed by low-flow-mediated constriction (L-FMC), a novel non-invasive method, complements the information obtained with "traditional" flow-mediated dilatation (FMD). DESIGN AND PATIENTS: In protocol 1, 12 healthy young volunteers underwent FMD and L-FMC measurements at rest and immediately after isometric exercise of the same hand. In protocol 2, 24 patients with coronary artery disease, 24 with congestive heart failure, 24 hypertensive patients and 64 healthy volunteers were enrolled to undergo L-FMC and FMD measurements. RESULTS: In protocol 1, exercise was associated with mean (SD) increases in radial artery blood flow, diameter and L-FMC (from -5.1 (1.5)% to -7.8 (3.4)%, p<0.05), while FMD was significantly blunted (from 6.0 (2.4)% to 3.0 (3.2)%, p<0.05). In protocol 2, both FMD and L-FMC were blunted in the patient groups. Receiver operating curve analysis showed that, as compared with FMD alone, the combination of L-FMC and FMD significantly improved the sensitivity and specificity in detecting patients diagnosed with cardiovascular disease (p<0.05). CONCLUSION: In the first protocol, FMD and L-FMC were shown to be reciprocally regulated. A blunted FMD may, in certain cases, be an expression of increased resting vascular activation and not only of impaired endothelial function. In the second protocol, a statistical approach showed that implementation of L-FMC provides a better characterisation than FMD of vascular function in cardiovascular disease. Vascular (endothelial) function is a complex phenomenon which requires a multifaceted approach; it is suggested that a combination of L-FMC and FMD will provide additive and complementary information to "traditional" FMD measurements.

Osteoid osteoma mimicking overuse syndromes in athletes.

This article reports the clinical features, findings at imaging, management and outcome of five athletes who presented with osteoid osteoma. The diagnosis was missed initially in all the athletes, who were managed for an overuse syndrome for many months before receiving a correct diagnosis. Osteoid osteoma can cause atypical pain, and therefore lead to delay in diagnosis and inappropriate management. Each injured athlete must be fully evaluated by history, physical examination and appropriate imaging investigations to minimize the rate of misdiagnosis and underestimation, unnecessary procedures, and delayed management.

A synovial ganglion of the knee: two cases in athletes.

The objective of the study is to describe two cases of proximal tibiofibular ganglion cysts in high level athletes. In May 2003 and March 2005 two athletes (one tennis player in the top eighty of the Italian national ranking and a gymnast belonging to the Italian rhythmic gymnastics national team) were referred to our institution complaining of postero-lateral knee discomfort and the presence of localized swelling over the fibular head and the antero-lateral aspect of the leg, with a clinically suspected diagnosis of ganglion cyst of the proximal tibiofibular joint. Ultrasonography clearly detected the fluid-filled structures while magnetic resonance imaging confirmed the diagnosis, also showing precisely the anatomic relationship between the ganglions and the surrounding structures. Both athletes underwent surgical excision and the histological examination was compatible with a proximal tibiofibular joint ganglion cyst; as yet they have had no recurrence.

Model-based analysis of flow-mediated dilation and intima-media thickness.

We present an end-to-end system for the automatic measurement of flow-mediated dilation (FMD) and intima-media thickness (IMT) for the assessment of the arterial function. The video sequences are acquired from a B-mode echographic scanner. A spline model (deformable template) is fitted to the data to detect the artery boundaries and track them all along the video sequence. The a priori knowledge about the image features and its content is exploited. Preprocessing is performed to improve both the visual quality of video frames for visual inspection and the performance of the segmentation algorithm without affecting the accuracy of the measurements. The system allows real-time processing as well as a high level of interactivity with the user. This is obtained by a graphical user interface (GUI) enabling the cardiologist to supervise the whole process and to eventually reset the contour extraction at any point in time. The system was validated and the accuracy, reproducibility, and repeatability of the measurements were assessed with extensive in vivo experiments. Jointly with the user friendliness, low cost, and robustness, this makes the system suitable for both research and daily clinical use.

Stress fractures of the ribs in elite competitive rowers: a report of nine cases.

OBJECTIVE: The objective was to report the clinical and imaging patterns of nine cases of stress fractures of the rib diagnosed in Italian Olympic rowers. PATIENTS AND METHODS: Nine patients with stress fractures of the rib detected from 103 (8.7%) Italian team rowers competing between May 2000 and May 2006 were identified based on the database of a sports medicine institute. All athletes were male. They were aged between 17 and 31 years (mean: 24.4). Patient weight, fracture location, rowing side and imaging methods employed were noted. RESULTS: The diagnosis was made based on history, clinical examination and Tc-99m MDP bone scintigraphy. Eight of the 9 fractures were located anterolaterally between the fourth and ninth rib. In 1 of the 5 athletes with standard radiographs, a fracture line was visible and in 4 there was callus formation. In 2 athletes sonography was performed, which detected discontinuity of the rib surface and callus formation (1 case each). CONCLUSION: Stress fractures of the ribs are relatively common in competitive rowers. They are characterized by increasing lateral chest pain and typical scintigraphic, radiographic and sonographic findings.

Cancer cell permeability-glycoprotein as a target of MDR reverters: possible role of novel dihydropyridine derivatives.

The overexpression of permeability-glycoprotein (P-gp) and other drug transporters (ATP-binding cassette) confers a multidrug resistance (MDR) phenotype on cells in various diseases, including many forms of cancer. Development of MDR is one of the main reasons of failure in malignant tumour chemotherapy, as tumour cells, by increasing drug efflux, acquire cross-resistance to many structurally and functionally unrelated anticancer agents, which therefore never achieve effective intracellular concentrations. Endeavouring to find MDR-reverters is a crucial task for exploring new anti-cancer therapeutic intervention. Although many P-gp inhibitors have so far been identified, it is widely recognised that their interaction with P-gp is a complex process and, presently, the details of the mechanisms of action are still a matter of debate. These compounds turned out, however, to be of limited clinical usefulness owing to their inherent pharmacological activities (first generation compounds) and their accessory, inhibiting activity on CYP enzyme system (second generation compounds). Moreover, recent advances of the knowledge on P-gp structure and function and on the mechanisms of P-gp inhibition will prove fruitful for the development of novel therapeutically effective P-gp inhibitors. A dibenzoyl-1,4-dihydropyridine compound (DP7) has been shown to be a powerful P-gp inhibitor, almost devoid of cardiovascular effects, but capable of inhibiting liver CYP3A. DP7 is considered a lead compound for the development of novel dihydropyridines which do not affect CYP enzyme system but still retain the activity towards ABC-efflux transporters.

Osteochondrosis dissecans of the shoulder glenoid fossa diagnosed in four throwing athletes.

The aim of this study was to report 4 observations of osteochondrosis dissecans (OCD) of the shoulder glenoid fossa diagnosed in throwing athletes. A retrospective review of medical and radiological records of throwing athletes, performed for the period 1992 to 2002, revealed 215 studies of the shoulder. The patients were elite throwing athletes suffering for recurrent shoulder pain. Four cases (1.86%) of OCD of the glenoid fossa were identified; conventional radiographs of the shoulder were taken for all patients followed by MR examination. All cases received a definitive surgical diagnosis.

Symptomatic accessory soleus muscle: report of 18 cases in athletes.

AIM: The aim of this paper was to investigate the prevalence and sports distribution in athletes. METHODS: Six hundred and fifty radiographs of athletes affected by tenderness and exertional pain in the region of the Achilles tendon, were observed over a period of 30 years. The clinical and diagnostic imaging materials were reviewed. RESULTS: Eighteen cases of accessory symptomatic soleus muscle were diagnosed: in 10 cases using soft tissue radiographic technique, in 8 cases using, in sequence, exclusively ultrasound and magnetic resonance. CONCLUSIONS: The presence of an accessory soleus muscle has been considered a rare even incidental occurrence; the review of our cases, substantially different for the evident symptoms, showed a frequency in athletes of 2.77% in accordance with the results of the anatomical and clinical literature. US and MRI are the best diagnostic modalities especially in differentiating accessory soleus muscle from soft tissue tumors not rare in this anatomic region.

Talar body fatigue stress fractures: three cases observed in elite female gymnasts.

OBJECTIVE: To introduce and emphasize the clinical and radiological findings of three talar body fatigue stress fractures in competitive athletes. DESIGN AND PATIENTS: Clinical and radiographic skeletal records of 24,562 athletes taken between 1962 and 2002 were retrospectively reviewed. Among these, 6851 files related to acute foot and ankle injuries or chronic post-traumatic sequelae were found. RESULTS: There were 925 (3.76%) stress fatigue fractures selected from the whole collection. Among these there were three cases (0.32%) of talar body stress fractures diagnosed in elite female gymnasts 15-17 years old. The negative first radiograph become positive 4-6 weeks later. Scintigraphy was positive at an early stage and consistent for the diagnosis. CT and MRI gave positive results 1-2 weeks after the beginning of symptoms which were always greatly diagnostic. CONCLUSIONS: The sports medicine literature lacks reports of talar body fatigue stress fractures. The poor initial sensitivity of radiography makes it problematic to establish an early diagnosis. A wise combination of scintigraphy, CT and MRI has therefore to be relied upon. Familiarity with this rare location for a stress fracture may prevent delayed diagnosis and long-lasting damage, both of which are important factors in competitive athletes.

Endothelium and hemorheology.

Hemorheological alterations which can be found in ischaemic vascular diseases are well known and widely studied; less clear is the relationship between these alterations and endothelial function. Our studies showed that modifications in endothelial function caused by physical stress are associated with a worsening in hemorheological parameters mainly in patients affected by ischaemic vascular diseases: major vascular alterations have been found in patients with very high levels of plasma markers endothelial dysfunction. The control of the basal tone of the vessels is given by the complex interaction between vasoconstrictor and vasodilator endothelial factors and when this equilibrium is broken we have the endothelial dysfunction. From a methodological point of view we can find an endothelial dysfunction index determining the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, which is one of the more powerful endogenous vasodilators and whose synthesis is catalysed by nitric oxide synthase (NOS), can be determined by the ratio between blood concentrations of citrulline and arginine (the co-product and the precursor of the way of NO synthesis), which represents the level of activity of the enzyme. A very affordable index of the endothelial dysfunction is the asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOS; in fact several studies demonstrated a strong relationship between ischaemic vascular diseases and high levels of plasma ADMA. Evaluation of these parameters is measured by means of high performance liquid chromatography (HPLC): this technique provides very affordable results and allows to obtain evaluations of substances in very small concentrations, like ADMA.

Pharmacokinetics of diphenhydramine in healthy volunteers with a dimenhydrinate 25 mg chewing gum formulation.

This pharmacokinetic study evaluated diphenhydramine in the plasma of healthy volunteers after a single 25 mg oral dose of dimenhydrinate (diphenhydramine theophyllinate), corresponding to 12.7 mg diphenhydramine, in a chewing gum formulation. Seven volunteers (4 men, 3 women; age: 26.3 +/- 1.2 years; body weight: 63.1 +/- 4.1 kg; height: 172.4 +/- 4.6 cm) chewed the gum for 1 h. Blood samples (10 ml) were collected at different time intervals up to 24 h. Blood plasma was subsequently processed and analyzed for diphenhydramine content using a GLC method and an NPD detector. Analytical data revealed the following kinetic parameters: AUC(0-24h): 155.2h x ng x ml(-1); AUC(0-infinity): 195.3 h x ng x ml(-1); Mean resident time: 16 h; t(1/2): 10 h; C(max): 14.5 ng x ml(-1); t(max): 2.6 h; and plasma clearance: 9.0 ml x min(-1) x kg(-1). This study indicates that the pharmaceutical formulation employed provided sustained plasma concentrations of diphenhydramine, presumably sufficient to support its clinical efficacy towards motion sickness owing to the almost complete (> 95%) release by the formulation of the active principle. Moreover, the maximal concentrations of diphenhydramine attained in plasma were much lower than the concentration threshold needed to produce drowsiness.

l-Deprenyl metabolism by the cytochrome P450 system in monkey (Cercopithecus aethiops) liver microsomes.

1. The aim was to clarify the kinetic and cytochrome P450 (CYP) enzymes involved in l-deprenyl metabolism by liver microsomal preparations from African green monkeys, an animal model extensively used in the study of Parkinson's disease. 2. CYP levels and monoxygenase activities were similar to those observed in microsomes from other monkey strains. The enzyme kinetics of both l-methamphetamine and l-nordeprenyl formation were characterized by a high- and low-affinity component. For l-methamphetamine, the apparent K(m1) and K(m2) were 1.07 +/- 0.01 and 350 +/- 2.7 micro M, and V(max1) and V(max2) were 4.70 +/- 0.01 and 8.9 +/- 0.02 nmol min(-1) mg protein(-1), respectively. For l-nordeprenyl, K(m1) and K(m2) were 0.96 +/- 0.05 and 168 +/- 15 micro M, and V(max1) and V(max2) were 3.34 +/- 0.02 and 3.91 +/- 0.02 nmol min(-1) mg protein(-1), respectively The ratio V(max)/K(m) for both metabolites was 2 orders of magnitude higher for the low K(m) component than for the high K(m), suggesting that the former component is the major determinant of l-deprenyl N-dealkylation. At 15 micro M l-deprenyl, both ketoconazole and 8-methoxypsoralen significantly inhibited l-methamphetamine and l-nordeprenyl formation, indicating that CYP3A and CYP2A enzymes were involved in both reactions. At 500 micro M l-deprenyl, however, inhibition studies suggest the involvement of CYP1A and 2D enzymes. 3. The metabolism of l-deprenyl by monkey liver microsomes is very efficient, indicating that CYP-dependent metabolism is relevant and could contribute to neuroprotection in primate models of Parkinson's disease.

Hyperthermia at 434 MHz in the treatment of overuse sport tendinopathies: a randomised controlled clinical trial.

The objective of this randomized study was to compare a thermotherapy system, hyperthermia at 434 MHz and conventional ultrasound in the treatment of overuse sports tendinopathies. The study group consisted of 44 athletes, 33 males and 11 females (age 26 +/- 4.56 years) affected by tendinopathies at lower extremities (patellar or achilles tendons). After elucidation of the kind of trial, 22 patients were randomly assigned to hyperthermia and 22 to ultrasound. The patients received after a pain measurement and ultrasound scanning 12 treatments, 3 times a week for 4 weeks. The same standardized examination was done at the end of treatment and 1 month after the end of treatment. The assessor physician was unaware of the treatment allocation. The patients were asked to rate the ultimate outcome on the base of pain resolution and return to sports activity. Both groups had a significant decrease of symptoms (P<0.001). Hyperthermia, however, demonstrated better effects on the reduction of VAS score and on the subjective overall satisfaction (77 %) of excellent and good results in comparison to the 33 % of ultrasound. In patients with chronic overuse tendinopathies hyperthermia at 434 MHz showed encouraging results, with short-term clinical improvement, safety and no side effects.

A controlled study on the effects of hyperthermia at 434 MHz and conventional ultrasound upon muscle injuries in sport.

BACKGROUND: Hyperthermia equipment using a 434 MHz applicator with water bolus elevate to therapeutic temperatures (from 41 to 45 degrees C) delineated volumes of tissue target, down to a depth of 3 to 5 cm. The aim of our study was to evaluate the efficacy of hyperthermia in the treatment of muscle injuries, in comparison with a conventional modality like ultrasound. METHODS: A prospective randomised controlled design was used. Forty patients, 29 males and 11 females, with mean age of 26.2+/-3 ranging between 18 and 35 years affected by acute muscular injuries of different sites and severity participated this study. Twenty-one patients received hyperthermia (group A) and the remaining 19 (group B) ultrasound. Both groups received nine applications, three times per week with a duration of 30' for the group (A), and 15' for the group (B). All the patients underwent a clinical examination including a pain measurement and a ultrasound scanning before, at the end and after one month follow-up. An additional ultrasonography was made after the fourth session to compare the effect of each treatment on the initial course of haematoma resolution. RESULTS: Both groups had a significant decrease of the pain (p< 0.001). The hyperthermia group showed a significantly higher effect on VAS score and on haematoma resolution after two weeks of treatment. CONCLUSIONS: Even with a limited number of cases our results show that the hyperthermia is a highly innovative, safe and reliable modality for the treatment of acute sport muscle injuries.

Localised hypertrophy of semimembranous muscle. A report of two cases in athletes.

We report two cases of localised hypertrophy of semimembranous muscle in young athletes diagnosed with ultrasonography, flow color-Doppler and MRI. The symptomatic case had the resolution of the pain after one month rest. At one year follow-up both cases are still asymptomatic, without any further increase of the hypertrophyc masses.

Acute avulsion fractures of the pelvis in adolescent competitive athletes: prevalence, location and sports distribution of 203 cases collected.

OBJECTIVE: To describe the prevalence, location and sports distribution of pelvic avulsion fractures in adolescent competitive athletes. DESIGN AND PATIENTS: One thousand two hundred and thirty-eight radiographs of the pelvis taken for focal traumatic symptoms in athletes with an age range of 11-35 years over a period of 22 years were reviewed. RESULTS: One hundred and ninety-eight adolescent athletes were affected by 203 avulsion fractures of the pelvic apophyses (five cases presented multiple locations). The localisation was the ischial tuberosity (IT) in 109 cases, anterior inferior iliac spine (AIIS) in 45 cases, anterior superior iliac spine (ASIS) in 39 cases, superior corner of pubic symphysis (SCPS) in 7 cases and iliac crest (IC) in 3 cases. Soccer (74 cases) and gymnastics (55 cases) were the sports with the highest number of avulsion fractures documented. CONCLUSIONS: Apophyseal avulsion fractures of the pelvis in adolescent competitive athletes are most common in soccer and gymnastics. The lesions are usually the consequence of sudden and forceful muscle-tendon contractions during sport activities. Plain radiographs, are determinant for the diagnosis.

Posterosuperior glenoid rim impingement as a cause of shoulder pain in top level waterpolo players.

OBJECTIVE: To further define the impingement occurring between the undersurface of the rotator cuff and the posterosuperior glenoid rim as a cause of shoulder pain in waterpolo athletes. EXPERIMENTAL DESIGN: A prospective design was used in the last three years. SETTING: Data were collected in Science Sports Institute of Rome. PARTICIPANTS: Eleven top level waterpolo players of both sexes all members of Italian National Waterpolo teams complaining of shoulder pain. INTERVENTION: All the eleven cases were previously examined with clinical test and X-ray and MR imaging in conventional and functional views, and then underwent arthroscopy. RESULTS: In four cases, X-ray showed erosions of the posterosuperior glenoid and in 5 cases, osteochondral defects on the posterior aspect of humeral head. In eleven cases, MR detected posterosuperior labral damages, partial tears of the undersurface of the rotator cuff and posterosuperior glenoid impingement. Furthermore arthroscopy detected in all cases the pathological findings associated with the posterosuperior glenoid impingement. CONCLUSIONS: Even if the shoulder pain in the overhead athlete may be multifactorial, this study provides further evidence that the posterosuperior glenoid impingement may be the major cause of shoulder pain in waterpolo athletes.

Isolated partial tear of subscapularis muscle in a competitive water skier. A case report.

Partial tears of the subscapularis tendon associated with anterior shoulder dislocation, are frequently described while the isolated lesions of this tendon are quite rare. We report the case of a 33 years old water-skier who injured his right subscapularis muscle during a forced movement of adduction and internal rotation. Ultrasound evaluation and then MRI were used to depict the entity of the lesion. The ruptured tendon was surgically repaired using a MITEK anchor system. Four months after surgery, the athlete returned back to his full athletic activity.