Alterations of the salivary and fecal microbiome in patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease known for its frequent concurrence with inflammatory bowel disease. PSC can progress to cirrhosis, end-stage liver disease, hepatobiliary cancer, and/or colorectal cancer. The etiopathogenesis of PSC remains poorly understood, and, as such, pharmacotherapy has yet to be definitively established. Little is known about the salivary microbiome in PSC and PSC-IBD. This study aimed to evaluate the oral microbiome of patients with PSC, with association to these patient's fecal microbial composition. METHODS: Saliva, fecal samples and Food Frequency Questionnaires were collected from 35 PSC patients with or without concomitant inflammatory bowel disease and 30 age- and BMI-matched healthy volunteers. 16S rRNA gene sequencing was performed using Illumina MiSeq platform. RESULTS: The salivary microbial signature of PSC was significantly altered as compared to healthy controls, independent of concomitant IBD, and was comprised of 19 significantly altered species, of which, eight species were consistently overrepresented in both fecal and saliva of patients with PSC, including Veillonella, Scardovia and Streptococcus. CONCLUSIONS: PSC is characterized by microbial dysbiosis in the gut and the salivary microbiome, independently from IBD. The PSC dysbiotic signature includes a reduction in autochthonous bacteria and an increased relative abundance of pathogenic bacteria, including an invasion of oral bacteria to the gut. PSC is a strong modulator of the microbial profile, in the gut and the oral microbiome. These results may lead to the development of biomarkers for screening and early diagnosis or the development of personalized medicine in PSC.

Evaluation of the sealing function of the acetabular labrum: an in vitro biomechanical study.

PURPOSE: To quantitatively evaluate the biomechanical sealing function of an intact labrum and the effect of labral-chondral separation, cerclage suture labral repair, vertical mattress suture repair and partial labrectomy on distraction load and hip joint centre (HJC) displacement. METHODS: Eight fresh-frozen cadaveric hips were tested using a navigation system for intra-operative kinematic analysis. A six-axis load cell was used to measure the manually applied force when performing the tests: hip pivoting movement and distraction. The HJC displacement that occurred during the distraction test has been evaluated in correspondence of seven different values of applied force. During the pivoting motion, the maximum value of HJC displacement was evaluated. Five different conditions were tested: labrum intact, labral-chondral separation, vertical mattress suture repair, cerclage suture repair, and partial labrectomy. RESULTS: With regard to HJC displacement using at fixed value of force, the paired sample t test underscored the statistically significant differences (p < 0.05) for each of the five tested conditions among themselves. Only the comparison of intact versus labral-chondral separation was not significantly different. During pivoting motion, a statistically significantly greater displacement was identified after labrectomy when compared with the cerclage suture repair (p = 0.03) and vertical mattress repair (p < 0.01) in medial-lateral direction. Along proximal-distal direction, a significant lower displacement after labrectomy was identified when compared to the cerclage suture repair (p = 0.03). Performing the pivoting motion at the extreme ranges of motion demonstrated a higher value of displacement after labrectomy when compared with all the previously tested conditions. CONCLUSIONS: These results suggest that labral repair is important in the function of the hip and that the vertical mattress suture technique may be better than the cerclage suture repair.

Sexual behaviour and desire to discuss mental health as reported by HIV-infected men who have sex with men.

We assessed sexually transmitted infection risk behaviours and desire to discuss mental health, as reported by 426 HIV-infected men who have sex with men receiving HIV care in eight urban clinics. Most of these patients (90%) had begun HIV care >1 year ago. In the past year, 74% had multiple sexual partners, 75% engaged in anal intercourse, 48% had >1 HIV-uninfected partner and 82% used illegal psychoactive drugs. Among those reporting anal intercourse, approximately 61% reported using a condom during the most recent episode. Among all patients, 70% wanted to talk with their clinicians about how they felt mentally or emotionally. Using a two-tailed chi-squared test, we found that patients who engaged in unprotected receptive anal sex were more likely to want such a conversation than those who did not (80% versus 62%, P < 0.01); and those who engaged in unprotected insertive anal sex were also more likely to want such a conversation (81% versus 63%, P < 0.01). The findings highlight the prevalence of risky sexual behaviour and of mental health concerns in the participating patient population. Patients reporting risky sexual behaviour were more likely to want to discuss how they felt mentally or emotionally than those not reporting such behaviour.

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB's regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation.

Injuries about the shoulder in skiing and snowboarding.

There has been a decrease in the overall injury rate, particularly the rate of lower-extremity injuries, for alpine skiing, with a resultant increase in the ratio of upper-extremity to lower-extremity injuries. The upper extremity is injured nearly twice as often during snowboarding than alpine skiing, with approximately half of all snowboarding injuries involving the upper extremity. Shoulder injuries are likely under-reported, as many patients seek evaluation for minor shoulder injuries with their local physicians, and not at the ski medical clinic, where most epidemiology studies obtain their data. Shoulder injuries account for 4 to 11% of all alpine skiing injuries and 22 to 41% of upper-extremity injuries. During snowboarding, shoulder injuries account for 8 to 16% of all injuries and 20 to 34% of upper-extremity injuries. Falls are the most common mechanism of shoulder injury, in addition to pole planting during skiing and aerial manoeuvres during snowboarding. Common shoulder injuries during skiing and snowboarding are rotator cuff strains, glenohumeral dislocations, acromioclavicular separations and clavicle fractures. It is still unclear, when comparing snowboarding and skiing injury data, which sport has the higher incidence of shoulder injuries. Stratifying shoulder injuries by type allows better delineation as to which sport has an increased incidence of certain injury patterns. The differing mechanisms of injury combined with distinct equipment for each sport plays a role in the type and frequency of shoulder injuries seen in these two subgroups. With the increased ratio of upper- to lower-extremity injuries during alpine skiing and the boom in popularity of snowboarding, shoulder injuries are seen with increasing frequency by those who care for alpine sport injuries. According to recent epidemiological data, only clavicle and humerus fractures have shown increased rates of incidence among alpine skiers. Over the past 30 years, there has been a general decrease in both upper- and lower-extremity injuries which can be attributed to improved designs of protective equipment, increased awareness of injury patterns and emphasis on prevention. In the future, physicians and therapists who treat this population must be comfortable and confident in their treatment algorithms to help keep skiers and snowboarders conditioned and ready for the slopes and develop strategies for the prevention of upper-extremity injuries associated with these activities.

Postero-medial elbow problems in the adult athlete.

The ligamentous, osseous, musculotendinous, and neural structures at the postero-medial side of the elbow are at risk for various injuries in overhead athletes. The combination of valgus and extension overload during overhead activities results in tensile forces along the medial stabilising structures, with compression on the lateral compartment and shear stress posteriorly. The combination of tensile forces medially and shear forces posteriorly can result in ulnar collateral ligament (UCL) tears, flexor-pronator mass injuries, neuritis of the ulnar nerve, posterior impingement, and olecranon stress fractures. Most symptomatic conditions of the overhead athlete can be treated conservatively initially. In cases where conservative treatment is unsuccessful surgical intervention is indicated. Recent advances in arthroscopic surgical techniques and ligamentous reconstruction ensure that the prognosis for return to pre-injury level is good.

Shoulder proprioception in baseball pitchers.

We examined proprioceptive differences between the dominant and nondominant shoulders of 21 collegiate baseball pitchers without a history of shoulder instability or surgery. A proprioceptive testing device was used to measure kinesthesia and joint position sense. Joint position sense was significantly (P =.05) more accurate in the nondominant shoulder than in the dominant shoulder when starting at 75% of maximal external rotation and moving into internal rotation. There were no significant differences for proprioception in the other measured positions or with kinesthesia testing. Six pitchers with recent shoulder pain had a significant (P =.04) kinesthetic deficit in the symptomatic dominant shoulder compared with the asymptomatic shoulder, as measured in neutral rotation moving into internal rotation. The net effect of training, exercise-induced laxity, and increased external rotation in baseball pitchers does not affect proprioception, although shoulder pain, possibly due to rotator cuff inflammation or tendinitis, is associated with reduced kinesthetic sensation.

Follicular variant of papillary thyroid carcinoma: a comparative study of histopathologic features and cytology results in 141 patients.

OBJECTIVE: To characterize the histopathologic features of follicular variant of papillary thyroid carcinoma (FVPC) and its cytology results on fine-needle aspiration (FNA) biopsy and compare them with those of papillary thyroid carcinoma (PC). METHODS: We searched the University of Massachusetts Medical Center pathology database for all surgical specimens associated with a diagnosis of FVPC or PC between January 1992 and February 1998 and reviewed the related pathology reports. In addition, the associated preoperative FNA results were analyzed. RESULTS: On initial assessment, FVPC was associated with a significantly lower incidence of cervical lymph node metastatic involvement in comparison with PC (5.6% versus 35.7%; P<0.001). Even though the mean size of FVPC was larger than that of PC (2.57 cm versus 1.75 cm; P<0.05), FVPC showed a lower incidence of thyroid capsule invasion (5.6% versus 11.4%), infiltrative resection margins (2.8% versus 20.0%; P = 0.01), local soft tissue invasion (7.0% versus 25.7%; P<0.005), and multicentricity (25.4% versus 47.1%; P<0.01). Lymphocytic thyroiditis was a common feature of both FVPC (36.6%) and PC (35.7%). FNA biopsy revealed the presence of malignant cells in 9.8% of patients with FVPC in comparison with 67.5% of patients with PC. Most cytology specimens of FVPC (58.8%) were interpreted as suspicious for a malignant lesion or as a follicular neoplasm. CONCLUSION: FVPC is associated with a significantly lower incidence of cervical lymph node metastatic lesions and invasive histologic features than is PC. Long-term prospective clinical studies are needed to determine whether these findings translate into a more benign natural history for this variant of PC. Results of FNA biopsy in FVPC are more commonly interpreted as suspicious rather than malignant; this factor has major implications for preoperative planning.

Expression of eukaryotic translation initiation factors 4E and 2alpha correlates with the progression of thyroid carcinoma.

Cell growth and proliferation depend on protein synthesis that is regulated, in part, by two eukaryotic translation initiation factors, eIF-4E and eIF-2alpha. These factors are transiently increased as normal cells respond to growth factors and are constitutively elevated in transformed cells. In cultured cells, eIF-4E facilitates cell cycle progression by increasing the expression of cell cycle promoting proteins including cyclin D1. Our previous study revealed elevated cyclin D1 expression in histologically more aggressive thyroid carcinomas as compared to conventional papillary carcinoma. We hypothesized that the increased cyclin D1 expression might correlate with increased eIF-4E expression. We, therefore studied the expression of eIF-4E by immunohistochemistry in 25 cases of conventional papillary carcinoma (CPC) and 28 cases of aggressive thyroid carcinomas (ATC), the latter included 11 tall cell/columnar cell variant of papillary carcinoma, 5 insular carcinomas, and 12 anaplastic carcinomas. We also analyzed the expression of eIF-2a in the same samples as this factor is usually regulated similarly to eIF-4E in cell culture models. Of the 25 CPC, 13 were eIF-4E positive (11 weakly and 2 strongly), and 19 were eIF-2a positive (14 weakly and 5 strongly). Conversely, of the 28 ATC, 25 were eIF-4E positive (4 weakly and 21 strongly), and 23 were eIF-2alpha positive (4 weakly and 19 strongly). There was a significantly increased expression of both eIF-4E (p < 0.001) and eIF-2alpha (p < 0.001) in ATC compared to CPC, suggesting that these translation initiation factors may play a role in the progression of thyroid cancer.

Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle.

Control of proliferation and differentiation by the retinoblastoma tumor suppressor protein (pRB) and related family members depends upon their interactions with key cellular substrates. Efforts to identify such cellular targets led to the isolation of a novel protein, EID-1 (for E1A-like inhibitor of differentiation 1). Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity. EID-1 is rapidly degraded by the proteasome as cells exit the cell cycle. Ubiquitination of EID-1 requires an intact C-terminal region that is also necessary for stable binding to p300 and pRB, two proteins that bind to the ubiquitin ligase MDM2. A pRB variant that can bind to EID1, but not MDM2, stabilizes EID-1 in cells. Thus, EID-1 may act at a nodal point that couples cell cycle exit to the transcriptional activation of genes required for differentiation.

Harvesting the human genome: the Israeli perspective.

The post-genome era is at our door, and soon the complete human genome sequence will be available for the next set of goals. Israel is well equipped and skilled to join the worldwide harvest of the human genome, but additional massive government investment is required. This will affect various domains of activity, including the fields of diagnostics and therapeutics. The technologies and know-how described above constitute the basis for future human genome applications in Israel.

Musculoskeletal injuries in the young tennis player.

Tennis is becoming increasingly popular, especially with young athletes. Despite recent advances in epidemiologic research of tennis injuries, there still is a need for more injury research in all of the racquet sports. The data that does exist show that the young athlete is susceptible to injury in these different sports. Injury patterns in the skeletally immature racquet sports athlete are becoming apparent. Although most of the sports result in similar injury patterns, such as a predominance of lower extremity injury, there are differences. It appears that the physical demands of the sport are becoming more clearly documented, and the adaptive response to these demands is becoming understood. The adaptive response reveals a common origin for many of the injuries in the different sports. This is related most often to repetitive microtrauma with resultant loss in flexibility and strength. The sports medicine practitioner must understand these differences, know the demands, do serial musculoskeletal evaluations for maladaptations, and adhere to a periodized prehabilitation program of preventative exercises to maximize performance and minimize injury risk.

The role of cell cycle regulatory protein, cyclin D1, in the progression of thyroid cancer.

Cell cycle progression is facilitated by cyclin-dependent kinases that are activated by cyclins including cyclin D1 and inactivated by cyclin-dependent kinase inhibitors (CDKIs) such as p27. Our previous studies have demonstrated decreased p27 expression in both papillary and more aggressive carcinomas of the thyroid compared to thyroid adenoma and almost similar level of cyclin D1 expression between thyroid adenoma and papillary carcinoma. These results indicate that CDKIs may have an important role in the carcinogenesis of the thyroid and that they probably have a limited role in malignant progression of the thyroid cancer. The role of cyclin D1 in malignant progression of thyroid carcinoma has yet to be established. We studied the expression of cyclin D1 by immunohistochemistry in 34 cases of conventional papillary carcinoma (CPC), 10 cases of minimally invasive follicular carcinoma (MIFC), and 32 cases of more aggressive thyroid carcinoma (ATC), which included 11 tall cell variants, one columnar cell variant of papillary carcinoma, seven insular carcinomas, and 13 anaplastic carcinomas. Cyclin D1 staining was classified by staining score as 0, negative; 1+, less than 25%; 2+, 25 to 50%; and 3+, more than 50% tumor cells staining positive. Kruskal-Wallis one-way ANOVA and Wilcoxon Rank Sum/Mann-Whitney U Test was used to assess the difference in the expression of cyclin D1 between the study groups. Twenty-eight out of the 34 CPCs were cyclin D1 positive, 24 (70%) were 1+, 3 (9%) were 2+, and one (3%) were 3+ positive. Seven of 10 MIFCs were cyclin D1 positive, five (71%) were 1+, and the remaining two (29%) were 2+ positive. On the other hand, 28 of 32 ATCs showed cyclin D1 immunostaining. Of these, three (9%) were 1+, five (13%) were 2+, and 20 (63%) were 3+ positive. This study demonstrates a significant overexpression of cyclin D1 in ATC compared CPC (P < .001) and MIFC (P < .005), suggesting that the cyclin D1 expression may play a role in tumor progression and may have prognostic significance in thyroid cancer.

Zoster paresis of the shoulder. Case report and review of the literature.

More than 95% of people in the United States are infected with the varicella zoster virus at some time in life, and this infection usually is manifested as chicken pox during childhood. The virus then establishes a latent infection of sensory ganglia, from which it may reactivate many years later to cause herpes zoster (shingles), a cutaneous painful rash along a dermatomal distribution. Less commonly, the varicella zoster virus may result in myotomal motor weakness or paralysis in addition to a painful dermatomal rash. A case of unilateral left C5-C6 segmental paresis attributable to herpes zoster in an otherwise healthy individual and a current review of the literature are presented. A case of zoster paresis of the shoulder muscles is presented to remind the orthopaedic community that this diagnosis may be confused with other diagnoses, including rotator cuff tear, and should be considered in the differential diagnosis of shoulder pain and shoulder girdle muscle weakness.

Cloning, expression, and functional characterization of the substrate binding subunit of rat type II iodothyronine 5'-deiodinase.

Type II iodothyronine 5'-deiodinase catalyzes the bioactivation of thyroid hormone in the brain. In astrocytes, this approximately 200-kDa, membrane-bound enzyme is composed of at least one p29 subunit, an approximately 60-kDa, cAMP-induced activation protein, and one or more unidentified catalytic subunit(s). Recently, an artificial type II-like selenodeiodinase was engineered by fusing two independent cDNAs together; however, no native type II selenodeiodinase polypeptide is translated in the brain or brown adipose tissue of rats. These data suggest that the native type II 5'-deiodinase in rat brain is unrelated to this artificial selenoprotein. In this report, we describe the cloning of the 29-kDa subunit (p29) of type II 5'-deiodinase from a lambdazapII cDNA library prepared from cAMP-induced astrocytes. The 3.3-kilobase (kb) cDNA encodes an approximately 30-kDa, 277-amino acid long, hydrophobic protein lacking selenocysteine. Northern blot analysis showed that a 3.5-kb p29 mRNA was present in tissues showing type II 5'-deiodinase activity such as brain and cAMP-stimulated astrocytes. Domain-specific, anti-p29 antibodies specifically immunoprecipitated enzyme activity. Overexpression of exogenous p29 or a green fluorescence protein (GFP)-tagged p29 fusion protein led to a >100-fold increase in deiodinating activity in cAMP-stimulated astrocytes, and the increased activity was specifically immunoprecipitated by anti-GFP antibodies. Steady-state reaction kinetics of the enzyme in GFP-tagged p29-expressing astrocytes are identical to those of the native enzyme in brain. Direct injection of replication-deficient Ad5-p29(GFP) virus particles into the cerebral cortex of neonatal rats leads to a approximately 2-fold increase in brain type II 5'-deiodinating activity. These data show 1) that the 3.3-kb p29 cDNA encodes an essential subunit of rat type II iodothyronine 5'-deiodinase and 2) identify the first non-selenocysteine containing subunit of the deiodinase family of enzymes.

Oligomerization reduces heparin affinity but enhances receptor binding of fibroblast growth factor 2.

The biological response of cells to fibroblast growth factors (FGFs) depends on heparan sulphate glycosaminoglycans sharing particular structural motifs. Heparin induced FGF dimerization has been suggested to mediate receptor dimerization and activation. Here we demonstrate that heparin-derived oligosaccharides that promote receptor binding and activation specifically induce the dimerization of basic FGF (FGF2). These heparin-induced dimers of FGF2 acquire high affinity for receptor binding and are biologically active. Using biotinylated FGF2 bound to immobilized streptavidin gradually saturated with biotin, enabled a quantitative analysis of heparin-dependent and heparin-independent FGF2 monomers and oligomers. Streptavidin induced FGF2 dimers bind and activate FGF receptors only in the presence of heparin. An excess of streptavidin, forcing biotin-FGF2 into monomers, reduces receptor binding and blocks FGF-dependent cell proliferation. All these suggest predominant receptor binding and activation by heparin associated FGF2 oligomers. Unexpectedly, heparin induced dimers and higher order oligomers lose most of their affinity towards heparin. Direct binding of soluble FGF receptors (FGFRs) to either monomers or dimers of FGF2, immobilized on heparin, confirm the preferred association of FGFRs with dimers of FGF2. Computerized molecular docking predicts a cis-oriented FGF2 dimer, stabilized by heparin, which complies with all the experimental data.

Proprioception in the posterior cruciate ligament deficient knee.

This study was undertaken to evaluate knee proprioception in patients with isolated unilateral posterior cruciate ligament (PCL) injuries. Eighteen subjects with isolated PCL tears were studied 1-234 months after injury. The threshold to detect passive motion (TTDPM) was used to evaluate kinesthesia and the ability to passively reproduce passive positioning (RPP) to test joint position sense. Two starting positions were tested in all knees: 45 degrees (middle range) and 110 degrees (end range) to evaluate knee proprioception when the PCL is under different amounts of tension. TTDPM and RPP were tested as the knee moved into flexion and extension from both starting positions. A statistically significant reduction in TTDPM was identified in PCL-injured knees tested from the 45 degrees starting position, moving into flexion and extension. RPP was statistically better in the PCL-deficient knee as tested from 110 degrees moving into flexion and extension. No difference was identified in the TTDPM starting at 110 degrees or in RPP with the presented angle at 45 degrees moving into flexion or extension. These subtle but statistically significant findings suggest that proprioceptive mechanoreceptors may play a clinical role in PCL-intact and PCL-deficient patients. Further, it appears that kinesthesia and joint position sense may function through different mechanisms.

Heparin differentially regulates the interaction of fibroblast growth factor-4 with FGF receptors 1 and 2.

Fibroblast growth factor-4 (FGF4), like other FGFs, shares a high affinity for the anionic glycosaminoglycans heparin and heparan sulfate (HS), which in turn enhance FGF-receptor (FGFR) binding and activation. Here we demonstrate using a cell free system that, at low concentrations of heparin, FGF4 binds only to FGFR-2, while much higher heparin levels are required for binding to FGFR-1. Chemical crosslinking of radiolabeled FGF4 to the soluble FGF receptors confirms the preferential formation of FGF4-FGFR-2 complexes under restricted heparin availability, with maximal ligand-receptor interactions at almost 20-fold lower heparin concentrations then those required for the affinity labeling of FGFR-1. In accordance, HS-deficient cells expressing FGFR-2 proliferate in response to FGF4 at extremely low exogenous heparin concentrations, while FGFR-1 expressing cells are completely unresponsive under the same conditions. We suggest that FGFR-2 is the preferred receptor for FGF4 under restricted HS conditions and that the bioavailability of structurally distinct HS motifs may differentially control receptor specificity of FGF4 in vivo.

Lateral ankle sprains: a comprehensive review: part 1: etiology, pathoanatomy, histopathogenesis, and diagnosis.

Ankle sprains are among the most common injuries sustained by athletes and seen by sports medicine physicians. Despite their prevalence in society, ankle sprains still remain a difficult diagnostic and therapeutic challenge in the athlete, as well as in society in general. The purpose of this section of our two-part study is to review scope of the problem, the anatomy and biomechanics of the lateral ankle ligaments, review the pathoanatomical correlates of lateral ankle sprains, the histopathogenesis of ligament healing, and define the mechanisms of injury to understand the basis of our diagnostic approach to the patient with this common acute and chronic injury. We extensively review the diagnostic evaluation including historical information and physical examination, as well as options for supplementary radiographic examination. We further discuss the differential diagnosis of the patient with recurrent instability symptoms. This will also serve as the foundation for part two of our study, which is to understand the rationale for our treatment approach for this common problem.

Lateral ankle sprains: a comprehensive review part 2: treatment and rehabilitation with an emphasis on the athlete.

This is the second part of a two-part comprehensive review of lateral ankle sprains. In the first part of our review, we discussed the etiology, natural history, pathoanatomy, mechanism of injury, histopathogenesis of healing, and diagnostic approach to acute and chronic lateral ligamentous ankle injuries. Conservative intervention and treatment of grade I-III and chronic, recurrent sprains of the lateral ankle ligaments and appropriate rehabilitation guidelines are the topics of this article. We review the use and benefit of different modalities and external supports and outline our five-phase intervention program of rehabilitation based on the histopathogenesis of ligament healing. We discuss the expected timing of recovery of the acute injury as well as the management of chronic, recurrent ankle sprains. Treatment of acute ankle sprains depends on the severity of the injury. Conservative therapy has been found to be uniformly effective in treating grade I and II ankle sprains. Some controversy exists regarding the appropriate treatment of grade III injuries, particularly in high-level athletes. Our belief is that the majority of these patients may also be treated well with conservative management. Other options for the management of grade III sprains will be briefly discussed at the end of this article.